Treatment Comparison: Peyronie's Disease

AI Disclosure: This comparison was compiled by a coordinated team of specialized AI research agents under human direction. Every factual claim cites a specific published source. The evidence was independently verified by two specialized AI reviewers using structured pair review. This is educational content — not medical advice.

How to use this document: This comparison draws from the published evidence base. Individual suitability depends on your clinical profile — discuss with your urologist using the Patient Guide framework.

PD treatments range from injectable enzymes with controlled efficacy data to surgical options for stable-phase patients with refractory disease. Each treatment fits a different clinical profile. The profiles below summarize the evidence base for each option using consistent fields, then surface comparison-specific insights only visible side-by-side, then provide a summary table for at-a-glance reference.

Section 1 — Treatment Profiles

CCH (Collagenase Clostridium Histolyticum / Xiaflex)

• What it is: A bacterial enzyme injected directly into the PD plaque to break down its collagen. The only FDA-approved injection for PD.
• Best evidence: IMPRESS Phase III double-blind RCTs (Gelbard 2013, n=832). Largest prospective predictor study: Cahill 2025 (n=826).
• Typical outcomes: IMPRESS reported -17° absolute curvature improvement (-34%) vs placebo -9.3° (-18%, P<0.0001) — a difference the AUA characterizes as "a modest difference of 7.7°." Fewer than half of CCH patients achieve clinically meaningful improvement (46% IMPRESS composite responder; 44% improved in Flores 2022, n=114). Real-world community data: 5.4° mean improvement (Tsambarlis per Ziegelmann 2020, n=45) — substantially below trial outcomes.
• Cahill 2025 modified-protocol outcomes: 27.5° median improvement (Most Recent definition) / 32.5° (Completed 8 cohort). ⚠️ Trost-modified protocol — NOT standard IMPRESS protocol (uses aggressive in-office modeling, 0.9 mg dose, wrapping, RestoreX in 98% of patients). The cohort's median baseline curvature was 65° — meaningfully higher than many patients will have. The 27.5° figure is anchored to that high-baseline cohort. NOT generalizable to community CCH practice.
• Predictors of response (Cahill 2025 multivariate): dorsal direction (favorable); baseline curvature degree (0.5° more improvement per 1° baseline, P<.0001); moderate or severe hourglass / indentation deformity (3-10° MORE improvement, P=.02 — counter-intuitive vs historical assumption); calcification status NOT a reliable failure predictor (P=.37); concurrent RestoreX traction associated with 19.5° greater improvement (P=.02, the strongest predictor of all factors assessed); active phase NOT a barrier (P=.48 NS). Patient motivation/engagement also predictive: self-assessed decreased motivation = 7° less improvement (Cahill 2025, P<.01). Patient engagement requirement: CCH outcomes depend partly on active participation in modeling and traction adjuncts.
• Limitations / caveats: 84.2% adverse event rate vs 36.3% placebo (IMPRESS, per AUA Nehra 2015); 0.36% penile fracture rate (3/832). Original IMPRESS trials excluded hourglass deformity, ED, ventral curvature, and significant calcification — pre-selected favorable population. COI on Cahill 2025 / Trost-modified protocol findings: Landon Trost is the inventor of RestoreX, part-owner of PathRight Medical, recipient of investigator-initiated grants from Endo Pharmaceuticals (CCH manufacturer), and Editor-in-Chief of J Sex Med (recused from this article's peer review per the published statement).
• Cost / access: ~$15,000-18,000 total before insurance ($6,940-8,895/cycle, median 2 cycles per Walton 2022). Out-of-pocket <$300/cycle. US-only — withdrawn outside the United States.

Hyaluronic Acid (HA, intralesional)

• What it is: A naturally-occurring molecule with anti-inflammatory and anti-fibrotic properties, injected into the plaque. Off-label for PD in the US; approved for PD in Italy.
• Best evidence: Two double-blind RCTs. Favilla 2017 (n=140): HA -4.60° vs verapamil 0.00° (P<0.001). Abdel Fattah 2024 (n=42): HA -9.4° vs verapamil -5.4° (P=0.038). Cilio 2024 (n=62, stable phase): -12.4° with multimodal mechanics (vacuum + stretching + modeling).
• Typical outcomes: -4.6° to -12.4° depending on study and adjunct protocol.
• Predictors: Limited data. Calcification NOT predictive of response (Cilio 2024, P=.847).
• Limitations / caveats: Despite positive RCT data, ICSM 2024 (5th Consultation) recommends AGAINST routine HA use outside clinical trials, and EAU guidelines recommend against routine use. Small samples; no placebo-only RCT of HA alone (only head-to-head vs verapamil); heterogeneous protocols. Pursuing HA in the US means knowingly diverging from current major guidelines.
• Safety: No significant or lasting adverse events reported across more than 600 patients in published studies.
• Cost / access: Variable; US off-label means insurance unlikely to cover.

