Risks of Progression After Early Androgen Deprivation Therapy for Biochemical Recurrence After Radical Prostatectomy

Current prognostic assessment of men with biochemical recurrence (BCR) after radical prostatectomy (RP) relies on data from the pre-2000s era when androgen deprivation therapy (ADT) was delayed until metastasis. Most men now initiate ADT at low PSA values before metastases, especially for high-risk disease in which expanded ADT improves metastasis-free survival. We defined rates of cancer progression and mortality in men treated with early ADT for post-RP BCR.

We conducted an observational study of 1108 men with nonmetastatic prostate cancer receiving ADT for BCR after RP from 1988 to 2019 from the Veterans Affairs SEARCH database. Fine and Gray competing risk models quantified risk of metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM) across key predictors.

The median follow-up after ADT among men who did not die of prostate cancer was 5.8 years (IQR 3.0-9.9). The median PSA at ADT was 1.3 ng/mL (IQR 0.4-4.9). Across all men, risks of metastasis, CRPC, and PCSM at 15 years after ADT were 28%, 27%, and 19%, respectively. In multivariable models, higher pre-ADT PSA, shorter pre-ADT PSA doubling time, higher pathologic grade group, and seminal vesicle invasion were associated with higher risk of metastasis, CRPC, and PCSM. We created predictive nomograms and tables estimating 3-, 5-, 10-, and 15-year risks of metastasis, CRPC, and PCSM by PSA at ADT, PSA doubling time at ADT, pathologic grade group, and seminal vesicle invasion. Risks of PCSM at 15 years after ADT initiation ranged from 2% to 60% across subgroups.

These contemporary prognostic estimates are more applicable to men receiving early ADT for post-RP BCR and can help identify high-risk patients who are candidates for intensified hormonal therapy.