Indications of a Survival Benefit from Primary Tumor Treatment in Uveal Melanoma: Association Between initial AJCC Stage and Metastatic Survival

In theory, a more advanced American Joint Committee on Cancer (AJCC) stage at the time of primary tumor diagnosis could correlate with shorter survival in metastatic uveal melanoma. However, this association has only been evaluated in relatively small cohorts. To address this, we investigated the prognostic relationship between AJCC stage and survival in a large cohort of patients who died from metastatic uveal melanoma. Among 1491 real-world patients, a higher AJCC stage at the time of primary tumor diagnosis was significantly associated with shorter survival. This association persisted even when the analysis was restricted to 350 patients already at stage IV, where a higher AJCC stage at primary tumor diagnosis continued to correlate with shorter survival (Log-rank test for trend, P < 0.001 for both comparisons). The relationship remained significant in multivariate Cox regression models, which included patient age as a covariate and the number of hepatic metastases upon detection of metastatic disease as a time-varying covariate, as well as in a Markov multi-state model. These findings suggest that primary tumor treatment, by preventing the tumor from advancing to a higher AJCC stage, may confer a survival benefit by potentially reducing the aggressiveness and growth rate of subsequent metastases.