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ARCHIVES OF ANDROLOGY 49:205–213 (2003) Copyright # 2003 Taylor & Francis 0148-5016/03 $12.00+.00 DOI: 10.1080/01485010390196788

EXTRACORPOREAL SHOCKWAVE THERAPY FOR PEYRONIE DISEASE

T. GROTH M. MONGA Department of Urology, University of Minnesota, Minneapolis, Minnesota, USA While surgery is the mainstay of therapy for Peyronie disease requiring correction of angulation, interest has grown in the application of extracorporeal shockwave therapy (ESWT) as a minimally invasive approach. This article reviews the current literature reporting the use of ESWT for Peyronie disease. Keywords

ESWT, Peyronie disease, shockwave therapy

Peyronie disease affects 1–3% of the male population [8, 29]. Approximately 10% of men with erectile dysfunction have been reported to have Peyronie disease [15]. The disease most commonly affects men older than 40 years and more than 75% of patients are between 45 and 65 years [11]. The disease was first described in a correspondence between Fallopius and Vesalius in 1561, but was later named after Francois de la Peyronie, who reported it in the medical literature in 1743 [12]. Although Peyronie disease was described several centuries ago, the pathophysiology of the disease remains elusive. NATURAL HISTORY OF PEYRONIE DISEASE Peyronie disease is a connective tissue disorder affecting the tunica albuginea and adjacent corpus cavernosum tissue [5]. There are two phases of the disease. The early phase consists of a perivascular inflammatory reaction. This period usually lasts 2–10 months and symptoms consist primarily of pain during erection. The disease either regresses or continues to the second phase. In the second or late phase of the disease, the initial inflammatory reaction progresses to form a fibrotic, calcified, and palpable plaque. Consequences of this plaque include symptoms associated with late-phase disease. These consist of penile deviation when the penis is erect and erectile dysfunction [15, 44].

Address correspondence to Manoj Monga, MD, Department of Urologic Surgery, University of Minnesota, 1420 Delaware St. SE, MMC 394, Minneapolis, MN 55455, USA. E-mail: endourol@yahoo.com

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TRADITIONAL THERAPY FOR PEYRONIE DISEASE Definitive treatment of Peyronie disease has eluded and frustrated physicians and patients. A variety of modalities have been tried, including oral, topical, injection, and surgical therapy. Oral regimens employed as therapies for Peyronie disease include vitamin E, potaba, colchicine, and tamoxifen. However, most studies regarding the efficacy of oral treatment are nonrandomized and uncontrolled by design, making interpretation of the effectiveness of therapy difficult [33]. Also, the few reported placebo arms demonstrate significant improvement in pain (75%), penile curvature (42%), and plaque size (25%), suggesting the need for caution in interpreting uncontrolled studies [41]. In addition to oral medication, a variety of intralesional injection therapies have been used. These include steroids, verapamil, and interferons. Several short-term noncontrolled studies have noted inconsistent response to steroids. Additionally, localized side effects of steroid use can, unfortunately, be quite severe and have included tissue atrophy and skin thinning. These side effects can make surgery, if needed, technically difficult to perform [4, 16, 45]. Furthermore, interferon and the calcium channel blocker verapamil have been reported to have only moderate success in the treatment of Peyronie disease [13, 22, 43]. Topical application of the above medications has been explored. Iontophoresis has been used to deliver both verapamil and dexamethasone. After a 5-month follow-up, results were similar to the placebo arm of Peyronie disease reported in earlier studies [42]. Surgical treatment of Peyronie disease has been used, primarily in cases refractory to conservative management. There are three categories of surgeries for penile curvature. They include tunical shortening and lengthening procedures, as well as placement of prostheses. The Nesbit and modified Nesbit techniques are shortening procedures and have met with positive results in 79–95% of cases [23, 26, 28, 37, 38]. However, complications of either procedure have included erectile dysfunction, penile hematoma, penile narrowing, urethral injury, herniation, glans numbness, and phimosis [16, 35, 37]. Since conservative modalities have shown questionable efficacy and the majority of patients may view surgical procedures as too invasive, urologists have sought new treatment methods for Peyronie disease.

