What is the recommended adjuvant treatment for a patient with carcinoma (Ca) of the penis, stage pT3N1M0, after penectomy and bilateral inguinal lymph node dissection (LND)?

Adjuvant Treatment for pT3N1M0 Penile Carcinoma After Penectomy and Bilateral Inguinal LND

For patients with pT3N1M0 penile carcinoma after penectomy and bilateral inguinal lymph node dissection, adjuvant chemotherapy with the TIP regimen (paclitaxel, ifosfamide, and cisplatin) is recommended as the optimal adjuvant treatment. 1

Treatment Decision Algorithm

Assessment of Patient's Status

• Current status: pT3N1M0 (primary tumor invading deep structures, single positive inguinal lymph node, no distant metastasis)
• Completed procedures: Penectomy and bilateral inguinal lymph node dissection (ILND)

Recommended Adjuvant Treatment

1. First-line recommendation: TIP chemotherapy regimen

   • 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 1

2. Alternative if TIP is contraindicated: 5-fluorouracil and cisplatin combination 1

   • Note: This regimen may require dose adjustments due to potential toxicities

Evidence Supporting This Recommendation

The NCCN guidelines recommend adjuvant chemotherapy for patients with high-risk features after surgical management of penile cancer. While there are limited data specifically for N1 disease, the guidelines support extrapolating from neoadjuvant data to use TIP in the adjuvant setting when high-risk features are present 1.

For patients with pN1 disease:

• The ESMO guidelines indicate that if only 0-1 nodes are positive without extranodal extension, no further treatment may be needed 1
• However, for pT3 disease with corporal invasion, more aggressive management is warranted due to the high-risk nature of the primary tumor

A multi-institutional study demonstrated that adjuvant chemotherapy was associated with improved overall survival in patients with positive pelvic lymph nodes after lymph node dissection, with median OS of 21.7 months vs. 10.1 months in those who did not receive adjuvant chemotherapy 2. While this study focused on pelvic node-positive disease, the principle supports adjuvant chemotherapy for high-risk disease.

Considerations for Adjuvant Radiation Therapy

Adjuvant radiation therapy should be considered in specific circumstances:

• If extranodal extension is present in the lymph node specimen 3
• If ≥2 positive inguinal nodes were found 1

A 2020 study comparing adjuvant treatments found that for patients with nodal positivity limited to the groin, radiation therapy was superior to chemotherapy alone, with an estimated average overall survival difference of 1,007 days 4. However, for a patient with only a single positive node (N1), chemotherapy remains the preferred approach based on current guidelines.

Monitoring and Follow-up

After completion of adjuvant chemotherapy:

• Clinical examination every 3 months for the first 2 years
• Imaging (CT or MRI) of the inguinal and pelvic regions every 6 months for 2 years
• Annual chest imaging to monitor for distant metastasis

Potential Pitfalls and Caveats

1. Delaying adjuvant therapy: Treatment should begin within 6-8 weeks after surgery to maximize efficacy

2. Undertreatment: Despite having only N1 disease, the T3 status indicates deep invasion, which warrants aggressive adjuvant therapy to prevent recurrence

3. Toxicity management: TIP regimen can cause significant toxicities including:

   • Myelosuppression
   • Nephrotoxicity
   • Neurotoxicity
   • Ototoxicity

   Close monitoring and appropriate dose modifications are essential

4. Radiation consideration: If extranodal extension is discovered on final pathology review, consider adding adjuvant radiation to the treatment plan, as studies show improved disease-specific survival with radiation in the presence of ENE 3

By following this treatment algorithm, the risk of recurrence can be minimized while optimizing survival outcomes for this patient with pT3N1M0 penile carcinoma.