Characteristics of Men With Peyronie's Disease and Collagenase Clostridium Histolyticum Treatment Failure: Predictors of Surgical Intervention and Outcomes - Beyond the Abstract

The pendulum of Peyronie’s disease (PD) treatment has swung away from invasive surgical treatment following the FDA approval of collagenase clostridium histolyticum (CCH; XIAFLEX®; Endo Pharmaceuticals, Dublin, Ireland), but the optimal candidates for this costly treatment remain incompletely defined. While surgery has been traditionally considered the gold standard definitive treatment for chronic phase PD, a recent study has indicated that it is being performed less frequently as primary therapy since the approval of CCH in 2013.1



The therapeutic potential of CCH was documented in the IMPRESS I and II trials.2 However, these trials maintained strict exclusion criteria including ventral curvature, curvature <30 or >90 degrees, plaque calcifications, hourglass deformity without curvature and concomitant anticoagulation therapy. Since their publication, investigators have explored the relative risks and benefits of broadening these indications to many of those excluded criteria.3-7 These studies have identified plaque calcifications and indentation deformities to be negative prognostic features for CCH treatment. Even still, our observation has been that many men who receive CCH in the community and present to our practice with persistently bothersome penile deformity do indeed have plaque calcification and hourglass noted on their initial evaluation. What has been even more striking is that many of these men report not having had a formal in-office deformity assessment using intracavernosal injection with or without penile Doppler duplex ultrasound (PDDUS) before treatment, as is recommended by the American Urological Association Guideline on PD.8

As a result of these observations, we elected to review our five-year experience with men who had received CCH at outside facilities prior to presenting to our practice with persistent bother due to PD. Patients were included if they had persistently compromised sexual function due to PD deformity or sufficient dissatisfaction with the appearance of the erect penis to seek urologic evaluation following CCH treatment. All patients underwent PDDUS and pharmacologic injection for PD deformity assessment at the time of initial consultation, as per our routine protocol. Only patients with evidence of curvature >30 degrees and/or narrowing deformity on examination of the erect penis were included. Patients completed the Peyronie’s Disease Questionnaire (PDQ) and International Index of Erectile Dysfunction (IIEF)-5. Baseline characteristics and results of physical examination, deformity assessment, and PDDUS were noted. Importantly, careful attention was paid during history taking and deformity assessment to determine whether patients had evidence of narrowing/hourglass deformity (differential girth loss assessed using a string and a ruler) or instability/hinge in the erect state (buckling of the erect penis at a point of narrowing with the application of axial pressure). Calcifications were assessed using ultrasound and graded according to our previously published grading scale.9 Patients were tracked longitudinally, and subsequent interventions and outcomes were recorded. Surgical interventions performed included tunica albuginea plication (TAP), plaque incision and grafting (PIG) or partial plaque excision and grafting (PEG) with or without TAP, and inflatable penile prosthesis (IPP) implantation with or without PIG. The primary outcome was surgery after CCH treatment, and secondary outcomes were ED, sensory changes and change in stretched penile length (SPL) after surgery for the surgical cohort.

In total, 67 new patients with prior CCH were identified (11.7%). All had persistent bother with PDQ Bother score 10.1 (SD 3.1) after a median of six CCH injections (range 2-24). Mean composite curvature was 69 degrees (SD 33.8), with 77.6% (52/67) having indentation, narrowing or hourglass and 38.8% (26/67) having hinge effect or instability. Calcification was noted in 38.8% (26/67) patients, with Grade 2/3 calcification being the most common. 49.3% (33/67) patients went onto surgery with 60.1% (20/33) undergoing PEG, 18.2% (6/33) undergoing TAP alone and 21.2% (7/33) undergoing IPP with PIG. Patients who underwent surgery had more severe curvature (82.6 vs 55.4 degrees, p = 0.001) and were more likely to have hinge effect/instability (54.5% vs 20.6%, p = 0.005). Mean composite curvature greater than or equal to 60 degrees predicted surgery with an odds ratio of 2.99 (p <0.01, 95% confidence interval: 1.62-4.35).

Postoperative sensory changes were noted in 20% (4/20) patients undergoing PEG, with 2/4 resolving by 8 months post-op. Of the remaining two patients, one had decreased glans sensitivity at a six-month follow-up but could still achieve orgasm, and the other had hypersensitivity at the site of a suture at six weeks but did not return for subsequent follow-up. Fifteen percent (3/20) of PEG patients had worsened erectile function, with two-thirds experiencing satisfactory erections with PDE5 inhibitors. The mean stretched penile length was increased for all surgical subgroups, with all PEG and TAP patients undergoing postoperative penile traction therapy. There were no associations noted between surgical complications and the number of CCH injections or the occurrence of CCH-related complications, although the overall number of surgical complications was low.

