What is the recommended initial management strategy for a patient with penile nodules (PND) and cobblestoning associated with Peyronie's disease?

Management of Penile Nodules and Cobblestoning in Peyronie's Disease

Initial Assessment and Disease Phase Determination

For patients presenting with penile nodules and cobblestoning associated with Peyronie's disease, the first critical step is determining whether the disease is in the active or stable phase, as this fundamentally dictates treatment strategy. 1

Disease Phase Classification

• Active disease is characterized by penile pain, progressive curvature, developing plaque, and dynamic symptoms typically lasting 3-12 months 2
• Stable disease shows symptoms unchanged for at least 3 months, minimal or no pain, established plaque, and stable curvature 2
• Document the diameter, location, number of nodules, morphology (papillary, nodular, ulcerous or flat), and relationship to other penile structures during physical examination 3

Treatment Algorithm for Active Phase Disease

If the patient has active disease with pain and progressive nodules, NSAIDs are the recommended first-line treatment, not collagenase injections. 1, 2

Active Phase Management Options

• NSAIDs should be prescribed for penile pain management, with pain assessed using a visual analog scale and periodically reassessed 1, 2
• Daily tadalafil 5 mg may reduce collagen deposition, lower curvature progression rates, and improve symptoms compared to controls 1, 2
• Avoid ineffective oral therapies including pentoxifylline, vitamin E, tamoxifen, procarbazine, potassium para-aminobenzoate (potaba), and omega-3 fatty acids, as these lack proven efficacy and may delay more effective interventions 1

Important Caveat for Active Phase

Intralesional collagenase is specifically a therapy for curvature reduction in stable disease—it does not treat pain or erectile dysfunction 2. Using collagenase for pain relief represents off-label use not supported by major guidelines and could delay appropriate pain management 2.

Treatment Algorithm for Stable Phase Disease

Once the disease has stabilized (symptoms unchanged for ≥3 months), treatment options depend on curvature severity, erectile function status, and the presence of a palpable plaque. 1, 4

Stable Phase Treatment Stratification

• For mild curvature (<30°): Observation may be appropriate if sexual function is not significantly impaired 2
• For moderate curvature (30°-90°) with intact erectile function and palpable plaque: Intralesional collagenase Clostridium histolyticum (CCH) injections are the only FDA-approved non-surgical therapy 4, 2
• For severe curvature (>60°) or failed conservative therapy: Surgical options should be considered after disease stability for 3-6 months 4

Collagenase Treatment Protocol

• Dosing: 0.58 mg (10,000 U) per injection into the plaque, with up to 8 injections over 24 weeks 4, 2
• Spacing: Proper spacing between treatment cycles (6 weeks) is required 4
• Expected outcomes: Average improvement is approximately 17° reduction in curvature versus 9.3° with placebo 4, 2
• Administration: Must be performed by a urologist experienced in urological disease treatment 4, 2

Patient Counseling for Collagenase

Patients must be counseled about potential adverse events, including 4, 2:

• Penile ecchymosis (84.2% of patients experience at least one adverse event, most mild or moderate)
• Swelling and pain
• Rare but serious complications like corporal rupture

Alternative Non-Surgical Options for Stable Disease

Penile traction therapy (PTT), extracorporeal shockwave therapy (ESWT), and vacuum erection devices (VEDs) have limited evidence but may be considered as adjunctive therapies. 1, 4

• ESWT shows positive results for pain relief but no effect on curvature or plaque size in RCTs 1
• PTT requires extended daily use (2-8 hours) and works through collagen remodeling, with no serious adverse effects reported in small studies 1
• VEDs affect intracorporeal molecular markers but have limited retrospective data only 1

Surgical Options When Conservative Management Fails

Surgery should only be considered after disease has been stable for 3-6 months and conservative therapies have failed or are inappropriate. 4

Surgical Algorithm Based on Erectile Function

• For patients with preserved erectile function:

  • Tunical shortening procedures (plication) for curvatures <60° 4
  • Tunical lengthening with grafting for curvatures >60° or complex deformities 4
  • Note: Tunical lengthening carries significant risk of postoperative erectile dysfunction (up to 50%) 4

• For patients with erectile dysfunction: Penile prosthesis implantation addresses both curvature and erectile dysfunction 4

Critical Pitfalls to Avoid

• Do not use collagenase for pain management in active disease—this is off-label use without guideline support and delays appropriate NSAID therapy 2
• Do not prescribe oral therapies (vitamin E, pentoxifylline, tamoxifen, etc.) as they lack proven efficacy and delay effective treatment 1
• Do not proceed to surgery during active disease—wait for 3-6 months of stability 4
• Do not use ESWT for curvature reduction—it only helps with pain, not deformity 1
• Ensure realistic patient expectations—collagenase provides modest improvement (average 17° reduction), not complete resolution 4, 2

Follow-Up Protocol

• Regular follow-up every 3 months for the first 2 years with physical examination and ultrasound to evaluate treatment response 3
• Assess impact on sexual function and quality of life at each visit 3
• Use ultrasound during follow-up to evaluate treatment response 3