Traction Therapy (RestoreX device)

• What it is: A penile traction device with a counter-bending mechanism designed for curvature correction. The only traction device with positive RCT data at <3 hours of daily use.
• Best evidence: Ziegelmann 2019 RCT (n=100). Combination evidence: Alom 2019 (n=113, abstract).
• Typical outcomes: -11.7° curvature improvement vs +1.3° in controls (ITT) at 30-90 min/day for 3 months; +1.5 cm length gain. Combined with CCH: 6.9× more likely to achieve ≥20° improvement vs CCH alone (Alom 2019).
• Predictors: Phase-independent (works in active or stable phase); strongest combination effect when paired with CCH per Cahill 2025 multivariate analysis (RestoreX largest single predictor across multiple models, 18.9-20° more improvement).
• Limitations / caveats: User compliance required for full benefit. COI: Landon Trost is the inventor of RestoreX and a coauthor on combination studies. The Cahill 2025 RestoreX finding is confounded by the cohort composition — 98% of post-2019 patients used the device, leaving insufficient power in the non-use arm to fully isolate RestoreX's independent effect from concurrent protocol changes.
• Cost / access: ~$500-1,000 device cost. No prescription required. ICSM 2024 issued a Conditional Recommendation for traction therapy with Moderate Quality of Evidence — the most current major-society endorsement.

Tadalafil Daily (PDE5 inhibitor)

• What it is: An oral medication primarily indicated for erectile function; 5 mg daily dose used as a component of PD oral protocols.
• Best evidence: Durukan 2024 (n=133, retrospective cohort).
• Typical outcomes: Does NOT prevent curvature progression (P=0.08). MAY shorten pain duration (9.1 vs 12.2 months, P=0.04, univariable Wilcoxon — not adjusted for confounders). Curvature was measured by self-photography rather than pharmacological erection + goniometer.
• Predictors: ED status — primarily helpful when ED accompanies PD.
• Limitations / caveats: Not a curvature treatment per the controlled data. Component of the Mayo Clinic oral PD protocol (Ziegelmann 2020): pentoxifylline + L-citrulline + tadalafil. The protocol's controlled efficacy specifically for curvature correction is limited.
• Cost / access: Generic prescription, ~$50-100/month depending on coverage. On-label for ED; off-label for PD specifically.

Intralesional Verapamil

• What it is: A calcium channel blocker injected directly into the plaque.
• Best evidence: Two double-blind RCTs comparing verapamil head-to-head with HA. Favilla 2017 (n=140) and Abdel Fattah 2024 (n=42). No placebo-controlled trial has tested verapamil alone.
• Typical outcomes: Verapamil was significantly inferior to HA in both controlled head-to-heads. Favilla 2017: 0.00° ± 0.00 curvature change in the verapamil arm vs HA -4.60° (P<.001). Abdel Fattah 2024: verapamil -5.4° vs HA -9.4° (P=.038). Uncontrolled studies report improvement (e.g., Levine 2002, n=156: 60% "objectively improved") but lack placebo arms. Standard published protocols use weekly to biweekly injection intervals; longer intervals have no published evidence base.
• Predictors: None reliably identified in controlled data.
• Limitations / caveats: No controlled curvature efficacy. Practical advantages (cost, availability, safety, ability to use in active phase) are real but do not overcome the absence of controlled efficacy.
• Cost / access: ~$60/year (Walton 2022). Off-label for PD; widely available.

Surgical Options

Surgery requires confirmed stable-phase disease. ICSM 2024 Recommendation #18 specifies ≥6 months of stability — a higher threshold than the 3-month general phase definition. None of the surgical options below are appropriate during active-phase PD. Surgery is reserved for stable patients with significant residual curvature or refractory disease after conservative management.

Plication

• What it is: Surgical placement of sutures on the convex side of the curve to shorten that side, straightening the penis.
• Best evidence: Osmonov 2022 ESSM Position Statement (systematic review of 131 studies). Garaffa 2024 (n=91, abstract).
• Typical outcomes: 48-100% straightening across studies; 58-96% satisfaction.
• Predictors: Moderate curvature with preserved erectile function.
• Limitations / caveats: Perception gap (Hudak): 84% had no measurable decrease in stretched penile length, but 78% perceived length reduction. Plication does NOT cause additional length loss beyond what PD itself produces (Garaffa 2024, P=0.466). >70% of patients report shortening BEFORE any surgery — the disease causes the shortening, not the procedure. Glans hypoesthesia in up to 53% of cases (mostly transient).
• Cost / access: $1,856-3,631 (Walton 2022). Standard surgical option.

