UTUC Unlikely After MIBC Trimodal Therapy

The malignancy developed in only 2.6% of patients who received the treatment, researchers reported

UPPER TRACT urothelial carcinoma (UTUC) seldom develops following trimodal therapy (TMT) for muscleinvasive bladder cancer, with a rate comparable to that associated with radical cystectomy, investigators reported. In addition, renal function may decline slightly in the first year after TMT, but then remains stable long-term.

Those are the findings of separate studies by investigators at Massachusetts General Hospital in Boston. TMT consists of transurethral resection of bladder tumor and radiation therapy combined with chemotherapy. It is an accepted alternative to radical cystectomy. Various chemotherapy agents used for TMT, such as

BCG response

continued from page 5

BCG responders and non-responders,” Lone said. “Particularly interesting is that in numerous other studies it’s been observed that the presence of Lactobacillus in urine is associated with a ‘healthier’ microbiome. Therefore, it was interesting to see this signature also observed in tumor tissue.”

Joshua J. Meeks, MD, PhD, an associate professor of urology, biochemistry and molecular genetics at the

En bloc vs resection

continued from page 5 population. “While it is technically feasible for smaller tumors, those cancers are generally not that aggressive, and recurrences can be managed with repeat resection and intravesical therapy without a major impact on survival,” Dr Ritch said. “What remains to be seen is whether this technique is going to be impactful in the larger more aggressive tumors where recurrences and progression can be more dangerous.”

The study was well designed and could have significant clinical implications, he said. “Randomized controlled studies like these are important because they assess novel surgical techniques in a thoughtful and meticulous manner, thereby eliminating much of the biases introduced by patient selection for one mitomycin, 5-fluorouracil, and cisplatin, are nephrotoxic. approach over the other,” Dr Ritch said. “Endoscopic resection in NMIBC has not changed over many decades, and it is important to introduce new technologies, safely, through well designed studies such as this.”

The studies are the first to describe the subsequent occurrence of UTUC after TMT for MIBC as well as the first to inform clinicians of the potential effect of TMT and chemoradiation on future renal function, said the senior author of both studies, Adam S. Feldman, MD, MPH, Director of Urologic Research/Vice Chair in the Department of Urology at Massachusetts General Hospital and Assistant Professor of Surgery at Harvard Medical School in Boston. The findings from these studies will better inform clinicians and patients who are considering their options for treatment of MIBC, Dr Feldman said.

Northwestern University Feinberg School in Chicago, said the role of the microbiome in the modulation of the immune system is intriguing, and now it is possible to dissect how the host, the tumor, and bacteria interact.

“We all think about profiling a tumor for a personalized medicine approach, but perhaps manipulating the microbiome is the next generation of medicine,” Dr Meeks said. “I am most impressed by their data showing that greater microbiome diversity is associated with response, rather than a single bacterial strain.

Sam S. Chang, MD, MBA, professor of urology and medicine and chief surgical officer at the Vanderbilt Ingram Cancer Center in Nashville, Tennessee, said the standard resection techniques are antiquated at best. “The authors should be applauded in performing a randomized trial to evaluate the possible beneficial impact of an en bloc resection. As with any new technique, how results will translate in real world situations is still unknown.”

While the new findings are intriguing, he noted, much larger studies with longer follow-up may help better define the benefits and risks of en bloc. “We

In a study of 271 patients who underwent TMT for MIBC and had a median follow-up of 51.8 months, Jillian Egan, MD, and colleagues found that UTUC developed in 7 patients (2.6%) following

46 months. The researchers concluded that post-TMT UTUC is “relatively rare.” completion of TMT. That rate is comparable to rates of UTUC after radical cystectomy for MIBC, Dr Feldman noted. The median time to recurrence was

In a separate study of 287 patients who underwent TMT for MIBC and had a median follow-up of 4.6 years, Affan Zafar, MD, and colleagues found that patients’ mean estimated glomerular filtration rate (eGFR; in mL/ min/1.73 m 2) declined slightly from 65.67 at baseline to 58.43 at 1 year. The eGFR values at 3, 5, and 10 years were 55.40, 54.54, and 57.30, respectively.

There are several trials using bacteria to augment the immune response, so hopefully we will have an answer soon.”

To date, no reliable clinical markers are available to predict BCG response. Dr Meeks said there are still many other hurdles to overcome as well. Studies such as the one conducted by Lone and colleagues “are really what we should aim for,” he said. “They begin with a finding from the clinic, employ patient-involved samples, and go right to the bench for mechanism. We look forward to seeing the arc back know for certain tumors, this technique may not be possible or the best technique,” Dr Chang said. “Careful studies evaluating our current diagnostic, therapeutic, and surveillance management are essential to escalating care when needed but also de-escalating care when appropriate.”

Roger Li, MD, a genitourinary surgeon at Moffitt Cancer Center in Tampa, Florida, said the participants had tumors measuring 3 cm or less, which is the lower end of the risk spectrum in NMIBC. “These tumors tend to be well treated with resection alone with perioperative chemotherapy infusion,” Dr Li said. “The theoretical risk of tumor cell implantation has not been definitively proven. In addition, postoperative chemotherapy administration may serve to eliminate the phenomenon of tumor cell implantation and thus

“Our data on renal function demonstrate that while there may be a slight decline in renal function in the first year after TMT, renal function should not be further affected long term,” Dr Feldman said. ■ from the bench, translating their findings to the bedside.”

Daniel P. Petrylak, MD, Chief of Genitourinary Oncology at Yale Cancer Center in New Haven, Connecticut, said the latest findings are intriguing because there is an urgent need for better treatments.

“Something as easy and cheap as affecting the microbiome is something that could clearly help patients in this situation,” Dr Petrylak said. “It certainly could be leveraged to improve treatments.” ■ abrogate this perceived risk associated with standard TURBT.”

He added that the longer operative time is not trivial, as multiple procedures are typically performed backto-back. While the study shows the feasibility of en bloc resection and that it may reduce recurrence rates in patients with small tumors, it remains to be seen how many patients would be candidates. “The inaccuracy of bladder cancer staging obtained through endoscopic resection has been well described,” Dr Li said. “En bloc resection is a method that has been proven to work well in smaller tumors, providing the anatomical specimen to the pathologist for straightforward evaluation. However, given the constraints to remove larger specimens transurethrally, the clinical impact of en bloc resection is really limited.” ■