Predictive value of baseline risk factors and early prostate-specific antigen (PSA) kinetics for achieving deep PSA decline in metastatic hormone-sensitive prostate cancer: implications for treatment intensification.

BACKGROUND

Early identification of treatment response is essential for risk-adapted management in metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to explore the predictive value of baseline clinicopathological factors and prostate-specific antigen (PSA) kinetics for deep PSA decline at 6 months in patients with mHSPC.

METHODS

A retrospective cohort study was conducted involving 364 patients with de novo mHSPC. The primary endpoint was defined as PSA at 6 months ≤0.2 ng/mL. Logistic regression analyses were performed to identify independent predictors, and a nomogram was constructed. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and calibration analysis.

RESULTS

Independent predictors of poor PSA response included baseline alkaline phosphatase (ALP) >100 IU/L [odds ratio (OR) =0.363, P=0.02], International Society of Urological Pathology (ISUP) grade group 5 (OR =0.215, P=0.01), perineural invasion (OR =0.345, P=0.006), high disease volume (OR =0.270, P=0.02), and PSA >0.7 ng/mL at 2 months (OR =0.027, P<0.001). A predictive nomogram demonstrated discrimination (AUC = 0.907) and calibration. In a subgroup analysis of patients with PSA >0.7 ng/mL at 2 months, docetaxel addition was associated with a higher likelihood of achieving PSA response (OR =7.810, P=0.01).

CONCLUSIONS

PSA at 2 months may serve as a useful biomarker for predicting deep PSA response in patients with mHSPC. The proposed nomogram may facilitate early risk stratification and warrants further validation in prospective multicenter studies.