PSA kinetics and predictors of PSA response in metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors.

BACKGROUND

PSA response is a key prognostic tool in metastatic hormone-sensitive prostate cancer (mHSPC). Data from SWOG 9346 and TITAN post-hoc analyses demonstrated the prognostic value of PSA thresholds at 6-7 months after androgen deprivation therapy (ADT) or ADT plus apalutamide. However, variability in thresholds and timing highlights the need to explore PSA kinetics in real-world cohorts. This study investigates PSA dynamics and their predictors following Androgen Receptor Signaling Inhibitors (ARSI) initiation.

METHODS

This multicenter study included mHSPC patients treated with ADT+ARSI between June 2017 and October 2024. Exclusions included ADT monotherapy, triplet therapy, or ARSI initiation >6 months post-ADT. PSA kinetics were analyzed over 12 months, focusing on SWOG (0.2-4 ng/ml) and TITAN (0.02-0.2 ng/ml) thresholds. Logistic regression and SHAP (SHapley Additive exPlanations) analysis identified predictors of achieving low (<0.2 ng/ml) or ultralow (<0.02 ng/ml) PSA at 6 months.

RESULTS

Among 586 mHSPC patients (median follow-up: 23 months), most had synchronous (58%), low-volume (58%), and ISUP grade 4-5 (64%) disease. At 6 months, 74%, 19%, and 7% achieved PSA <0.2 ng/ml, 0.2-4 ng/ml, and >4 ng/ml (SWOG cutoffs), while 36%, 35%, and 29% achieved PSA <0.02 ng/ml, 0.02-0.2 ng/ml, and >0.2 ng/ml (TITAN cutoffs). Baseline PSA <50 ng/ml and metachronous disease were strong predictors of ultralow PSA.

CONCLUSION

SWOG and TITAN thresholds offer distinct PSA stratifications, with SWOG grouping more patients into the lowest PSA category and TITAN providing a more balanced distribution. Baseline PSA and metachronous disease are key predictors of favorable PSA responses, emphasizing their importance in guiding management.