Merkel Cell Carcinoma Stage Is Strong Predictor of Recurrence Risk

About 80% of patients with pathologic stage I Merkel cell carcinoma (MCC) are without recurrence at 5 years compared with 28% of patients with stage IV MCC, according to findings from a study published in JAMA Dermatology.

Researchers assessed risk factors associated with recurrence, stage-specific and overall recurrence risk, timing and type of recurrences, and postrecurrence survival among patients with MCC.

A total of 618 patients (median age, 69 years [range, 11-98]; 63% men) with pathologically confirmed MCC were prospectively enrolled from January 2003 to April 2019. Of the cohort, 223 patients had a recurrence.

The overall median follow-up was 3.1 years (range, 3 days to 13 years), and the median follow-up of surviving patients was 4.3 years.

Immunosuppression was strongly associated with an increased risk of recurrence (hazard ratio [HR], 2.4; 95% CI, 1.7-3.3; P < .001), and female sex (HR, 0.5; 95% CI, 0.4-0.7; P < .001) and unknown primary tumor (HR, 0.4; 95% CI, 0.3-0.7; P = .001) were associated with a reduced risk of recurrence, after adjustment for stage. Older age was associated with an increased risk of recurrence (HR, 1.1; 95% CI, 1.0-1.3; P = .06 per 10-year increase). The primary tumor site was not statistically significantly associated with an increased recurrence risk (P = .44).

The overall 5-year recurrence rate was 40% (95% CI, 36%-43%) for patients with all stages of MCC and was stable over time, ranging from 39% to 40% for different time periods.

The recurrence risk in the first year after diagnosis was high and related to stage: 11% for pathologic stage I, 33% for pathologic stage IIA/IIB, 30% for stage IIIA, 45% for pathologic stage IIIB, and 58% for pathologic stage IV. At 5 years, 80% of patients with pathologic stage I cancer were without recurrence compared with 28% of those with stage IV.

The highest risk of recurrence occurred 1 to 3 years after initial treatment for all stages, and 94% of recurrences were within 3 years of initial treatment.

MCC-specific survival was excellent (95% at 5 years for those with pathologic stage I) for patients who presented with local-only disease, according to the study authors. Patients with distantly metastatic disease had a poor prognosis (41% 5-year MCC-specific survival for those who had pathologic stage IV disease).

For patients who initially presented with stage I to II disease and had a local recurrence, MCC-specific survival was minimally affected and was 85% at 5 years. MCC-specific survival was relatively low and not statistically significantly different ain  patients with stage III cancer with local recurrence, those with stage III cancer with nonlocal recurrence, and those with stage IV cancer with any recurrence (P = .89).

Among several study limitations, the recurrence rates, disease-specific survival, and overall survival in this study may be different from national rates, and referral bias may exist. In addition, the median age of the cohort (69 years) is younger than that in national data sets such as the National Cancer Database (76 years), and more than 75% of the cohort received radiation therapy compared with the national rate of patients with MCC, which is about 50%.

“These data should assist in appropriately focusing surveillance resources on patients and time ranges in which MCC recurrence risk is highest (within the first 3 years after diagnosis) and potentially de-escalated after that time frame,” stated the investigators.

Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

McEvoy AM, Lachance K, Hippe DS, et al. Recurrence and mortality risk of Merkel cell carcinoma by cancer stage and time from diagnosis. JAMA Dermatol. Published online February 23, 2022. doi:10.1001/jamadermatol.2021.6096