What is the recommended initial treatment approach for a patient with invasive penile cancer and bulky inguinal and pelvic lymph nodes?

Management of Invasive Penile Cancer with Bulky Inguinal and Pelvic Lymph Nodes

Neoadjuvant cisplatin-based chemotherapy followed by surgical consolidation is the recommended initial treatment approach for patients with invasive penile cancer and bulky inguinal and pelvic lymph nodes. 1

Initial Assessment and Treatment Algorithm

Neoadjuvant Chemotherapy

• TIP regimen (paclitaxel, ifosfamide, cisplatin) is the preferred neoadjuvant chemotherapy for patients with bulky lymph nodes (N2-3) and should be considered standard prior to inguinal lymph node dissection (ILND) 1
• The TIP regimen consists of:
  • Paclitaxel 175 mg/m² IV over 3 hours on day 1
  • Ifosfamide 1200 mg/m² IV over 2 hours on days 1-3
  • Cisplatin 25 mg/m² IV over 2 hours on days 1-3
  • Repeated every 21 days 1
• Response rates of approximately 50% have been observed in the neoadjuvant setting 1
• Long-term progression-free survival is estimated at 36.7% with this approach 1
• Improved progression-free and overall survival are associated with objective response to chemotherapy 1

Surgical Management After Neoadjuvant Therapy

• Patients responding to neoadjuvant chemotherapy should undergo consolidative surgery with curative intent 1
• Even patients who did not experience progression during neoadjuvant chemotherapy should be considered for surgery if resection is feasible 1
• For patients with pelvic lymph node involvement, ipsilateral pelvic lymph node dissection (PLND) should be performed 1, 2
• Complete surgical management of inguinal and pelvic lymph nodes should be performed within 3 months of diagnosis (unless neoadjuvant chemotherapy has been administered) 1

Alternative Approaches

Radiation Therapy Options

• For patients unable to undergo surgery or chemotherapy, definitive/primary lymph node radiotherapy (with or without chemosensitization) can be considered 1
• Adjuvant radiotherapy (with or without chemosensitization) should be offered to patients with pN2/N3 disease, including those who received prior neoadjuvant chemotherapy 1
• For patients with T3-4 or N1 disease, circumcision followed by EBRT with chemotherapy is recommended:
  • 45-50.4 Gy to whole penile shaft, pelvic lymph nodes, and bilateral inguinal lymph nodes
  • Boost primary lesion with 2 cm margins and gross lymph nodes to a total dose of 60-70 Gy 1

Adjuvant Therapy Considerations

• Adjuvant chemotherapy may be considered for high-risk patients with surgically resected disease, particularly those with pathological pelvic lymph node involvement (pN3) 1
• For high-risk patients, adjuvant EBRT or chemoradiotherapy can be considered, especially for those with:
  • Pelvic lymph node metastases
  • Extranodal extension
  • Bilateral inguinal lymph nodes involved
  • ≥5 cm tumor in lymph nodes 1

Prognostic Considerations

• Early intervention for lymph node metastases significantly impacts survival 3, 2
• Five-year disease-free survival rates vary significantly by nodal stage:
  • 93.4% for pN0
  • 89.7% for pN1
  • 30.9% for pN2
  • 0% for pN3 4
• Patients with more than two invaded lymph nodes have poor survival outcomes 4

Important Caveats and Pitfalls

• Bleomycin-containing regimens should be avoided due to unacceptable pulmonary toxicity 1
• Clinical staging often underestimates the extent of lymph node involvement; careful pathological assessment is essential 5
• For patients with fixed inguinal lymph nodes, neoadjuvant chemotherapy is strongly recommended before attempting surgical resection 3
• The quality of evidence for management of lymph node-positive penile cancer is generally poor due to the rarity of the disease and lack of randomized controlled trials 1, 2
• Regular and careful follow-up is critical, as early detection of recurrence increases the likelihood of curative treatment 2