ANZUP's A little below the belt magazine | July 2021

A little below the belt Conducting clinical trial research to improve outcomes for bladder, kidney, testicular, penile and prostate cancers

AN ANZUP CANCER TRIALS GROUP PUBLICATION

ISSUE 15, JULY 2021

Make a difference with ANZUP We need your help to improve outcomes for people affected by these below the belt (prostate, testicular, penile, bladder and kidney) cancers and for future generations.

Any donation, large or small, goes straight into the hands of experts to find the answers we need.

To find out more or to donate please go to https://anzup.org.au/donate/

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What is ANZUP? The Australian and New Zealand Urogenital and Prostate Cancer Trials Group was formed in 2008, bringing together a world-leading multidisciplinary team of doctors, nurses, other health care professionals, scientists, researchers, and community representatives, all working in areas related to urogenital cancer.

ANZUP has members in every state and territory in Australia and New Zealand, with an increasing international membership.

Urogenital cancers are those coming from the testicles, prostate, kidney, penis or bladder.

Australian Registered Charity: ACN 133 634 956 New Zealand Registered Charity: CC51217

ANZUP aims to improve outcomes for people affected by these cancers. We do this by performing clinical trials to generate new evidence for better treatments, or ways of providing other support.

Our members and investigators are widely dispersed and busy, working in a range of disciplines. A trial idea only comes to fruition when we are able to provide opportunities for people to meet, work through the science, develop the trial concepts, and write and work through all the other documentation and processes. Then it is necessary to initiate, run, monitor and report the trial results. All of this relies on the volunteered time of our members and is separate from the other needs ANZUP has to source the much larger amounts of funding to support the trials themselves.

“Every meaningful advance in treatment has been a result of testing a new idea in a clinical trial.”

Professor Ian Davis, ANZUP Chair

ANZUP acknowledges the Traditional Owners of the lands on which our company is located and where we conduct our business.

We pay our respects to ancestors and Elders, past and present. ANZUP is committed to honouring the First Peoples’ unique cultural and spiritual relationships to the land, waters and seas and their rich contribution to society.

The paper used in this edition is called Maine Recycled Digital – Silk. It is made with fibre derived only from sustainable sources and produced with a low reliance on energy from fossil fuels. The purchase of carbon offsets compensates for emissions produced over an international supply chain, from seedling through to final delivery to the customer.

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What’s inside 05 Message from the Chair, Professor Ian Davis 07 CEO Update 09 Consumer Advisory Panel (CAP) Update 10 Rally the troops 12 Friends of ANZUP 13 Prostate Cancer Specialist Nurses improving quality of care for cancer patients 16 Do you have a story you could share with others?

17 New ANZUP Trials coming soon 19 Scientists sit-up for world-first clinical trial into prostate cancer 21 Spotlight on prostate cancer 23 A new class of effective therapy for men with metastatic castration-resistant prostate cancer 25 Worldwide prostate cancer trial now open internationally 26 ENZAMET – NEJM, QoL Translational update 27 ANZUP co-badged study ProPSMA wins ACTA Trial of the Year for 2021 28 ANZUP trials – prostate 32 Spotlight on bladder and urothelial cancer 34 This is the only cancer where survival rates are decreasing in Australia. It’s time to talk about it.

36 World first trials investigating targeted bladder cancer treatment

ANZUP Cancer Trials Group Limited Registered office Level 6, Lifehouse Building 119-143 Missenden Road Camperdown NSW 2050 T: +61 2 9562 5042 F: +61 2 9562 5008 www.anzup.org.au

@ANZUPtrials / @BelowTheBeltANZ

ANZUPtrials / BelowTheBeltCancer

37 ANZUP trials – bladder 39 Spotlight on testicular cancer 41 International Germ Cell Cancer Collaborative Group update: positive news for seminoma germ cell cancer patients 42 ANZUP trials – testicular 44 Spotlight on kidney cancer 46 I firmly believe a clinical trial saved my life 49 Hillcrest Foundation supports ANZUP’s Kidney Cancer Project / New ANZUP website 50 Strengthening immune therapy in kidney cancer – the goal of the KEYPAD clinical trial 51 ANZUP trials – kidney 53 Spotlight on penile cancer 55 Trials in follow up

ANZUP

58 Community Fundraising

61 Below the belt #YourWay

@ANZUPtrials

60 How does your donation make a difference?

62 Belt Research Fund

ANZUP Cancer Trials Group

ACN 133 634 956 ABN 32 133 634 956

Editors Lucy Byers and Gillian Bailey Graphic Design by Designcycle

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64 See your suburb #YourWay / The mini challenges 65 2021 Move #YourWay results / Fundraising heroes 66 2021 Move #YourWay ambassadors 69 #YourWay Sponsors and Supporters 71 Corporate Supporters and In-Kind Supporters

Message from the Chair, Professor Ian Davis Welcome to this latest edition of “A little below the belt.”

2021 is an Olympic year! Strangely, it’s a number not divisible by 4; the host country, Japan, is in the grip of the worldwide COVID-19 pandemic; athletes will do the Games by a fly-in / fly-out model, assuming quarantine issues are solved; but hey, international sport is back! The Olympic Games always includes the old favourites: the athletics, the swimming, and more modern additions like sailing, but most Games also include something different as a demonstration sport. This year, being in Japan, it’s sumo wrestling as it was in 1964. I bet many people are like me: we will sit down to watch it, entirely ignorant of the sport, probably balancing a bowl of chips on a soonto-be-sumo waistline, and within 10 minutes we will be shouting at the television: “Hey, that was a kinjite! That wouldn’t know his azukari from his ebanzuke!” We’ll be armchair experts in no time. You know it’s true.

It’s funny how quickly we become experts in areas we really know nothing about. Sometimes it goes even further where people feel the need to put in their opinions and try to override a true expert, and that can be hilarious. It’s been called “correctile dysfunction” and here’s a great example from Twitter: @gary4205: Maybe you should learn some actual SCIENCE then, and stop listening to the criminals pushing the #GlobalWarming SCAM! @AstroKatie: I dunno, man, I already went and got a PhD in astrophysics. Seems like more than that would be overkill at this point.

It can also get dangerous, for example when Certain People promote unproven ideas like injecting highly poisonous bleach into your veins, and other people carry the story and give it weight equal to the recommendations made by people who really know what they’re doing. The media is often complicit in this and justifies it somehow by thinking that every side of a story must be given equal value, when this is clearly not true.

The most recent examples have been the firestorm of publicity around the extremely rare complications associated with the AstraZeneca COVID-19 vaccine.

Everybody has an opinion on this, and everybody suddenly seems to know everything about virology, vaccinology, RNA biology, haematology, public health, cold chain logistics, statistics, and probability theory. Never mind that some of the responses equate to, “This bridge is a little bit rickety. Clearly it’s much better if I swim the crocodile infested waters instead.” The risk to your life of crossing the road to get to the vaccine clinic is hundreds of times higher than the risk of the vaccine itself. For the record: I’ve had the AZ vaccine (twice), gladly and with profound gratitude, and fully aware of the tiny risks. My advice to everyone is to get whatever version of the vaccine you are offered, as soon as you get the chance.

It’s worth stopping to think, though. How many decisions do we make every day? How do we decide on the right course of action? Sometimes you can genuinely use your own experience: I know that road is always busy at this time of day and they’re doing roadworks this week; I’ll take the alternate route instead even though it’s longer and I’ll get there much sooner. The penalty for making the wrong decision because you are misinformed might be a bit of inconvenience.

We don’t have that luxury in health care. Get it wrong, and people die. Some viruses are not just “a little flu” or “one day – it’s like a miracle – it will disappear.” Sometimes our decisions have huge ramifications, and might affect people beyond just ourselves including those we love. Will I ignore that growing lump? A bit of blood in the urine – nah, must have been the beetroot. Wow, my testicle is getting bigger, that’s going to impress them on the beach. No, I must have just pulled a muscle working in the garden, the pain will go away. I’ve been diagnosed with a serious disease and now I have to choose between two options that both sound horrible for me. What if I get it wrong? What if I regret my decisions later? What am I going to do?

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Sometimes it’s clear what has to be done, but very often in medicine there is no clear right answer, or maybe there are several answers that are all right in different ways but you still have to choose one. You take an aspirin for your headache, and you expect it to go away. It probably will, and you will think nothing further of it. You don’t take into account the science behind how it works, or the technology in producing it, or the fact that you might bleed to death or have a stroke because of that tablet (you almost certainly won’t! But you might...) You’ve already made a risk-benefit calculation, probably without even knowing it; or someone has made that calculation for you and you haven’t questioned it. There’s evidence that this will help you in this situation, and you’ve followed the evidence.

Unfortunately, it’s not always so clear cut, and cancer is a great example of that. Sometimes there just is no evidence to guide us, in which case we take advice from experts who draw on their experience and extrapolate from other situations. That is not evidence-based practice, it’s “eminence-based” practice, but at least it’s better than “effluence-based” practice, which is what you might get if you go on the internet and get unfiltered and unverified information.

What can we do about this? It’s pretty clear that we will be able to make better decisions if we are better informed, with reliable evidence that has been tested and shown to stand up. That is what organisations like ANZUP do. We work with people affected by below the belt cancers (cancers of the prostate, kidney, bladder, testicle, or penis). We recognise that people affected by these cancers need information to support the decisions they must make. Our job is to provide that information where we can, but ANZUP goes further: we try to generate the evidence where it does not exist.

That means coming up with new ideas, and testing them properly in well-designed clinical trials. Our hope is that the outcomes of those trials will help us move the whole field ahead, by informing health policy, changing practice, and generating new research questions. The end result of all this is that we want to improve outcomes for people affected by these cancers.

We have examples where we’ve been able to do this quite effectively. ANZUP led a large international clinical trial in prostate cancer, which has changed the way that disease is managed in many parts of the world, including Australia. We have proven that another novel treatment for prostate cancer was superior to the previous standard of care. We are testing new approaches in bladder cancer and testicular cancer, and are hoping to have similar trials in penile cancer soon. We have also shown that some ideas that seemed really good and sensible actually did not work and should not be used. “Negative” results like that are also very important information: did you know that outcomes for people with COVID-19 treated with hydroxychloroquine are actually worse, when the studies are done carefully?

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This accumulation of evidence doesn’t happen by accident or in isolation. It takes careful planning, a great deal of energy from a lot of people, considerable money, and (to everyone’s annoyance) lots and lots of time. One of the reasons why some people are suspicious of COVID-19 vaccines is that they came to market so quickly, and it’s true that this was extremely unusual: vaccines usually take years before they become available. The global catastrophe meant that it had to be accelerated, and resources were put into it to make it happen, but of course the longest follow-up we have right now for anyone injected with a COVID-19 vaccine cannot be more than a year so how can we be confident of long-term safety? Still, the benefits were clear (actually, they were quite extraordinary), they are very very safe, the technologies are not new so we can extrapolate to some extent from what we knew before, and of course they need to be rolled out as soon as possible.

Wouldn’t it be great if we could get safe and effective new cancer treatments out to the people who need it like we have with COVID-19 vaccines? Well, we can’t do that just yet, but that doesn’t mean we stop trying. You might be reading this magazine because you’ve been personally affected by a below the belt cancer, or you know someone who has, or perhaps you’re just curious. You will find inside these pages a truly amazing group of people doing truly amazing work that is already making a difference. We are constantly aware of the needs of people affected by these cancers, because we work with them, care for them, live with them, and some of us are them. We know the science, because we have spent years preparing for these moments. We know what needs to be done and we are working hard to make it happen.

How can you help? You already have. You’re thinking about below the belt cancers, which are often forgotten or overlooked or tucked away out of sight and Below the Belt. You’re thinking about how important and valuable it is to have the necessary evidence to guide decision making and improve outcomes. You’re perhaps thinking about clinical trials in a new light, understanding why they are necessary and how hard they are to do. Perhaps you’re in a position where you might participate in a clinical trial. Perhaps you’re in a position where you might donate to support our research. Perhaps you can help us make other people aware of the importance of all these things. Whatever it is: you’re here, we thank you, and we hope what you find in these pages not only answers some questions for you but stimulates new ones as well. If that turns out to be the case, it actually means you’re one of us at heart.

Please enjoy this edition of “A little below the belt.”

IAN DAVIS Chair, ANZUP

A message from the CEO, Margaret McJannett ANZUP is a cancer cooperative trials group whose mission is to conduct clinical trial research to improve treatment and outcomes for people affected by bladder, kidney, testicular, penile and prostate cancer. This group of cancers are called urogenital cancers, but we refer to them as below the belt cancers.

Despite the ongoing challenges of outbreaks and snap lockdowns due to COVID-19, ANZUP has remained committed to conducting high quality below the belt cancer trials and research.

The need for improved cancer treatments and outcomes does not stop. And just as we did last year when the pandemic first reared its ugly head, we have continued to be responsive to the health advice and adjust our trials operations and plans in order to maintain productivity, while always ensuring the health and wellbeing of our ANZUP team, members and our trial participants.

We have continued with our virtual Zoom meetings allowing us to host our pipeline of innovative concept development workshops and meetings. We held the second virtual fundraising event, #YourWay, which saw 146 participants around Australia and New Zealand move anywhere, anyway and at any time throughout the month of May. We are very grateful to all our generous donors, raising over $75,000 which will be directed to supporting our pipeline of future clinical trials via the Below the Belt Research Fund https://anzup.org.au/ awards-and-grants/below-the-belt-research-fund/.

Due to the current situation we have been forced to move our face to face annual conference in July to a virtual meeting in October. We also made the difficult decision to postpone our Melbourne Pedalthon cycling fundraising event but are keeping our fingers crossed our Sydney Pedalthon will still go ahead later in the year.

But most importantly, throughout all the ups and downs, we have continued to develop and are soon to open some exciting new research studies which are keeping us extremely busy.

The first is a research project, CLIMATE, which focusses on testicular cancer. Micro-ribonucleic acid (miRNA), is a blood test under investigation which evaluates a protein commonly found in testicular cancer. Early studies have found that miRNA is detectable in blood samples of men who have known testicular cancer. The aim of this study is to evaluate the role for miRNA in predicting the risk of cancer recurrence following orchidectomy (surgical removal of one or both testicles) in men who do not have any additional treatment.

If the protein is found following testicular cancer surgery it will indicate if further treatment, or a watch and wait approach, will be necessary.

The second is a trial which also focusses on a blood protein – but this time in prostate cancer. The GUIDE trial aims to show that some men may be able to have breaks in treatment rather than having chemotherapy continuously, which is currently the standard of care.

EVOLUTION is another new prostate cancer trial. This trial is combining radionuclide therapy with immunotherapy and be given to patients who are no longer responding to hormone therapy. The study is supported by the Prostate Cancer Foundation of Australia.

Removing the kidney (or part of a kidney) by surgery is currently the best treatment if you have kidney cancer.

Our next new trial, RAMPART will investigate if taking one drug (durvalumab) or a combination of two drugs (durvalumab and tremelimumab) can prevent or delay kidney cancer coming back following surgery.

All our existing trials have continued and some have reached important milestones. The DASL-HiCAP trial, which only opened last year (during COVID-19), is a new cancer trial for treatment of men with high risk, clinically localised prostate cancer. Even with COVID-19 restrictions and challenges worldwide, we are delighted that this ANZUP led international trial has now opened in Australia, New Zealand, Canada and most recently, Ireland, the UK and USA.

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Outcomes of the trial will be measured in terms of whether the addition of darolutamide decreases the risk of spread of prostate cancer to other parts of the body as well as improving quality of life and decrease the risk of prostate cancer death.

The American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium is the preeminent genitourinary oncology event held each year. This year at ASCO GU the ANZUP TheraP trial results were presented. TheraP is the first randomised trial comparing a novel radionuclide active treatment, to the current standard-of-care chemotherapy for men with metastatic castration-resistant prostate cancer. These men had disease that had already progressed after standard chemotherapy.

This unique treatment involves first “mapping” the cancer with a PET scan, then treatment with a radioactive substance, Lutetium-177, attached to a similar molecule as used for the PET scan. This novel dual approach of imaging and treatment is called “theranostics.” A favourable response has been demonstrated and this is the first trial in the world comparing a radioactive treatment to an active and effective treatment, and has provided evidence that this might be a good alternative option to chemotherapy for men with advanced and pretreated prostate cancer.

As well as the TheraP trial results being presented at ASCO GU, they were also featured in a high profile medical journal, ‘The Lancet’.

Other ANZUP trial news includes: • O ur BCG+MM study in bladder cancer welcomed the first international site, Nottingham University Hospital in the UK, onto the trial and the first patient was recruited. This large-scale, randomised trial will determine the effects of adding mitomycin (a chemotherapy agent) to BCG (a bacteria) on cure rates, survival, side effects, and quality of life.

• C ancer Trials Ireland held their first ‘Cancer Retreat’.

This virtual ‘Cancer Retreat’ – was a day-long online event that provided an opportunity to discuss how the cancer trials community works together, how that might be improved, and the challenges and opportunities that may emerge in the coming five years. ANZUP was invited to speak at this inaugural event.

• T he ANZUP co-badged study, ProPSMA, won the Australian Clinical Trials Alliance (ACTA) Trial of The Year. This was the 2nd year in a row that ANZUP has been recognised for this prestigious award. This clinical trial is investigating a new type of scan which provides whole body images of prostate cancer spread. Early experience suggests this new technology, called PSMA PET/CT (prostate specific membrane antigen positron

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emission tomography/computed tomography), is superior to current scanning techniques. PSMA PET/ CT has capacity for wide availability at relatively low cost. Performing a single better test rather than several less accurate scans will also be cheaper, improve patient experience and expose patients to lower amounts of radiation.

• O ur ENZA-p Clinical Trials Protocol featured in the BJUI Journal - congratulations to Professor Louise Emmett and all the ENZA-p team for getting this published.

• W e also recently launched our first ever tax appeal.

Every dollar raised from the appeal will go directly towards clinical trial research of ‘below the belt’ cancers. The focus of our tax appeal was prostate cancer and our practice-changing ENZAMET clinical trial.

All current and new trial activity would not be possible without our committed membership. Their ongoing support and dedication to ANZUP, even in light of the current bumps in the road, has allowed us to continue to bridge gaps in knowledge and search for more favourable treatment options, as well as better outcomes, for people affected by below the belt cancer. We also acknowledge the importance of the next generation of scientists and clinical researchers. They will pave the way for clinical trials to come so we continue to seek opportunities to educate and mentor our members.

All the work currently being undertaken and planned would not be possible without the incredible generosity and support of those in the community. Thank you to everyone who has donated to ANZUP - your help allows us to continue to build on and develop high quality, cutting edge, clinical trials. The level of support we receive from our membership and from the wider community, organisations large and small, is nothing short of extraordinary.

If you are interested in receiving regular updates from us, we invite you to join “Friends of ANZUP.” This community will help you stay connected with the work we do. It’s free and you can join by going to https://anzup.org.au/ join-us-friends-of-anzup/.

And finally, I would like to express my gratitude and thanks to the many thousands of patients who participate in ANZUP trials. With your support and cooperation, we can continue to improve treatments and outcomes for the patients and their families affected by below the belt cancers.

On behalf of the ANZUP management team please enjoy this edition of ‘A little below the belt’.

MARGARET MCJANNETT CEO, ANZUP

Consumer Advisory Panel (CAP) update

By Belinda Jago, CAP Chair

The ANZUP Consumer Advisory Panel (CAP) are a group of dedicated volunteers who have had a cancer diagnosis themselves or have cared for a family member/loved one with cancer.

