Impact of adjuvant radiation therapy on survival and recurrence in patients with stage I-III Merkel cell carcinoma: A retrospective study of 312 patients.

To the Editor: The therapeutic recommendations for American Joint Committee on Cancer I-III stage Merkel cell carcinoma (MCC) include surgery and adjuvant radiation therapy (aRT) on the tumoral bed, along with lymph node (LN) dissection and/or aRT of LN area in case of regional disease. However, the impact of aRT on outcomes remains controversial. In a previously reported cohort of French patients with MCC, 1 Jaouen F. Kervarrec T. Caille A. et al. Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: a retrospective study. J Am Acad Dermatol. 2021; 84: 921-929 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar we retrospectively compared outcomes in 86 patients who had undergone only surgery versus those in 226 patients who had undergone surgery and aRT (tumor bed only, n = 120; LN basin only, n = 22; or both sites, n = 78; unknown site, n = 6). Detailed procedures (type of surgery and site of aRT) are described in Supplementary Table I (available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). The median time between surgery and aRT was 8.5 weeks (Quartil 1-Quartil 3, 6.1-11.4). Patients who had received aRT were significantly younger (P = .001) and had more frequently undergone sentinel lymph node biopsy (SLNB) (P = .002) than those from the surgery-only group (Table I). When taking into account all types of recurrences, patients who had received aRT had significantly longer recurrence-free survival (RFS) (P < .0001) than those from the surgery-only group (Supplementary Fig 1, A, available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). On multivariate analysis, aRT was independently associated with a reduced risk of disease recurrence (hazard ratio [HR], 0.48; 95% CI, 0.00-0.78) (Supplementary Table II, available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). When focusing on the pattern of recurrence, patients who had received aRT had significantly increased local RFS (P < .0001) and regional LN RFS (P < .0001) than those from the surgery-only group, but there was no impact of aRT on in-transit RFS (P = .11) and distant metastasis–free survival (P = .15) (Supplementary Fig 1, available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). On multivariate analysis, aRT remained significantly associated with a reduced risk of local (HR, 0.01; 95% CI, 0.00-0.10) and regional LN recurrence (HR, 0.46; 95% CI, 0.00-0.82) (Supplementary Table III, available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). Patients who had received aRT had significantly longer disease-specific survival (DSS) (P = .01) (Fig 1). On multivariate analysis, aRT was independently associated with a reduced risk of death due to MCC (HR, 0.47; 95% CI, 0.00-0.89) (Supplementary Table II, available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). The pattern of recurrence according to the site of aRT and nodal status at baseline are provided in Supplementary Tables IV and V (available via Mendeley at https://doi.org/10.17632/mgfk4npkr6.1). Table IBaseline characteristics of the 312 patients included, according to primary treatment Characteristics All, n (%)N = 312 Surgery and aRT, n (%)N = 226 Surgery only, n (%)N = 86 P value (Fisher exact test) Age Age < median 77.2 y 157 (50.3) 127 (56.2) 30 (34.9) .001 Age ≥ median 77.2 y 155 (49.7) 99 (43.8) 56 (65.1) Sex Male 149 (47.8) 111 (49.1) 38 (44.2) .45 Female 163 (52.2) 115 (50.9) 48 (55.8) Primary location, n (%) Limb 174 (55.8) 131 (58.0) 43 (50.0) .36 Head and neck 106 (34.0) 70 (31.0) 36 (41.9) Trunk 8 (2.5) 6 (2.6) 2 (2.3) Occult 23 (7.4) 18 (8.0) 5 (5.8) Unknown 1 (0.3) 1 (0.4) 0 (0) Performance status 0-1 261 (83.6) 194 (85.8) 67 (77.9) .07 2-3 28 (9.0) 16 (7.1) 12 (14.0) Unknown 23 (7.4) 16 (7.1) 7 (8.1) Immunosuppression Present 44 (14.1) 34 (15.0) 10 (11.6) .58 Absent 268 (85.9) 192 (85.0) 76 (88.4) Macroscopic lymph node invasion Present 65 (20.8) 48 (21.2) 17 (19.8) .76 Absent 246 (78.9) 177 (78.3) 69 (80.2) Unknown 1 (0.3) 1(0.5) 0 (0) Sentinel lymph node biopsy ∗ Among 246 patients with no macroscopic lymph node metastases. Not performed 155 (63.0) 100 (56.5) 55 (79.7) .002 Negative 71 (28.9) 58 (32.8) 13 (18.8) Positive 18 (7.3) 17 (9.6) 1 (1.5) Unknown 2 (0.8) 2 (1.1) 0 (0) AJCC stage I 127 (40.7) 88 (38.9) 39 (45.3) .33 IIA 75 (24.0) 52 (23.0) 23 (26.7) IIB 15 (4.8) 11 (4.9) 4 (4.7) IIIA 41 (13.2) 35 (15.5) 6 (7.0) IIIB 49 (15.7) 36 (15.9) 13 (15.1) Unknown 5 (1.6) 4 (1.8) 1 (1.2) Margin status Negative 256 (82.1) 188 (83.2) 68 (79.1) .23 Positive 35 (11.2) 22 (9.7) 13 (15.1) Unknown 21 (6.7) 16 (7.1) 5 (5.8) Bold indicates the P value concerning the sentinel lymph node biopsy characteristic (it only concerns 246 patients and not 312 because it can not be realized in patients with macroscopic lymph node metastases). AJCC, American Joint Committee on Cancer; aRT, adjuvant radiation therapy. ∗ Among 246 patients with no macroscopic lymph node metastases. Open table in a new tab Bold indicates the P value concerning the sentinel lymph node biopsy characteristic (it only concerns 246 patients and not 312 because it can not be realized in patients with macroscopic lymph node metastases). AJCC, American Joint Committee on Cancer; aRT, adjuvant radiation therapy.