What is the role of adjuvant chemotherapy and radiation therapy in an elderly patient with carcinoma of the penis (ca penis) after wide local excision with bilateral inguinal and pelvic lymph node dissection?

Adjuvant Therapy for Penile Cancer After Lymphadenectomy

Adjuvant chemotherapy with cisplatin-based regimens (specifically paclitaxel/ifosfamide/cisplatin) is recommended for this elderly patient with bilateral inguinal and pelvic lymph node dissection, particularly if pathology reveals pN2-3 disease (≥2 positive nodes, extracapsular extension, or poorly differentiated metastases). 1

Adjuvant Chemotherapy Recommendations

Indications for Adjuvant Chemotherapy

• Adjuvant chemotherapy is specifically recommended for patients with pN2-3 disease (≥2 positive inguinal lymph nodes, extracapsular nodal extension, or poorly differentiated metastases). 1

• By extrapolation from neoadjuvant data showing 50% response rates and 30% disease-free survival at 36 months, it is reasonable to administer paclitaxel/ifosfamide/cisplatin (TIP) in the adjuvant setting if not given preoperatively and pathology demonstrates high-risk features. 1

• The rationale is compelling: patients with regionally advanced disease who achieve clinical/pathological response to chemotherapy have significantly improved 5-year survival (50% for CR/PR vs 7.7% for progression). 2

Specific Chemotherapy Regimen

• Four cycles of TIP (paclitaxel, ifosfamide, cisplatin) represents the standard cisplatin-based regimen based on neoadjuvant trial data demonstrating tolerability and efficacy. 1

• Alternative regimens include paclitaxel/cisplatin/5-fluorouracil, though TIP has the strongest evidence base. 1

• Important caveat: The elderly patient's fitness for cisplatin-based chemotherapy must be carefully assessed, as these regimens carry significant toxicity and require adequate renal function, performance status, and absence of severe comorbidities. 1

Adjuvant Radiation Therapy Recommendations

Evidence for Adjuvant Radiation

• Adjuvant postoperative radiation to the inguinal region should be strongly considered if pathology reveals >1 metastatic lymph node and/or extracapsular extension, as inguinal failure rates after lymphadenectomy alone range from 25-77%. 1

• One retrospective series demonstrated that postoperative groin radiation reduced inguinal recurrence from 60% (3/5 patients) to 11% (1/9 patients) in high-risk cases. 1

• However, the role remains controversial due to limited prospective data, and larger confirmatory series are lacking. 1

Radiation Technique and Dosing

• If adjuvant radiation is pursued, a dose range of 45-50.4 Gy to the inguinal/pelvic lymph node regions is reasonable, based on extrapolation from other squamous cell carcinomas and limited penile cancer data. 1

• Radiation should target areas of extracapsular extension or residual high-risk disease identified on pathology. 1

Critical Decision Algorithm

Step 1: Pathology Review

• If pN0 (no positive nodes): No adjuvant therapy recommended; proceed to surveillance only. 1
• If pN1 (1 positive node, no extracapsular extension): Consider observation vs adjuvant chemotherapy based on other high-risk features (grade, lymphovascular invasion). 1
• If pN2-3 (≥2 positive nodes, extracapsular extension, or poorly differentiated): Adjuvant chemotherapy strongly recommended. 1

Step 2: Patient Fitness Assessment

• Assess cisplatin eligibility: adequate renal function (GFR >60 mL/min), ECOG performance status 0-1, no severe hearing loss, no severe neuropathy, no significant cardiovascular disease. 1
• For elderly patients who are cisplatin-ineligible, the benefit of alternative regimens is unproven, and supportive care with close surveillance may be more appropriate. 1

Step 3: Radiation Decision

• If pathology shows >1 positive node OR extracapsular extension: Add adjuvant radiation (45-50.4 Gy) to inguinal/pelvic regions. 1
• Radiation can be sequenced between chemotherapy cycles if both modalities are used, though optimal sequencing lacks definitive evidence. 1

Important Caveats and Pitfalls

Evidence Limitations

• All adjuvant chemotherapy recommendations are extrapolated from neoadjuvant studies and small retrospective series—no prospective randomized trials of adjuvant chemotherapy exist in penile cancer. 1

• The evidence grade is III with recommendation level C, reflecting the rarity of this disease and lack of high-quality prospective data. 1

Elderly Patient Considerations

• Age alone should not exclude patients from adjuvant therapy, but functional status, comorbidities, and treatment goals (quality of life vs aggressive disease control) must be carefully weighed. 1

• Bleomycin-containing regimens should be avoided in elderly patients, heavy smokers, or those with compromised lung function due to high rates of pulmonary toxicity and fatalities. 1

Surveillance Requirements

• Regardless of adjuvant therapy decisions, intensive surveillance is mandatory: clinical examination every 3-6 months for years 1-2, then every 6-12 months for years 3-5. 1

• Imaging surveillance should include chest imaging every 6 months and abdominopelvic CT/MRI every 3 months for the first year, then every 6 months, given the high recurrence risk in this population. 1