The CAP plays a vital role in the provision of advice and feedback from a community perspective on ANZUP’s research strategy and priorities, and on community engagement and support. We also provide advice on trial design and conduct, recruitment, and two-way communication strategies to support dissemination of research findings back to the community.

CAP members are drawn from a broad range of backgrounds and have a wide perspective of the needs of cancer sufferers.

The past 12 months have been a very anxious time for patients, carers and their families. They have had to deal with a cancer diagnosis as well as the added stress of the pandemic.

However, the patients were certainly in good hands with health professionals and the health services providing their care. They were able to adapt delivery of care ensuring patient safety and clinical care was not compromised. We are extremely grateful to our dedicated health providers for their extraordinary efforts during this difficult time.

The CAP continues to participate in ANZUP activities using virtual meeting platforms. In some respects, it gave us a greater opportunity to attend as travel costs and personal time were greatly reduced.

We have actually had a really busy 6 months with the need to review a number of Participant Information and Consent Forms for new clinical trials.

We were also able to take part in the recent Renal Cell Carcinoma (RCC) Horizon Scanning Meetings. They are a series of structured activities and discussions to identify and explore the top research priorities for RCC research in Australia and New Zealand. From a consumer perspective we are very pleased to see this important activity being initiated for kidney cancer patients. Their future outcomes will benefit from pursuing the identified priorities.

On a global scale, being in Australia/New Zealand has been the best place to be. We are very much looking forward to the future where vaccination programs will allow us to travel again and see the return of face-to-face ANZUP meetings that we all love so much.

We have some special highlights in this edition of CAP members helping to support and promote the importance of clinical trials. Melissa Le Mesurier provided a very personal insight about her cancer diagnosis and treatment along with Shomik Sengupta who led her treatment and is an ANZUP Board member – please see page 34 for details and a must read.

We also had a first for the ANZUP CAP. One of our longer-term members, Colin O’Brien and a prostate cancer patient, recently presented a concept (an idea for a new research project) at the Prostate Concept Development Workshop.

The CAP were once again very active with the recent Below the Belt Move #YourWay fundraising campaign held in May through participating, fundraising and donating. It was a fun way to set some targets you wouldn’t normally, (I don’t usually walk that far each month!), and raise awareness and funds. For Victorians part of this challenge was once again done in lockdown.

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In the media:

Rally the troops We channelled our pain into action

BELINDA JAGO

“We raised nearly $14,000”

Credit: Take 5 magazine | July 2021

Belinda Jago, 61 Melbourne, Victoria Taking a deep breath, I looked at my daughter’s oncologist, Associate Professor Guy Toner. “I’d like to volunteer” I announced. “I want something to focus on”.

Four months earlier, I’d lost my 19-year-old daughter, Bec, to kidney cancer. For five years she’d battled the disease with a smile on her face. No matter how tough it got, she’d always stayed positive.

Surrounded by a close group of friends, Bec managed to still enjoy a few teenage rites of passage, like her year 12 formal. She event went to schoolies in Surfers Paradise, although her dad, Tony and I had to stay nearby so we could help with pain management at night.

When she passed away, we were devastated, as were our sons, Matt, 21 and Tom, 16. But even in the midst of our grief, we knew we wanted to use the experience to make change. So, I approached Guy about volunteering for the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), where he worked as Deputy Chair.

BELINDA RACKING UP KM’S BELINDA & BEC

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He suggested a position on their consumer advisory panel. Like me, everyone on the panel had personal experience with what ANZUP called “below the belt” cancers. We used our consumer perspective to give opinions and advice on upcoming trials.

Getting to help people just like my family was the most amazing experience.

Over the years, ANZUP grew and now, 10 years later, we’re also raising hundreds of thousands of dollars through the Move Your Way challenge.

For the second year in a row, Tony and I took part.

Over a month, with the help of 20 friends and family members, we walked a combined 1100km under the team name Bec’s Troops and raised nearly $14,000.

Losing our daughter at such a young age was tragic but I’m determined to do my bit in making the world a better place. You only get one chance at life.

To learn more about ANZUP, visit www.anzup.org.au.

BELINDA & FAMILY

‘Our family – we all miss Bec so much I’m determined to help make a difference’

BEC

Y UR WAY

To learn more about Below the Belt Your Way go to page 61.

Tony Jago

Belinda Jago

I committed to walk 300 kms for the month of May and have to say it was looking very doubtful as the 10 days first week were spent in the Whitsundays. While that was great, it wasn’t good for racking up the km’s.

So, a big high five to everyone who has so magnificently supported the Becs Troops team through walking, exercising, fundraising and donating.

When I got back to work, I put my head down and started walking hard to get as many km’s on the board as I could, while helping to raise money for #ANZUP. I didn’t think I would get there but just kept trying to reach my goal (300 kms) and was spurred on by two main motivators: • I am so proud of the work Belinda does as the Chair of the ANZUP Consumer Advisory Panel.

As a volunteer she works tirelessly often late at night, weekends, week nights, spare time. She organised the Becs Troops Team to get involved and what a great result, nearly $13,000 raised so far – woo hoo.

Congratulations Belinda.

• Of course, my other motivator is Bec, she sat on my shoulder for every kilometre and spurred me on whenever I started to struggle.

Belinda and I walked many km’s together and often talked about Bec while pounding the pavement. This often started a few tears as we walked, I’m sure people who saw us wondered what was going on. If only they knew.

We got there and am very proud of what we have achieved as a team. Thanks to all the family and friends who contributed to make it so successful, we really appreciate your support.

It has been a great month and while we could not celebrate our success together we all made the most of the “team” event in #lockdown style. Thanks to the team for sharing your day and we have put together a great team photo. Hopefully we will be able to catch up and celebrate together at a later date.

Some great milestones have been achieved by the team with some remarkable individual efforts and together we have: • raised in excess of $12.7k • walked over 1100kms • danced and exercised for more than 148 hrs This has been a true team collaboration and Tony and I feel immensely grateful for everyone who has pitched. It makes a difference and helps support clinical trials for #belowthebelt cancers and improve future outcomes for patients like Bec. To our beautiful Bec – you asked us if we would miss you and we surely, surely do every day, and 10 years on it still often feels like yesterday. But you live in our hearts and inspire us to make the most of our lives that we have the privilege to live and being part of the #YourWay challenge is one of the ways for us to give back and help others.

Thanks once again to our family and friends – you are awesome. Take care and stay safe.

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Have you or your loved ones been affected by below the belt – prostate, kidney, bladder, penile and testicular – cancers? Do you want to join a community that gives you access to the latest forums, publications, fundraising activities and trials?

Join “Friends of ANZUP” and connect with people whose lives have been impacted by below the belt cancers, and learn from ANZUP clinical experts and researchers.

“Friends of ANZUP” provides: • Information about clinical trials research and how to access them, • Support from people who understand the challenges of living with below the belt cancers, • The community magazine, ‘A little below the belt’ featuring: o regular updates and stories from health professionals and researchers, o cancer survivors and cancer trial participants points of view, • Invitation to the annual Community Engagement Forum.

Join “Friends of ANZUP” and help us achieve our mission to improve the outcomes and treatment for those living with testicular, penile, prostate, kidney and bladder cancers.

If we can encourage people to ask: “Is there a clinical trial suitable for me?” then we have achieved a major step forward.

To find out more visit: https://anzup.org.au/join-us-friends-of-anzup/ or email friends@anzup.org.au 12 A LITTLE BELOW THE BELT

Prostate Cancer Specialist Nurses improving quality of care for cancer patients Prostate cancer can take a significant toll on all areas of life – including an individual’s physical and mental health, and their relationships.

“But having access to this is incredibly important and gives men greater confidence that they can navigate the challenges of prostate cancer.

This is why the Prostate Cancer Foundation of Australia (PCFA) has nearly 90 Prostate Cancer Specialist Nurses and Telenurses situated in hospitals and cancer care centres across the country, providing on-the-ground specialist support to help patients, and their families, navigate the unfamiliar journey.

“Our research confirms that men who get support from our Prostate Cancer Specialist Nurses and Telenurses are better able to manage their diagnosis and navigate the health system.”

Prostate cancer is the most commonly diagnosed cancer in Australian men, with nearly 17,000 men newly diagnosed each year.

PCFA’s Director of Nursing Programs, Adjunct Prof Sally Sara, said having the support of a specialist nurse could vastly improve quality of life and survivorship outcomes for men impacted by the disease.

Adjunct Prof Sara said with one in five men with prostate cancer experiencing long-term anxiety and depression, specialist nurses are there to ensure no one goes through a diagnosis alone.

Australia’s only Prostate Cancer Specialist Nursing Service was first launched by PCFA in 2012 and has since expanded from 12 nurses to around 90 nurses.

In early 2021, the charity also launched the nation’s first Prostate Cancer Specialist Telenursing Service, further improving accessibility to support.

To find out more, or connect with a nurse, phone Prostate Cancer Foundation of Australia on 1800 22 00 99, or visit www.pcfa.org.au.

Prostate Cancer Specialist Nurses provide:

“From the point of diagnosis, our nurses offer expert education and information about treatment plans, referrals to services both in the hospital and community, and provide an ongoing point of contact and support for men and families,” she said.

• Expert

nursing advice during diagnosis, treatment, and recovery

“It’s common for patients to struggle with understanding their treatment options and accessing evidence-based information about the pros and cons of surgery, chemotherapy, and radiation treatment or hormone therapy.

• Care and support for partners and families

ADJUNCT PROF SALLY SARA

• C onnection to local prostate cancer services • Access to local support groups

• H elp with managing treatment sideeffects, such as erectile dysfunction and incontinence.

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International Clinical Trials Day May 20th marked International Clinical Trials Day, an opportunity to celebrate those who strive to find answers to the tough clinical questions. The improvements in health outcomes as a result of clinical trials are momentous, enabling the development of new interventions, helping to raise standards of treatment, and – crucially - benefiting patients by enabling faster access to the latest treatment.

Education and innovation International Nurses Day International Nurses Day is celebrated around the world every May 12, the anniversary of Florence Nightingale’s birth.

The theme for 2021 was Nurses: A Voice to Lead – A vision for future healthcare. In 2021, we seek to show how nursing will look into the future as well as how the profession will transform the next stage of healthcare.

ANZUP nurses lead the way and support clinical trials research, transforming the next stage of healthcare.

ANZUP thanks all nurses for the extraordinary contribution they make every day.

Clinical trials hail as far back as the Old Testament.

Daniel’s subscription to a diet of pulses and water had left him fit and healthy, whilst his companions, subsisting on meat and wine (at the recommendation of King Nebuchadnezzar II), fell ill. It was this discovery, the isolation of diet as the cause for poor health, that many deem the first clinical trial.

Most famously however, was Dr. James Lind’s discovery aboard the HMS Salisbury on this day in 1747, which is widely recognised as the first true clinical trial. Whilst working as a naval surgeon at sea, Dr. James Lind acted on a hunch that the humble citrus fruit could cure scurvy.

He isolated six pairs of scurvied seamen, administering a different remedy to each. Lind’s experiment proved his instinct was correct, providing evidence that there was a clear link between the introduction of oranges and lemons into the diet of seamen, and scurvy prevention. Lind’s discovery revolutionised modern medicine and paved the way for clinical trials to come.

Today (very much on dry land) clinical trials have evolved into procedures focusing on patient safety and requiring informed consent from all participants.

ANZUP’s clinical trials bring together all of the professional disciplines and groups involved in researching and treating below the belt cancers to identify gaps in evidence and areas of clinical need.

We thank all ANZUP members for their dedication to finding answers to clinical questions, and to all the patients who participate in clinical trials. We celebrate them for their commitment to improving health outcomes for themselves and all those affected by testicular, bladder, kidney, penile and prostate cancers.

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Cancer Trials Ireland, Cancer Retreat On Friday 21st May Cancer Trials Ireland hosted Ireland’s inaugural Cancer Retreat – a virtual event where the cancer clinical trials community could meet at a watershed moment for cancer trials in Ireland.

Why a watershed moment? Two main reasons.

First, in Ireland we are entering a new funding model, and cycle, for state-funded cancer trials in 2022.

The Irish government, through the Health Research Board, has mandated the introduction of ‘clusters’ (re-organised trial sites) and the inclusion of academic partners (universities) in ‘cluster’ and ‘network’ grant applications. As such, Cancer Trials Ireland joined with the Royal College of Surgeons, Ireland (RCSI) to apply for grant funding as the Cancer Clinical Trials Network.

These application processes signalled a change in how the Network (Cancer Trials Ireland) and the trial sites (clusters) would work together from 2022, and that alone merited discussion.

The second reason is, of course, the pandemic.

COVID-19 has had a huge impact on cancer services in Ireland, just as it has around the world. So how could and should we, as a community, respond – both in the services we provide for patients, and as a voice within the health system.

The day rolled out via a publish session first – with three panels – followed by two members-only sessions (including breakout groups) around 1) Our Disease Specific Sub-Group meetings (how we as a network involve and collaborate with investigators in Ireland) and 2) Trial logistics – accrual, feasibility, trial complexity, the upcoming EU Clinical Trials Regulation.

The Retreat, or rather most of its participants, also had to contend with a Ransomware attack that effectively shut down emails for the Irish health system – a crisis that is ongoing at the time of writing. Nevertheless, the community rallied and showed great commitment to re-register for the Retreat through personal email addresses and attend the event in whatever capacity they could.

More than 250 people attended the opening session, which included a panel discussion featuring Profession Ian Davis, the chair of ANZUP Cancer Trials Group.

Prof Davis spoke as part of a panel discussing “ambition for cancer trials in Ireland”, along with the head of the Irish Health Research Board, the CEO Irish Cancer Society (the largest patient organisation in the country) and an industry body representative, Roisin Molloy (IPHA / Merck).

Responding to a question about why ANZUP chooses to collaborate with Cancer Trials Ireland, Prof Davis said it was because the organisations share goals, vision and commitment for solving problems.

“Our mission is very much the same – we’re here to improve outcomes for cancer patients, and we were looking for partners in that part of the world that would enable us to move into the UK and Europe. We found Cancer Trials Ireland was a highly accomplished organisation that worked in a very similar way to ourselves in ANZUP”, said Prof Davis.

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DO YOU YOU HAVE DO HAVE A STORY A STORY YOU COULD YOU COULD SHARE WITH SHARE WITH OTHERS? OTHERS? Shareyour yourstory storywith with us us here Share here anzup@anzup.org.au anzup@anzup.org.au Create awareness and let others know they are Create not aloneawareness and let others know they are not alone.

FIGHT CANCER

BELOW THE BELT • TESTICULAR • PROSTATE • BLADDER • KIDNEY • PENILE 16 A LITTLE BELOW THE BELT

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ANZUP trials coming soon

New ANZUP trials coming soon Clinical trials are essential for discovering new treatments for diseases, as well as new ways to detect, diagnose, and reduce the chance of developing the disease. That means learning about what we are dealing with (both the disease, and the person affected by it); understanding what treatment approaches might be available, and what is coming up; testing the new ideas to see if they are safe, whether they actually work and make a difference, how often they should be administered, the cost of the new treatment and if there are any side effects.

Below are four new ANZUP clinical trials that will be opening soon. They aim to improve treatments and outcomes for testicular, prostate, and kidney cancer patients. They will test gaps in knowledge, and hopefully lead to greater understanding of these cancers whilst also providing more treatment options in the future.

Testicular cancer: CLIMATE (ANZUP1906) Assessing the Clinical utility of miR-371a-3p as a marker of residual disease in Clinical Stage 1 Testicular Germ Cell Tumour, following orchidectomy.

Testicular cancer is the most common cancer diagnosed in men aged between 15 and 39 in Western countries, however it can occur at any age. Most men diagnosed with testicular cancer will have cancer confined to the testicle, without evidence of spread to other areas of the body. These men are highly likely to be cured following surgical removal of the testicle (orchidectomy) alone, and most will not require additional chemotherapy or radiotherapy. Sometimes, a man may choose to undergo preventive chemotherapy or radiotherapy, which reduces the risk of their cancer coming back; however, this may result in long-term side effects for some men.

For this reason, most men in Australia are recommended “active surveillance,” which involves regular reviews with their doctor, computerised tomography (CT) scans and blood tests, but no chemotherapy or radiotherapy.

With this approach, most men will be spared from unnecessary treatment and side effects. However, a small number of these men will have recurrent cancer detected during active surveillance. Reassuringly, these men are also highly likely to have a positive outcome following additional treatment.

A new blood test, micro-ribonucleic acid (miRNA), which evaluates a protein commonly found in testicular cancer, is under investigation. Early studies have found that miRNA is detectable in blood samples of men who have known testicular cancer.

“Testicular cancer is a highly curable cancer, however, in those who need treatment, side effects from treatment can result in long term impact on quality of life. Sometimes, patients are given treatment when there is a high suspicion of recurrence of testicular cancer, but not all of these patients actually have a recurrence. Current blood tests and scans can only be so good at confirming recurrence of testicular cancer. A new blood test is being developed that looks very promising at being an extremely sensitive and specific blood test for testicular cancer. CLIMATE is an ANZUP study aimed at determining whether this blood test, miR-371, is sufficiently accurate in order to be used to guide treatment or non-treatment, thereby improving QOL in testicular cancer survivors.”

CLIMATE Principal Investigator, Associate Professor Ben Tran

CLIMATE is a new collaboration between ANZUP and the Walter and Eliza Hall Institute of Medical Research.

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ANZUP trials coming soon Prostate Cancer: GUIDE (ANZUP 1903) A randomised non-comparative phase II trial of biomarker-driven intermittent docetaxel versus standard-of-care (SOC) docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

The purpose of this study is to see if a prostate cancer marker in the blood (mGSTP1) can be used to guide chemotherapy treatment. Based on the level of this blood marker, some men may be able to have breaks in treatment rather than having chemotherapy continuously which is the current standard of care. This study will tell us if having these treatment breaks guided by mGSTP1 can improve how men feel during treatment while still treating the prostate cancer effectively.

Prostate Cancer: EVOLUTION (ANZUP 2001) A Phase II Trial of dual Immunotherapy and Lu-PSMA in metastatic castration resistant prostate cancer (mCRPC).

Although men with metastatic prostate cancer initially respond to hormone treatments, many will develop castration-resistant prostate cancer, i.e., their cancer continues to grow despite hormone treatment. This condition is called mCRPC. Immunotherapy and 177 Lutetium PSMA-617 (Lu-PSMA for short) are two treatments that we hope might help men in this situation.

Ipilimumab and nivolumab are immunotherapy drugs that activate the body’s own immune response to kill cancer cells. Both ipilimumab and nivolumab allow the immune system to “see” the cancer, seek it out and destroy it.

These treatments are given intraveneously (IV) and have been effective in treating other cancers like melanoma, kidney and lung cancers, but studies of ipilimumab and nivolumab in men with prostate cancer remain experimental at present.

Lu-PSMA is a type of treatment called radionuclide therapy that can be used to treat prostate cancer by bringing radioactive atoms into the cancer cells. Many prostate cancers, in particular those that have spread or become resistant to hormonal therapies, have a substance on their cell surface called prostate specific membrane antigen (PSMA). Lu-PSMA attaches to PSMA on the surface of prostate cancer cells and delivers radiation to the cancer cell, without much radiation exposure to other parts of the body. Recent studies have

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“The GUIDE study is investigating how we can use a blood marker to optimise chemotherapy treatment in metastatic prostate cancer. Using this marker, we aim to personalise chemotherapy to minimise side effects and improve quality of life while ensuring that treatment is still effective.”

