Early PSA Kinetics for Low- and Intermediate-Risk Prostate Cancer with Favorable Treatment Response Treated with HDR Brachytherapy, SBRT, Hfrt, and Cfrt

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It is not well understood how the various modern radiation techniques influence post-treatment prostate specific antigen (PSA) kinetics. We examine initial PSA kinetics with a decay rate model to determine how to assess treatment response for patients treated with HDR, SBRT, hypofractionated (HFRT), and conventionally fractionated IMRT (CFRT). This retrospective study uses a prospective database at a single institution. We included patients with low or intermediate risk prostate cancer (T1-T2; GS 6 or 7; PSA < 20 ng/mL), treated without androgen deprivation therapy between 2002 and 2017, and free from biochemical failure per Phoenix criteria. Only patients with at least 2 PSA measurements in the first 2 years of follow-up were included. Treatment techniques included HDR, SBRT, HFRT (70.2 Gy in 2.7 Gy/fx) and CFRT. Pre-treatment PSA (iPSA) obtained within 90 days of RT start. Time to nadir was measured from RT completion date. iPSA was compared to PSA levels at subsequent follow ups at 6-month intervals. PSA decay rate was modeled using longitudinal regression analysis with generalized estimating equation (GEE) methods to adjust for within patient correlations; we considered the influence of age, Gleason Score (GS), iPSA, and T-stage on decay rates in multivariable models. PSA half-life, i.e. time for PSA to drop to 50% of a given time period’s initial PSA, was estimated from decay rate coefficients. A shorter follow-up for SBRT and HDR cohorts limited analysis to a 2-year interval. Of 628 patients in this study, 81 received HDR, 65 SBRT, 67 HFRT, and 415 CFRT. Patients receiving HDR and SBRT more frequently were younger and had lower T-stage, while CFRT patients were more likely to have higher iPSA and GS 4+3. In the first year of follow-up, lowest PSA levels, as absolute value (ng/mL) and relative to iPSA (PSA%), were lower among HFRT (1.1, 16%) and CFRT (1.0, 17%) when compared with SBRT (1.8, 29%) and HDR (1.4, 26%) (p=0.056). PSA half-lives during the 1-year interval were also shorter among HFRT and CFRT when compared with SBRT and HDR, 4.2 and 4.1 months for CFRT and HFRT compared with 5.4 and 5.3 months for SBRT and HDR (p=0.015). Using PSA measured within a 2-year interval, both absolute PSA and relative to iPSA values were lowest in HFRT (0.58, 9%) and CFRT (0.51, 10%) when compared with SBRT (1.5, 24%) and HDR (1.1, 23%) (p=0.015). However, PSA half-lives within the 2-year interval did not differ between all four treatments (p=0.22). Notably, HDR and SBRT decay rates did not significantly differ at either follow-up interval (p=0.84). Based on PSA decay modeling, adjusting for within patient correlations, both HFRT and CFRT show more rapid early PSA response within 1 year compared to HDR and SBRT. At the 2-year interval PSA decay rates are similar among all four treatments.