What is the management approach for prostate cancer that has metastasized to the penis?

Management of Prostate Cancer Metastasis to the Penis

For prostate cancer that has metastasized to the penis, the recommended management approach is systemic therapy with TIP regimen (paclitaxel, ifosfamide, cisplatin) as first-line treatment, followed by surgical consolidation if there is response to chemotherapy. 1

Systemic Therapy Options

• TIP regimen is the preferred first-line chemotherapy for metastatic penile involvement, consisting of paclitaxel 175 mg/m² IV over 3 hours on day 1, ifosfamide 1200 mg/m² IV over 2 hours on days 1-3, and cisplatin 25 mg/m² IV over 2 hours on days 1-3, repeated every 21 days 1, 2
• Response rates of approximately 50% have been observed with TIP regimen, with long-term progression-free survival estimated at 36.7% 1, 2
• 5-fluorouracil and cisplatin can be considered as an alternative to TIP for patients who cannot tolerate the TIP regimen, though toxicities may require dose reductions 2
• Bleomycin-containing regimens should be avoided due to unacceptable toxicity 2, 1

Androgen Deprivation Therapy (ADT)

• For the underlying prostate cancer, ADT through bilateral orchiectomy or LHRH agonists should be continued or initiated as the backbone of systemic therapy 3, 2
• Combined androgen blockade (CAB) with the addition of a nonsteroidal antiandrogen to castration therapy may provide a small survival benefit (1-5% absolute reduction in mortality at 5 years) but with increased toxicity 2, 3
• For patients with metastatic castration-resistant prostate cancer, docetaxel 75 mg/m² every 3 weeks with prednisone 5 mg orally twice daily may be considered 4, 5

Surgical Management

• If there is response to systemic therapy, consolidative surgery with curative intent should be considered 1
• For patients with penile involvement, partial penectomy should be considered if a functional penile stump can be preserved and negative margins can be obtained 2
• Inguinal lymph node dissection (ILND) should be performed if there is evidence of inguinal lymph node involvement 2

Radiation Therapy

• For patients unable to undergo surgery or chemotherapy, definitive radiotherapy (with or without chemosensitization) can be considered 1
• For T3-4 or N1 disease, circumcision followed by EBRT with chemotherapy is recommended, with doses of 45-50.4 Gy to the whole penile shaft, pelvic lymph nodes, and bilateral inguinal lymph nodes, followed by a boost to the primary lesion with 2 cm margins and gross lymph nodes to a total dose of 60-70 Gy 2

Adjuvant Therapy Considerations

• Adjuvant chemotherapy may be considered for high-risk patients with surgically resected disease, particularly those with pathological pelvic lymph node involvement 1
• Adjuvant EBRT or chemoradiotherapy can be considered for high-risk patients, especially those with extranodal extension or ≥5 cm tumor in lymph nodes 2, 1

Monitoring and Follow-up

• Regular clinical examinations of the penis and inguinal region are essential 2
• If clinical examination is abnormal, imaging studies such as ultrasound, CT, or MRI of the inguinal region should be performed 2
• PSA monitoring should continue to assess the response of the underlying prostate cancer to therapy 2, 5

Important Caveats

• The quality of evidence for management of metastatic penile cancer is generally poor due to the rarity of the disease and lack of randomized controlled trials 1
• Treatment decisions should prioritize quality of life given the palliative nature of therapy in this advanced disease setting 2, 3
• The prognosis for patients with metastatic prostate cancer to the penis is generally poor, with 5-year survival rates for metastatic prostate cancer around 37% 5