Comprehensive Characterization of Metastatic Patterns and a Redefined Prognostic Framework in Metastatic Prostate Cancer.

BACKGROUND

Metastatic prostate cancer (mPCa) exhibits highly complex metastatic patterns. Comprehensive evaluation of distinct metastatic patterns and their integrated prognostic impact remains lacking.

METHODS

Patients with mPCa were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and metastatic patterns were systematically characterized. Cancer-specific survival (CSS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using multivariable Cox regression. Based on metastatic characteristics, patients were classified into seven pattern-based categories and subsequently consolidated into four risk groups (low, intermediate, high, and very high). Temporal robustness was assessed across diagnostic periods, and prognostic discrimination was compared with the conventional M classification using Harrell's C-index and time-dependent area under the receiver operating characteristic curve (AUC).

RESULTS

A total of 13,325 patients with mPCa were identified. Compared with M1b disease, liver-only and multiple visceral metastases were associated with significantly poorer survival (all HR > 1, p < 0.05), whereas lung-only and other single visceral metastases showed comparable outcomes (all p > 0.05). Concomitant distant lymph node involvement adversely affected survival primarily in M1b disease (all HR > 1, p < 0.05), while concomitant bone involvement worsened outcomes in most subgroups except those with multiple visceral sites. Integrating these findings, the four-tier risk stratification model demonstrated clear stepwise discrimination for both CSS (Low risk as reference; Intermediate: HR = 1.63, 95% CI, 1.45-1.84, p < 0.001; High: HR = 2.04, 95% CI, 1.76-2.37, p < 0.001; Very high: HR = 3.99, 95% CI, 3.39-4.71, p < 0.001) and OS (Low risk as reference; Intermediate: HR = 1.53, 95% CI, 1.38-1.70, p < 0.001; High: HR = 1.93, 95% CI, 1.70-2.19, p < 0.001; Very high: HR = 3.48, 95% CI, 2.99-4.06, p < 0.001). Temporal robustness analysis showed consistent stepwise survival gradients across both diagnostic periods. Compared with the conventional M classification, the four-tier risk model showed higher C-index values for CSS (0.695 vs 0.638) and OS (0.696 vs 0.639), with consistently higher time-dependent AUCs at 12, 36, and 60 months.

CONCLUSIONS

Survival varies substantially across metastatic patterns in mPCa. A simplified four-tier risk stratification model integrating multidimensional metastatic features may provide incremental prognostic information beyond conventional M staging, although further external validation is required before clinical implementation.