GUIDE Principal Investigator, Dr Kate Mahon The GUIDE Trial is another exciting partnership between ANZUP and the Chris O’Brien Lifehouse.

shown that Lu-PSMA is a promising treatment for men with metastatic prostate cancer that is no longer under control after several standard treatments.

The aim of this study is to see if combining ipilimumab and nivolumab with Lu-PSMA can further improve the anti-cancer effects of Lu-PSMA. It is thought that ipilimumab and nivolumab and Lu-PSMA may work together to treat the cancer. Lu-PSMA can potentially kill cancer cells and break up the tumour into small pieces that may be recognised by your immune system while ipilimumab and nivolumab helps your immune system to be activated to find and attack your cancer.

This new treatment combination may lead to shrinkage or stabilisation of previously progressing tumours and therefore hopefully stop or reverse the growth of your cancer. We plan to enrol 100 Australian men in this trial.

“The EVOLUTION trial will investigate the combination of radiotherapy with immunotherapy to treat patients with advanced prostate cancer, and to see if they have a better response and outcome during their treatment.”

EVOLUTION Principal Investigator, Associate Professor Shahneen Sandhu EVOLUTION is a partnership between ANZUP Cancer Trials Group Limited (ANZUP) and Prostate Cancer Foundation of Australia (PCFA).

ANZUP will be collaborating with ARTnet, the Australian Nuclear Science and Technology Organisation (ANSTO) and the NHMRC CTC, University of Sydney to conduct this trial. We thank and acknowledge BMS and Novartis for funding and product support.

Media Release 10 June 2021

Scientists sit-up for world-first clinical trial into prostate cancer The nation’s leading prostate cancer researchers have announced a ground-breaking Phase II clinical trial which could help prevent the deaths of more than 3,100 Australian men every year.

The trial will be led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) with co-funding from Prostate Cancer Foundation of Australia (PCFA).

Known as EVOLUTION, it will be the first clinical trial of its kind to test the effectiveness of a new generation of radiotherapy treatment with existing forms of immunotherapy, which has previously failed in treating prostate cancers.

PCFA CEO Professor Jeff Dunn AO said the project was leading the world in prostate cancer research.

“The Phase II EVOLUTION Clinical Trial could lead to major advances in the treatment of advanced prostate cancer around the world, helping to prevent the deaths of more than 3,100 Australian men each year from this disease,” Prof Dunn said.

“ANZUP’s world-leading team of researchers, working with treatment centres to recruit patients around the country, will investigate whether immunotherapy, when partnered with Lutetium-177-PSMA (Lu-PSMA), can deliver life-saving results for men.

“Right now, we have no way of defeating aggressive forms of prostate cancer, which impose an incredibly heavy burden on men and their families, who commonly have to endure the fear and distress of not knowing how quickly the cancer will spread.

“The EVOLUTION Clinical Trial will help us to evaluate whether radiotherapy and immunotherapy combined can create a new pathway for combatting prostate cancer once and for all.

“Around 17,000 men are diagnosed with prostate cancer each year in Australia, and more than 3,100 men will die – it is a disease that takes a tragic toll on our lives.

“We are committed to funding ground-breaking projects that save lives.”

Next week is PCFA’s Sit-Up 45 Challenge, calling on Aussies to do 45 sit-ups a day during Men’s Health Week (June 14-20) to raise vital funds for PCFA and the EVOLUTION Clinical Trial.

ANZUP Chair Professor Ian Davis urged Australians to support prostate cancer research.

“The Phase II EVOLUTION Clinical Trial simply wouldn’t be possible without funding from organisations such as PCFA,” Prof Davis said.

“I would urge all Australian men and women who want to make a difference in our fight against prostate cancer to support our work by registering for the Sit-Up 45 Challenge via situp45.org.au.

“The challenge calls on people to do 45 daily sit-ups during the week in solidarity with the 45 Australian men who are diagnosed with prostate cancer every day.

“Sit-up to prostate cancer and help us fund the EVOLUTION Clinical Trial to eliminate a silent killer in our community.”

Aussies can still get involved in Sit-Up 45 by registering at www.situp45.org.au.

The EVOLUTION Clinical Trial sites and patient eligibility guidelines will be announced later this year.

The project will monitor and compare PSA levels for 12 months in response to the clinical trial treatment, capturing tissue samples to analyse patient responses.

With one Australian man diagnosed every 30 minutes, there are estimated to be 230,000 Australian men alive today who have been impacted by prostate cancer.

For more information about PCFA, visit www.pcfa.org.au or call 1800 22 00 99.

“We are proud to see PCFA launch the Sit-Up 45 Challenge, to help continue this work.

The EVOLUTION clinical trial sites and patient eligibility guidelines will be announced later this year. The project will monitor and compare PSA levels for 12 months in response to the clinical trial treatment, capturing tissue samples to analyse patient responses.

With one Australian man diagnosed every 30 minutes, there are estimated to be 230,000 Australian men alive today who have been impacted by prostate cancer.

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ANZUP trials coming soon Kidney Cancer: RAMPART (ANZUP1606) Renal Adjuvant MultiPle Arm Randomised Trial (RAMPART): An international investigator-led phase III multi arm multi stage multi-centre randomised controlled platform trial of adjuvant therapy in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse.

Removing the kidney (or part of a kidney) by surgery is currently the best treatment if you have kidney cancer. The current standard treatment after surgery is ‘active monitoring’. This means no further treatment, but having regular checks, so that if the cancer does come back, further treatment options can be considered as early as possible.

Surgery, together with ongoing regular follow-up and observation, is the standard approach for people diagnosed with kidney cancer that has required removal of the kidney (or part of a kidney) by surgery.

For some people the cancer may return which is when other treatment is offered. We are aiming to find out whether taking one drug (durvalumab) or a combination of two drugs (durvalumab and tremelimumab) can prevent or delay kidney cancer coming back.

It is anticipated that 1750 participants will be enrolled in this study in Australia, New Zealand, UK, France, USA and other countries.

It has been shown to be effective in treating a number of different types of cancer, particularly when used in combination with other cancer treatments.

Other drugs similar to those in this study have been shown to be effective in people with more advanced kidney cancers. In Australia, nivolumab (a drug similar to durvalumab) used by itself or in combination with ipilimumab (a drug similar to tremelimumab) are current approved treatments for people with kidney cancer that has spread outside the kidney. They are not approved for treatment of kidney cancer that has been removed, like yours.

Given similarities in the mode of action to these drugs, and based on prior research findings, we think durvalumab and tremelimumab are worthwhile drugs to test for patients to see if it will prevent or delay kidney cancer returning.

“Most kidney cancers can be cured by removing them surgically, but some are destined to come back again. Many treatments have been tested to see if that risk of cancer recurrence can be reduced but until recently none had worked, so the standard of care is to watch our patients carefully after surgery and offer additional treatment if the cancer does come back. We know treatments that activate the immune system can be effective in kidney cancer that has spread, and have been shown to reduce the risk of cancer recurrence after surgery in other types of cancer. RAMPART will test two different ways of activating the immune system compared to our best standard of care, to see if this treatment is effective in reducing the risk of kidney cancer recurrence. Information presented in 2021 at a major cancer conference using a similar but different approach gives support to the idea that this question should be tested.”

RAMPART Principal Investigator (Australia), Professor Ian Davis

Durvalumab is a type of treatment called an immunotherapy, and may sometimes be referred to as an ‘anti-PDL1 drug’ or ‘immune checkpoint inhibitor’. It works by helping your own immune system to attack the cancer.

Durvalumab is currently being tested by itself or in combination with other treatments in many types of cancer. Early studies have shown that durvalumab works well and has side effects that can usually be controlled.

Durvalumab has been studied in clinical trials involving more than 13,000 people with various cancer types. It has been shown to be effective in some settings but has not been tested yet in people with kidney cancer that has been removed.

Tremelimumab is another immunotherapy treatment for cancer. It may sometimes be called an ‘anti-CTLA4 drug’ or ‘immune checkpoint inhibitor’. It also works by helping your immune system to attack the cancer.

Tremelimumab has been studied in clinical trials in over 1,500 people.

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Spotlight on prostate cancer The prostate is a walnut-sized gland located in front of the rectum, behind the base of the penis, and below the bladder. It surrounds the urethra, the tube-like channel that carries semen and urine through the penis. The main function of the prostate is to make seminal fluid, the liquid in semen that protects, supports, and helps transport sperm.

In 2020:

16,700+

estimated new diagnoses in Australia

95%

five year survival rate after diagnosis

3,150+ deaths in Australia each year

What is prostate cancer?

cancer. It is more common in older men, with 67 per cent of cases diagnosed in men over 65 years of age.

Prostate cancer begins when healthy cells in the prostate change and grow uncontrollably, forming a tumour. A tumour can be benign or cancerous. A cancerous tumour is malignant, meaning it can grow and spread to other parts of the body. A benign tumour means the tumour can grow but will not spread.

In 2020, it was estimated that 16,741 new cases of prostate cancer would be diagnosed in Australia.

Prostate cancer is slightly unusual when compared with other cancer types. This is because many prostate tumours do not spread rapidly to other parts of the body. Some prostate cancers grow at a very slow rate and may not cause problems or symptoms for years, or sometimes ever. Even when prostate cancer has spread to other parts of the body often it can be managed for a long time. So people with prostate cancer, and even those with advanced prostate cancer, may live with good health and quality of life for many years. However, if the cancer cannot be well controlled with existing treatments, it can cause symptoms like fatigue and pain and sometimes can lead to death.

An important part of managing prostate cancer is monitoring it for growth over time, in order to find out if it is growing slowly or rapidly. Based on the pattern of growth, your doctor can then decide the best available treatment options and when to give them.

Prostate cancer is the second most common cancer diagnosed in Australia and the fourth most common cause of cancer death. By the age of 85, it is estimated one in seven men will be diagnosed with prostate

The five-year survival rate for men diagnosed with prostate cancer has increased over the years from 60 per cent to 95 per cent. Nearly all patients who present with localised disease will live beyond five years.

In 2020, deaths from prostate cancer were estimated to be 3,152.

Prostate cancer symptoms Symptoms are not usually seen with early prostate cancer. Advanced prostate cancer symptoms can include: • Frequent urination, particularly at night; • Pain on urination; • Blood in the urine; • A weak urine stream; • Pain in the pelvis or back • Weak legs or feet If the disease becomes more widespread and found in the bones, it can cause unexplained pain, fatigue and weight loss.

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Spotlight on prostate cancer Causes of prostate cancer Some of the risk factors for prostate cancer: • A ge, increasing greatly if you are aged over 50 years; • F amily history of prostate, breast or ovarian cancer, especially BRCA1 and BRCA2 gene mutations;

3. Surgery will become an option if the tumour has not spread outside the prostate. The prostate and some of the surrounding tissue will be removed, including the seminal vesicles. This is called a radical prostatectomy.

4. Radiotherapy can take two forms: a. external beam radiation therapy – where a machine outside the body directs radiation towards the prostate gland

• A brother or father diagnosed with prostate cancer before the age of 60 years • T here is also an association with high testosterone levels.

b. i nternal radiation therapy (brachytherapy) – where small radioactive ‘seeds’ are placed inside the prostate.

Treatment Options

5. Cryosurgery involves inserting long needles through the perineum into the prostate. Very cold gases are then passed through the needles, which freezes the prostate and destroys cancer cells.

If you do not have a family history of prostate cancer, you may want to consider tests for early detection after discussing the risks and benefits with your general practitioner (GP).

If you have a family history of prostate cancer, your GP should discuss the option for annual PSA testing.

Your general practitioner (GP) will assess your symptoms, conduct a physical examination and arrange blood tests if needed. Your GP should also discuss your needs (including psychological, physical, social and information needs) and suggest sources of reliable information and support.

Treatment and care of people with cancer is usually provided by a multidisciplinary team, i.e a team of health professionals, both medical and allied health.

Your health care team will help decide the optimal course of treatment and take into consideration:

6. Hormone therapy involves reducing the levels of certain hormones in the body, so the cancer can slow its growth or even shrink. Hormone therapy for prostate cancer is also called androgen deprivation therapy (ADT).

7. Chemotherapy can also be used to treat prostate cancer.

8. Immunotherapy for prostate cancer works by helping a patient’s own immune system fight back against cancer cells. It is used to treat advanced cancer or cancer that has spread.

Clinical Trials

• the stage of the disease • the location of the cancer • the severity of symptoms • your general health and wishes.

Treatment may take various forms and may not be recommended straight away. Options include: 1. Watchful waiting where you might be monitored in case symptoms develop or change.

2. A ctive surveillance when you will likely have regular blood tests to check your PSA level, regular digital rectal examinations, and maybe ultrasounds or biopsies. If the cancer starts to grow or there are signs it is worsening, you might begin treatment.

New drugs and treatment approaches are constantly being developed and researched. New combinations of different strategies and therapies, as well as the development of new drugs, are constantly being trialled and tested to see if they can further improve treatment options and quality of life for men with advanced prostate cancer. Please talk with your doctor to see if there is a clinical trial suitable for you.

You can read more about ANZUP prostate cancer trials on page 28.

References: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-rankings-data-visualisation https://www.cancer.org.au/about-cancer/types-of-cancer/prostate-cancer/ https://www.prostate.org.au/awareness/for-recently-diagnosed-men-and-their-families/advanced-prostate-cancer/treatment/are-therenew-treatments/

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Global news: A new class of effective therapy for men with metastatic castration-resistant prostate cancer

PROFESSOR MICHAEL HOFMAN

Each year The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium is held.

It is the preeminent genitourinary oncology event, co-developed by committees with representatives from the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO). The Symposium offers focused educational sessions and abstract presentations organised into each below the belt cancer type.

This year ANZUP reported the results of its “TheraP” (ANZUP 1603) clinical trial at this event.

TheraP is the first randomised trial comparing 177LuPSMA-617 (Lu-PSMA), a novel radioactive treatment, to the current standard-of-care chemotherapy called cabazitaxel for men with metastatic castration-resistant prostate cancer. These men had disease that had already progressed after standard chemotherapy.

This unique treatment involves first “mapping” the cancer with a PET scan, then treatment with

a radioactive substance Lutetium-177 attached to a similar molecule as used for the PET scan.

This novel dual approach of imaging and treatment is called “theranostics.”

The primary endpoint of the study was to compare the effects of the two treatments on change in PSA, a blood biomarker of prostate cancer. A favourable response was demonstrated, defined by reduction of PSA by 50% or more. This occurred in 66% of men assigned to receive 177Lu-PSMA-617 compared to 37% with cabazitaxel chemotherapy.

In addition, 177Lu-PSMA-617 also delayed the time to progression. This is defined by a rise in PSA or progression on CT or bone scans. Patients assigned to receive 177Lu-PSMA-617 were 37% less likely to progress. At 12 months, 19% of men assigned to 177 Lu-PSMA-617 had not progressed, compared to 3% with cabazitaxel. Tumour shrinkage on CT scanning occurred in 49% assigned to receive 177 Lu-PSMA 617 compared to 24% with cabazitaxel.

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The 177Lu-PSMA-617 resulted in less side effects to patients than cabazitaxel. Severe adverse effects reported by physicians occurred in 33% with 177 Lu-PSMA-617 compared to 54% with cabazitaxel.

Patients reported less symptoms with 177Lu-PSMA-617 including hair loss, diarrhoea, fatigue, insomnia, dizziness, urinary symptoms, sore hands/feet and skin rash.

Study Chair Prof. Michael Hofman, of the Peter MacCallum Cancer Centre, said “The theranostics imaging test enables selection of men likely to benefit, whilst the treatment kills tumours and spares normal tissues. This new class of targeted treatment offers men quality of life and better response rates than chemotherapy. It is likely to be available globally in the next 2 years.”

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“TheraP is the first trial in the world comparing Lu-PSMA to an active and effective treatment, and has provided evidence that Lu-PSMA might be a good alternative option to chemotherapy for men with advanced and pre-treated prostate cancer. This is the culmination of years of work by a large team of clinicians, researchers, and community representatives,” said ANZUP Chair Professor Ian Davis.

Worldwide prostate cancer trial now open internationally A new cancer trial for men with high risk, clinically localised prostate cancer has now opened in Australia, New Zealand, Canada, USA, Ireland and the UK. The DASL- HiCaP trial (ANZUP1801), led by ANZUP Cancer Trials Group, enrolled its first patient at the Chris O’Brien Lifehouse in Camperdown, Sydney in April 2020.

Prostate cancer remains the most common cancer in Australian men and the leading cause of cancer related-mortality for men in developed countries. This new randomised phase 3 study aims to demonstrate that the addition of a new potent oral hormonal therapy, darolutamide,

“It was great to see DASLHiCaP open for recruitment in Canada, after many months of negotiations and setbacks due to COVID-19. I look forward to the trial opening in more sites across Canada in the coming months.”

to standard radiation therapy and testosterone suppression, improves the outcomes of men with localised high-risk prostate cancer.

Outcomes of the trial will be measured in terms of whether the addition of darolutamide decreases the risk of spread of prostate cancer to other parts of the body as well as improving quality of life and potentially decrease the risk of prostate cancer death.

This trial aims to recruit and follow up 1,100 eligible patients across over 100 cancer centres internationally – so it is exciting to see the trial opening at all centres with patient recruitment also beginning.

“Our hope is that this trial will define a new treatment paradigm by decreasing the risk of a relapse after local therapy for high risk localised prostate cancer.”

Study Co-Chair Professor Christopher Sweeney

A/Professor Tamim Niazi DASL-HiCaP Co-Chair

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ENZAMET – NEJM, QoL Translational update Doctors commonly start men newly diagnosed with metastatic prostate cancer on androgen deprivation therapy (otherwise known as ADT), along with a standard anti-androgen tablet (such as Cosudex or Anandron).

These drugs work in prostate cancer by shutting off the supply of testosterone, which is the fuel that drives prostate cancer growth. While this standard treatment is very effective, doctors and researchers are constantly striving for ways to improve treatment and increase patient survival from metastatic prostate cancer.

The striking results from the ENZAMET clinical trial, presented at the Plenary Session of the 2019 American Society of Clinical Oncology (ASCO) meeting, and published in the New England Journal of Medicine, have achieved just that.

ENZAMET is a large Phase 3 study that shows that giving enzalutamide to men just starting ADT reduced the risk of death at 3-years by a third, relative to giving ADT with the standard anti-androgen drug. Enzalutamide also significantly increased the time until the cancer showed signs of growing, either by symptoms, scans, or rising PSA. Before these findings, enzalutamide was given only to men with metastatic prostate cancer after ADT stopped working. This study now suggests that enzalutamide should be considered much earlier in the course of the disease, around the time of starting ADT when patients are diagnosed with metastatic cancer.

The ENZAMET trial began in 2014 and recruited 1125 patients from 83 medical centres around the world. Men with metastatic prostate cancer starting first-line ADT were enrolled in the study. The average age of the men in the study was 69 years; 11% of men had metastatic disease outside of the bones and lymph nodes.

The study is led by the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group.

The positive findings from the ENZAMET trial mean that men with metastatic prostate cancer may have another treatment option.

