Resumo

Objectives: To identify clinicopathologic predictors that can accurately stratify sentinel lymph node biopsy-negative melanoma patients by risk of progression, to improve prognostic accuracy and guide personalised treatment decisions. Introduction: Recent approval of adjuvant pembrolizumab for resected stage IIB/IIC melanoma necessitates tools to precisely stratify high versus low risk patients, to guide treatment decisions and prevent inappropriate immunotherapy toxicity. Using multivariable analyses, this study demonstrates that tumor-infiltrating lymphocyte scoring effectively distinguishes high and low risk subgroups, offering a cost-effective method of guiding personalised treatment decisions. Materials / method: Multicenter, retrospective cohort study of 1229 cutaneous melanoma patients treated at 2 UK hospitals between 2004-2017, who underwent SLNB. TIL score, Breslow thickness, ulceration, SLNB status, and other clinicopathological factors were examined as potential predictors using Kaplan-Meier curves, univariate analyses, multivariable logistic regression and Cox proportional hazards modeling. Progression was defined as recurrence at local, intransit, regional or distant sites. Regression model fit was assessed by -2 log likelihood, overall chi-square statistics and Hosmer-Lemeshow goodness of fit Results: The median follow-up duration was 9.5 years, during which the melanoma progression rate after SLNB was 20%. In SLNB-negative patients, TIL score and Breslow thickness were the strongest independent predictors of progression in multivariate analyses. Non-brisk TILs were associated with three-fold higher progression risk and lower progression-free survival compared to absent (p=0.003) or brisk TILs, particularly in stage II patients. Non-brisk TILs and Breslow thickness >2mm identified a high-risk subgroup. In these patients, progression-free survival was 20% lower in males than females (p<0.001 Conclusion: Breslow and TIL scores interact to reliably predict PFS in SLNB-negative melanoma and discriminate between high and low-risk stage II patients. Incorporating SLNB and TIL statuses in prognostic tools holds promise for identifying high-risk patients who may benefit from adjuvant immunotherapy and low-risk patients who may safely forego it.