TECHNIQUE OF EXTRACORPOREAL SHOCKWAVE THERAPY FOR PEYRONIE DISEASE Extracorporeal shockwave therapy (ESWT) has been the gold standard in treating urolithiasis and has also been used as an efficient method in treating calcification of connective tissue in orthopedics and salivary stones [20]. New studies suggest that ESWT may be a viable alternative to current therapies for Peyronie disease (Table 1). The cumulative world literature reports the use of ESWL in 843 patients with Peyronie disease to date. Patients have been treated with the Storz Minilith (83%), Siemens Multiline (10%),Wolf Piezolith 2500 (2%) EPOS Ultra Device (2%), and Siemens Lithostar (3%). The number of shockwaves used in treatment has ranged from 1000 to 4000 and 72% of all patients were treated with 3000–4000 shock waves. The number of treatment sessions ranged from 1 to 10 and 94% of all patients were involved in a study group that had been treated greater than 2 sessions.


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Studies varied with regard to patient selection criteria. Many studies did not delineate selection criteria for patients with Peyronie disease [9, 10, 17, 21, 25], while some excluded patients with a calcified plaque on ultrasound and others selected patients who had previously failed other treatment modalities [1, 19, 32]. Five studies used no anesthesia, one study used general anesthesia, one study used local anesthesia, one study used intravenous sedation, and the remaining 13 studies did not report if any anesthesia was utilized. Localization of the plaque was done with a 7.5-MHz ultrasound in the majority of all cases. Lebret et al., reported the use of plaque injection with a contrast agent for radioscopic localization during treatment with ESWT [25]. CLINICAL RESULTS WITH ESWT FOR PEYRONIE DISEASE Unfortunately, the literature supporting ESWT as a modality for Peyronie disease is plagued by many of the same study design problems that characterize the literature for oral, topical, and intralesional therapy. Study groups have frequently consisted of both acute and chronic phase patients, and inclusion and exclusion criteria for participation in the study are often poorly defined. Several studies did not report the disease duration of patients prior to starting treatment [25, 32]. Differences in symptoms, depending on the phase of the disease, complicate the ability to define and evaluate success. Randomization to sham procedures has not been performed, and long-term follow-up with systematic standardized subjective questionnaire and objective measurements of curvature and plaque size is lacking. Since the symptoms associated with Peyronie disease can spontaneously improve or worsen, treatment has to be correlated with natural history of the disease [14, 15, 36]. One of the initial reports describing the use of ESWT in the treatment of Peyronie disease was by Butz in 1995. Butz reported a 92% decrease in angulation and a 92% decrease in pain in 12 patients with Peyronie disease. Since that time, several studies have noted similar promising results using this modality [6]. While all studies have reported positive results while using ESWT in treating Peyronie disease, the definition of success has varied. The studies also vary in stage of disease treated, choice of lithotripter and anesthetic, number of shockwaves and energy utilized, number of sessions of shockwave treatments, and duration of follow-up. Success rates with ESWT range from an 11–92% decrease in angulation, a 25–100% decrease in pain, a 25–78% improvement in sexual function, and a 35–80% positive opinion with the therapy (Table 1). The cumulative results for all reported studies was a decrease in deviation in 53% of all patients and a decrease in pain in 83% of patients. Sexual improvement was noted in 57% of patients with sexual difficulties and 66% of all patients reported a positive opinion of therapy. The two largest studies to date on treatment of Peyronie disease with ESWT were conducted by Colombo et al. (n ¼ 90) and Gianneo et al. (n ¼ 153) [9, 17]. Both studies were noncontrolled and the stage of the patient population was not reported. Both studies used the Storz Minilith lithotripter and were similar in the number of shockwaves used (3000 and 3000–4000, respectively). They did differ on the number of shockwave sessions used: Colombo et al. used 3 sessions and Gianneo et al. used 6–8 sessions. The studies both noted dramatic reduction in patient pain after therapy with ESWT: 94 and


208

52

90

15

153

25

22

35

26

Butz and Teichert [7]

Colombo et al. [9]

Sautter et al. [39]

Gianneo et al. [17]

Michel et al. [30]

Hauck et al. [19]

Leriche et al. [27]

Lebret et al. [24]

Reference

NR Storz 3000 Minilith SL1 NR Storz 3000 Minilith SL1 NR Dornier 3000 EPOS ULTRA Device NR Storz 3000–4000 Minilith SL1 Late Storz 1000 Minilith SL1 Mixed Storz 2000 Minilith SL1 NR Storz 2000 Minilith SL1 Mixed Siemens 3000 Multiline