ENZAMET – Health Related Quality of Life (HRQoL) Health-related quality of life (HRQoL) in a randomised phase 3 trial of enzalutamide with standard first line therapy for metastatic, hormone-sensitive prostate cancer (mHSPC).

In the ANZUP-led ENZAMET trial, using enzalutamide along with androgen deprivation therapy (ADT) in men with metastatic prostate cancer who were “hormonenaïve” (men just starting ADT), reduced the risk of death, and significantly increase the time until cancer showed signs of growing.

ANZUP researchers know health-related quality of life is very important to men and their families.

So in the ENZAMET trial health-related quality of life of participants was measured. ANZUP evaluated aspects of health-related quality of life such as comfort, happiness, and well-being in men who received enzalutamide, and compared their experience with men receiving standard anti-androgen drug.

To study the health-related quality of life in ENZAMET participants, 3 widely-used questionnaires assessed the impact of treatment on several aspects such as physical comfort, mood, appetite, sleep, and sexual function. Men rated their own experience on these questionnaires covering these comprehensive domains.

Pleasingly, the results of the quality of life evaluation revealed that men who received enzalutamide reported their general health was steady and their overall quality of life stable. The use of enzalutamide delayed the onset of unpleasant symptoms. Although enzalutamide treatment negatively affected some aspects of health early on, this did not outweigh the subsequent quality of life benefits in the men’s cancer journey.

Translational work The ENZAMET trial is proving to be a gold mine for translational research, with planned studies in genomics, cytokines and lipidomics planned for 2021. ANZUP has an engaged world class team of translational researchers who meet regularly to consider the most important cutting-edge questions in order to improve treatment and outcomes for our patients. If you wish to support ANZUP’s Translational Research Program please go to https://anzup.org.au/what-is-gu-cancer/spotlight-on-translational-research/. Other completed trials such as TheraP are also a great reservoir of potential translational sub-studies, and any interested investigators are encouraged to contact the relevant study principal investigator to discuss.

26 A LITTLE BELOW THE BELT

ANZUP Co-Badged Study ProPSMA wins ACTA Trial of the Year for 2021 For the second year in a row an ANZUP study has won ACTA Trial of the Year. Congratulations to Study Principal Investigator Professor Michael Hofman and everyone who made this trial possible.

Prostate cancer is recognised as a silent disease in that there are often no symptoms present during the early stages. Once symptoms do begin to develop, the cancer is often further advanced and may have spread beyond the original tumour site. Imaging accuracy is critical to determining the best treatment plan for men who have received a prostate cancer diagnosis.

The award-winning trial uses a new imaging technique called PSMA PET/CT which can detect small sites of tumour spread that may not be detected with conventional imaging.

During the trial, 300 men with newly diagnosed prostate cancer participated across ten sites. Each participant had a whole-body 3D scan using a radioactive substance that detects a molecule called prostate specific membrane antigen (PSMA), which is readily found on the surface of prostate cancer cells. This was then followed by a PET/CT scan that produced detailed images of the cancer spread. The trial team found that PSMA PET/CT had an accuracy of 92% compared to 65% accuracy achieved with conventional imaging.

The findings were published in the peer-reviewed journal, The Lancet, in March 2020. ProPSMA was funded by a clinical trials grant from the Prostate Cancer Foundation of Australia and Movember.

Prof Hofman shared that the trial has already established a new standard of care for the assessment of men with prostate cancer.

“The results are being included in national and international clinical guidelines, and Ga-68 PSMA has also been approved by the US Food and Drug Administration,” he added.

A LITTLE BELOW THE BELT 27

ANZUP trials - prostate ANZUP is currently running a number of prostate cancer trials.

For more details information about these trials, go to the ANZUP prostate cancer trials web page: https://anzup.org.au/clinical-trial/enza-p/

ENZA-p ANZUP 1901 Status: Open and recruiting Location: Australia wide Planned sites: 12 Patients recruited: 54 • Patients required: 160

Enzalutamide is a potent hormone therapy that prevents testosterone from reaching prostate cancer cells, thereby stopping cancer growth. It is already widely used in men with prostate cancer that has stopped responding to standard hormone treatments (castration-resistant prostate cancer). However, most cancers become resistant to enzalutamide over time, with almost 1 in 4 being resistant from the start of treatment.

Many prostate cancers, in particular those that have spread or become resistant to hormonal therapies, have a substance on their cell surface called prostate specific membrane antigen (PSMA). Lutetium-177 PSMA (Lu-PSMA for short) is a new treatment in advanced prostate cancer. Lu-PSMA is a radioactive molecule that attaches to the surface of prostate cancer cells throughout the body. This drug is given as an injection through the vein and allows targeted radiation to be delivered directly to prostate cancer cells.

Smaller pre-clinical studies have demonstrated synergistic effects by combining Lu-PSMA with enzalutamide. It is possible that Lu-PSMA can prevent early resistance to enzalutamide, extending the time that men benefit from treatment.

The ENZA-p clinical trial aims to compare the effectiveness of enzalutamide in combination with Lu-PSMA, versus enzalutamide alone for the treatment of prostate cancer. This is a randomised study, so half the men in this trial will be randomly allocated to receive Lu-PSMA and enzalutamide, and the other half will be randomly allocated to receive enzalutamide alone.

We plan to enrol 160 participants across Australia.

For more information please refer to https://anzup.org.au/clinical-trial/enza-p/ Current locations for the ENZA-p trial: NSW • Calvary Mater Newcastle • Chris O’Brien Lifehouse • GenesisCare Northern Cancer Institute St Leonard’s • Liverpool Hospital • St Vincent’s Hospital VIC • Austin Health • Peter MacCallum Cancer Centre • The Alfred Hospital QLD • Royal Brisbane and Women’s Hospital SA • Royal Adelaide Hospital WA • Fiona Stanley Hospital • Sir Charles Gairdner

ENZA-p is funded through the Prostate Cancer Research Alliance (PCRA) – a program jointly funded by the Australian Government and the Movember Foundation (Movember).

28 A LITTLE BELOW THE BELT

A LITTLE BELOW THE BELT 28

ANZUP trials - prostate

DASL-HiCaP ANZUP 1801 Status: Open and recruiting Location: Australia & Internationally Activated sites: 39 Patients recruited: 196 • Patients required: 1100

The purpose of this study is to see if a new tablet drug, darolutamide, combined with the current best treatments, can improve outcomes for men with high risk prostate cancer that has not spread beyond the prostate area.

Previous studies have shown promising results for darolutamide preventing disease progression and improving survival for men with advanced prostate cancer.

This is a randomised controlled trial, which means that, in addition to best standard treatments, half the participants on the study will receive darolutamide, and the other half will receive placebo.

DASL-HiCaP is being led internationally by ANZUP with another exciting opportunity to collaborate with our partners at the NHMRC Clinical Trials Centre, the Canadian Cancer Trials Group, Cancer Trials Ireland (Ireland and UK), and the Memorial Sloan Kettering Cancer Center and Prostate Cancer Clinical Trials Consortium in the US. The University of Sydney is the Sponsor and and the NHMRC Clinical Trials Centre is the global coordinating centre.

We plan to enrol 1,100 men from Australia, New Zealand, Canada, US, Ireland, and the UK. We thank and acknowledge Bayer for providing funding and product fo the DASL-HiCaP Trial.

For more information please refer to https://anzup.org.au/clinical-trial/dasl-hicap-trial/ Current locations for the DASL-HiCAP trial: AUSTRALIA NSW • Border Medical Oncology Research Unit • Calvary Mater Newcastle • Campbelltown Hospital • Chris O’Brien Lifehouse • GenesisCare Newcastle • Gosford Hospital • Liverpool Hospital • Northern Cancer Institute-St Leonards • Prince of Wales Hospital • St George Hospital

• St Vincent’s Public Hospital, Sydney • Sydney Adventist Hospital • Wollongong Hospital VIC • Box Hill Australia • Peter MacCallum Cancer Centre • Peter MacCallum Cancer Centre (Bendigo Campus) • Peter MacCallum Cancer Centre (Moorabbin Campus) QLD • Icon Cancer Centre-Gold Coast University Hospital • Princess Alexandra Hospital • Radiation Oncology Princess Alexandra Hospital Raymond Terrace • Royal Brisbane and Women’s Hospital • Townsville Hospital SA • Ashford Cancer Centre Research WA • Fiona Stanley Hospital • Sir Charles Gairdner TAS • Royal Hobart Hospital IRELAND • Bon Secours Hospital, Cork NEW ZEALAND • Auckland City Hospital • Palmerston Hospital CANADA • Jewish General Hospital • Queen Elizabeth II Health Sciences Centre USA • Memorial Sloan-Kettering Cancer Center (MSKCC) • MSKCC - Commack (Satellite site) • MSKCC - Nassau (Satellite site) • MSKCC - Basking Ridge (Satellite site) • MSKCC - Westchester (Satellite site) • MSKCC - Monmouth (Satellite site)

A LITTLE BELOW THE BELT 29

Co-badged trials - prostate

#UpFrontPSMA Status: Open & recruiting Location: Australia wide Activated sites: 4 Patients recruited: 50 • Patients required: 140

Most prostate cancer cells have a molecule on their surface called prostate cancer specific membrane antigen (PSMA). PSMA can be targeted with Lutetium-177 PSMA (Lu-PSMA), a radioactive drug that kills prostate cancer cells anywhere in the body. This investigational drug is not approved for use in Australia by the Federal Government’s Therapeutic Goods Administration (TGA). It is a new form of treatment that is effective in some patients with metastatic prostate cancer. It is a radioactive substance that, after injection into a vein, attaches to prostate specific membrane antigen (PSMA). The treatment enables delivery of highly targeted radiation to cancer cells. The emitted radiation only travels about 1mm, which means it mainly causes the death of cancer cells, while avoiding healthy cells, and seems to be well tolerated with few side effects. This is called radionuclide therapy or theranostic therapy. The purpose of this randomised controlled clinical trial is to compare the effectiveness of Lu-PSMA therapy followed by docetaxel chemotherapy versus docetaxel chemotherapy on its own. Previous clinical trials have shown promising activity of Lu-PSMA in treatment of patients with metastatic prostate cancer.

Docetaxel is a chemotherapy drug that is approved by the TGA to treat prostate cancer and has been used for many years in the treatment of metastatic prostate cancer.

Since Lu-PSMA radiotherapy and docetaxel chemotherapy are both effective in treating metastatic prostate cancer, it is possible that using Lu-PSMA in addition to standard docetaxel chemotherapy at the beginning of the treatment course may improve patient outcomes when compared to treatment with docetaxel alone.

30 A LITTLE BELOW THE BELT

A recent phase 2 clinical trial, showed the effectiveness of Lu-PSMA when used as a last treatment option and helped control disease progression.This study brings the use of Lu-PSMA forward as a first option to patients, with the hope of disease eradication and potential cure.

The trial is open and recruiting.

For more information please refer to https://anzup.org.au/clinical-trial/upfrontpsma-trial/ Current locations for the #UpfrontPSMA trial: NSW • St Vincent’s Hospital Sydney QLD • Royal Brisbane and Women’s Hospital VIC • Peter MacCallum Cancer Centre • Austin Hospital

#UpFrontPSMA is funded through the Prostate Cancer Research Alliance (PCRA) – a program jointly funded by the Australian Government and the Movember Foundation (Movember).

Co-badged trials - prostate

NINJA Status: Open & recruiting Location: NSW and VIC Activated sites: 16 Patients recruited: 120 • Patients required: 474

The NINJA clinical trial aims to compare two emerging schedules of radiotherapy in the treatment of intermediate or high risk prostate cancer. Participants will be randomly assigned to one of two radiotherapy schedules as part of this study. In schedule 1 (called Stereotactic Body Radiotherapy) participants will receive 5 radiotherapy treatments over 2 weeks, and in schedule 2, (called Virtual High Dose Rate Boost), participants will receive Stereotactic Body Radiotherapy delivered in 2 treatments over 1 week followed by 12 treatments of conventional external beam radiotherapy over 2 and a half weeks. It is hoped this research will potentially improve the accuracy and quality of radiotherapy treatment in prostate cancer.

This study will include 474 men. Currently we have active sites across Australia and New Zealand with 120 patients currently enrolled.

This trial is open and recruiting. If you are interested in participating in the trial, please refer to https://anzup.org.au/clinical-trial/ninja/ This study is being led by the TransTasman Radiation Oncology Group and co-badged with ANZUP. The study is being funded by Cancer Australia, and we acknowledge MDI for providing the study drug.

Current locations for the NINJA trial: NSW • Calvary Mater Newcastle • Campbelltown Hospital • GenesisCare Hurtsville • GenesisCare Newcastle • Liverpool Hospitals • Illawarra Cancer Centre • St George Hospital • Westmead Hospital VIC • Peter MacCallum Cancer Centre (Parkville) • Peter MacCallum (Moorabbin) QLD • Princess Alexandra Hospital • Princess Alexandra (ROPART) SA • Genesis Care South Australia WA • 5D Clinics • Genesis Care Fiona Stanley Hospital NEW ZEALAND • Waikato Hospital NZ

A LITTLE BELOW THE BELT 31

Spotlight on bladder and urothelial cancer What is bladder cancer?

The bladder is a hollow organ in the pelvis that holds urine before it is is eliminated by the body during urination. This function makes the bladder a crucial part of the urinary tract. The urinary tract is also made up of the kidneys, ureters, and urethra. The renal pelvis is a funnel-like part of the kidney that collects urine and sends it into the ureter. The ureter is a tube that runs from each kidney into the bladder. The urethra is the tube that carries urine out of the body.

The prostate gland is also part of the urinary tract.

The bladder, like other parts of the urinary tract, is lined with a layer of cells called the urothelium.

This layer of cells is separated from the bladder wall muscles, called the muscularis propria, by a thin, fibrous band called the lamina propria.

Bladder cancer starts when healthy cells in the bladder lining – most commonly urothelial cells – change and grow uncontrollably, forming a mass called a tumour.

Urothelial cells also line the renal pelvis and ureters.

Cancer that develops in the renal pelvis and ureters is also considered a type of urothelial cancer and is often called upper tract urothelial cancer. In a lot of cases, it is treated similarly to bladder cancer.

A tumour can be cancerous or benign. A cancerous tumour is malignant, meaning it can spread and grow to other parts of the body. A benign tumour means the tumour can increase in size but will not spread. Benign bladder tumours are quite rare.

Types of bladder cancer Bladder cancer takes different forms: • u rothelial carcinoma, formally known as transitional cell carcinoma, is the most common form of bladder cancer (80-90%) and starts in the urothelial cells in the bladder wall’s innermost layer • s quamous cell carcinoma begins in the thin, flat cells that line the bladder • a denocarcinoma is a rare form which starts in mucusproducing cells in the bladder.

32 A LITTLE BELOW THE BELT

Bladder cancer may be limited to the lining of the bladder (non-muscle invasive bladder cancer NMIBC), invade the bladder wall (muscle invasive bladder cancer MINC) or spread further to lymph nodes or other organs (advanced or metastatic bladder cancer).

Among Australia’s 15 most common malignancies, bladder cancer remains the only one with survival rates that have worsened over the past 30 years.

Bladder cancer was the 11th most commonly diagnosed cancer in Australia in 2020. In 2020, it was estimated 3098 cases of bladder cancer would be diagnosed in Australia (2389 males and 710 females).

This is equivalent to an estimated incidence rate of 9.6 cases per 100,000 persons. Bladder cancer is more common in men than women and in people aged over 60 years. In addition, it was estimated there would be 1016 deaths in Australia from bladder cancer but from 2012 – 2016 on average, 54.3% of people diagnosed with bladder cancer survived 5 years after diagnosis.*

Bladder cancer can be treated effectively if found early and before it spreads outside the bladder.

Spotlight on bladder and urothelial cancer Bladder cancer symptoms The most common symptom of bladder cancer is blood in the urine (haematuria), which usually occurs suddenly and is generally not painful.

Other less common symptoms include: • Problems emptying the bladder; • A burning sensation when passing urine; • Pain when urinating; • Need to pass urine often; • Back pain or lower abdominal pain.

Causes of bladder and urothelial cancer Environmental risk factors are thought to be more important than genetic or inherited susceptibility when it comes to bladder cancer. Some factors that can increase the rise of bladder and urothelial cancer include: • smoking; • older age; • family history; • diabetes treatment using the drug pioglitazone; • w orkplace exposure to certain chemicals used in dyeing in the textile, rubber and petrochemical industries; • use of the chemotherapy drug cyclophosphamide; • c hronic urinary tract infections.

Common treatment approaches Many times, the best option might include more than one of type of treatment. Surgery, alone or with other treatments, is used to treat most bladder cancers.

Early-stage bladder cancers can often be removed.

But a major concern in people with early-stage bladder cancer is that new cancers often form

in other parts of the bladder over time. Taking out the entire bladder (called radical cystectomy) is one way to avoid this, but it causes major side effects.

If the entire bladder is not removed, other treatments may be used to try to reduce the risk of new cancers.

Whether or not other treatments are given, close follow-up is needed to watch for signs of new cancers in the bladder.

Depending on the stage of the cancer and other factors, treatment options can include: Bladder cancer surgery - type of surgery done depends on the stage of the cancer.

Intravesical therapy - the doctor puts a liquid drug right into your bladder rather than giving it by mouth or injecting it into your blood.

Chemotherapy - it can be given in 2 different ways, either straight into the bladder or given in pill form or injected into a vein or muscle. The drugs then go into the bloodstream and travel throughout the body.

Radiation therapy - uses high-energy radiation to kill cancer cells.

Immunotherapy - is the use of medicines to help a persons own immune system recognise and destroy cancer cells.

Targeted therapy - as researchers have learned more about the changes inside cells that cause cancer, they have developed newer drugs that target some of these changes. These targeted drugs work differently from other types of treatment, such as chemotherapy, and they may work in some cases when other treatments don’t.

Clinical trials - several ground-breaking bladder cancer trials using some of the therapies listed above, are currently underway in Australia. You can read more about ANZUP’s bladder cancer trials on pg 37.

The worsening bladder cancer survival rates over the past 30 years can mainly be attributed to Australia’s ageing population as the percentage of patients diagnosed with bladder cancer over the age of 80 years has gradually increased. Early identification and referral can lead to timely diagnosis. In addition, the hope is that novel approaches are identified through clinical trials and help reverse the trend of deteriorating survival rates in bladder cancer.

* https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/summary

A LITTLE BELOW THE BELT 33

In the media:

This is the only cancer where survival rates are decreasing in Australia It’s time to talk about it.

Credit: Cassandra Green | Body and Soul | April 29, 2021

Melissa Le Mesurier thought she just had a bad UTI. She couldn’t have been more shocked to find out it was cancer.

Four years ago, Melissa Le Mesurier went to the doctor for what she thought was a persistent UTI. Little did she know she was about to be diagnosed with bladder cancer, the only cancer where survival rates are decreasing in Australia.

Her symptoms were minimal. She was having trouble passing urine but feeling the urge to go. It gradually got worse and after not being able to pass urine for 12 hours on holiday, she knew it was time to see a specialist.

Her urologist, Professor Shomik Sengupta performed a cystoscopy (visualisation of the bladder via a camera) and a tumour was found. Just a few weeks later she was back in to get it removed (thankfully it hadn’t invaded the muscle wall or metastasised elsewhere in the body).