Grafting

• What it is: Excision or incision of the plaque followed by placement of a graft material to restore tunical length on the affected side.
• Best evidence: Osmonov 2022 ESSM systematic review.
• Typical outcomes: Similar straightening rate to plication. Curvature recurrence: 50-87% in longer-term follow-up (Osmonov ESSM 2022). Collagen fleece may have lower recurrence (0% in one series).
• Predictors: Severe curvature with preserved erectile function.
• Limitations / caveats: High long-term recurrence rate. ED risk up to 39% (mostly transient). More complex procedure than plication. ED outcome data uses the IIEF questionnaire, which has not been validated for PD (Osmonov 2022) — ED rates are indicative, not precise.
• Cost / access: Variable, generally higher than plication.

Prosthesis

• What it is: Surgical implantation of an inflatable or malleable penile prosthesis, often combined with manual modeling to address curvature.
• Best evidence: Multiple series; Ziegelmann 2020 review.
• Typical outcomes: Best for PD with significant erectile dysfunction. More than 25% of patients are dissatisfied with straightness despite achieving <20° residual curvature in the OR — "functionally straight" may not match patient expectations (Ziegelmann 2020).
• Predictors: PD with significant erectile dysfunction that has failed medical therapy.
• Limitations / caveats: Irreversible procedure. ED outcome data across most studies uses the IIEF questionnaire, which has not been validated for PD (Osmonov 2022) — ED rates are indicative, not precise. Prior CCH does NOT increase surgical complications (Trost 2023).
• Cost / access: Highest of the surgical options. Standard for refractory PD with ED.

Section 2 — Comparison Insights Visible Only Side-by-Side

These are observations that emerge when treatments are placed against each other, not when each is read in isolation.

1. The Verapamil vs HA head-to-head was a single trial

Favilla 2017 (n=140) was a double-blind RCT testing verapamil and HA against each other. The result: verapamil 0.00° ± 0.00 curvature change vs HA -4.60° (P<0.001). Both treatments are evaluated in the same randomized cohort with the same outcome assessment. This is more powerful than treating verapamil and HA evidence as separate narratives. (See the Verapamil and HA profiles above for sample size and study design context — the comparison is dramatic, but it is also based on one RCT in each treatment's primary evidence base.)

2. Both "definitive" treatments have substantial failure rates

CCH and grafting both look like high-confidence options when read in isolation. Side-by-side: fewer than half of CCH patients achieve clinically meaningful improvement (46% IMPRESS composite responder; 44% Flores 2022) — and grafting has 50-87% curvature recurrence in longer-term follow-up (Osmonov 2022). Both treatments produce outcomes most patients are satisfied with at the time of the procedure; both have meaningful long-term failure profiles. The expectation-setting matters when patients are weighing one against the other.

3. Active treatment vs passive treatment

CCH outcomes depend partly on active patient participation. Cahill 2025 found that self-assessed decreased motivation predicted 7° less improvement (P<0.01); higher PDQ bother and psych scores predicted better outcomes; concurrent RestoreX traction was the strongest single predictor of CCH response. Verapamil, by contrast, is delivered passively — the patient receives the injection and waits.

This is a meaningful patient-choice axis the per-treatment narratives don't put together. Patients weighing options should know that the better-evidenced treatments often demand engagement (modeling, traction, adherence) while the less-evidenced options often don't.

Section 3 — Comparison Summary Table

Cost figures are US-centric (Walton 2022, claims database, n=89,205). International readers will see substantially different figures depending on healthcare system.

Section 4 — What This Means for Your Appointment

This comparison presents the evidence landscape. The questions that turn the evidence into a treatment plan are conversations with your urologist. Some that may be useful to bring:

• Phase determination: "What is my disease phase right now? Am I in active phase (curvature still progressing) or stable phase (no change for ≥3 months)? Which treatments in this comparison are appropriate for my phase?"

• CCH predictors: "Of the predictors known for CCH response — direction, baseline curvature, hourglass status, calcification, concurrent traction, phase — which apply to me, and how do they affect what I should expect?"

• Treatment engagement: "How much active participation does each option I'm considering require? What modeling, traction, or adherence is part of the protocol you would prescribe?"

• Cost and coverage: "How does my insurance affect the practical options? Are off-label uses likely to be covered?"

• Provider experience: "What is your experience with each of these treatments, and what evidence are you drawing on? Are you familiar with the most recent published outcomes data, including Cahill 2025 for CCH and Favilla 2017 for HA / verapamil?"

• If considering surgery: "How are you confirming I have been in stable phase for the ≥6 months that surgical eligibility requires? What documentation supports that classification?"

The evidence base does not produce a single "best" treatment for PD. The right treatment depends on disease phase, clinical profile, and patient priorities — including how much the patient wants to actively participate in their own treatment course.

This treatment comparison was researched by a coordinated team of specialized AI agents under human direction. Every factual claim cites a specific published source and was independently verified by two specialized AI reviewers using structured pair review with documented pushback. This is educational content — not medical advice. Always discuss treatment decisions with your healthcare provider. For full study-by-study evidence, see the Evidence Reference.