Stage Type Number Patients of of of (n) disease lithotripter shockwaves

Table 1. Review of literature on effects of shock waves

7 kJ

Level 7 (0.35 mJ=mm2) 50 bars

Level 3–4 (0.07–0.11 J=mmq) 12 kV

NR

NR

NR

kV Used

1

General

NR

Sedation

2

4–10

NR

NR

NR

None

NR

Types of anesthetic

5

6–8

1–3

3

1–7

Number of sessions

3

NR

6

1

15

NR

NR

9

11

63

50

76

68

NR

25

40

73

NR

56

100

96

100

94

83

37

63

NR

58

67

43

NR

48

35

NR

65

NR

67

60

72

54

8

21

30

0.7

NR

1

5.70

Hematoma None

19

7

90

0.7

NR

None

75

None

None

None

None

None

NR

None

None

Duration Side effects (%) Decreased Improved Subjective of follow-up angulation Decreased sexual improvement Hematoma Urethral Cutaneous function (%) (months) (%) pain bleed bleed (%) (%)


209

Late

54

31

Lebret et al. [25] Michel et al. [31] Neururer et al. [34] Awogu et al. [2]

12

NR

12

Suvaskovic and Hindmarsh [40] Butz [6] 3500

NR

19

Bauman et al. [3]

Minilith SL1

Mixed Storz 2000–4000 NR Minilith SL1 NR Wolf NR NR Piezolith 2500 NR Minilith 3000–3500 NR SL1

70

Colombo et al. [10]

15–21 kV

24

Storz 3000 Minilith SL1 Mixed Lithostar 4000 Siemens [mean]

Level 4–6 (6.4–9.6 mJ) Level 4–5

12 kV

7 kJ

Energy density (0.11–0.17 mJ=mm2) Level 2–5

NR

Abdel-Salem et al. [1]

16

65

Storz 3000 Minilith SL1 Mixed Siemens 3000 Multiline Late Storz 1000 Minilith NR NR 3000

28

Hamm et al. [18]

Late

37

Hussain et al. [21]

Early Storz NR Minilith SL1 Mixed Storz 3000 Minilith SL1

57

Mirone et al. [32]