“The good news was that with early detection and treatment, this type of cancer has a five year survival rate of 95%. It’s not so good news for those diagnosed with a bladder cancer that has spread into the bladder wall (69% survival rate) or beyond the bladder cancer wall (33%). So, all in all, I considered myself lucky,” she says.

However, awareness and diagnosis isn’t always that easy.

“If your doctor suspects you have bladder cancer, they will examine you and arrange tests,” says her urologist Professor Sengupta.

“The tests you have will depend on your specific situation and may include: general tests (usually blood and urine) to check your overall health and body function, tests to find cancer (usually scans and internal inspection of the bladder using a fibreoptic instrument known as a cystoscope), and further tests (usually additional scans) to see if the cancer has spread (metastasised). Some tests may be repeated later to see how the treatment is working.”

As the diagnosis process is somewhat invasive, there is no national testing scheme, the same way they detect bowel and breast cancer.

This means that patients must self-report symptoms, which is a much less reliable form of detection.

Without more awareness for this type of cancer and the symptoms, diagnosis can be delayed, and survival chances drop significantly.

So what are the symptoms?

“The most common symptom of bladder cancer is blood in the urine (haematuria). This usually occurs suddenly and is generally not painful. Other less common symptoms include: a burning sensation when passing urine, pain when urinating, needing to pass urine often, problems emptying the bladder, back pain or lower abdominal pain,” Professor Sengupta says.

Melissa, however, didn’t have the full gamut of symptoms.

Article source and copyright attributed here: https://www.bodyandsoul.com.au/health/this-is-the-only-cancer-where-survival-rates-are-decreasing-in-australia/news-story/7d78d9d08c1d7c29a28 ec0e7c139a511?utm_campaign=EditorialSB&utm_source=body%2Bsoul&utm_medium=Facebook&utm_content=SocialBakers

34 A LITTLE BELOW THE BELT

“Other than not being able to empty my bladder at times, I didn’t have any of the tell-tale signs of bladder cancer which include blood in your urine and pain when passing urine,” she says.

She also didn’t fit the bill of the usual bladder cancer patient either.“It was completely out of the blue – I was literally stunned into silence when first told it was cancer. I think even my urologist was surprised because I was otherwise relatively healthy and didn’t fit the usual patient profile of an older male who smoked.

Only about 20% of people that get bladder cancer are women and most are aged over 65.”

Melissa’s story highlights why it’s so important that testing occurs even if the patient doesn’t necessarily fit into the generalised category of who gets bladder cancer. Unfortunately, it can strike anyone.

The fact that bladder cancer survival rates are decreasing is certainly not the news Le Meuriser wants to hear.

“It’s certainly scary and disappointing to find out bladder cancer is not only becoming more prevalent, but it is the only one among Australia’s 15 most common cancers where survival rates have deteriorated over the past 30 years,” she says.

Professor Sengupta says that bladder cancer’s much lower survival rate is caused by two things. Firstly, the survival rate for other types of cancers is improving with new technology, funding and awareness campaigns. Secondly, Australia’s ageing population means that the percentage of patients over 80 years old who are diagnosed has increased.

Patients of this age are frequently unsuitable for treatment, so the survival rate is much lower for them.

To improve the survival rate, Professor Sengupta has a few recommendations: • “ Earlier detection: by improving awareness among general practitioners and the lay population. It is crucial that symptoms suspicious for bladder cancer lead to prompt medical assessment and appropriate tests.

• A ppropriate and prompt application of existing treatments: to minimise delayed or suboptimal treatment.

• D evelopment of newer treatments that are more effective.”

Le Meuriser had already faced a number of hurdles in her life when she was diagnosed with cancer. Her son was diagnosed with cystic fibrosis at birth, and she also had major bowel surgery (unrelated to the cancer) the same year she was diagnosed.

You could say she was familiar with the medical industry by this point.

So, when the opportunity arose to be a part of a new clinical trial from ANZUP she jumped at the opportunity.

One of the treatments for bladder cancer involves injecting the Bacillus Calmette–Guérin (BCG) vaccine, which was originally created in France in the early 1900s from a live bovine tuberculosis bacteria. Originally developed to stave off tuberculosis, the immunotherapy is also effective in treating early-stage bladder cancer.

The trial Le Meuriser took part in involved the first six, weekly doses of the BCG that is usually prescribed, followed by a further nine monthly treatments alternating BCG with a chemotherapy drug called mitomycin.

“The trial is still recruiting participants, and it is hoped its results will show reduced recurrence. Thankfully (touch wood) nearly four years later I’m still cancer free,” she says.

Professor Sengupta says that these types of clinical trials are particularly important to develop new treatments for the cancer, and hopefully improve the survival rate.

“The ANZUP Cancer Trials Group is active in all areas to try and improve outcomes from bladder cancer,” he says.

To support the effort, ANZUP held a fundraising campaign in May, which both Professor Sengupta and Melissa Le Meuriser were involved with.

It raised money for ‘below the belt’ cancer research including bladder, kidney, prostate, testicular and penile cancers.

Find out more about the Below the Belt Events or donate here.

A LITTLE BELOW THE BELT 35

In the media:

World first trials investigating targeted bladder cancer treatment Credit: Government of Western Australia, South Metropolitan Health Service July 05, 2021 After recovering from a malignant melanoma more than three decades ago, it was the diagnosis of bladder cancer that completely changed 67 year old Frank Waters’ life.

“My outlook on life has been significantly altered – now I’m very grateful just to be here,” Frank said.

The Dawesville grandfather had surgery in October last year to remove his prostate.

Having worked various jobs since the age of 13, the cancer treatment and subsequent recovery forced him in to early retirement.

With more time on his hands, Frank chose to take part in a world first research trial run by Fiona Stanley Hospital (FSH), SUBDUE-1, which investigates the injection of a new type of cancer therapy directly into the bladder.

The drug, known as Durvalumab, is commonly used to treat several cancers that have spread including bladder cancer and has previously been injected into a vein.

Led by Fiona Stanley Hospital (FSH) Head of Urology Professor Dickon Hayne, the trial was developed with ANZUP and supported by an ANZUP Below the Belt grant and also the Spinnaker Foundation.

“This trial is the first time any of this class of drugs, known as check point inhibitors, have been injected directly into the bladder,” Dickon said.

“We will then look at the bladder tissue some weeks after the injection to see if the drug is effectively treating the cancer.

FRANK WATERS (BACK RIGHT) WITH HIS FAMILY.

FSH is also leading the way with another bladder cancer research trial, ZiP-UP, which has just included it’s first patient.

The trial will recruit 20 patients over the next 12 months to investigate a new type of PET scan to detect localised and metastatic bladder cancer.

“PET scans combine normal CT scans with a radioactive tracer that ‘sticks’ to the cancer so you can see where it is,” Dickon said.

“In a cancer where outcomes are worsening throughout Australia, better staging and therapy planning are absolutely essential.

“We are pleased to have included the first patient in this important diagnostic study which, in the future, has the potential to develop into a new therapy.”

For Frank, he is willing to do whatever it takes to reclaim his health which includes investing in research.

“Without research there is no future for any cancer treatment – while it may not necessarily help me it could save my grandchildren.”

“By giving the drug directly into the bladder, it’s hoped it will treat cancers that might otherwise progress creating an entirely new treatment for bladder cancer.”

FRANK AND HIS GRANDCHILD Article source and copyright attributed here: https://smhs.health.wa.gov.au/News/2021/07/05/World-first-trials-investigating-targeted-bladder-cancer-treatment

36 A LITTLE BELOW THE BELT

ANZUP trials - bladder ANZUP is currently running a number of bladder cancer trials.

For more details information about these trials, go to the ANZUP bladder cancer trials web page: https://anzup.org.au/clinical-trials/bladder-cancer-trials/

BCG+MM ANZUP 1301 Status: Open & recruiting Location: Australia Activated sites: 15 Patients recruited: 352 Patients required: Stage one: 130 / Stage two: 370

Non-muscle invasive bladder cancer is common and causes substantial suffering. It requires removal or irradiation of the bladder within five years in more than 30% of people with high-risk tumours, despite best current treatment.

Recent preliminary studies show promising results from adding mitomycin (MM), a chemotherapy drug, to current treatment with BCG (Bacillus Calmette-Guérin, a strain of modified bacteria which stimulates an immune response to early cancer cells).

This randomised trial will determine the effects of adding mitomycin on cure rates, survival, side effects and quality of life. This could potentially provide a simple and costeffective treatment for patients who suffer from this cancer.

This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know.

ANZUP collaborates with the University of Sydney through the National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC).

This ANZUP investigator-initiated study is being funded

by Cancer Australia and the National Health and Medical Research Council. We acknowledge Omegapharm and Merck Sharp & Dohme for providing the study drugs.

Current site locations for the BCG + MM trial are: NSW • Concord Repatriation General Hospital • John Hunter Hospital • Nepean Hospital • Northern Cancer Institute (GenesisCare) • Southside Cancer Care Centre • The Tweed Hospital • Westmead Hospital VIC • Austin Health • Epworth HealthCare (Richmond) • Frankston Hospital • Royal Melbourne Hospital • The Alfred Hospital WA • Fiona Stanley Hospital QLD • Redcliffe Hospital UK • Nottingham University Hospital

A LITTLE BELOW THE BELT 37

ANZUP trials - bladder

PCR-MIB ANZUP 1502 Status: Open & recruiting Location: Australia wide Activated sites: 6 Patients recruited: 27 • Patients required: 30

Opened in mid-2016, this trial is aimed at managing bladder cancer that has spread into the wall of the bladder. A combination of chemotherapy and radiotherapy is the current standard treatment. This study aims to assess if it is safe and effective to add an additional new drug called pembrolizumab to the standard therapy of chemotherapy and radiation therapy.

Pembrolizumab is a new treatment that “takes the brakes off” the immune system, allowing it to attack cancers more effectively. Studies of pembrolizumab in widespread bladder cancer have shown benefit, with cancer shrinkage observed in about two thirds of people, and in some cases long periods of disease control. At present, pembrolizumab, is approved for use in Australia for the treatment of advanced melanoma in adults.

This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know.

We thank and acknowledge MSD for their funding and product support.

If a clinical trial proves that a treatment is more effective than existing options, it may become the new standard of care for patients in the future.

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Current site locations for the PCR-MIB ANZUP clinical trial: NSW • Chris O’Brien Lifehouse • Liverpool Hospital • Prince of Wales Hospital • Royal North Shore Hospital VIC • Austin Hospital WA • Sir Charles Gairdner Hospital

Participation in cancer trials is voluntary & patients can withdraw from a study at any time

Spotlight on testicular cancer The testicles are part of the male reproductive system. There are normally 2 testicles, and they are located under the penis in a sac-like pouch called the scrotum. They can also be called gonads or testes.

The testicles produce sperm and testosterone. Testosterone is a hormone that plays a role in the development of masculine characteristics and the male reproductive organs.

30

928

estimated diagnoses

estimated deaths

in Australia in 2020

from testicular cancer in 2020

What is testicular cancer?

Cancer that develops in a testicle is called testicular cancer or cancer of the testis. Usually only one testicle is affected, but in some cases both. About 90 to 95 per cent of testicular cancers start in the cells that develop into sperm - these are known as germ cells.

In 2020 a total of 30 deaths from testicular cancer were estimated. And encouragingly, the five year survival rate for men diagnosed with testicular cancer is close to 97.2 per cent.

Testicular cancer symptoms

Compared with other types of cancer, testicular cancer is rare. But testicular cancer is the second most common cancer in young men (aged 18 to 39) excluding non-melanoma skin cancer. However, this form of cancer is highly treatable, even when cancer has spread beyond the testicle.

Testicular cancer may cause no symptoms. The most common symptom is a painless swelling or a lump in a testicle.

It was estimated only 928 men would be diagnosed with testicular cancer in Australia in 2020. This equates to 1% of all cancers in men. For Australian men, the risk of being diagnosed with testicular cancer by the age of 90 is 1 in 192. The rate of men diagnosed with testicular cancer has grown by more than 50% over the past 30 years, however the reason for this is not known.

• Change in the size or shape of the testicle;

Germ cell tumours are the most common testicular cancers. Under a microscope there are two main types that are quite different when observed – seminoma and non-seminoma cells. Seminoma cells usually occur in men aged 25-45 but can also occur in men over the age of 60 or at any age. This form of testicular cancer develops more slowly than non-seminoma cancers. The faster developing, rarer form of testicular cancer occurs in younger men in their late teens and early 20s.

Less common symptoms include: • Feeling of heaviness in the scrotum;

• P ain or ache in the lower abdomen, the testicle or scrotum; • Back pain; • Feeling of unevenness; • T enderness or tenderness of the breast tissue (due to hormones created by cancer cells).

If found early, testicular cancer is one of the most curable cancers.

This is why self-checking in so important.

A LITTLE BELOW THE BELT 39

Spotlight on testicular cancer Causes of testicular cancer

Understanding testicular cancer, the treatments available and possible side effects can help you decide your treatment pathway. You may also want to talk to your doctor about how treatment for testicular cancer may affect your fertility.

A couple of factors that may increase a man’s risk of testicular cancer include an undescended testicle as an infant, or family history, mainly having a father or brother who has had testicular cancer.

In addition, personal history may contribute to testicular cancer. If you have had cancer in one testicle you are more likely to develop cancer in the other testicle. It is also found that infertility may be another possible cause.

There is no known link between testicular cancer and injury to the testicles, hot baths, wearing tight clothes or sporting strains.

Testicular cancer treatment Treatment for testicular cancer depends on the type of cancer you have and how far it has spread. Your medical team will advise the best treatment for you. They will consider various points: • your general health • the type of testicular cancer • the size of the tumour • the number and size of any lymph nodes involved • i f the cancer has spread to other parts of your body.

If testicular cancer does spread, it most commonly spreads to the lymph nodes in the pelvic and lower abdominal regions.

In almost all cases if testicular cancer is suspected, the affected testicle is surgically removed in an operation called an orchiectomy. A laboratory will then examine the tissue to confirm the type of cancer and the stage it is at.

After the surgery, you may not need any further treatment but will be closely monitored. This is called surveillance. If other treatments are required they may include chemotherapy or radiotherapy to stop the spread of cancer cells to other parts of the body. Some people may require further surgery.

Testicular cancer clinical trials Several decades ago testicular cancer was a disease with a very poor prognosis. But now, because of new treatments, tested carefully in clinical trials, it is almost always curable even when it has spread. However, even though there are excellent treatments available, we still need to do more. This can only happen through understanding the science and by performing clinical trials to see which treatments are most likely to help further improve outcomes. ANZUP is involved in clinical trials in testicular cancer through its clinical trials program.

Speak with your doctor if you would like to know more about testicular cancer clinical trials and also read about ANZUP’s trials on page 42.

References https://www.cancer.org.au/about-cancer/types-of-cancer/testicular-cancer.html https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-summary-data-visualisation

40 A LITTLE BELOW THE BELT

International Germ Cell Cancer Collaborative Group update: positive news for seminoma germ cell cancer patients The story of testicular cancer has been one of success for several decades. The initial advance came with the introduction of chemotherapy. Further improvements have occurred, as with the rest of modern oncology.

The difficulties of testicular cancer are now more readily identifiable through improved diagnostic means and supportive care, and in addition, treatment strategies can be continuously refined for different groups of patients.

To standardise disease classification and treatment strategies for such a rare disease it was realised early that national and international collaboration was necessary.

A very recent, excellent example of such joint efforts is the International Germ-Cell Cancer Collaborative Group (IGCCCG) consortium who undertook an update on the characteristics of a patient that can be used to estimate the chance of recovery from a germ cell cancer or the chance of the disease recurring, i.e. prognostic factors.

Types of Testicular Cancer

The disease classification of the International GermCell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumours, but has, up until recently, relied on data of only 660 patients with seminoma treated between 1975 and 1990. The IGCCCG decided to re-evaluate the classification for seminoma in a database from a larger international consortium of 30 different contributing groups to the main database and a further 6 contributors for validation. This update included modern treatment data and investigated screening for additional patient characteristics that can predict the patient’s eventual response to an intervention or treatment. An update on survival rates was also provided.

The most common type of testicular cancer is a germ cell tumour (GCT).

There are two main types of GCT: seminoma and nonseminomatous germ cell tumours (NSGCT).

Seminoma • S eminomas tend to grow and spread more slowly than NSGCT • I f seminoma spreads from the testicle, it is most often and best treated with chemotherapy and/or radiation

Nonseminoma • Very variable in appearance and prognosis • T here are four main types of NSGCT that can appear alone, but most often appear as a “mixed” NSGCT

The latest IGCCCG update provides a contemporary perspective on the outcomes for men diagnosed with seminoma. In the last few decades, we have reassuringly seen progressive improvement in the survival of men diagnosed with this condition, with an increasing majority now able to expect a cure following treatment. This is great news for our patients.

The update was undertaken for both seminoma and non-seminoma germ cell tumours, i.e. the two main types of testicular cancer. Compared with the results of the original IGCCCG group of patients, it was shown that there is now a substantially improved survival for patients with metastatic seminoma germ cell cancer.

The results of the IGCCCG update analysis will now allow the testicular cancer multidisciplinary team to help counsel patients with seminoma more accurately in respect to the treatment outcome they can expect and also help shape future trials in seminoma. And also of importance, the original IGCCCG classification was shown to retain its relevance in metastatic seminoma, but with clearly improved outcomes.

Dr Ciara Conduit, Medical Oncologist & ANZUP Clinical Research Fellow A LITTLE BELOW THE BELT 41

ANZUP trials - testicular

ANZUP is currently running a number of testicular cancer trials.

For more detailed information about these trials, go to the ANZUP testicular cancer trials web page: https://anzup.org.au/clinical-trial/tiger/

TIGER ANZUP 1604 Status: Open & recruiting Location: Australia wide & Internationally Activated sites: 4 (Australia) Patients recruited: 11 • Patients required: 60 + 420 internationally

This randomised phase III trial will study how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumours that have returned after a period of improvement or did not respond to treatment.

Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumour cells.

They either kill the cells by stopping them from dividing or stop them from spreading. Giving chemotherapy before a stem cell transplant halts the growth of cancer cells by stopping them from dividing or by killing them.

Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumours.

42 A LITTLE BELOW THE BELT

Up to 420 patients will be enrolled in Australia, New Zealand and other countries. Currently we have 11 patients enrolled and 4 sites open in Australia.

Please speak with your doctor if this is of interest to you or someone you know.

ANZUP is collaborating with the Alliance for Clinical Trials in Oncology (USA) and EORTC (Europe) and the NHMRC Clinical Trials Centre.

We thank and acknowledge the Movember Foundation for their funding support to conduct the TIGER trial.

For more information, please go to the trials page on the ANZUP website: https://anzup.org.au/clinical-trial/tiger/ Current site locations for the TIGER trial are: NSW • Chris O’Brien Lifehouse VIC • Eastern Health • Peter MacCallum Cancer Centre QLD • Princess Alexandra Hospital

P3BEP

ANZUP trials - testicular

ANZUP 1302 Status: Active & recruiting Location: Australia wide & Internationally Activated sites: 69 Patients recruited: 165 • Patients required: Stage 1 (150) Stage 2 (350)

The current standard practice for the treatment of germ cell tumours is the use of the chemotherapy combination called BEP, which consists of three chemotherapy agents – Bleomycin, Etoposide and Cisplatin – administered on a three-weekly cycle. BEP is given with a drug called pegylated G-CSF (or pegfilgrastim) that stimulates white blood cell production.

