Tumor-infiltrating lymphocyte scoring improves progression risk prediction in stage II melanoma: A retrospective cohort study

Abstract

Background

The American Joint Committee on Cancer eighth 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 the American Joint Committee on Cancer eighth edition substaging and TIL scoring as predictors of progression in stage II melanoma.

Methods

Retrospective cohort study of 366 sentinel lymph node negative stage II melanoma patients from 4 UK hospitals (2004-2017), with long-term follow-up.

Results

Twenty-three percent 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 (brisk vs non-brisk: odds ratio: 0.298, P = .009; absent vs non-brisk: odds ratio: 0.436, P = .049) and progression-free survival. Nonbrisk 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 progression-free survival 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 the American Joint Committee on Cancer eighth edition 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.