Evaluation of Lymph Node Ratio Association With Long-term Patient Survival After Surgery for Node-Positive Merkel Cell Carcinoma.

Importance: Merkel cell carcinoma (MCC) carries the highest mortality rate among cutaneous cancers and is rapidly rising in incidence. Identification of prognostic indicators may help guide patient counseling and treatment planning. Lymph node ratio (LNR), the ratio of positive lymph nodes to the total number of examined lymph nodes, is an established prognostic indicator in other cancers.
Objectives: The primary objective was to evaluate the association between LNR and patient survival after surgery for node-positive MCC. The secondary objective was to evaluate whether the survival rates associated with adjuvant therapies vary by patient LNR status. Design, Setting, and Participants: Retrospective cohort study of patients with node-positive MCC treated with surgery and lymphadenectomy. We queried the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) registry for patient records. Data originated from 2004 through 2017 for the NCDB and from 1973 through 2016 for the SEER registry. The SEER registry comprises a population-based US cohort while cases from the NCDB include all reportable cases from Commission on Cancer-accredited facilities and represents approximately 70% of all newly diagnosed cancers in the United States. All data analysis took place between August 1, 2018, and February 11, 2019. Exposures: The ratio of positive lymph nodes to the total number of examined lymph nodes, LNR, was stratified into quartiles. Main Outcomes and Measures: Overall survival (NCDB) and disease-specific survival (SEER).
Results: We identified 736 eligible cases in the NCDB and 538 eligible cases in the SEER registry. Among these 1274 patients, the mean (SD) age was 71.1 (11.5) years, and 401 (31.5%) were women. After controlling for clinical and tumor factors including AJCC N staging, patient LNR of 0.07 to 0.31 (hazard ratio [HR], 1.37; 95% CI, 1.03-1.81) and greater than 0.31 (HR, 2.84; 95% CI, 2.10-3.86) was associated with significantly worse survival than an LNR less than 0.07. Univariate supplementary analysis performed in the SEER data set revealed a similar association of LNR with disease-specific survival. For patients with an LNR greater than 0.31, treatment with surgery and adjuvant chemoradiation therapy was associated with improved survival compared with surgery and adjuvant radiation therapy alone (HR, 0.61; 95% CI, 0.38-0.97), while this was not found for patients with an LNR of 0.31 or lower (HR, 0.93; 95% CI, 0.65-1.33). Conclusions and Relevance: For lymph node-positive MCC, LNR offers a potentially prognostic metric alongside traditional TNM staging that may be useful for both patient counseling and treatment planning after surgery.