In summary, this study highlights the importance of comprehensive PD deformity assessment prior to initiation of invasive treatment, and consideration of the published literature when counseling patients on the likelihood of treatment success with CCH. We noted high rates of narrowing deformity, which exists on a spectrum of girth loss from mild indentation to a complete circumferential hourglass. This type of deformity can easily be assessed after intracavernosal injection using a string and a ruler. Calcification was also relatively common, highlighting the importance of ultrasonographic assessment prior to CCH. In general, those patients who underwent surgery did well, with low rates of persistent complications beyond 6-12 months.

The pendulum of PD treatment will ultimately swing back towards surgical correction as the optimal CCH candidates continue to be delineated and the scope of this novel treatment narrows. In the meantime, it is critical that urologists provide comprehensive counseling to all PD patients, including the risks and benefits of all treatment options. This counseling must be tailored based on the deformity characteristics noted during in-office deformity assessment using intracavernosal injection. For offices unable to perform PDDUS, we recommend that penile ultrasound be ordered to assess for plaque calcification in any CCH candidates. Such information is critical for appropriate counseling on treatment expectations. Further multi-center studies are needed to assess outcomes of patients with varying PD characteristics in a prospective fashion and to further delineate optimal CCH candidates.

Written by: Petar Bajic, MD, Fellow, Andrology & Male GU Reconstruction, Rush University Medical Center, Chicago, Illinois, Twitter: @PBajicMD; Laurence A. Levine, MD, Practicing Urologist, Professor of Urology, Rush University Medical Center, Chicago, Illinois, Twitter: @LevineUrology

References:

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  2. Gelbard, Martin, Irwin Goldstein, Wayne J.g. Hellstrom, Chris G. Mcmahon, Ted Smith, James Tursi, Nigel Jones, Gregory J. Kaufman, and Culley C. Carson. “Clinical Efficacy, Safety and Tolerability of Collagenase Clostridium Histolyticum for the Treatment of Peyronie Disease in 2 Large Double-Blind, Randomized, Placebo Controlled Phase 3 Studies.” Journal of Urology 190, no. 1 (2013): 199–207.
  3. Wymer, Kevin, Matthew Ziegelmann, Joshua Savage, Tobias Kohler, and Landon Trost. "Plaque calcification: An important predictor of collagenase Clostridium histolyticum treatment outcomes for men with Peyronie's disease." Urology 119 (2018): 109-114.
  4. Alom, Manaf, Yifan Meng, Kiran Lata Sharma, Joshua Savage, Tobias Kohler, and Landon Trost. "Safety and Efficacy of Collagenase Clostridium Histolyticum in Peyronie's Disease Men With Ventral Curvatures." Urology 129 (2019): 119-125.
  5. Cocci, Andrea, Fabrizio Di Maida, Giorgio Ivan Russo, Marina di Mauro, Gianmartin Cito, Marco Falcone, Andrea Minervini et al. "How Atypical Penile Curvature Influence Clinical Outcomes in Patients with Peyronie's Disease Receiving Collagenase Clostridium Histolyticum Therapy?." The world journal of men's health 38, no. 1 (2020): 78-84.
  6. Amighi, Arash, Keith Vincent Regets, Justin James Nork, Neil Mendhiratta, Jesse Nelson Mills, and Sriram Venkata Eleswarapu. "Safety of Collagenase Clostridium histolyticum Injection Therapy for Peyronie Disease in Patients Continuing Antiplatelet or Anticoagulant Therapy." The Journal of Sexual Medicine 17, no. 2 (2020): 353-356.
  7. Ziegelmann, Matthew J., Daniel Heslop, Matthew Houlihan, Petar Bajic, Sevann Helo, Landon Trost, and Tobias Kohler. "The Influence of Indentation Deformity on Outcomes with Intralesional Collagenase Clostridium histolyticum Monotherapy for Peyronie's Disease." Urology (2020).
  8. Nehra, Ajay, Ralph Alterowitz, Daniel J. Culkin, Martha M. Faraday, Lawrence S. Hakim, Joel J. Heidelbaugh, Mohit Khera et al. "Peyronie’s disease: AUA guideline." The Journal of urology 194, no. 3 (2015): 745-753.
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