Effectiveness and Safety of Treatments for Early‐Stage Merkel Cell Carcinoma: A Systematic Review and Meta‐Analysis of Randomized and Non‐Randomized Studies
January 20, 2025
Journal
Cancer Medicine
Publication Date
January 20, 2025
Authors
Merkelcell.org Summary
The two main treatments for Merkel cell carcinoma (MCC) are surgery and radiation therapy. This study reviewed nearly 50 research papers, including data from over 46,000 patients with MCC at stages I to III (Stage I means the cancer is small and hasn’t spread beyond the skin, while stage III means it has spread to nearby lymph nodes—small glands that help fight infections—but not to other organs). The study compared patients who had surgery alone with those who had surgery followed by radiation therapy.
The results showed that adding radiation therapy after surgery helped patients live longer, with about a 20% increase in survival rates. It also reduced the chance of the cancer coming back by about 65%. Radiation therapy was especially effective at preventing the cancer from returning to the same area where it started, though it was less effective at stopping it from spreading to other parts of the body.
Because this study combined data from many smaller studies, it provides stronger evidence that adding radiation therapy after surgery may improve outcomes compared to surgery alone. However, not all the studies showed the same results. Some found higher survival rates, while others found lower rates, and this study reported the average improvement. It’s also possible that patients who only had surgery might have had other health issues that lowered their survival rates. Overall, it’s important to talk to your medical team about your treatment options—whether surgery alone or surgery with radiation—to find the plan that’s best for you.
Abstract
Objective
The lack of consensus on the benefits and harms of standard therapies, including surgery (SRx), radiotherapy (RTx), chemotherapy (CTx), and their combinations among early‐stage MCC, prompted this study.
Methods
A systematic review and meta‐analysis of randomized and non‐randomized studies published between January 01, 1972, and January 31, 2023, and having overall survival (OS), local recurrence (LR), regional recurrence (RR), disease‐specific survival (DSS), and/or disease‐free survival (DFS) as outcomes was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (ELSEVIER), and Web of Science (CLAVIRATE) databases. Hazard ratios (HRs) and their variances were pooled using the inverse variance heterogeneity model.
Results
Forty‐nine studies representing 46,215 participants were included in the meta‐analysis. A statistically significant improvement in OS was observed for groups administered adjuvant RTx (SRx + RTx) compared to SRx only (HR = 0.78, 95% CI, 0.62–0.99), albeit with statistically significant heterogeneity (Q = 532.30, p < 0.001) and a large amount of inconsistency (I 2 = 94%, 95% CI, 93.0–95.5). Both LR (HR = 1.52, 95% CI, 0.37–6.19) and RR (HR = 0.41, 95% CI, 0.09–1.78) were not statistically significant. In addition, DSS (HR = 0.58, 95% CI, 0.24–1.40) was not statistically significant but DFS was (HR = 0.35, 95% CI, 0.13–0.93). Subgroup analyses revealed that adjuvant radiotherapy was more effective in local than regional MCC. The E‐value suggested that the RTx dose was a confounder of the observed effectiveness of adjuvant RTx; and also, the use of CTx following adjuvant RTx, did not impact the strength of evidence for OS.
Conclusions
Although adjuvant RTx improves survival and recurrence outcomes among early‐stage MCC, the safety and effectiveness of standard therapies in MCC remains poorly studied and, thus, affects the synthesis of evidence across important patient and clinical characteristics. Future research on the comparative effectiveness of different therapies is needed.