2

NR

NR

3

3–10

3–6

5

5

1–3

NR

None

NR

NR

Local anesthesia

NR

None

NR

None

NR

None

3

3–5

NR

3

5

NR

29

NR

12

24

6

18

3

NR

11

NR

92

28

NR

39

58

74

25

69

54

64

47

77

92

NR

100

80

71

100

25

94

91

81

60

79

NR

50

44

NR

58

78

NR

NR

25

96

NR

76

NR

NR

NR

76

NR

NR

NR

NR

61

71

NR

78

None

NR

None

NR

None

NR

None

90

6

50

None

None

33

NR

None

NR

None

NR

None

30

7

4

None

None

None

NR

None

Cutaneous bleed NR

NR

None

None

13

None

51

2


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96%, respectively. However, Colombo et al. noted a 25% decrease in penile angulation after treatment, whereas Gianneo et al. noted a 68% decrease in penile angulation after treatment. Because the stage of the disease was not reported in each study and because of some discrepancies in research design, it is difficult to discern the cause for these differences. A controlled nonrandomized study conducted by Mirone et al. investigated the effectiveness of ESWT alone or in combination with perilesional injection of verapamil compared to patients treated with verapamil alone. A total of 130 patients with stable Peyronie disease were entered in the study. A decrease in pain was reported by 59% of patients treated with verapamil alone, compared with 76% of those treated with ESWT and 83% of those treated with a combination of ESWT and verapamil. A reduction in curvature was reported by 65% of patients treated with verapamil alone, compared with 79% of those treated with ESWT and 76.2% of those treated with a combination of ESWT and verapamil. Larger randomized studies using validated questionnaires and objective measurements of angulation are needed to confirm this trend toward superior results with ESWT compared to intralesional verapamil therapy [32]. Hauck et al. compared ESWT to a control group treated with oral placebo. In the study, 22 patients with Peyronie disease late phase (average 12 months duration) who had failed previous oral treatment were treated with ESWT. Sixty percent had ultrasonographic evidence of calcifications and 100% had deviation of penis upon erection as measured by self-photography. The control group (n ¼ 23) consisted of patients with Peyronie disease who had not received any previous therapy. These patients had the earlier stage disease (average 6 months duration), none had calcifications, and only 61% had deviation of the penis upon erection. Although Hauck et al. found no significant difference in pain or improvement in the ESWT group when compared to the control group, obvious differences in inclusion criteria weaken the study. The two study groups were not comparable with regard to previous treatment, disease duration, calcification, or deviation of penis when erect. Also, the methods used to treat patients with ESWT in this study are different from others cited in the literature in that patients were treated with 2 sessions of 2000 shockwaves, while most other studies utilize 3–4 sessions of > 3000 shockwaves [19]. No serious complications were reported in any of the studies. The reported complications for ESWT therapy included hematoma (1–90%), urethral bleed (0–33%), petechiae (2%), and penile or buttock ecchymosis (up to 13%]. However, in all cases these complications were self-limiting and resolved over the course of 1–2 days. There have been only two long-term studies of Peyronie therapy with ESWT. Awogu et al. and Bauman et al. reported long-term follow-up of 24 and 29 months, respectively. Awogu et al. noted that improvement in angulation and pain was maintained over a follow-up period of 24 months. Also, Bauman et al. reported no worsening of any clinical symptoms over a follow-up period of 29 months. These studies suggest that the results from this therapy may be durable over time [2, 3]. The impact of patient selection, lithotripters selection, and treatment technique on efficacy is difficult to discern due to large variance in study design. A comparison of results based on the stage of Peyronie disease, number of shocks or type of lithotripter used is presented in Table 2. There appears to be a trend toward greater decrease in patient pain and angulation with multiple session ( >3) protocols of ESWT.


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Table 2. Success rates based on treatment protocols

Patient selection Early stage disease Mixed stage disease Late stage disease Number of shockwaves <2000 2000–3000 >3000 Number of sessions <3 3–5 6 Lithotripter Storz Minilith Siemens Multiline Wolf Piezolith 2500 EPOS Ultra Device Siemens Lithostar

No. of patients

Decreased pain (%)

Decreased angulation (%)

Improved sexual function (%)

57 233 149

79 75 94

77 44 71

76 31 82

147 349 201

88 80 88

65 42 65

61 56 56

334 165 153

83 80 96

41 65 68

43 82 67

689 80 19 15 24

86 82 100 100 71

56 40 NR NR 58

67 25 44 60 58

CONCLUSION ESWT holds promise as a minimally invasive approach to Peyronie disease, but there is no clear consensus on technique or long-term efficacy. Long-term randomized, shamcontrolled studies with standardized equipment and technique, sufficient sample size, and standardized follow-up must be conducted to accurately assess the efficacy of ESWT for Peyronie disease. REFERENCES 1. Abdel-Salem Y, Budair Z, Renner C, et al. (1999): Treatment of Peyronie’s disease by extracorporeal shock wave therapy: evaluation of our preliminary results. J Endourol 13:549–552. 2. Awogu O, Shah N, Car T, et al. (2002): Extracorporeal shock-wave therapy for Peyronie’s disease — two year results (abstract). J Urol 167(suppl):204–205. 3. Bauman M, Tauber R, Barmbek AK (1998): A new treatment in Peyronie’s disease: extracorporal shockwave therapy (abstract). J Endourol 12(suppl):S167. 4. Bodner H, Howard AH, Kaplan JH (1954): Peyronie’s disease: cortisone-hyaluronidasehydrocortisone therapy. J Urol 134:400. 5. Brock G, Hsu GL, Nunes L, et al. (1957): The anatomy of the tunica albuginea in the normal penis and Peyronie’s disease. J Urol 157:76–281. 6. Butz M (1995): Treatment of Peyronie’s disease (PD) by extracorporeal shockwaves (ESW) (abstract). J Endourol 9(suppl):S165. 7. Butz M, Teichert HM (1998): Treatment of Peyronie disease by extracorporeal shockwaves (abstract). J Urol 159(suppl):118. 8. Carrieri MP, et al. (1998): A case-control study on risk factors for Peyronie disease. J Clin Epidemiol 51:511–515.


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ESWT for Peyronie disease