Defining Favorable Prognosis in Bone Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Receptor Signaling Inhibitors.

BACKGROUND

This study aimed to identify patients who would benefit from androgen receptor signaling inhibitor (ARSI) therapy in metastatic hormone-sensitive prostate cancer (mHSPC) with bone metastasis (BM). Therefore, we developed a risk stratification model based on the prognostic impact of BM number.

METHODS

We retrospectively analyzed 244 patients with mHSPC and BM treated with ARSI plus androgen deprivation therapy between March 2018 and November 2024. Prognostic thresholds for BM number were assessed using four cutoffs (≥ 4, ≥ 6, ≥ 11, and ≥ 21). The cutoff with the highest hazard ratio (HR) for castration resistance-free survival (CRFS) was incorporated into a multivariable Cox model along with other clinical variables. Independent prognostic factors were used to construct a risk stratification model, and CRFS and overall survival (OS) were compared with the CHAARTED criteria.

RESULTS

At a median follow-up of 31.3 months, ≥ 11 BM showed the strongest prognostic effect for CRFS (HR: 2.62) and OS (HR: 3.01). Multivariable analysis identified ≥ 11 BM (HR: 2.47, 95% CI: 1.45-4.21, p = 0.001), ≥ Gleason score (GS) 9 (HR: 2.07, 95% CI: 1.12-3.45, p = 0.005), and ≥ cT3b (HR: 2.16, 95% CI: 1.14-4.07, p = 0.018) as independent adverse factors. Patients were classified into favorable-risk (no risk factors), intermediate-risk (one risk factor), and poor-risk (two risk factors) groups, which demonstrated significantly different CRFS and OS outcomes (both p < 0.001). Compared with the low-volume disease, as defined by the CHAARTED criteria, the favorable-risk group represented a significantly larger proportion of patients (39.3% vs. 26.6%, p < 0.001) with comparable CRFS (HR: 0.66, p = 0.33) and OS (HR: 0.51, p = 0.18).

CONCLUSIONS

This risk model suggests that patients without ≥ 11 BM, ≥ GS9, and ≥ cT3b may benefit from ARSI plus androgen deprivation therapy for mHSPC. Moreover, it identifies a significantly larger favorable-risk subgroup than the CHAARTED criteria, potentially enhancing clinical precision in treatment selection.