What is the adjuvant treatment role for a patient with carcinoma (ca) of the penis, post-operative wide local excision, bilateral inguinal dissection, and pelvic dissection, with one positive lymph node and extranodal extension (ENE), should it be radiation (radio) therapy, chemotherapy (chemo), or a combination of both?

Adjuvant Treatment for Penile Cancer with One Positive Node and Extranodal Extension

For your patient with one positive lymph node and extranodal extension (ENE) after bilateral inguinal and pelvic dissection, adjuvant radiotherapy is the preferred treatment, with a dose of 54 Gy for ENE. 1

Evidence-Based Recommendation

The presence of ENE in your patient classifies this as pN3 disease, which fundamentally changes the adjuvant treatment approach. The most recent and highest-quality evidence from the 2023 EAU-ASCO guidelines provides clear direction:

Adjuvant Radiotherapy is Superior to Chemotherapy

• Jaipuria et al demonstrated significantly longer overall survival with adjuvant radiotherapy (54 Gy for ENE) compared to adjuvant chemotherapy in patients with more than two positive lymph nodes but negative pelvic nodes: 48 months versus 14 months (p < 0.0001). 1

• For pN3 disease (defined as either ENE or pelvic LN+), Ager et al reported that 121 of 146 patients received adjuvant radiotherapy with a 5-year recurrence-free survival rate of 51%. 1

• Critically, the risk of in-field failure was twice as high for lower radiation doses (50 Gy), indicating that adequate dosing is essential. 1

Chemotherapy Alone is NOT Recommended

• A recent meta-analysis examined adjuvant chemotherapy and found no difference in survival between patients receiving adjuvant chemotherapy and those undergoing observation (hazard ratio 0.95% CI 0.48–1.80). 1

• There are no strong data supporting the use of adjuvant chemotherapy to improve overall survival following surgical resection. 1

Chemoradiotherapy as an Alternative

• Maibom et al reported on inguinopelvic chemoradiotherapy in 21 patients where all had ENE and two-thirds had bilateral inguinal disease, achieving a median overall survival of 84 months and 5-year survival rate of 57%. 1

• This represents a reasonable alternative if combined modality therapy is feasible, though the radiation-alone data from Jaipuria is more directly applicable to your patient's scenario.

Specific Treatment Algorithm for Your Patient

Primary Recommendation: Adjuvant Radiotherapy

• Deliver 54 Gy to the inguinal regions for ENE 1
• Consider extending the field to include the pelvic region given the pelvic dissection was performed 1
• Ensure adequate dose delivery, as doses below 50 Gy are associated with twice the risk of in-field failure 1

Alternative: Chemoradiotherapy

• If institutional expertise and patient performance status allow, inguinopelvic chemoradiotherapy can be considered, particularly given the bilateral inguinal dissection and presence of ENE 1
• This approach showed median OS of 84 months in patients with ENE 1

NOT Recommended: Chemotherapy Alone

• Adjuvant chemotherapy alone has no proven survival benefit over observation 1
• The only scenario where chemotherapy might be considered is if it was not given preoperatively and high-risk features are present, but even then, radiation is preferred for ENE 1

Critical Pitfalls to Avoid

• Do not underdose radiation: 50 Gy is insufficient for ENE; use 54 Gy minimum 1
• Do not rely on chemotherapy alone in the adjuvant setting for ENE, as it has no proven survival benefit 1
• Do not omit adjuvant treatment entirely: ENE is a high-risk feature that warrants aggressive adjuvant therapy 1

Supporting Evidence from Older Guidelines

The 2013 ESMO guidelines support this approach, stating that when ≥2 nodes are positive or when extranodal extension is found, pelvic LND should be performed with consideration of postoperative radiotherapy. 1 While these guidelines mention "consider adjuvant chemotherapy," the more recent 2023 data clearly demonstrates radiotherapy superiority. 1