Efficacy of Single-Fraction Postoperative Radiotherapy in Resected, Early-Stage Merkel Cell Carcinoma with High-Risk Features

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high recurrence risk. Postoperative radiotherapy (PORT) improves the local recurrence rate (LRR) in early-stage MCC with risk factors per NCCN guidelines: primary tumor size > 1cm, head/neck (HN) location, immunosuppression, lymphovascular invasion (LVI), and positive/narrow surgical margins. Conventionally fractionated PORT (C-PORT, ∼50 Gy in 25 fractions) is often recommended for localized MCC with these risk factors; however, some institutions elect observation. Prior studies suggest LRR of ∼20% for stage I/II MCC with high-risk features managed with surgery alone. C-PORT significantly decreases LRR but may cause significant morbidity and financial toxicity. We have previously reported that single fraction (SF)-PORT with 8 Gy achieves high rates of in-field control both in the metastatic and adjuvant settings with minimal morbidity. Here, we present updated long-term outcomes of SF-PORT, offered as an alternative to C-PORT with the hypothesis that it improves LRR relative to observation while minimizing toxicity, for resected stage I/II MCC. A retrospective, single-institution analysis was completed for stage I/II MCC patients receiving SF-PORT following surgical management. The primary objective was estimating the LRR, defined as recurrence within 2 cm of the primary tumor. Patients with resected, stage I/II MCC with at least one high-risk feature were offered C-PORT as standard of care or SF-PORT as an alternative. Forty-six patients (median age: 74.5; range 50-96 years) received SF-PORT to the primary tumor site at a median 44 days after wide local excision (85%), shave/excisional biopsy (13%), or Mohs (2%). Fifty-four percent of patients had 1 high-risk feature, 35% had 2, and 11% had 3 or more. HN (74%) was the most common primary site, 26% of tumors were > 1cm, 26% were LVI+, and 15% of patients were immunosuppressed (pathological margin status was often not available). There were no local recurrences (LRR = 0%) at a median follow-up time of 2.3 years. In-field locoregional control was 96% (44/46 patients) with 2 in-field, regional recurrences observed in draining nodal basins of HN primary lesions. There were 2 out-of-field regional nodal recurrences (1 patient with IMS; neither received elective nodal SFRT). Of 9 patients who received elective nodal SF-PORT, 8 did not have a successful sentinel lymph node biopsy. No MCC-specific deaths were observed. The most common side effect was in-field, grade 1 erythema (13%); no side effects > grade 1 (CTCAE v5) were noted. SF-PORT is associated with a very low LRR which has proven durable with long-term follow-up. The LRR for SF-PORT appears lower than historical controls treated with surgery alone for patients with resected, stage I/II MCC with high-risk features.