Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy

INTRODUCTION: Distinct PSA kinetics have been reported across the breadth of radiation modalities used to definitively treat prostate cancer. This study uses a patient-specific model to characterize and compare ideal PSA kinetics for low- and intermediate-risk prostate cancer following definitive treatment with conventionally fractionated (CFRT), hypofractionated (HFRT), ultra-hypofractionated or stereotactic body radiation therapy (SbRT), or brachytherapy, both high-dose-rate (HDR) and low-dose-rate (LDR). METHODS: This retrospective analysis includes patients with low- or intermediate-risk prostate cancer treated with definitive radiation between 1998 and 2018 at a single, NCI-designated Comprehensive Cancer Center. Patient demographics, treatment characteristics, and follow-up information were prospectively collected in an institutional database. Eligible patients had at least two PSA measurements within 24-months of treatment and were free from biochemical recurrence and receipt of androgen deprivation therapy. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed by radiation modality. Ideal PSA kinetics were characterized for each modality and compared. RESULTS: Of 1,047 patients included, 45% had low-risk prostate cancer, 37% had favorable intermediate-risk, and 19% had unfavorable intermediate-risk. The majority of patients were treated with CFRT or LDR; the smallest subset was 52 patients (5%) who received SbRT. nPSA measurements within the two-year follow-up period were significantly higher for those treated with ablative modalities, both as absolute nPSA values and relative to initial PSA (iPSA). Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% of those treated with non-ablative therapy (CFRT, HFRT, and LDR) reached a critical nPSA threshold of ≤0.5 ng/mL, while only 23% of SbRT and 33% of HDR cohorts achieved the same threshold. The overall incidence of bPSA was 13.3% and was not affected by treatment modality, Gleason Score, or prostate volume. A piecewise linear regression showed no statistically significant difference in the PSA decay rates between radiation modalities over time, though there was a trend toward faster PSA decay in ablative therapies between the 6–24-month period. CONCLUSION: Ablative therapies, such as HDR and SbRT, are associated with a latent PSA response and higher nPSA when compared to non-ablative therapies. Multivariate logistics modeling revealed younger age, iPSA above the mean, presence of bPSA, and receipt of ablative therapy as significant predictors for not achieving an nPSA ≤0.5 ng/mL. Understanding the different PSA kinetic profiles for the various radiation modalities is critical to assess treatment response and survey for disease recurrence.