The purpose of this study is to determine whether giving the same dose of BEP on a two-weekly schedule will be more effective and better tolerated than a three-weekly schedule. The two-weekly schedule is called “accelerated BEP” and the three-weekly schedule is called “standard BEP”.

Up to 500 patients will be enrolled in the study in Australia, New Zealand and other countries. Currently we have 69 sites open in Australia and New Zealand, and 165 patients enrolled. We have also set up the trial in the US, in Ireland with the support of Cancer Trials Ireland and the Medical Research Council, Cambridge University, UK. This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know.

For more information, please go to the trials page on the ANZUP website: https://anzup.org.au/ clinical-trial/p3bep/.

ANZUP collaborates with the University of Sydney through the NHMRC CTC to conduct P3BEP Trial.

This ANZUP investigator initiated study is being funded by a Cancer Australia grant.

Current locations for the P3BEP trial: NSW • Calvary Mater Newcastle • Chris O’Brien Lifehouse • Concord Repatriation General Hospital • Macquarie Cancer Clinical Trials • Nepean Hospital • Prince of Wales Hospitall QLD • Princess Alexandra • Queensland Childrens Hospital • Royal Brisbane & Womens Hospital VIC • Austin Health • Border Medical Oncology • Eastern Health • Peter MacCallum Cancer Centre SA • Flinders Medical Centre • Royal Adelaide Hospital WA • Fiona Stanley Hospital TAS • Royal Hobart Hospital NEW ZEALAND • Auckland Hospital • Christchurch Hospital • Starship Hospital –Paediatric • Palmerston North Hospital • Christchurch Children’s Haematology Hospital UK • Royal Marsden Hospital • University Hospital Southampton • Cambridge University Hospital Paediatric • Royal Preston Hospital • Beatson West of Scotland Cancer Centre • St James’s Hospital – Leeds • Belfast City Hospital • Bristol University Hospital • Velindre Hospital • St Bartholomew’s Hospital • Nottingham University Hospital • Derriford Hospital, Plymouth

• Northern General Hospital • Aberdeen Royal Infirmary • University College Hospital, London USA • Lucile Packard Children’s Hospital Stanford • Washington University School of Medicine • Rady Children’s Hospital • Geisinger Medical Center • University of Texas Science Center at San Antonio • Carolinas Medical Center • Memorial Sloan Kettering Cancer Center • Augusta University Medical Center • Vanderbilt University Medical Center • Memorial Health University Medical Center • University of Mississippi Medical Center • Palmetto Health Richland • Methodist Children’s Hospital of South Texas • University of Wisconsin Hospital • East Tennessee Children’s Hospital • Miller Children’s and Women’s Hospital Long Beach • Roswell Park Cancer Center • USC / Norris Comprehensive Cancer Care • Broward HealthCare • Dana Farber Cancer Center • UT Southwestern Simmons Cancer Center • LA Biomedical Research Institute at Harbor – UCLA • Dayton Children’s Hospital • Mayo Clinic • Advocate Children’s Hospital – Oak Lawn • Loma Linda University Medical Center • University of Iowa • Presbyterian Hospital New Mexico • Saint Mary’s Hospital • Hackensack University Medical Center • Providence Sacred Heart Medical Center and Children’s Hospital • Dell Children’s Medical Center A LITTLE BELOW THE BELT 43

Spotlight on kidney cancer Every person has two kidneys located above the waist on both sides of the spine. These bean-shaped organs are each about the size of a small fist and are located closer to the back of the body than to the front.

Each kidney works independently so the body can function with less than one complete kidney.

The kidneys filter blood to remove excess minerals, salts and impurities, as well as extra water. Blood pressure, red blood cell production, and other bodily functions are controlled by hormones produced by the kidneys.

In 2020 it was estimated:

2.9%

men

of all newly diagnosed cancers in Australia

are almost twice as likely to be diagnosed as women

4,100+ diagnoses

of kidney cancer in Australia

What is kidney cancer?

Kidney cancer has become increasingly more commonly diagnosed and survival rates continue to improve. This cancer is the 7th most diagnosed cancer in Australia and in 2020 it was estimated there would be 4,193 new cases of kidney cancer diagnosed (2,755 males and 1,438 females). Kidney cancer is rare in people under 40 but risk does increase with age. Also, men are almost twice as likely to be diagnosed with kidney cancer as women.

Kidney cancer generally refers to renal cell cancer, which develops in the lining of the small tubes in the kidney. There is usually just a single tumour in one kidney, but sometimes there may be more than one tumour, or tumours in both kidneys. Kidney cancer can be subdivided into several different types, based on the appearance of the cancer cells under a microscope as well as other genetic factors. About 90% of kidney cancers are renal cell cancer, and the most common subtype is clear cell renal cancer.

44 A LITTLE BELOW THE BELT

Other types of kidney cancers include: • U rothelial carcinoma. This is also called transitional cell carcinoma. It constitutes 5% to 10% of the kidney cancers diagnosed in adults. Urothelial carcinoma begins in the area of the kidney where urine collects before moving to the bladder, called the renal pelvis. This type of kidney cancer is treated like bladder cancer because both types of cancer begin in the same cells that line the renal pelvis and bladder.

• W ilms tumour is most common in children and is treated differently from kidney cancer in adults. About 1% of kidney cancers are Wilms tumors. A different approach to treatment is used for this type of kidney cancer. This type of tumour is more likely to be successfully treated with radiation therapy and chemotherapy than the other types of kidney cancer when combined with surgery.

• Sarcoma of the kidney is rare. This type of cancer develops in the soft tissue of the kidney, i.e. the thin layer of connective tissue surrounding the kidney, called the capsule; or surrounding fat. This form of kidney cancer is usually treated with surgery.

However, sarcoma commonly comes back in the kidney area or spreads to other parts of the body. After the first surgery additional surgery or chemotherapy may be recommended.

Spotlight on kidney cancer In 2020, it was estimated there would be 917 deaths from kidney cancer (616 males, 301 females) and the five-year survival rate for Australians diagnosed with kidney cancer was 79%, although most people with kidney cancer localised only to the kidney can be cured.

Kidney cancer symptoms In its early stages, kidney cancer often does not produce any symptoms. Many are diagnosed with the disease when they see a doctor for a different reason.

Symptoms may include: • blood in the urine (haematuria); • pain or a dull ache in the side or lower back that is not due to an injury; • a lump in the abdomen; • rapid, unexplained weight loss; • constant tiredness; • fever not caused by a cold or flu.

If you are experiencing some of these symptoms, please see your doctor.

Causes of kidney cancer The causes of kidney cancer are not known, but factors that put some people at greater risk include: • Obesity – Excess body fat may alter certain hormones that can lead to kidney cancer.

• Smoking – Up to one-third of all kidney cancers are thought to be related to smoking. People who smoke have almost twice the risk of developing kidney cancer as non-smokers.

• H igh blood pressure – Whether it is caused by another medical condition or due to being overweight, high blood pressure increases the risk of kidney cancer.

• K idney failure – People with end-stage kidney disease have an increased risk of developing kidney cancer.

• F amily history – People who have family members with kidney cancer, especially a sibling, are at a greater risk.

• I nherited conditions – About 3–5% of kidney cancers occur in people with particular inherited syndromes, such as von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, and hereditary papillary RCC. • E xposure to toxic substances at work – After regular exposure to certain chemicals, such as arsenic, cadmium or some metal degreasers, the risk of kidney cancer may be higher.

Treatment options Treatment will depend on the type of kidney cancer, the stage of the cancer and your general health. The main treatment for kidney cancer is surgery alone or with radiotherapy and will depend on the stage of the cancer. All treatment has benefits and side effects, which need to be discussed with your multidisciplinary cancer care team.

Treatment for kidney cancer is provided by a multidisciplinary team, comprising a urologist, urologic oncologist, medical oncologist and radiation oncologist. This team will regularly meet and discuss the patient’s medical history, organise appropriate tests, assess the test results, and together determine the most appropriate treatment care plan.

Clinical trials One treatment option is taking part in a clinical trial.

A trial will help confirm whether novel medicines are safe and effective to introduce as new treatment for more kidney cancer patients. During a trial your health and progress is monitored extremely closely and as a participant in a trial you may also gain access to a treatment option that is not yet available to the wider public.

If you have already had one or more forms of cancer treatment and are looking for a new treatment option, you may be suitable for a clinical trial. Or, if you have just been diagnosed with cancer, the time to think about joining a trial is before you have any treatment.

Read more about the ANZUP kidney cancer trials on page 51.

Reference: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-summary-data-visualisation

A LITTLE BELOW THE BELT 45

I firmly believe a clinical trial saved my life Juliet De Nittis is a 53-year mother of one from Victoria. In early 2019, Juliet discovered she had a tumour big enough to cover her entire left kidney.

When were you diagnosed?

I was diagnosed in February 2019, which was the day before my daughter’s 16th birthday. I had to pretend I didn’t know.

What symptoms did you have?

Initially a lot of back pain. My period was really heavy and painful, which was unusual as I never had this problem in the past. This was due to the tumour growing so large.

How did you feel when you received your diagnosis?

Initially I wasn’t surprised and I thought to myself it will be alright. What I didn’t know was that it was actually a rare cancer and that it was aggressive.

My first thought was that they would just take the kidney out. I also wasn’t aware that it had spread to my lungs.

At this stage I didn’t receive a lot of information as there was a big rush to get me started on the clinical trial.

My biggest fear was as a parent, I wanted to be there for my daughter. Especially when they said if the treatment didn’t work, I would have a year or two.

Luckily I have well and truly exceeded my expiry date.

What treatment have you had?

I was placed on the UNISoN trial and given a new immune treatment to see if it helped me. My cancer was a rare kidney cancer (non clear cell cancer).

Non-clear-cell kidney cancers occur in about 25% of people with kidney cancer; and because it is rare there are no treatments currently reimbursed in Australia.

46 A LITTLE BELOW THE BELT

When I discussed my options with my specialist Associate Professor David (Dave) Pook he said because of the type of cancer I had, if we had nothing to treat me with, I would be dead.

The medical staff, all of them; doctors, study coordinators and incredible, competent, endlessly patient, fabulous nurses and auxiliary staff at Monash Clayton Clinical Trials Centre are brilliant, kind and professional – vitally important and have helped myself and fellow patients every step of the way through our trial experience.

I firmly believe that the UNISoN trial saved my life.

How did your friends and family help you during treatment?

My friends and family were my absolute support and coping mechanism, although my husband at the time was the opposite, so I left him.

My friend Helen Smith was an incredible support.

Not only is she my employer but she has helped in so many ways.

The house that we are actually renting now is all thanks to a work colleague, as it was a house they bought.

This is because real estate agents don’t like terminal patients signing leases.

As my daughter and family remind me (especially at every birthday since my diagnosis), I may not be important to many people but I am everything to a few people – as we all are!

How are you feeling now?

I’m scared some days, then other days I get really excited and think oh it’s all good. Then at the back of my brain there is that fear because it seems and feels too good to be true.

There are still a lot of side effects, which has impacted me not being able to work at the moment. Then I think things could be worse, don’t take anything for granted, which is a good thing.

You said you firmly believed the trial saved your life.

Can you elaborate on this?

Absolutely, as there was no treatment for rare cancers and for this particular cancer.

The cancer I have is renal cell carcinoma (RCC) with sarcomatoid and extensive rhabdoid differentiation (which is clear and non-clear) which is a highly aggressive form of RCC. Due to the sarcomatoid being so aggressive and spreading so rapidly, there wasn’t anything to combat that. Previous trials looked at normal renal cell carcinoma but not the rare ones.

Ironically it seems to be the actual sarcomatoid is what made the treatment a success. So once the immune system teams are trained they can actually spot it out.

Dave has said to me, that I’ve had a greater success rate than others because of the aggressiveness of it.

So what was the worst-case scenario part and response part of my cancer is actually what saved me. Interestingly, I didn’t actually have to have the combination of drugs because the nivolumab was successful on its own, which was originally for melanomas. They discovered that the melanomas didn’t come back. Even as I was getting treated, I must have had a melanoma on my hand that disappeared. The connection is incredible.

Is there anything else you would like to mention?

For patients, carers and community to support these clinical trials.

I joined the trial not just with the hope the treatment may help me in some way but also to contribute to research for future cancer patients, and with enormous gratitude for previous cancer patients who have participated in trials that have led to my current treatment, including much loved family and extended family members.

I was completely surprised by the success I have had. You definitely wish for it but you cannot allow yourself to truly believe it! I have been incredibly lucky in that my tumours responded to the experimental drug and they have been stable since December 2019.

To emphasise my point, I found out some really bad news that my step dad has just been diagnosed with cancer. I was upset but at the same time my first thought there may be a clinical trial for him? It gives you hope.

When there’s no hope it really does give you hope.

Juliet’s doctor was Associate Professor David Pook A/Prof David Pook specialises in the treatment of prostate, kidney, bladder and testicular cancers.

He is the principal investigator on multiple international clinical trials treating urological cancers with experimental drugs including novel combinations of immunotherapy.

He is a clinical research fellow in the Prostate Cancer Research Group at Monash University where he helps develop prostate cancer models which can be used to test novel treatments. He is also the Deputy Chair of the Kidney Cancer Subcommittee of the Australia and New Zealand Urological and Prostate Cancer Trials Group.

What is happening with kidney cancer rates in Australia?

Both people diagnosed and survival rates?

Clear cell kidney cancer

Non-clear cell kidney cancer

75%

25%

Kidney cancer has become increasingly more commonly diagnosed and survival rates continue to improve. Kidney cancer is the 7th most diagnosed cancer in Australia.

A LITTLE BELOW THE BELT 47

How many people every year are diagnosed with kidney cancer?

In 2020 it was estimated there were 4,193 new cases of kidney cancer diagnosed (2,755 males and 1,438 females). Kidney cancer is rare in people under 40 but risk does increase with age. Also, men are almost twice as likely to be diagnosed with kidney cancer as women.

What symptoms should people look out for?

Most people with kidney cancer have no symptoms.

Many are diagnosed with the disease when they see a doctor for a different reason.

Symptoms may include: - blood in the urine (haematuria); - p ain or a dull ache in the side of lower back that is not due to an injury; - a lump in the abdomen; - rapid, unexplained weight loss; - constant tiredness; - fever not caused by a cold or flu.

What are some of the clinical trials that you are working on at the moment?

I am testing a drug called cabozantinib in rarer types of kidney cancer (non clear-cell) which are no longer responding to immunotherapy. This is important as there are no funded treatments for these types of kidney cancer in Australia. I am also involved in testing immunotherapy as a preventer of cancer returning after surgery. This is exciting as a recent trial has shown that this is effective.

What are you most excited by with regards to kidney cancer treatments?

It is exciting to be able to say kidney cancer treatment is now at a transition point. For a while, treatment options for kidney cancer included surgery alone.

We now have more to offer as a standalone treatment or in combination. Targeted therapies are now being used and target specific molecules in cells to block cell growth. We are now also well aware of the role immunotherapy plays in cancer treatment and are excited to be part of clinical trials of immunotherapy in kidney cancer. Current trials will allow us to understand how this form of treatment will benefit patients with kidney cancer – both the rare and common forms of the disease.

48 A LITTLE BELOW THE BELT

Immunotherapy works to enhance the immune system of your body. Antibodies can now be given to take “the handbrake” off the immune system by blocking so-called checkpoints. This allows the immune system to attack kidney cancer and for the first time we have seen kidney cancer disappear in some patients.

We are eager to explore how immunotherapy can be integrated with existing therapies and current treatment combinations. Clinical trials in immunotherapy allow us to test various combinations of this type of treatment to try to increase the number of patients who respond well to treatment.

Developments have been happening in other cancer areas. Better understanding of biology has allowed the use of precision medicine which is now filtering through to kidney cancers. This is taking time as kidney cancer does not exhibit a lot of DNA mutations which can be targeted by medicines. Clinical trials and ongoing research will enable us to search for more alterations in cell function which may be targeted by future medicines.

All the research being undertaken suggests we will witness a rapid increase in the number of available kidney cancer treatments in the next year or two, leading to some people having very positive outcomes from their kidney cancer treatment.

At the same time, it is likely that more targeted immunotherapy treatments that are now being tested in other cancers will be modified for use in kidney cancer and enter clinical trials, further improving outcomes in the years to come.

What advice would you give to people with regards to preventing kidney cancer?

Not smoking or quitting smoking. Up to one third of kidney cancers are thought to be due to smoking. Not ignoring symptoms such as pain, weight loss or blood in the urine may enable cancers to be discovered early and cured with surgery.

What treatment plan did you put in place for Juliet?

Juliet has a type of kidney cancer called non clear-cell kidney cancer (clear-cell is the more common type).

In Australia there are no treatment options for this type of cancer funded by the PBS. Juliet agreed to take part in an ANZUP trial testing the immunotherapy drug, nivolumab in her cancer type.

In doing this, she is helping future patients who develop this disease by allowing us to test how well this drug works in this situation.

Hillcrest Foundation supports ANZUP’s Kidney Cancer Project ANZUP is extremely grateful to the Hillcrest Foundation for providing $70,000 and to the Ken and Asle Chilton Trust for the discretionary funding of $4,800, which will be used to fund important translational research as part of ANZUP’s kidney cancer UNISoN Trial.

With their support, ANZUP will be able to look further into the tumour tissue samples and blood tests from the people who were on the UNISoN kidney cancer clinical trial.

From this, they will be able to learn if we can predict which people are most likely to benefit from certain treatments and who will need one drug and who will

benefit from two. The outcome, is to learn if we can predict which people are most likely to benefit from the single treatment or combined treatment, providing a more targeted approach to treatment for people with kidney cancer. This will enable a clearer treatment path, which we hope will reduce uncertainty and anxiety.

Through this partnership and support, ANZUP can make a real difference to improving treatment and outcomes for people with kidney cancer and future generations.

NEW

ANZUP website ANZUP has a NEW website and it can be accessed using the same address: www.anzup.org.au The website provides all the information and resources you have come to know – but has been refreshed and revamped to provide an improved user experience.

If you would like to join ‘Friends of ANZUP’– remember this is free – just select the ‘Join ANZUP’ button.

You can still find information about all our research studies and clinical trials, newsletters and other publications, research papers, patient support materials and resources, upcoming events, and most importantly ways in which you can support ANZUP.

Take a look around the new website and if you require any assistance with navigation please do not hesitate to contact us at anzup@anzup.org.au.

A LITTLE BELOW THE BELT 49

Strengthening immune therapy in kidney cancer – the goal of the KEYPAD clinical trial People with kidney cancer may meet a surgeon, have their cancer removed, and many people then are thankfully free of the cancer. If kidney cancer spreads and grows, then more treatments are needed. Treatments for advanced kidney cancer have evolved quickly in the last few years, with treatments that boost the immune system now having a key role in treatment. As immune therapies have been shown to be effective in some people, ANZUP’s research focuses on strengthening these therapies, trying to make them work for more people and for longer.

In 2017 ANZUP opened a kidney cancer clinical trial called KEYPAD. This study is testing if a drug often used to treat osteoporosis, (thinning of the bones), can strengthen the outcomes of immune therapy for people with clear cell renal cell carcinoma (the commonest form of kidney cancer). Immune therapies have been shown to be effective in about a quarter of patients with clear cell renal cell carcinoma after a standard treatment (sunitinib or pazopanib) is no longer working.

