Early-stage melanoma, squamous and basal cell carcinomas have local control rates of >90% with wide excision after pathologically clear margins and >95% with Mohs micrographic surgery. Local control rates for these approaches are not well defined in Merkel cell carcinoma (MCC). Herein, we analyzed data from 80 patients (pts) in a Seattle-based IRB-approved registry who had local MCC and underwent surgical excision with pathologically clear margins. Patients who had local radiation therapy after surgery were excluded as radiation affects recurrence rate independent of surgery. We also performed meta-analysis of 13 published studies (846 pts) based on a random-effects model. For the 80 pt cohort, local recurrence rate (LRR; ≤2 cm from the primary tumor) was 10%. In-transit recurrence rate (ITR; >2cm from primary) was 1%. Regional nodal recurrence rate (RRR) was 5%. This cohort had low-risk characteristics with small primary tumors (74% were ≤1 cm, 23% were 1-2, and 4% were >2 cm). No residual tumor was found in 60% of re-excisions while 29% had closest pathologic margins <1 cm. Meta-analysis of 9 published studies (745 pts) who underwent excision with clear pathological margins yielded 16.4% LRR [95% CI 8.3-26.5], 9.5% ITR [95% CI 5.4-14.6], and 32.1% RRR [95% CI 19.1-46.7]. Data from 4 studies (101 pts) who underwent Mohs yielded 3.6% LRR [95% CI 0-16.3], 12.8% ITR [95% CI 6.4-21.1], and 20.7% RRR [95% CI 13.8-38.3]. In each cohort, LRR/IRR following surgical excision with pathologically clear margins was >10%. This suggests MCC is more likely to recur near the excision site than other skin cancers and may reflect biological difference in the MCC local extension pattern (discontinuous spread beyond pathologically clear margins). Even for pathologically negative excisions, higher risk tumors may benefit from adjuvant radiotherapy.

Merkel cell carcinoma (MCC) is a rare skin cancer with a high propensity for recurrence. Persons with chronic immunosuppression have a higher risk of developing MCC and a more aggressive disease course. Immunotherapy treatment enhances the immune system’s ability to fight MCC and is associated with improved disease-specific survival. However, the immunotherapy efficacy in immunosuppressed MCC patients is not well categorized. This study explores and aims to compare differences in immunotherapy efficacy between different forms of immunosuppression, and between immunocompetent versus immunosuppressed MCC patients. In this project, I determined the patient cohort from a Seattle-based prospective registry of 1,529 MCC patients and identified 36 patients treated with immunotherapy and who had chronic immunosuppression. I collected treatment response data from medical records, and analyzed the results. Of the 36 patients, 13 patients (36%) had a complete response (CR), 3 patients (8%) had a partial response (PR), and 20 patients (56%) had progressive disease (PD). Disease progression and survival status varied greatly among different types of immunosuppression. Five types of chronic immunosuppression were represented in these 36 patients and were evaluated for an objective response (CR or PR): chronic lymphocytic leukemia (CLL, 3/13, 23%), autoimmune disorders (AD, 3/9, 33%), solid organ transplant (SOT, 2/4, 50%), HIV/AIDs (2/3, 67%), and other hematologic malignancies (OHM, 6/7, 86%). In comparison, in a study of immunocompetent patients, 28 of 50 (56%) had objective responses to immunotherapy. Toxicities were also high in immunosuppressed patients, as 9/36 (25%) patients stopped treatment due to toxicities. Immunotherapy efficacy in patients with chronic immunosuppression appears to be dependent on the type of immunosuppression. While there is reason for optimism for patients with certain types of immunosuppression, MCC treatment for patients with CLL remains a major concern.