Impact of the Nadir Androgen Receptor Signaling Inhibitor-Derived Integrative Response Model in Real-World Patients...

Area of Science:

• Oncology
• Urology
• Clinical Research

Background:

• Early prostate-specific antigen (PSA) decline during androgen receptor signaling inhibitor (ARSI) therapy correlates with better outcomes in metastatic castration-sensitive prostate cancer (mCSPC).
• The Nadir ARSI-Derived Integrative Response (NADIR) model was developed to predict favorable early PSA response using Phase III trial data.
• The real-world performance of the NADIR model in clinical practice is not well-established.

Purpose of the Study:

• To evaluate the predictive performance of the NADIR model for early favorable PSA response in a real-world mCSPC cohort.
• To assess the model's calibration and discrimination in a clinical setting.
• To explore the association between NADIR scores and clinical outcomes like castration-resistant prostate cancer (CRPC)-free survival and overall survival (OS).

Main Methods:

• Retrospective review of 186 mCSPC patients treated with first-line ARSI therapy.
• Calculation of NADIR scores and assessment of early favorable PSA response (PSA ≤ 0.2 ng/mL within 6 months).
• Evaluation of model discrimination (AUC) and calibration, with survival analysis (Kaplan-Meier) stratified by NADIR score tertiles.

Main Results:

• The NADIR model showed acceptable discrimination for predicting early favorable PSA response (AUC = 0.74).
• Higher NADIR scores were significantly associated with achieving an early favorable PSA response (OR per 10% increase = 1.74, p < 0.001).
• CRPC-free survival significantly differed across NADIR score tertiles, indicating prognostic value.

Conclusions:

• The NADIR model demonstrates acceptable predictive performance in a real-world mCSPC cohort.
• The findings suggest the NADIR model's utility in routine clinical practice for individualized pretreatment management.
• Further validation could support its integration into clinical decision-making for mCSPC patients.