Indications for Adjuvant Chemotherapy in Penile Squamous Cell Carcinoma
Adjuvant chemotherapy with TIP (paclitaxel, ifosfamide, cisplatin) is indicated for penile squamous cell carcinoma patients with high-risk pathological features including pelvic lymph node metastases, extranodal extension, bilateral inguinal lymph nodes, or ≥3 positive inguinal lymph nodes. 1
High-Risk Features Requiring Adjuvant Therapy
Adjuvant chemotherapy should be administered to patients with any of the following high-risk features:
- Pelvic lymph node metastases
- Extranodal extension
- Bilateral inguinal lymph nodes involved
- ≥3 positive inguinal lymph nodes
- Lymph node(s) ≥5 cm in size 2, 1
Patients Who May Not Require Adjuvant Chemotherapy
- pN0 (no positive lymph nodes)
- Single positive lymph node without adverse features
- pN1 disease with only 0-1 positive nodes without extranodal extension 1
Recommended Adjuvant Chemotherapy Regimen
The TIP regimen is the standard of care for adjuvant therapy:
- 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
- Repeat every 21 days 2, 1
Alternative Regimen
If TIP is contraindicated, 5-fluorouracil and cisplatin can be considered, though toxicities may require dose adjustments 2, 1.
Timing of Adjuvant Therapy
- Adjuvant therapy should be initiated within 6-8 weeks after surgery to maximize efficacy 1
- Complete surgical inguinal and pelvic lymph node management should be completed within 3 months of diagnosis (unless neoadjuvant chemotherapy was given) 1
Evidence Supporting Adjuvant Chemotherapy
The recommendation for adjuvant chemotherapy is based on extrapolation from neoadjuvant data, as there are insufficient direct data on adjuvant chemotherapy in penile cancer 2. However, recent evidence suggests benefit:
- A multi-institutional study demonstrated that adjuvant chemotherapy is associated with improved overall survival in patients with positive pelvic lymph nodes after lymph node dissection 3
- Patients who received adjuvant chemotherapy had a median overall survival of 21.7 months compared to 10.1 months in those who did not 3
Adjuvant Radiation Therapy Considerations
For high-risk patients, adjuvant radiation therapy should be considered in addition to chemotherapy, particularly for:
- pN2/N3 disease
- Extranodal extension
- ≥3 positive lymph nodes 1
Some evidence suggests that adjuvant radiation therapy may be superior to chemotherapy alone in patients with nodal positivity limited to the groin 4.
Common Pitfalls to Avoid
- Delaying adjuvant therapy beyond 6-8 weeks after surgery
- Underestimating the importance of extranodal extension as a high-risk feature
- Using bleomycin-containing regimens (associated with unacceptable toxicity)
- Failing to consider adjuvant radiation in addition to chemotherapy for high-risk patients 2, 1
- Inadequate surveillance after treatment 1
Surveillance After Adjuvant Therapy
- Clinical examination every 3-6 months for the first 2 years, then every 6-12 months thereafter
- Chest imaging every 6 months for the first 2 years, and annual chest imaging thereafter
- Abdominopelvic imaging every 3 months for the first year, then every 6 months thereafter 1