What is the best medication for erectile dysfunction (ED) in patients with a history of prostate cancer who have undergone surgery?

Best Erectile Dysfunction Medication for Post-Prostatectomy Patients

Oral phosphodiesterase type 5 inhibitors (PDE5i) are the first-line treatment for erectile dysfunction after prostate cancer surgery, with all FDA-approved agents (sildenafil, tadalafil, vardenafil, and avanafil) showing comparable efficacy in this population. 1, 2

First-Line Treatment: PDE5 Inhibitors

All FDA-approved PDE5i agents should be offered as first-line therapy, with the choice based on patient preference regarding dosing flexibility and side effect profile. 1, 2

Specific Medication Options and Dosing

• Sildenafil: Start at 50-100 mg on-demand, taken 30-60 minutes before sexual activity 2
• Tadalafil: Either 10-20 mg on-demand OR 5 mg daily dosing (both equally effective) 1, 2, 3
• Vardenafil: On-demand dosing with comparable efficacy to other agents 1, 2
• Avanafil: On-demand dosing with lowest rates of dyspepsia among PDE5i 1, 2

Critical Evidence from Post-Prostatectomy Studies

FDA trials specifically in bilateral nerve-sparing radical prostatectomy patients (N=303) demonstrated that tadalafil 20 mg significantly improved erectile function, with 54% achieving successful vaginal penetration (vs 32% placebo) and 41% maintaining erections for successful intercourse (vs 19% placebo). 3

Important Dosing Principles

• Start conservatively and titrate to maximum dose for optimal efficacy 1, 2
• Patients require proper education that sexual stimulation is necessary and multiple attempts (4-8 weeks) may be needed before declaring treatment failure 1
• Response rates are lower in post-prostatectomy patients compared to general ED population due to more severe baseline dysfunction 1, 2

Critical Safety Contraindications

PDE5i are absolutely contraindicated with concurrent nitrate use due to life-threatening hypotension risk. 2

Testosterone therapy is contraindicated in patients on active surveillance or androgen deprivation therapy. 2

Adjunctive Testosterone Therapy

Consider testosterone supplementation ONLY if serum testosterone is <300 ng/dL AND the patient is NOT on active surveillance or androgen deprivation therapy. 2

• Combination therapy (PDE5i + testosterone) is more effective than PDE5i alone in hypogonadal men 2
• Check morning total testosterone level before initiating PDE5i to identify potential hypogonadism 4

Essential Supportive Interventions

Lifestyle modifications significantly enhance PDE5i effectiveness and should be implemented concurrently: 2

• Smoking cessation, weight loss, increased physical activity, and reduced alcohol consumption 2
• PDE5i combined with aerobic exercise is more effective than PDE5i alone 2
• Pelvic floor physical therapy may improve sexual function outcomes 2
• Psychosexual counseling or couples therapy addresses psychological components and improves treatment outcomes 2

Timeline and Recovery Expectations

Erectile function recovery can continue for 2-4 years after surgery, so PDE5i trials should be revisited even if initially unsuccessful. 1

Early penile rehabilitation (within 45 days of surgery) with PDE5i may assist with smooth muscle preservation through increased tissue oxygenation, though trials have not demonstrated improved unassisted erectile function. 1

Common Pitfalls to Avoid

Incorrect PDE5i use accounts for a large percentage of treatment failures: 1

• Taking medication with large meals (reduces absorption)
• Lack of adequate sexual stimulation
• Declaring failure after insufficient trial period (need 4-8 weeks of proper use)
• Not titrating to maximum tolerated dose

Second-Line Options When PDE5i Fail

If PDE5i therapy is ineffective after proper dosing and adequate trial period, refer to urology for: 1

• Intraurethral prostaglandin pellet (alprostadil)
• Intracavernosal prostaglandin injection
• Vacuum erection device
• Penile prosthesis
• Combination therapy (e.g., sildenafil + vacuum device)

Most Common Adverse Effects

Expected side effects include headache, flushing, dyspepsia, nasal congestion, back pain, myalgia, visual disturbance, and dizziness. 1

• Avanafil has lowest rates of dyspepsia 1
• Tadalafil has lowest rates of flushing 1
• Vardenafil and avanafil have lowest rates of myalgia 1

Special Considerations for Nerve-Sparing Status

Patients who did not undergo nerve-sparing surgery are at highest risk of poor erectile function recovery and respond less robustly to PDE5i. 1

Baseline erectile function and comorbidities (diabetes, cardiovascular disease) significantly impact recovery potential. 1