Integrating NCCN and LATITUDE in metastatic castration-sensitive prostate cancer: a TITAN analysis

To evaluate whether an integrated classification combining the CHAARTED and LATITUDE criteria improves prognostic stratification and to explore treatment effects across risk groups, including further stratification by metastasis timing, in metastatic castration-sensitive prostate cancer (mCSPC). This post hoc analysis included 1,052 patients from the TITAN trial (NCT02489318) randomized to receive apalutamide plus androgen deprivation therapy (ADT) or placebo plus ADT. Patients were classified into double low, intermediate, and double high groups based on the CHAARTED and LATITUDE criteria and further stratified by metastasis timing. Model discrimination was assessed using Harrell's concordance index (C-index). Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazards models, with baseline imbalances adjusted by inverse probability of treatment weighting. The integrated classification based on the CHAARTED and LATITUDE criteria significantly improved prognostic stratification, yielding a higher C-index for OS (0.645) than the CHAARTED (0.628; p = 0.011) or LATITUDE (0.621; p = 0.003) criteria alone. When further stratified by metastasis timing, apalutamide was associated with improved OS across most subgroups; however, no clear benefit was observed in the double low group with synchronous metastasis (hazard ratio: 0.93; 95% confidence interval [CI]: 0.48-1.79; p = 0.8). Integrating the CHAARTED and LATITUDE criteria significantly improves prognostic stratification in patients with mCSPC. While further stratification by metastasis timing suggested no clear survival benefit in the double low synchronous subgroup, wide CIs indicate substantial uncertainty. These exploratory findings require prospective validation.Clinical Trial Registration: NCT02489318.