1133P - Only early adjuvant radiotherapy, particularly of the tumor bed rather than the lymph node region, improves prognosis in Merkel cell carcinoma: Results from the prospective German MCC registry

Background

Merkel cell carcinoma (MCC) is an aggressive skin cancer with neuroendocrine differentiation. Locoregional metastases are already present in ∼30% of patients at initial diagnosis and recurrences occur in ∼40% of cases during the first 2 years, even after initial complete resection. We evaluated the impact of locoregional treatment management on the course of the disease under real-world conditions before the widespread introduction of immune checkpoint inhibitors.

Methods

Between 1998 and 2017, 1049 patients with a pathologically confirmed MCC diagnosis were included in the prospective German MCC registry of the DeCOG. Patient and tumour characteristics of MCC were assessed and the locoregional treatment management analysed.

Results

Median age of MCC patients at first diagnosis was 74.0 years, 50.4% of the patients were male (n= 529). The primary tumour was located most frequently located in the head/neck region (32.2%, n=338) and the upper extremities (29.1%, n=305). At initial diagnosis, the majority of patients had localized disease without lymph node involvement or distant metastasis (AJCC < stage III disease 68.6%, n=720). At a median follow up of 10 years, progression-free (PFS) at 36 and 72 months was 68.5% (95% CI 65.3-71.7) and 61.2% (95% CI 57.7-64.9); overall survival (OS) 78.4% (95% CI 75.6-81.3) and 67.3% (95% 63.8-71.0), respectively. Safety margins of more than 1 cm improved the PFS (HR 0.62, 95% CI 0.42-0.91) and OS (HR 0.64, 95% CI 0.64-0.96), but an increase to more than 2 cm did not result in any additional benefit (PFS HR 0.89, 95% CI 0.61-1.31; OS HR 0.82, 95% CI 0.57-1.17). Delay of adjuvant radiotherapy of the tumor bed for more than 8 weeks after surgery resulted in a significant inferior PFS (HR 2.32, 95% CI 1.20-4.50) and reduced OS (HR 1.49, 95% CI 0.78-2.86). Additional irradiation of the lymph node region gave no additional benefit (PFS HR 1.46, 95% CI 0.79-2.70; OS HR 0.74, 95% CI 0.40-1.38).

Conclusions

MCC patients benefit most from safety margins of 1 cm and early adjuvant radiotherapy of the tumor bed within 8 weeks after surgery. No survival benefit was observed for larger margins or additional radiotherapy of locoregional lymph nodes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J.C. Becker: Financial Interests, Personal, Advisory Board: Amgen, Merck, Recordati, Sanofi, Boehringer Ingelheim Ingelheim, Almirall; Financial Interests, Personal, Other, Member of a DMSB: 4SC; Financial Interests, Personal, Invited Speaker, Training of medical staff on Merkel cell carcinoma: Incyte; Financial Interests, Institutional, Research Grant: IQVIA, Alcedis, Merck; Non-Financial Interests, Principal Investigator, Clinical trial on SCC and AK: Regeneron. U. Leiter-Stoppke: Financial Interests, Personal, Advisory Board, and speaker's honoraria: Sun Pharma, Regeneron, Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre, Novartis, Almirall Hermal; Financial Interests, Institutional, Research Grant: MSD. F. Meier: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, MSD, Sanofi, Philogen, Immunocore; Financial Interests, Personal, Invited Speaker: Sanofi, Immunocore. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Sanofi, MSD, SunPharma, Amgen, GSK, Pierre Fabre, Immunocore, Delcath; Financial Interests, Institutional, Advisory Board: MSD, Novartis, BMS, Immunocore, Philogen, Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre, SunPharma, GSK, Onkowissen, Pierre Fabre; Financial Interests, Institutional, Writing Engagement: BMS; Financial Interests, Institutional, Research Grant: BMS, SunPharma, Sanofi; Financial Interests, Institutional, Local PI: Philogen, Genentech, 4SC, BioNTech, Iovance, Pierre Fabre, Regeneron, Sanofi, Replimune, Immatics, MSD, Pfizer, Agenus; Financial Interests, Institutional, Coordinating PI: BMS, Immunocore, Novartis, Genmab, Seagan; Financial Interests, Personal, Steering Committee Member: Immunocore, IO Biotech; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. P. Mohr: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Merck Sharp & Dohme, Novartis, GSK, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Sharp & Dohme, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis; Non-Financial Interests, Principal Investigator: Bristol Myers Squibb, Merck Sharp & Dohme, Regeneron, Sanofi, Novartis, Sun Pharma. P. Terheyden: Financial Interests, Personal, Advisory Board: Almirall, Biotest, BMS, Sanofi; Financial Interests, Personal, Invited Speaker: Almirall, Bristol Myers Squibb, Sanofi, Kyowa Kirin, Biofrontera, 4SC; Financial Interests, Personal, Other, Travel support: BMS, Pierre Fabre. S. Ugurel-Becker: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp and Dohme, Merck Serono, Novartis; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb, Merck Serono; Non-Financial Interests, Leadership Role: Dermatologic Cooperative Oncology Group (DeCOG). All other authors have declared no conflicts of interest.