The KEYPAD study is a really interesting clinical trial where we’ve worked with MSD and Amgen Australia to see whether treating people with a drug that has been used for protecting their bones will make immune therapy work better for people who have the commonest form of kidney cancer – clear cell renal cell carcinoma.

Craig Gedye 50 A LITTLE BELOW THE BELT

In the KEYPAD clinical trial, people with advanced clear cell kidney cancer will be offered treatment with two medicines (in the form of antibodies, a type of protein), pembrolizumab and denosumab. The study will question if these drugs taken together can increase the ability of the body’s immune system to recognize and control kidney cancer.

“What we’re learning about immune treatments is that they don’t necessarily depend on the kind of cancer; rather they depend on whether the person’s immune system is ready and waiting to attack the cancer,” says Associate Professor Gedye. “The new generation of immune therapies try to teach a new trick to the immune system, to recognise and attack the cancers in your body.”

Blood and cancer samples will also be collected from the trial patients to better understand why some people benefited from this combination of treatment and why some people did not. It is hoped that there is an improvement in treatment without any change in side effects.

The recruitment aim for the KEYPAD study is a total of 70 participants. Even throughout the uncertainties posed

by COVID-19, recruitment has remained steady. Only 19 more patients are required to join the study to complete recruitment. To find out more about the trial go to page 51 or visit https://anzup.org.au/clinical-trial/keypad/ If you would like further information about this study and help to determine if this clinical trial will improve outcomes for kidney cancer patients, then please speak with your doctor.

KEYPAD trial eligibility Adults with unresectable or metastatic clear cell renal cell carcinoma with no history of significant autoimmune disease and no previous treatment with immunotherapy. If you think you are eligible for this trial please talk to your doctor.

ANZUP trials – kidney

ANZUP is currently running a number of kidney cancer trials.

For more details information about these trials, go to the ANZUP kidney cancer trials web page: https://anzup.org.au/clinical-trials/kidney-cancer-trials/

KEYPAD ANZUP 1601 Status: Open & recruiting Location: Australia wide Activated sites: 15

The most common kind of advanced kidney cancer is called clear cell kidney cancer. This trial aims to improve survival rates for people with this cancer.

Patients recruited: 51 • Patients required: 70

Renal cell carcinoma (RCC) is the 7th most diagnosed cancer in Australia and the 14th most common cancer in Western populations. Approximately 90% of kidney cancers are renal cell carcinomas (RCC). At the moment the five-year survival rate for Australians diagnosed with kidney cancer is 78.5%, although most people with kidney cancer localised only to the kidney can be cured.

ANZUP collaborates with the University of Sydney through the NHMRC CTC to conduct the KEYPAD Trial.

Immune therapies have been shown to be effective in about a quarter of patients with clear cell renal cell carcinoma after the standard treatment (sunitinib or pazopanib) has failed.

NSW • Calvary Mater Newcastle • Northern Cancer Institute • Concord Repatriation General Hospital • St George Hospital • Border Medical Oncology Research Unit • St Vincent’s Hospital Sydney

This study will test if denosumab, a drug frequently used to treat osteoporosis, (thinning of the bones), can team up with immune therapy to improve survival and increase the chance of the cancer shrinking for people with clear cell kidney cancer.

In the trial, people with advanced clear cell kidney cancer will be offered treatment with two antibodies (a type of protein). This trial will investigate if these drugs taken together can increase the ability of the body’s immune system to attack kidney cancer cells.

It is hoped that by combining pembrolizumab with denosumab, will stimulate the immune system, so that the immune therapy will work better in the tumours.

We thank and acknowledge Amgen and MSD for providing product and funding to support our KEYPAD Trial.

We are currently running the KEYPAD trial at the following locations:

QLD • Royal Brisbane & Women’s Hospital • Sunshine Coast University Hospital • Icon Cancer Care • The Townsville Hospital SA • Flinders Medical Centre VIC • Eastern Health • Monash Health Clayton • Ballarat Oncology and Haematology Services WA • Fiona Stanley Hospital

A LITTLE BELOW THE BELT 51

ANZUP trials – kidney

UNICAB ANZUP 1802 Status: Open & recruiting Location: Australia wide Activated sites: 11 Patients recruited: 21 • Patients required: 48

This study aims to find how safe, tolerable and effective a new treatment called cabozantinib is for non-clear cell kidney cancer.

All patients will take cabozantinib orally every day, until the medication is no longer effective. There is no placebo (inactive treatment), which means that everyone who takes part in the trial will receive the active cabozantinib drug.

Cabozantinib is an anti-cancer drug that works by blocking cancer cell growth. Cabozantinib has previously been used in the treatment of many cancers, including clear cell kidney cancer and thyroid cancer. However, it has not been tested in people with non-clear cell kidney cancer.

Cancer trials can be undertaken in different settings. Depending on the trial, it may occur in a hospital, a clinic or the patient’s home.

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We are currently running the UNICAB trial at the following locations: NSW • Border Medical Oncology • Calvary Mater, Newcastle • Campbelltown Hospital • Macquarie University • St. George Hospital QLD • Royal Brisbane & Women’s Hospital SA • Adelaide Cancer Centre • Flinders Medical Centre VIC • Goulburn Valley Hospital, Shepparton (teletrial) • Eastern Health • Monash Medical Centre, Clayton ANZUP collaborates with the Centre for Biostatistics and Clinical Trials (BaCT) to conduct the UNICAB Trial.

We thank and acknowledge Ipsen for providing product and funding to support our UNICAB Trial.

Spotlight on penile cancer The penis is the external genital organ of a man. It is composed of three chambers of spongy tissue that contain smooth muscle and many blood vessels and nerves. The corpora cavernosa makes up two of the chambers located on both sides of the upper part of the penis. The corpus spongiosum is located below the corpora cavernosa and surrounds the urethra. The urethra is the tube through which semen and urine exit the body at an opening called the meatus. At the tip of the penis, the corpora cavernosa expands to form the head of the penis, or glans.

What is penile cancer?

Penile cancer symptoms

Penile cancer is a rare type of cancer and occurs on the foreskin, on the skin of the penile shaft, or the glans (head) of the penis. It occurs mostly in uncircumcised men (men who still have foreskin around the head of the penis). Circumcision is the removal of the foreskin and may reduce the risk of penile cancer.

People with penile cancer may experience a variety of symptoms. Symptoms may include: • a growth or sore on the head of the penis (the glans), the foreskin or on the shaft of the penis that doesn’t heal in a couple of weeks • bleeding from the penis or under the foreskin • a hard lump on or under the foreskin

The stats*

• an odorous discharge under the foreskin

Penile cancer is rare. In 2020 there were an estimated 136 cases of penile cancer diagnosed and 24 deaths from this disease. In 2012–2016, on average, 73.8% of males diagnosed with penile cancer survived 5 years after diagnosis. And it was estimated that in 2020 males had a 1 in 1,391 (or <0.1%) risk of being diagnosed with penile cancer by the age of 80.

• c hanges in the colour of the skin on the penis or foreskin • t hickening of the skin on the penis or foreskin that makes it hard to pull back the foreskin • p ain in the shaft or tip of the penis • s welling at the tip of the penis • a rash on the penis or a constant red patch of skin that does not resolve • l umps in the groin due to swollen lymph nodes.

136 men

Were estimated to be affected by penile cancer in Australia in 2020.

Reference *https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/summary

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Spotlight on penile cancer Causes of penile cancer The cause of penile cancer is not known in most cases.

However, there are several risk factors.

Infection with human papilloma virus is a risk factor for cancer of the penis. Some other conditions that affect the appearance of the skin of the penis can lead to cancer, so it’s important to see your doctor if you notice white, red or scaly patches.

Other risk factors for penile cancer include: • not being circumcised • smoking tobacco • increasing age • certain skin conditions such as psoriasis • HIV/AIDS • premalignant lesions/conditions • exposure to ultraviolet (UV) radiation.

Who treats penile cancer?

Based on your treatment options, you might have different doctors of various specialties on your treatment team. For penile cancer, the multidisciplinary team often includes a surgeon, a doctor called a urologist who specialises in urinary tract problems, a medical oncologist, and a radiation oncologist. Your healthcare team may also include a variety of other health care professionals, oncology nurses, social workers, pharmacists, counsellors and psychologists, dietitians, and others.

How is penile cancer treated?

Surgery is the main treatment for most men with penile cancers, but sometimes radiation therapy may be used, either instead of or in addition to surgery. Other local treatments might also be used for early-stage cancer.

Chemotherapy may be given for some larger tumours or if the cancer has spread.

As well as medical treatment for penile cancer it is also important to adjust to living with the diagnosis.

A specialist nurse, psychologist, social worker, a GP and support groups can all help and provide ways of coping.

Thinking about taking part in a clinical trial Progress in treating penile cancer has been hindered by its rarity so it is difficult to recruit enough patients to penile cancer clinical trials.

Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to receive state-of-the art cancer treatment, management and care that is not yet available to the wider public.

Clinical trials are also the best way for a multidisciplinary team to learn better methods to treat this rare form of cancer.

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor or contact ANZUP.

Although penile cancer is a relatively rare disease, its consequences are incredibly life changing for the men who develop it.

Evidence supports the view that factors such as embarrassment, fear, the potential impact on sexuality and a cancer in a sexual organ all impact on patients’ seeking help, resulting in a delay in going to a healthcare professional. See your doctor early and ensure you talk about treatment and the affects on sexual health and fertility.

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ANZUP trials in follow up

Trials in follow up Once a clinical trial is finished, researchers scrutinise all the information collected during the course of the study. Reviewing all the data allows researchers to decide whether the results mean the new drug or device should continue to the next phase of clinical trial, or, when applicable, seek approval for broader use by the appropriate authorities. Once a new drug or device has been proven to be effective and safe, it may become part of standard treatment for the condition or disease.

Review and analysis of the information can take an extended period of time. So there may be a delay before the results of a clinical trial are known. This is definitely the case with larger trials that can involve thousands of people from many hospitals both in Australia and overseas. In large multi-centre trials, the examination of the data and outcomes may take place over several years.

If you have taken part in a trial and specified you wish to know the overall results of the trial, the researchers should make them available to you directly. Usually results of all completed studies will also be made available in papers or reports published in scientific journals.

ANZUP now has nine trials in follow-up across four of the below the belt cancer types – bladder, testicular, prostate and kidney cancer.

ANZUP Trials 1. ENZAMET – Prostate Cancer ANZUP 1304 Enzalutamide is a new hormone treatment taken as tablets. Previous trials have proven that enzalutamide improves survival and quality of life in men with prostate cancer that has stopped responding to standard hormone treatments and chemotherapy.

This large, international randomised trial was undertaken to determine if treatment with enzalutamide can improve survival and quality of life in men starting hormone treatment for newly diagnosed prostate cancer that has spread beyond the prostate. The trial was led from Australia by ANZUP in collaboration with the NHMRC Clinical Trials Centre. It involved 1,125 men from Australia, New Zealand, Canada, the US, Ireland, and the UK.

Findings from the ENZAMET trial, led by ANZUP, have shown that men with this sort of cancer who receive enzalutamide with standard treatment have a 33% improvement in survival compared to men receiving standard treatment alone and a 60% improvement in the time it takes to detect the cancer growing again. These results were much better than it was thought they might be when the trial began.

The ANZUP investigator initiated studies were financially supported by Astellas, who also provided enzalutamide.

2. ENZARAD – Prostate Cancer ANZUP 1303 ENZARAD is a randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cancer.

Enzalutamide is a new hormone treatment taken as tablets. Previous trials have proven that enzalutamide improves survival and quality of life in men with prostate cancer that has stopped responding to standard hormone treatments and chemotherapy. This large, international randomised trial will determine if treatment with enzalutamide can improve survival and quality of life in men starting radiation and hormone therapy for prostate cancer that does not seem to have spread beyond the prostate.

The trial has been led from Australia by ANZUP in collaboration with the NHMRC Clinical Trials Centre.

The trial accrued 802 men from 69 sites across Australia, New Zealand, Canada, the US, Ireland, and the UK. Recruitment closed on 30th June 2018.

The ANZUP investigator initiated studies were financially supported by Astellas, who also provided enzalutamide.

This landmark Australian led clinical trial, ENZAMET, has now shown that hormone therapy with a drug called enzalutamide can improve the survival of some men with advanced, hormone-sensitive prostate cancer.

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ANZUP trials in follow up 3. Pain Free TRUS B – Prostate Cancer ANZUP 1501 A prostate biopsy involves taking small pieces of the prostate through a needle so that it can be looked at through a microscope. A Trans Rectal Ultrasound (TRUS) guided biopsy is the usual method and involves insertion of a thin needle through the wall of the rectum into the prostate using the guidance of an ultrasound probe. An injection of a local anaesthetic (lignocaine) around the prostate is the standard method of reducing the discomfort of a prostate biopsy.

Methoxyflurane (Penthrox®) is a drug given with a simple inhaler and is widely used by first-aid services to reduce pain. This randomised trial will determine if the discomfort of prostate biopsies can be reduced by giving men inhaled methoxyflurane in addition to their standard injections of local anaesthetic.

This is a phase 3 double-blind placebo-controlled randomised trial of methoxyflurane with peri prostatic local anaesthesia to reduce the discomfort of trans rectal ultrasound-guided prostate biopsy.

This study has accrued a total of 420 participants across Australia and New Zealand and has now completed recruitment.

This ANZUP investigator initiated study was funded by Cancer Australia. We acknowledge MDI for providing the study drug.

4. T heraP – Prostate Cancer ANZUP 1603 Lutetium-177 PSMA radionuclide therapy (Lu-PSMA) is a new treatment for advanced prostate cancer. Lu-PSMA is a radioactive molecule that specifically attaches to cells with high amounts of PSMA on the surface of the cells. This allows the radioactivity to be delivered mainly to the prostate cancer cells wherever they have spread, while sparing most normal tissues. Previous small studies of Lu-PSMA showed promising activity in patients with advanced prostate cancer.

This randomised study has compared Lu-PSMA, with a type of chemotherapy called cabazitaxel, which is the standard treatment for advanced prostate cancer when other treatments have stopped working. Half the participants received Lu-PSMA and half received cabazitaxel. This trial enrolled 200 participants in Australia.

ANZUP was able to report interim results of the TheraP clinical trial at the American Society of Clinical Oncology (ASCO) Annual Scientific Virtual Meeting on Friday 29 May 2020.

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A favourable response, defined by reduction of PSA by 50% or more, occurred in 66% of men assigned to receive Lu-PSMA compared to 37% with cabazitaxel. Results of the trial also demonstrated the treatment had less severe side effects than chemotherapy.

Patient follow-up is ongoing with initial results suggesting the new treatment may delay progression of prostate cancer.

TheraP is a partnership between ANZUP Cancer Trials Group and the Prostate Cancer Foundation of Australia (PCFA) with support from the Australian Nuclear Science and Technology Organisation (ANSTO), Endocyte, It’s a Bloke Thing, Movember and CAN4CANCER.

5. UNISoN – Kidney Cancer ANZUP 1602 In this clinical trial ANZUP will test whether new immune treatments can help people with rare kidney cancer (‘nonclear cell’ cancer).

Non-clear cell kidney cancer represents approximately 25% of people with kidney cancer; and because it is rare there are no treatments currently reimbursed in Australia.

The UNISoN trial is now closed to recruitment and is in follow up. This trial is investigating immune treatments in two different ways; firstly the trial is investigating how well one immune treatment (nivolumab) works alone.

If this is unhelpful by itself, then people can continue taking nivolumab but also add in a 2nd immune treatment (ipilimumab). The trial will also discover how many people will benefit from one drug alone, and by doing detailed laboratory testing of people’s cancer samples, we hope to also learn who will only benefit from taking both treatments together.

Nivolumab and ipilimumab have been used alone or together in many cancers, so the side-effects are well known and should be manageable. Immune treatments help some people with cancer, especially those with melanoma, common (clear cell) kidney cancer, lung and bladder cancer.

Unfortunately they are much less effective in other cancers (like pancreas, prostate and brain cancers). Nivolumab and ipilimumab have not been tested in people with non-clear cell kidney cancers, so ANZUP is delighted to ask this question, and hopes to help people with this rare disease.

We thank and acknowledge BMS for providing the study drug and funding to conduct the UNISoN trial.

Trials in follow up Co-badged Trials 6. proPSMA – Prostate Cancer Prostate cancer is the most commonly diagnosed cancer in Australian men. If detected early, when disease has not spread, there is a high chance of cure. Relapse, however, is not uncommon despite careful selection of patients prior to surgery or radiotherapy. This, in part, reflects a failure to detect disease spread at baseline due to limited accuracy of current scanning techniques. More accurate scanning may improve outcomes by redirecting patients with disease spread from unsuccessful local treatments to more appropriate management.

This clinical trial will investigate a new type of scan which provides whole body images of prostate cancer spread.

Early experience suggests that this new technology, called PSMA PET/CT (prostate specific membrane antigen positron emission tomography/computed tomography), is superior to current scanning techniques.

PSMA PET/CT has capacity for wide availability at relatively low cost. Performing a single better test rather than several less accurate scans will also be cheaper, improve patient experience and expose patients to lower amounts of radiation.

This is a randomised study at multiple centres around Australia comparing PSMA-PET/CT to conventional imaging. If the initial work-up does not demonstrate tumour spread, patients will cross-over to the other imaging arm. We hope to prove that PSMA-PET/CT has superior diagnostic performance, should be used as a firstline test for staging prior to surgery or radiotherapy and will result in significant changes to patient management.

Results of this trial will be used to support funding of this new technology in Australia and internationally.

The trial has now closed to recruitment and enrolled 300 participants in Australia.

7. FASTRACK II – Kidney Cancer Surgery is the standard treatment for primary kidney cancer. However, in some cases, surgery is either not possible or other health problems make surgery high risk. This study involves a relatively new, highly precise multidirectional radiotherapy technique called Stereotactic Ablative Body Radiotherapy (SABR) which will be applied to all participants.

The aim of the study is to test the ability of the technique to control cancer within the kidney for those people for whom surgery is not an option, and to examine the side effects of the treatment, including how it may affect your kidney’s function.

8. NMIBC-SI - Bladder Cancer Non-muscle invasive bladder cancer (NMIBC) makes up approximately 70-80% of all bladder cancer diagnoses. NMIBC is bladder cancer that has not yet invaded through the wall of the bladder. Treatment is generally intended to reduce the risk of the bladder cancer recurring or progressing to muscle invasive disease. Treatment involves endoscopic resection to the bladder tumours followed by potential intravesical chemotherapy or immunotherapy.

Although treatments can significantly reduce the risk of recurrence and progression, there are both benefits and harms that are likely to vary between treatment options. However, little is known about the impact of these treatments on patients’ quality of life.

Phase I of the project involved qualitative research to develop a draft Non-Muscle Invasive Bladder Cancer Symptom Index (NMIBC-SI).

The second phase of the project aims to evaluate the psychometric properties of the NMIBC-SI. This was conducted across two field tests: • F ield Test 1 was a cross-sectional study design asking participants to complete the draft NMIBC-SI questionnaire either on paper or lectronically. The purpose of Field Test 1 is to produce a shorter version of the NMIBC-SI by eliminating items with poor psychometric properties.

• F ield Test 2 used a prospective longitudinal study design to evaluate the clinical validity of the final version of the NMIBC-SI. Participants were asked to complete the NMIBC-SI along with comparative questionnaires at different time-points during their treatment. The purpose of Field Test 2 is to assess the reliability, validity and responsiveness of the final version of the NMIBC-SI to ensure it is fit for purpose in clinical research.

