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.
BACKGROUND: AJCC 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. OBJECTIVE: To evaluate AJCC substaging and TIL scoring as predictors of progression in stage II melanoma. METHODS: Retrospective cohort study of 366 SLN(-) stage II melanoma patients from four UK hospitals (2004-2017), with long-term follow-up. RESULTS: 23% 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. LIMITATIONS: Retrospective study design and unknown generalizability. CONCLUSION: Stage 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.