Prognostic Impact of PSA Nadir After Radiotherapy, ADT for Localized Prostate Cancer

Prostate-specific antigen (PSA) nadir ≥0.1 ng/mL within 6 months of radiotherapy (RT) completion is strongly prognostic for long-term outcome measures in patients receiving RT plus androgen deprivation therapy (ADT) for localized prostate cancer, according to a study that will be presented at the American Society of Clinical Oncology 2023 Annual Meeting.

RT plus ADT is considered a standard-of-care treatment for intermediate- and high-risk localized prostate cancer. Identification of early surrogate measures for long-term outcomes measures—including prostate cancer-specific survival (PCSS), metastasis-free survival (MFS), and overall survival (OS)—may expedite the development of systemic therapies to accompany RT plus ADT while identifying patients for therapy (de)escalation.

Praful Ravi, MRCP, MBBChir, and colleagues conducted an individual patient-data analysis of 10,415 patients from 16 randomized, controlled trials assessing RT plus ADT in the international Intermediate Clinical Endpoints in Cancer of the Prostate repository. Patients with evaluable PSA follow-up were eligible for inclusion.

Researchers grouped patients based on their trial-allocated treatment: RT alone (n=2629), RT plus short-term ADT (3-6 months; n=6033), and RT plus long-term ADT (18-36 months; n=1753). PSA nadir was defined as the lowest PSA recorded within 6 months of RT completion.

A 12-month analysis for PCSS, MFS, and OS was performed, and multivariable Cox proportional hazards regression was used to estimate associations between PSA nadir <0.1 ng/mL or ≥0.1 ng/mL and MFS and OS. Additionally, a multivariable Fine and Gray distribution was used for PCSS to account for competing risk of non-prostate cancer-related deaths.

After a median follow-up of 10.1 years, 98%, 84%, and 77% of patients allocated to the RT alone, RT plus short-term ADT, and RT plus long-term ADT groups, respectively, achieved a PSA nadir ≥0.1ng/mL within 6 months of RT completion.

After model adjustment, PSA nadir ≥0.1 ng/mL was associated with poorer PCSS, MFS, and OS in patients allocated to the RT plus short-term ADT and RT plus long-term ADT groups. Researchers noted a weaker association in patients allocated to RT alone.

“PSA nadir ≥0.1ng/mL within 6 months after RT completion was strongly prognostic for PCSS, MFS, and OS in patients receiving RT plus ADT for localized prostate cancer in this individual patient-data analysis,” Dr. Ravi and colleagues concluded. “This could be used as an early signal-seeking end point in trials evaluating novel systemic therapies with RT plus ADT and to help identify patients for therapy (de)escalation trials.”