Tumor-Infiltrating Lymphocyte Scoring Improves Progression Risk Prediction in Stage II Melanoma: A Retrospective Cohort Study.
Adigbli G., Reed B., Khera B., Sangha M., Thadani S., Wilder-Smith A., Wojtowicz M., Pissaridou M., Mustafa A., Ieremia E., Espinosa O., Dunne J., Issa F., Cassell O.
BackgroundAJCC 8th edition substaging might be suboptimal for predicting melanoma progression. Using it to select stage II patients for adjuvant immunotherapy risks overtreating low-risk stage IIB/IIC patients and undertreating high-risk stage IIA patients. Prognostic capability of tumor-infiltrating lymphocytes (TILs) is unclear in stage II melanoma.ObjectiveTo evaluate AJCC substaging and TIL scoring as predictors of progression in stage II melanoma.MethodsRetrospective cohort study of 366 SLN(-) stage II melanoma patients from four UK hospitals (2004-2017), with long-term follow-up.Results23% of melanomas progressed (median 9.5-year follow-up). Among those, 41.5% were stage IIA, 41.5% IIB, and 17.1% IIC. TIL scoring independently predicted progression risk (non-brisk vs brisk: OR 0.298,p=0.009; non-brisk vs absent: OR 0.436,p=0.049) and PFS. Non-brisk TILs, present in 80% of progressing tumors, denoted high risk. TIL scoring split patients into high and low risk across substages: stage IIA patients with non-brisk TILs had similar 5-year PFS to stage IIB/IIC patients with absent/brisk TILs.LimitationsRetrospective study design and unknown generalizability.ConclusionStage II melanoma progression is poorly predicted by AJCC 8 substage. TIL scoring offers improved risk stratification across substages and could serve as a cost-effective method to better identify patients who may benefit from adjuvant immunotherapies.