Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma

Survival Analyses of 6908 Cases From the National Cancer Data Base

Shailender Bhatia; Barry E. Storer; Jayasri G. Iyer; Ata Moshiri; Upendra Parvathaneni; David Byrd; Arthur J. Sober; Vernon K. Sondak; Jeffrey E. Gershenwald; Paul Nghiem

Disclosures

J Natl Cancer Inst. 2016;108(9) 

In This Article

Abstract and Introduction

Abstract

Background: Merkel cell carcinoma (MCC) has a high risk of recurrence after initial surgical therapy. Adjuvant radiation therapy (RT) and chemotherapy may be used to reduce the risk of locoregional and systemic recurrence, respectively, but there are conflicting data regarding their impact on survival. We performed a retrospective analysis of MCC cases from the National Cancer Data Base (NCDB) to assess whether adjuvant therapy was associated with differences in survival.

Methods: Six thousand nine hundred and eight MCC patients with staging, treatment, and survival data were included. Multivariable analyses were conducted for overall survival (OS) with various treatment modalities while adjusting for prognostic variables including age, sex, comorbidities (Charlson/Deyo score), margin status, primary tumor site and size, and lymph node status. All statistical tests were two-sided.

Results: For localized MCC (stage I: n = 3369, stage II: n = 1474 ), surgery plus adjuvant RT was associated with statistically significantly better OS than with surgery alone in multivariable analyses (stage I: hazard ratio [HR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.80, P < .001; stage II: HR = 0.77, 95% CI = 0.66 to 0.89, P < .001). In patients with regional nodal metastases (stage III: n = 2065 ), neither adjuvant RT nor chemotherapy was associated with statistically significantly improved or worsened OS.

Conclusions: In this study of the largest MCC cohort reported to date, adjuvant RT was associated with improved OS in stages I-II MCC. Neither adjuvant RT nor chemotherapy was associated with improved OS in stage III MCC. These results, with the limitations of retrospective analyses, are consistent with earlier studies suggesting benefit with adjuvant RT but do not support the routine use of adjuvant chemotherapy in MCC.

Introduction

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with an estimated 1600 cases per year in the United States.[1–3] The reported incidence has tripled over the past 20 years, and the health impact of MCC is growing rapidly.[1,2,4] The increasing incidence could in part be because of improved diagnosis (eg, adoption of the cytokeratin-20 antibody[5]) but likely also reflects the higher prevalence of known risk factors for MCC: T-cell immune suppression and Caucasian ethnicity in individuals older than age 50 years with extensive prior sun exposure.[6]

The prognosis for MCC patients is closely linked to stage at presentation. Per the American Joint Committee on Cancer (AJCC) classification system, stages I and II represent lower-risk and higher-risk localized primary disease, respectively, while stages III and IV represent the presence of nodal and distant metastases, respectively. The reported five-year relative survival for patients with localized, nodal, or distant metastatic disease at presentation is 64%, 39%, or 18%, respectively.[3] Although surgery is curative for some patients with stages I-III, relapses are common.[7] Because MCC tumors are generally considered to be sensitive to radiation therapy (RT) and/or chemotherapy, these therapies are commonly considered for adjuvant therapy after surgery in patients at high risk of loco-regional and systemic recurrence, respectively. Nonetheless, there are limited and sometimes conflicting data regarding the impact of adjuvant RT and chemotherapy on survival of MCC patients.

Previously reported studies of adjuvant RT and/or chemotherapy for MCC patients are mostly retrospective and have several limitations, which include small sample sizes and minimal information on potential confounders to address selection and treatment biases.[8–14] The largest published studies evaluating the effects of adjuvant RT and chemotherapy in MCC analyzed 1166 and 102 patients, respectively.[8,14] In our study, we assessed the survival impact of adjuvant RT and/or chemotherapy in 6908 MCC cases in the National Cancer Data Base (NCDB), a national tumor registry that captures approximately 70% of all cancer diagnoses in the United States. This retrospective study represents the largest known cohort of MCC patients (total n = 12 301) analyzed to date and also includes data on chemotherapy and comorbidity status, neither of which were available in prior studies using the Surveillance, Epidemiology, and End Results (SEER) database.[8,9]

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