How the Emergence of Immunotherapy has Impacted Practice Patterns for Treatment and Management of Merkel Cell Carcinoma

The adoption of immunotherapy for patients with Merkel cell carcinoma (MCC) has contributed to changing practice patterns at an institutional and national level, which match with emerging data regarding the optimal treatment of this disease, according to the results of a retrospective review published in the Annals of Surgical Oncology.

Furthermore, investigators stated that competing mortality factors likely prohibit overall survival (OS) from being an accurate surrogate outcome measure for fully understanding specific factors associated with disease-specific survival (DSS) for patients with MCC.

“This study demonstrates that there is a divergence of factors associated with [DSS] and [OS]. This indicates that reliance on [OS] may have limitations in studying MCC outcomes,” the investigators concluded.

A total of 174 patients who were treated for MCC between 2002 and 2020 were identified via ICD-9 and ICD-10 codes, 159 of whom were evaluable for the analysis. In order to provide context, investigators examined national trends utilizing the Surveillance, Epidemiology, and End Results (SEER) Program database.

The median age of patients at the time of diagnosis was 75 years (range, 41-98). Additionally, 61% of the population male and 96% White. The median follow-up for patients was 3.1 years (range, 0-25). At the most recent follow-up, 36% of patients (n = 58/159) had died, with 21 deaths due to MCC. A total of 53% of patients in the population had clinical stage I disease, 21% had clinical stage II, 14% had clinical stage III, 3% had clinical stage IV, and 8% were unknown.

Ninety-six percent of patients underwent initial surgery for MCC. Moreover, radiation therapy was performed in 57% of patients, 14% received chemotherapy, and 17% received immunotherapy.

Looking at institutional trends, the rate of radiation alone to the lymph node basin decreased from 8% in 2002 to 2008 to 3% in 2015 to 2020. Radiation and surgery together increased from 0% to 14% over the same period, as did surgery alone, which increased from 33% to 58%.

Patients with non-distant metastatic disease who were 85 years or older (OR, 0.05; 95% CI, 0.01-0.17, P <.001), cN-positive disease (OR, 0.14; 95% CI, 0.05-0.45, P <.001), and in-transit disease at time of diagnosis (OR, 0.23; 95% CI 0.07-0.85, P = .027) were associated with not to undergoing wide local excision and surgical staging of lymph nodes.

Over 3 consecutive 5-year periods, the treatment with radiation therapy and chemotherapy for institutional patients decreased from 75% to 49% and from 42% to 4%, respectively. Over that same period, the frequency of immunotherapy increased from 0% to 24% of patients.

In terms of national treatment trends, data from 6766 patients were available via the SEER database, which identified an increase in the rate of surgical resection between 2004 and 2016 from 0.422 to 0.578 per 100,000 persons. The data translates to an average annual percentage change of 2.7% per year (95% CI, 1.6%-3.8%). Moreover, sentinel lymph node biopsy use increased from 0.156 to 0.300 per 100,000 persons from 2004 to 2016, equal to an average annual percentage change of 6.4% per year (95% CI, 4.6%-8.2%).

Patients with non-distant metastatic disease, advanced age, clinical T2 disease, and in-transit disease at diagnosis were associated with decreased recurrence-free survival. Advanced age and clinical T2 disease were also associated with DSS, along with cigarette smoking and MCC with an unknown primary. Associated factors with worse overall survival included age of 75 years or older, immunocompromised state, trunk as the primary site, and clinical T2 disease.

Reference

Esposito A, Jacobs D, Ariyan S, et al. Merkel cell carcinoma: changing practice patterns and impact on recurrence-free and overall survival at a single institution and nationally. Ann Surg Oncol. Published online September 7, 2021. doi:10.1245/s10434-021-10727-2