Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study

Abstract

Purpose: Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas.

Patients and methods: On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined.

Results: Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend) < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage.

Conclusion: At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.

Fig 1.

Kaplan-Meier melanoma-specific survival probabilities by tumor-infiltrating lymphocyte grade are shown for patients with melanomas (n = 2,728) with median follow-up of 7.6 years. Patients with a single primary melanoma were diagnosed in 2000 and those with multiple primary melanomas were diagnosed from 1998 to 2003. Patient follow-up for vital status was complete to the end of 2007 in most centers and to the end of 2008 in British Columbia, Canada, and Torino, Italy. Thus, only patients with multiple primary melanomas would have been followed longer than 8 years, which explains the decrease in the number of participants at risk of death after 8 years in the table.