Background:To clarify the timing of treatment initiation for non-metastatic castration-resistant prostate cancer (nmCRPC), we investigated the impact of baseline prostate-specific antigen (PSA) at treatment initiation on outcomes, the stability of PSADT estimation at low PSA levels, and the prognostic significance of PSADT.Methods:We retrospectively analyzed 129 consecutive nmCRPC patients between 2000 and 2023. All patients were divided by PSADT ≤ 10 months (n= 109) or >10 months (n= 20). PSA progression-free survival (PSA-PFS) and metastasis-free survival (MFS) were assessed by the Kaplan–Meier method, with predictive factors analyzed using Cox proportional hazards modeling. PSA-PFS was further compared across baseline PSA subgroups (<3, 3–5, 5–10, >10 ng/mL) in the PSADT ≤ 10 months cohort.Results:Patients with PSADT ≤ 10 months had worse MFS than patients with PSADT > 10 months (4-year: 71.9% vs. 100%;p= 0.021). In the PSADT ≤ 10 months group, novel androgen receptor pathway inhibitor (ARPI) treatment significantly improved PSA-PFS compared to those who did not (median: 44.0 vs. 16.6 months;p< 0.001). In multivariate analysis, prior definitive local therapy (Hazard Ratio [HR] 0.409,p< 0.001), ARPIs as first-line treatment (HR 0.421,p< 0.001) and lower baseline PSA at treatment initiation (HR 0.961,p= 0.004) were significantly predictive factors for PSA-PFS. PSADT estimation remained accurate when calculated from PSA nadir values ≥0.5 ng/mL.Conclusions:In patients with nmCRPC with PSADT ≤ 10 months, early initiation of ARPIs at lower PSA levels was associated with improved PSA-PFS. PSADT stabilized at PSA levels of >0.5 ng/mL. These findings support earlier ARPI initiation to optimize outcomes in high-risk nmCRPC.
背景：为明确非转移性去势抵抗性前列腺癌（nmCRPC）的治疗启动时机，本研究探讨了治疗起始时基线前列腺特异性抗原（PSA）水平对预后的影响、低PSA水平下PSA倍增时间（PSADT）评估的稳定性，以及PSADT的预后意义。 方法：回顾性分析2000年至2023年间连续收治的129例nmCRPC患者。所有患者按PSADT ≤ 10个月（n=109）或>10个月（n=20）分组。采用Kaplan-Meier法评估PSA无进展生存期（PSA-PFS）和无转移生存期（MFS），并通过Cox比例风险模型分析预测因素。在PSADT ≤ 10个月队列中，进一步比较不同基线PSA亚组（<3、3-5、5-10、>10 ng/mL）的PSA-PFS。 结果：PSADT ≤ 10个月患者的MFS显著差于PSADT > 10个月患者（4年生存率：71.9% vs. 100%；p=0.021）。在PSADT ≤ 10个月组中，接受新型雄激素受体通路抑制剂（ARPI）治疗的患者PSA-PFS显著优于未接受者（中位时间：44.0 vs. 16.6个月；p<0.001）。多变量分析显示，既往接受过根治性局部治疗（风险比[HR] 0.409，p<0.001）、ARPI作为一线治疗（HR 0.421，p<0.001）以及治疗起始时较低的基线PSA水平（HR 0.961，p=0.004）是PSA-PFS的显著预测因素。当基于PSA最低值≥0.5 ng/mL计算时，PSADT评估保持准确性。 结论：对于PSADT ≤ 10个月的nmCRPC患者，在较低PSA水平早期启动ARPI治疗与改善PSA-PFS相关。PSADT在PSA水平>0.5 ng/mL时趋于稳定。这些发现支持对高危nmCRPC患者更早启动ARPI治疗以优化临床结局。
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