ANZUP was running this trial in collaboration with Cancer Australia and Cancer Council NSW. This study is being sponsored by the University of Sydney.

This study was funded by Cancer Australia and Cancer Council NSW. It was sponsored by USYD and co-badged with ANZUP.

For more information on our trials in follow up go to our website https://anzup.org.au/clinical-trials/follow-up/

This study is led by TROG and co-badged by ANZUP Cancer Trials Group and is now closed to recruitment and is in follow up.

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Community fundraising

Mary Kate on Newtown

GABS Festival

On Monday 8 March 2021, in celebration of International Women’s Day and women working in research, Mary Kate on Newtown opened the doors of her fashion boutique to help raise funds and awareness for those affected by below the belt cancers.

The Great Australasian Beer Spectapular (GABS) was held with Festivals in Sydney, Melbourne and Brisbane during May and June and this year they supported ANZUP as one of their official charity partners.

“Together, we can help forge a gender equal world, celebrate women’s achievement across all areas of life including cancer research, raise awareness against bias and take action for equality so that in the future there are more women working in medicine and research.”

ANZUP’s Nisha Rana said at the event.

A percentage of online purchases in the lead up to International Women’s Day, as well as an in-store discount at the event, were all donated to ANZUP to support vital clinical trials research.

We thank Mary Kate on Newtown for hosting this successful and informative fundraising fashion night.

Globally recognised as one of the best beer festivals in the world, GABS is like Disneyland for craft beer enthusiasts of all ages. Not only was there amazing street food, other beverages including non-alcoholic options, but the event stared Below the Belt ambassador, comedian and testicular cancer survivor Michael Shafar who performed his comedy show during the festival in support of ANZUP. We also sold (and sold out!) ANZUP and Below the Belt merchandise at the events and received 10% of all raffle sales for the biggest beer prize. Along with ongoing communications raising awareness about ANZUP and Below the Belt activities via their channels, providing a feel-good factor of giving back to cancer research.

The event raised over $6,000 for ANZUP. Our thanks go to the GABS Festival organisers for their support.

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Golf #YourWay Day As part of the Move #YourWay Challenge, Origin Energy organised the Origin Energy Golf Day at Massey Park Golf Club in Concord Sydney on Tuesday 11 May. After 18 holes the team were provided with a presentation about ANZUP, below the belt cancers, why clinical trials are so important and ANZUP’s latest research.

It was great to receive support once again from the team at Origin Energy. Since 2015, Origin Energy staff and the Foundation have donated over $70,000 to ANZUP through their matched giving program and participating in ANZUP’s Below the Belt events.

We are extremely grateful for their continued support and look forward to their participation in next Sydney Pedalthon.

#LaughYourWay Comedy night The 2021 Below the Belt Move #Your Way Challenge kicked off with a charity comedy night #LaughYourWay on Saturday 1 May, at Seed Spaces at Glebe, who generously supported ANZUP with the venue and onsite support.

Hosted by ANZUP’s Below the Belt ambassador, testicular cancer survivor and comedian Michael Shafar, the evening welcomed over 65 attendees all there to laugh, raise awareness and funds for below the belt cancer research.

Michael invited his comic pals Suren Jayemanne, Daniel Muggleton and Sam T to support the event and the cause. The four comedians (some of the best in Australia) brought the house down with their hilarious one liners and anecdotes.

Thank you to all those who attended and their support, the comedians who donated their time and the prize donors.

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How does your donation make a difference?

All contributions, large or small, get us closer to finding better treatments for cancer.

Clinical trials are a costly exercise, but the outcomes are so worthwhile.

This is where your donated funds go:

$500 – $1000

$5000 – $10000

Sponsor a travel fellowship

Support a concept workshop

Will support the attendance of an ANZUP multidisciplinary member at a conference or scientific meeting.

Will allow us to hold a face-to-face Concept Development Workshop to discuss new research ideas and concepts to consider developing into a future grant applications.

$50k – $250k

Kick off a pilot study Will allow us to invest in a pilot study to test the feasibility of promising drug therapies, surgical methods, post-operative care and palliative care options.

Any donation to ANZUP over $2 is fully tax deductible.

If you would like to donate to ANZUP, you can donate through our website www.anzup.org.au/donate or by calling ANZUP on +61 2 9562 5042

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Below the Belt Move #YourWay

Y UR WAY The 2021 Below the Belt Move #YourWay Challenge in May welcomed 146 challengers and 31 teams who ‘moved’ their way anytime, anywhere and with anyone collectively completing 18,976 kms and 638 hours.

Whether they were walking, running, doing yoga, cycling, or dancing, they were also raising awareness and funds for below the belt cancer research.

The challenge has raised $75,000. We thank all those who completed the challenge, supported or donated. We can’t wait to do it all again next year!

146

$75,000

31

CHALLENGERS

RAISED

TEAMS

638 HOURS

18,976 KM’S

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Below the Belt Move #YourWay

Below the Belt Research Fund Every cent we raise through the Below the Belt events goes directly towards clinical trial research via the Below the Belt Research Fund. In 2020, ANZUP’s Below the Belt Research Fund provided much needed seed funding to support five ANZUP members to progress new trial ideas to the point of becoming full scale studies.

LOUISE EMMETT

Professor Louise Emmett and Professor Michael Hofman – PRIMARY 2: A prospective, multicentre, randomised study of Ga-68PSMA /CT + mpMRI vs mpMRI alone for prostate cancer diagnosis

MATTHEW ROBERTS

Dr Matthew Roberts – De-Intensification of Post ProstatEctomy Radiotherapy (DIPPER) incorporating clinical and imaging - based risk stratification: Part 1 Pilot study (additional site)

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MRI is now routinely utilised for the diagnosis of prostate cancer in Australia. However, it still misses about 15-20% of important cancers, and about half of the biopsies undertaken after MRI are negative, because MRI is not completely accurate. PSMA PET is a new technique that is helpful in staging men who have already been diagnosed with prostate cancer. The PRIMARY trial - currently underway is assessing the value of PSMA PET in men who are suspected of having prostate cancer, and are undergoing both an MRI and a prostate biopsy.

This trial proposes to randomise men between MRI + biopsy (if required) - the current standard of care in Australia, and MRI /PSMA + biopsy (if required). The study hypothesis is that PSMA MRI will

This clinical trial will use modern PET scanning (PSMA PET/CT) in men who have a rising PSA level after prostate surgery to select those who can potentially avoid or minimise additional (radiation, hormone) treatments safely. Previous studies reported that these men who have a negative or confined PSMA PET have good treatment responses to limited radiation treatment without hormones compared to men whose cancer has spread. Some men with a negative PSMA PET who were not treated did not progress over 3 years, suggesting that some men can be spared treatment altogether.

The purpose of this trial is to determine if some men with low risk cancer who can be safely monitored,

both reduce unnecessary biopsies and improve accuracy of prostate cancer diagnosis, compared to using MRI alone. Also, a health economics analysis to assess cost to the community and QOL for men with prostate cancer is an important component of this trial.

To date, the study has enrolled 230/309 men, and the results are looking promising for combination of PSMA and MRI to be more accurate than MRI alone in diagnosing important prostate cancers. There is the potential for imaging to play a much bigger role in diagnosis of prostate cancer and for the number of biopsies required to be safely reduced.

then avoid treatment side effects without compromising disease control.

This trial will be limited to men who are deemed as “Low Risk” for spreading cancer using criteria from the European prostate cancer guidelines. If the PSMA PET result is negative, the trial will randomly choose close surveillance and delayed treatment or standard radiation treatment. If the PSMA PET result is positive and confined, men will receive standard radiation treatment to the prostate and the other half will receive additional hormone treatment. If positive and spread outside the prostate area, selected treatments and responses will be monitored for some years.

Below the Belt #YourWay

ALEX TAN

Dr Alex Tan –

PRIUS MR: Prostate Re-Irradiation Using SABR and MRI Guidance This study aims to demonstrate the feasibility of using the next generation of radiotherapy machine with an onboard MRI scanner (known as an MR-linac, or MRL) to give further radiation to the prostate in men who have previously received prostate radiation and now have a recurrence in the prostate gland.

The efficacy and tolerability of this approach has been demonstrated in a number of small series using a conventional radiation machine, but the dose and method of delivery have varied significantly and thus the results are difficult to generalise or apply clinically.

Controlling the recurrent cancer this way can spare men the toxicity of hormone therapy which, while usually effective, carries a raft of side effects that can significantly impact quality of life.

The potential exists for reirradiation to be delivered to a higher dose and with less risk of toxicity by harnessing the unique potential of the MRL to deliver treatment more accurately.

If this treatment is feasible on the MRL, the intention is to broaden this to a national study to explore in more detail the optimal dose for this treatment.

ANIS HAMID

Dr Anis Hamid –

MEMENTO: Biomarker discovery in metastatic hormone sensitive prostate cancer (MEtastatic Prostate Cancer MEthylation and Transcriptional biOmarker Study) In recent years, we have learned that changes in prostate cancer genes can influence the risk of developing metastatic prostate cancer. This study aims to improve our understanding of how genes are controlled in metastatic prostate cancer, and specifically how gene control might determine how men respond to standard treatments (such as hormone therapy and chemotherapy).

By way of examining cancer biopsies taken at the diagnosis of metastatic prostate cancer, we will test for an important genomic feature called DNA methylation – a process involved in ‘silencing’ genes. We believe DNA methylation will provide important information about why some cancers are more aggressive than others and why men may respond to treatments differently. We will use DNA methylation information from the tumours and compare it to information of how men diagnosed with metastatic prostate cancer responded to standard treatments. We then hope to use this as a strong foundation to design larger studies to test DNA methylation in prostate cancer clinical trials, to prove that it is an important test in the clinic to identify the risk of aggressive disease and to tailor the optimal treatment choice for patients. Ultimately, this study aims to build on our scientific knowledge of prostate cancer in order to improve ‘precision care’ of men with metastatic prostate cancer.

ANDREW WEICKHARDT

Associate Professor Andrew Weickhardt – Ga-PSMA PET as a potential Imaging biomarker post tyrosine kinase inhibition of metastatic clear cell Renal cell Cancer (PIRC) – a pilot study

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Immunotherapy and tyrosine kinase inhibitors (tablet targeted therapies) have revolutionised the treatment of advanced clear cell renal cell cancer (ccRCC), the most common type of kidney cancer. Computed tomography (CT) scans are used to determine where the cancer is and how it is responding to treatments. CT scans have limitations, however, only showing us tumour deposits physically and not reflecting how active they are.

A new type of positron emission tomography (PET) scan, targeting “prostate specific membrane antigen” (PSMA), appears very useful in diagnosing the extent of ccRCC spread before treatment and to see if the treatment is working. This is likely because RCC deposits have many small blood vessels, with the PSMA protein being found in these blood vessels, and not because it is related to the prostate.

Many tablet targeted therapies affect cancer blood vessel development, and as such, this project seeks to understand whether a PSMA PET scan is useful in visualising patients’ tumours after they have been treated with these therapies.

Additionally, we want to understand if tumours that remain active on PSMA PET might be sensitive to another tablet targeted therapy, potentially allowing us to tailor the right treatment, to the right patient, at the right time.

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Below the Belt Move #YourWay

See your suburb #YourWay See Your Suburb #YourWay invited family and friends to attempt the 5km, 10km and or 20km challenge while seeing parts of the Inner West never seen before. It could be undertaken as a self-guided walk or cycle and was suitable for all ages.

Thank you to Inner West Council for helping ANZUP raise funds for below the belt cancer research.

The mini challenges WEEK 1: Show us #YourWay 1 - 7 May 2021 The first mini challenge was for participants to snap a selfie of how they ‘moved’ their way. They could have been running, swimming, jumping, dancing, lifting weights at the gym - or a little bit of everything.

Congrats to our Week 1 winner Sam Rickard, who hit the gym and smashed his fitness goals. Sam won a bottle of Larrikin Gin, donated kindly by our supporters at Larrikin Gin and Kilderkin Distillery, Ballarat..

WEEK 2: Share why you are moving #YourWay 8 - 16 May 2021 This week the mini challenge was to explore participants ‘why’.

Whether they loved exercising, wanted to get healthier, worked in healthcare or someone they loved had been affected by below the belt cancers.

We asked the question what motivated them to join us in the challenge? After all, sharing stories is a key part of raising awareness about below the belt cancers.

Congratulations to Bec’s Troops who won a Spice Tailor hamper. Bec’s Troops had a team of over 20 people participating, raising awareness and funds in memory of Bec Jago.

WEEK 3: Where are you moving #YourWay 17 - 23 May 2021 In week 3 of the Below the Belt #MoveYourWay Challenge, we wanted to know where in the world participants were getting out there and moving.

Participants snapped a selfie with an iconic photo of where they were completing the challenge.

Well done to Sam McFedries, who explored Sydney with her incredible fitness goal. Sam included images of her walking at the harbour and along Sydney’s key walking tracks. Sam won a Twelve South office accessories pack.

WEEK 4: Celebrate #YourWay 24 - 31 May 2021 This challenge was about celebrating your #MoveYourWay Challenge successes. Did participants smash their km goal?

Did they try a new sport? Or reach their fundraising target? Well, Joe Bakhmoutski did.

“Time flies when you’re having fun - especially in lockdown! It’s been a great month of running around AND raising money for this great cause, but... I could never do it without YOU! A month later with your help, our team raised $4,970 for below the belt cancer clinical trials! This one is not for the faint-hearted... It was a challenge - and we have delivered! This involves a bucket of ice cold water and... You know the rest!”

Congratulations Joe, who won a Big Drop Brewing pack.

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Below the Belt #YourWay

2021 Move #YourWay results We are thrilled to announce we have raised $75,000 and donations are still coming in.

Fundraising heroes Congratulations to all our challengers who raised vital funds for clinical trials. We would like to give a special thank you to our top fundraising team and individual heroes:

Top Fundraisers

OVERALL CHAMPIONS

TEAMS

• The Below the Belt Move #YourWay Champion: Dave Pook

1. Bec’s Troops – $13,590

• Most kilometres walk / run – male: Sho Waller

2. Team VU – $5,043

• Most kilometres walk / run – female: Maya Linden

3. Below the Belt Babes – $3,616

• Most kilometres cycled – male: Dave Pook

4. The Young and the Rest of Us – $3,558

• Most kilometres cycled – female: Ciara Conduit

5. Monash GU Trials – $2,280

• Most hours – male: Gary Clarke

INDIVIDUALS 1. Tony Jago – $2,946

• Most hours – female: Nicole Tankard • Most kilometres by team: #GOG • Most hours by team: Below the Belt Babes

2. Belinda Jago – $2,143 3. Margaret McJannett – $1,790 4. Julijana Trifunovic – $1,702 5. Sam Rickard – $1,308

BELINDA AND TONY JAGO

DAVID POOK

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Below the Belt Move #YourWay

2021 Move #YourWay ambassadors

Montaigne

Michael Shafar

We were very excited to welcome Jessica Cerry, AKA Montaigne, as one of the 2021 Below the Belt #YourWay ambassadors.

Montaigne is an Australian singer-songwriter-musician who is going from strength to strength; previously a Triple J Unearthed High School finalist, then an Australian Eurovision Song Contest representative, singing in the 2021 Mardi Gras and joined us for the 2021 #YourWay Challenge.

Michael is a testicular cancer survivor and stand-up comedian, (who you might recognise from Channel 10’s The Project, ABC’s Comedy Bites and triple j’s Good Az Friday) and a 2021 Move #YourWay Ambassador.

Montaigne collected the songs that inspired her to #MoveYourWay in a personalised #YourWay Spotify Playlist.

Michael is back with an all new show ready to give 110%! There’s a reason why he is one of the most exciting new comedians in Australia right now and sells out his shows across the country.

110% sees Shafar raw, honest and as irreverent as ever, discussing the surprising benefits of going through chemotherapy during Melbourne’s lockdown, the perils of skinny jeans and the power of bagels.

Kaarle McCulloch Kaarle McCulloch is our very own Olympic champion, a four-time world champion and a fifteentime national champion. Kaarle has been the Below the Belt Pedalthon ambassador since 2015 and also a Move #YourWay ambassador since 2020.

“I am super pleased to be involved with the Below the Belt #YourWay campaign. It is going to provide people with the flexibility to be involved in a way that has meaning to them in the current world circumstances.

For me it means I can be involved in a way that is more than being an ambassador. I’ll be tracking all my training activity so that others can follow along with what it’s like to train like an Olympian all the while raising funds for ANZUP and helping them fund the trials that find better ways to treat cancers below the belt”.

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Below the Belt #YourWay

Jonny Harrison

Manu Feildel

Ball Park Music

“As a long-time supporter of the Pedalthon and an Ambassador of the Below the Belt events I think it’s a wonderful evolution to the #YourWay challenge in response to the events thrown at us in the last 18 months.

Now more than ever it’s really important that people find their own way to stay healthy and active, and also to continue to raise awareness for the amazing work the ANZUP team are doing.

We were delighted to announce that celebrity chef (and 2011 winner of Dancing with the Stars) Manu Feildel nominated ANZUP as his charity for the 2021 Dancing with the Stars.

We were delighted to welcome Ball Park Music as supporters of our 2021 #MoveYourWay Challenge.

Like most athletes around the world I’ve had my season turned upside down with most events cancelled or deferred.

While it can be tough to find the motivation to keep training, setting goals can help you keep moving forwards and that’s a key reason why I’ll be joining the #YourWay challenge.

Not only did Manu get his cha cha going on the dance floor, he also helped raise awareness and funds for better treatments and outcomes for patients with below the belt cancers.

Ball Park Music is a five-piece indie rock/pop band based in Brisbane, Australia, made up of frontman Sam Cromack, Jennifer Boyce, Paul Furness, and twins Dean and Daniel Hanson. Their 2011 single “It’s Nice to Be Alive” was featured in the 2014 film Blended and the fifth season of Gossip Girl. Ball Park Music have had 10 different songs featured in Triple J’s Hottest 100.

BPM pulled together a playlist of their favourite bops and invited everyone to #ListenYourWay and #DanceYourWay.

As an endurance cyclist who races 24 Hour mountain bike events I’m trying to think outside the box for my #YourWay challenge.

Needless to say it will involve lots of time and km’s on the bike!”

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Below the Belt Move #YourWay

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Below the Belt #YourWay

Thanks to our #YourWay Sponsors and Supporters SPONSORS

SUPPORTERS

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Below the Belt Move #YourWay

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Thanks to our Partners, Corporate and In-kind Supporters Corporate Supporters

In-Kind Supporters

We are very fortunate to have our corporate supporters and partners who enable ANZUP to better support our members and ultimately, patients and their families. Our 2021 corporate supporters include:

We acknowledge and thank the following organisations for the generosity they have shown by providing their services pro-bono.

Astellas, AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen and Pfizer Oncology.

AFI Branding, The Saturday Paper and FC Lawyers.

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Y UR WAY

SUPP RTING ANZUP CANCER TRIALS

Fight Cancer Below the Belt Join us in the fight to improve the treatment and outcomes of those with below the belt cancers

Find out more at www.belowthebelt.org.au

ANZUP Cancer Trials Group Level 6, Lifehouse Building, 119-143 Missenden Road, Camperdown NSW 2050 Tel: +61 2 9562 5042 Email: anzup@anzup.org.au www.anzup.org.au