Sinonasal Mucosal Melanoma: A Comparison of Outcomes between Surgical Resection and Immune Checkpoint Inhibition

Introduction: Mucosal melanoma of the head and neck is rare with a poor prognosis. The NCCN suggested management paradigm coincides with the historically utilized recommendation of surgical resection with adjuvant radiation for all surgically resectable tumors. With the introduction and integration of immune checkpoint inhibition (ICI) durable treatment responses and improvement in overall survival have been observed. Using retrospective data, we sought to evaluate the relative roles of surgery and checkpoint inhibition for mucosal melanoma of the paranasal sinuses.

Patients and Methods: A retrospective review of 102 patients with malignant mucosal melanoma of the sinonasal region was conducted at a single institution from 1997 to 2018. Patients were separated into three cohorts based on whether they were treated with surgical resection, ICI (either single agent CTLA-4, PD-1, or combination CTLA-4 and PD-1 blockade), or surgery and ICI together. Radiotherapy was used as adjuvant treatment for an equal proportion of patients within each group. Outcomes of interest were disease specific and overall survival at 5 years calculated using the Kaplan–Meier method. Multivariate analysis was performed using Cox regression. Patients were excluded if duration of follow-up was less than 24 months.

Results: A total of 94 patients (67 patients undergoing surgical excision, 10 undergoing ICI, and 17 undergoing surgery plus ICI) were included in the analysis. Overall, 79.8% patients received radiation with no difference among the three groups. In the surgical group the mean age at presentation was 67 years with 34 (51%) patients staged as T4 at diagnosis. In the ICI group the mean age was 71 years with 9 (90%) patients staged as T4. In the surgery plus ICI group, the mean age at presentation was 68 years with seven (41%) patients presenting at stage T4. But 30% of patients in the ICI group had distant metastases at presentation, while 4.4 and 17.6% of patients presented with metastases in the surgery and surgery plus ICI groups, respectively. Disease specific survival (DSS) and overall survival (OS) at 5 years was 36, 30, and 58% in the surgery, ICI, and surgery plus ICI group and 33, 30, and 42% for the surgery, ICI, and surgery plus ICI group, respectively. OS was not statistically significant between the three groups, though there was a trend toward better OS in patients receiving both surgery and ICI (p = 0.075), whereas DSS was significantly improved in patients receiving surgery plus ICI (p = 0.05). In multivariate analysis, increasing T-stage was the only variable associated with worse survival (hazard ratio = 1.682, CI: 1.134–2.494, p = 0.01).

Conclusion: There was a significant improvement in disease-specific survival and a trend toward improved overall survival for patients undergoing both surgery and ICI compared with either modality alone. Despite those patients receiving ICI having a higher rate of advanced disease and distant metastases, their survival outcomes were not significantly different to those receiving surgery alone. Prospective research should evaluate the optimal treatment paradigm for mucosal melanoma. Until we have further data, we recommend a combination of surgery, immune checkpoint inhibition, and radiation when feasible.