Prognostic Factor Analysis and Nomogram Development in Castration-Resistant Prostate Cancer with Visceral Metastases...

To identify independent prognostic factors in castration-resistant prostate cancer (CRPC) patients with visceral metastases, construct and internally validate a prognostic nomogram for individualized risk stratification, and generate a hypothesis-driven framework that may inform future candidate selection for radionuclide therapies-including lutetium-177 PSMA-617 (¹⁷⁷Lu-PSMA-617) and radium-223 dichloride (²²³Ra)-pending prospective targeted radionuclide therapy (TRT)-specific validation.

A retrospective cohort study was conducted on 98 CRPC patients with imaging-confirmed visceral metastases treated at the institution from January 2017 to December 2023. Baseline demographics, tumor parameters, laboratory biomarkers, and treatment data were systematically collected. The primary endpoint was overall survival (OS); the secondary endpoint was progression-free survival (PFS). Kaplan-Meier analysis, univariate and multivariate Cox proportional hazards regression models, and a six-factor prognostic nomogram were used. Model performance was assessed by Concordance Index (C-index), bootstrap-corrected calibration curves (1000 iterations), and time-dependent receiver operating characteristic analysis.

Among 98 patients (median age 68 years), median follow-up was 19.2 months, with 72 deaths (73.5%). Median OS was 13.2 months (95% confidence interval [CI]: 11.5-15.0 months); median PFS was 7.5 months (95% CI: 6.6-8.5 months). Six independent adverse prognostic factors for OS were identified: Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (hazard ratio [HR] = 1.89, p < 0.001), multiorgan visceral metastases (HR = 1.52, p = 0.008), alkaline phosphatase ≥240 U/L (HR = 1.58, p = 0.004), hemoglobin <110 g/L (HR = 1.45, p = 0.024), albumin <35 g/L (HR = 1.62, p = 0.004), and prostate-specific antigen decline <50% (HR = 1.78, p < 0.001). The nomogram achieved a C-index of 0.712 (OS) and 0.698 (PFS); time-dependent area under the curve (AUC) ranged from 0.672 to 0.748 across 6-24 months.

CRPC patients with visceral metastases carry a dismal prognosis. The six-factor nomogram provides a quantitative prognostic framework that may support evidence-based risk stratification in this high-risk subpopulation. Important to note that no patient in this cohort received radionuclide therapy; the model is derived from a non-TRT cohort and should be regarded as hypothesis generating. Its utility as a TRT selection instrument warrants prospective validation in cohorts receiving ¹⁷⁷Lu-PSMA-617 or ²²³Ra. Integration with molecular biomarkers-prostate-specific membrane antigen (PSMA) expression quantification, AR-V7 status, and DNA damage repair profiling-remains essential for future validation.