Clinical course of Merkel cell carcinoma: A DeCOG multicenter study of 1049 patients

April 26, 2025

Journal

European Journal of Cancer

Publication Date

April 26, 2025

Authors

Lodde G, Leiter U, Gesierich A, Eigentler T, Hauschild A, et al, Becker J

Merkelcell.org Summary

Merkel cell carcinoma (MCC) is a rare but fast-growing skin cancer that often comes back even after treatment. By studying large groups of patients, doctors can find patterns that help improve care. This study looked at 1,049 people who were diagnosed with MCC between 1998 and 2017, mostly in Germany.
About one in three patients already had advanced disease (stage IIIA or higher) by the time they were diagnosed. MCC most often showed up on the head and neck (32% of cases) or on the arms (29%). After five years, 83% of patients were still alive, and 64% had not had their cancer worsen. Patients whose cancer returned in several places at once had a lower chance of survival compared to those whose cancer came back in just one spot, no matter whether the cancer stayed nearby or spread farther.
If patients were receiving radiation, the timing of radiation treatment was important. Patients who received radiation therapy within eight weeks after diagnosis lived longer and had a 36% lower risk of their cancer getting worse. This supports other studies showing that radiation should be started early for the best results (Increased risk of recurrence and disease-specific death following delayed post-operative radiation for Merkel cell carcinoma)). On the other hand, adding radiation to nearby lymph nodes didn’t seem to make a difference for patients with limited spread of MCC (stage II or IIIA).
The study also looked at surgery. When doctors removed 1 to 2 centimeters of healthy skin around the tumor (surgical margins), patients did best. Taking even larger margins didn’t lead to better outcomes.
One important note: this study happened before immunotherapy became a common treatment for MCC. Since immunotherapy was introduced, outcomes for patients with MCC have improved a lot (Outcomes of Merkel Cell Carcinoma in the Era of Immune Checkpoint Blockade).
In summary, the study found three main points:
1) Early radiation, specifically within 8 weeks of being diagnosed, improves outcomes.
2) Targeting nearby lymph nodes with radiation doesn’t always help.
2) Surgical margins of 1–2 cm may work best, and bigger isn’t better.
While each patient is different, finding these patterns can help doctors make better treatment choices.

Abstract

Background

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with neuroendocrine differentiation characterized by frequent recurrences. Large epidemiological databases (e.g., SEER, IARC) lack granularity in analyzing associations between tumor, patient characteristics, locoregional interventions and recurrence patterns.

Patients and methods

Within the pre-immunotherapy era (1998–2017) the DeCOG MCC registry included 1049 patients with histopathologically confirmed MCC. Patient/tumor characteristics, treatment details, and outcomes were analyzed. Primary endpoints were progression-free probability (PFP) and disease-specific survival (DSS).

Results

Median age at diagnosis was 74 years; 50.4 % were males. Primary tumors most frequently occurred on the head/neck (32.2 %) and upper extremities (29.1 %). One-third of patients presented with stage ≥IIIA disease. At a median follow-up of 10 years, 36- and 60-months PFP rates were 69.0 % and 63.9 %, respectively; DSS rates were 86.9 % and 82.6 %. Surgical margins of 1–2 cm provided the best PFP and DSS improvement; margins > 2 cm did not further improve clinical outcome. Similarly, for stage IIIA patients a complete lymph node dissection (CLND) did neither improve PFP nor DSS. Early radiotherapy (<8 weeks post-diagnosis) significantly improved PFP (HR 1.36) and DSS (HR 1.79). Expansion of radiotherapy to lymph node bed showed no additional benefit. Patients with multiple metastases at first recurrence had poorer DSS (HR 2.0) compared to those with single metastases, irrespective of locoregional or distant spread.

Conclusions

MCC outcomes are optimized with surgical margins of 1–2 cm and timely adjuvant radiotherapy. Larger margins, CLND in stage IIIA, or extended treatment radiation fields did not improve survival outcomes.
View the clinical publication