The Association of Radiation Therapy and Chemotherapy on Overall Survival in Merkel Cell Carcinoma: A Population-Based Analysis

Abstract

Purpose/objective(s) Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neoplasm traditionally managed with surgical resection followed by radiotherapy (RT). With the recent approval of checkpoint inhibitors, chemotherapy is less commonly utilized. We analyzed the impact of RT and chemotherapy on overall survival (OS) in patients with MCC using Surveillance, Epidemiology, and End Results (SEER), a population-level database. Materials and methods We performed retrospective analyses on SEER 18 Custom Data registries for MCC (ICD-0-3 8247). Data from 1980 to 2016 was queried for analysis, and an initial list of 9,792 patients was populated (ICD: C00, C07.9, C44, C80.9). Selection for cases with chemotherapy and RT status, single primary tumor, primary tumor location and surgery treatment type yielded 5,002 cases for analysis. Baseline characteristics were compared with Chi-square or Mann-Whitney U test. Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias. Results Median follow-up time was 178 months (68 to 217 months). Independent prognostic factors positively correlated with increased OS, for both unadjusted Multivariate analysis and IPTW adjusted MVA were age, male sex, year of diagnosis, stage, RT status, and chemotherapy status. On adjusted MVA, use of chemotherapy was associated with worse OS (hazard ratio: 1.22 [95% CI 1.1-1.35], p<0.001), whereas RT was associated with improved OS (HR:0.9 [95% CI, 0.83-0.97], p=0.008). Conclusions The current study demonstrates that RT is associated with improved survival for patients with MCC. Chemotherapy was associated with worse OS. This supports the recent clinical shift towards immune checkpoints inhibitors as standard of care in the metastatic setting, and promising trials in the adjuvant and advanced settings.

Keywords: chemo radiotherapy (chemo-rt); chemotherapy; merkel cell carcinoma; overall survival; radiation therapy; radiotherapy.

Figure 1. CONSORT diagram of selection criteria for Merkel cell carcinoma (MCC) cases in the SEER 18 population-based cancer database.

From 9,747 total database entries, 5,002 cases of MCC without exclusion criteria were identified and evaluated further. SEER: Surveillance, Epidemiology, and End Results; CONSORT: Consolidated Standards Of Reporting Trials.

Figure 2. Overall survival (OS) for MCC in SEER 18 stratified by chemotherapy status. A: OS derived from raw unadjusted data. B: OS after IPTW adjustment.

HR: hazard ratio; CI: confidence interval; IPTW: inverse probability of treatment weighting; NOS: not-otherwise-specified; UVA: univariate analysis; MVA: multivariate analysis; MCC: Merkel cell carcinoma; OS: overall survival.

Figure 3. Forest plot describing the estimated effect of the interaction of chemotherapy with other prognostic factors on MCC overall survival.