What is the management and staging for Merkel cell carcinoma of the thigh with inguinal nodal metastasis (mets)?

Merkel Cell Carcinoma of the Thigh with Inguinal Nodal Metastasis: Staging and Management

For Merkel cell carcinoma of the thigh with confirmed inguinal nodal metastasis, proceed with inguinal lymph node dissection followed by adjuvant radiation therapy (50-54 Gy to the nodal basin and 50-56 Gy to the primary site), with consideration of adjuvant chemotherapy on a case-by-case basis, though survival benefit is not established. 1

Staging

This presentation represents regional disease (Stage III) according to AJCC/NCCN staging criteria, which divides Merkel cell carcinoma into local, regional, and disseminated disease. 1 The presence of inguinal nodal metastasis from a thigh primary automatically classifies this as regional disease with significantly worse prognosis compared to node-negative disease. 2

Required Staging Workup

• Confirm nodal involvement with fine-needle aspiration or core biopsy using an appropriate immunopanel (CK-20 and pancytokeratins). 1
• Obtain imaging (CT, MRI, or PET/CT) to exclude distant metastasis before proceeding with regional treatment. 1, 3
• If distant metastasis is detected, management shifts to the metastatic disease pathway. 1

Management Algorithm

Step 1: Multidisciplinary Tumor Board Consultation

All patients with clinically node-positive disease require multidisciplinary evaluation before initiating treatment, with strong consideration for clinical trial enrollment when available. 1, 4

Step 2: Surgical Management

Lymph node dissection is the recommended initial therapy for clinically evident adenopathy in the groin, followed by postoperative radiation if indicated. 1

• Perform inguinal lymph node dissection (completion lymphadenectomy). 1
• Concurrently or subsequently perform wide local excision of the primary thigh lesion with 1-2 cm lateral margins extending to the investing fascia when clinically feasible. 3
• Achieve histologically negative margins, but do not pursue extensive surgery that would significantly delay adjuvant radiation therapy. 1
• Minimize extensive tissue movement during reconstruction to allow expeditious initiation of radiation therapy. 1, 3

Step 3: Adjuvant Radiation Therapy

Radiation therapy is strongly recommended for regional disease and significantly improves time to recurrence and survival. 1, 2

Radiation Dosing for Extremity MCC with Nodal Involvement:

• Primary site: 50-56 Gy at 2 Gy/day standard fractionation with bolus to achieve adequate skin dose. 1, 3
• Inguinal nodal basin after lymph node dissection: 50-54 Gy. 1
• Use wide margins (5 cm) around the primary site when possible. 1
• Expeditious initiation is critical—delay in starting adjuvant radiation has been associated with worse outcomes. 1, 3

The evidence supporting adjuvant radiation is robust: a meta-analysis demonstrated that local adjuvant radiation after complete excision lowered the risk for both local and regional recurrences, and a review of 82 cases showed radiotherapy to regional lymph nodes was associated with prolonged time to recurrence (46.2 vs. 11.3 months) and survival (103.1 vs. 34.2 months). 1, 2

Step 4: Adjuvant Chemotherapy Consideration

Adjuvant chemotherapy is not routinely recommended for regional disease as adequate trials have not demonstrated survival benefit, but it may be considered on a case-by-case basis if clinical judgment dictates. 1

If chemotherapy is used for regional disease, options include:

• Cisplatin ± etoposide
• Carboplatin ± etoposide 1

Important caveat: Available retrospective data do not suggest prolonged survival benefit for adjuvant chemotherapy in regional disease. 1 Most NCCN institutions reserve chemotherapy primarily for stage IV distant metastatic disease. 1

Prognostic Factors

Regional lymph node involvement is independently associated with significantly diminished survival (hazard ratio 4.08,95% CI 1.55-10.75). 2 Patients with regional disease have a 5-year actuarial survival rate of 42% compared to 68% for stage I disease. 5

Lymphadenectomy was independently associated with prolonged disease-free survival (median 28.5 vs. 11.8 months) in one study, though the impact on overall survival was not statistically significant. 2

Surveillance After Treatment

Perform complete skin and regional lymph node examination every 3-6 months for the first 2 years, then every 6-12 months thereafter. 1, 3

• The median time to recurrence is approximately 8 months, with 90% of recurrences occurring within 24 months. 1, 3
• Imaging studies should be performed as clinically indicated; for high-risk patients like those with regional disease, routine imaging should be considered. 1
• PET/CT scans may be useful to identify and quantify metastases. 1

Management of Recurrence

If local or regional recurrence develops, patients should receive multidisciplinary re-evaluation with consideration for additional surgery, radiation, systemic therapy, or clinical trial enrollment. 1