Comparison of PSA Kinetics Between Hypofractionated Stereotactic Body Radiation Therapy, Conventionally Fractionated External Beam Radiation, and High-dose-rate Brachytherapy

Abstract

Clinical outcomes in prostate cancer patients have been linked to a lower PSA nadir and a more rapid decline in PSA after treatment (e.g. PSA kinetics). Furthermore, dose escalation with external beam radiation therapy (EBRT) has been associated with improved clinical outcomes. The evidence for a low α/β ratio for prostate cancer, and the desire to shorten treatment, has led to the use of hypofractionated radiation therapy to deliver a higher bioequivalent dose. At UCSF low and low-intermediate risk prostate cancer patients are treated definitively with hypofractionated stereotactic body radiation therapy (SBRT) monotherapy, with a dose and fractionation based on HDR brachytherapy monotherapy. We undertook this retrospective study to compare the biological response (kinetics of PSA decline and PSA nadir) after definitive monotherapy with SBRT compared with EBRT and HDR. We hypothesize that the hypofractionated treatment regimen should result in a more rapid PSA decline than conventionally fractionated EBRT and be equivalent to HDR. One hundred eighty-two patients were retrospectively identified with low and intermediate risk defined as Gleason G3+3 PSA < 20 or G3+4 PSA < 15 treated with definitive external beam monotherapy to the prostate only, with at least 3 serial PSAs and 1 year of follow up. Patients were also excluded if they failed therapy by the ASTRO Phoenix definition. Twenty-seven patients treated with SBRT to the prostate with 38 Gy in 4 daily fractions met the same criteria, as did 13 patients treated with HDR, treated with either 950 cGy x 4 fractions or 1050 cGy x 3 fractions. PSA slope is the change in PSA versus time. Median follow-up for the SBRT, EBRT, and HDR cohorts were 37, 62 and 19 months, respectively. The median PSA nadirs for SBRT, EBRT and HDR were 0.26, 0.66 and 0.20 ng/mL respectively, and the median PSA slopes were -.057, -0.003, and -0.054 ng/mL/month, respectively. The rate of PSA decline was significantly slower with EBRT compared with either SBRT or HDR (p < 0.001). The distributions of PSA nadir values statistically differed between all pairs of treatments, although the time to observed nadir was significantly longer with HDR. The hypofractionated regimen delivered by SBRT resulted in a rapid decline in PSA similar to HDR, but faster than EBRT, reflecting the similarity in dose and fractionation of SBRT and HDR. The short follow up for the HDR cohort, and the long median time to PSA nadir (74 months), does not allow comparison of the HDR nadir. The exclusion of failures and long follow up are reflected in the low PSA nadir for EBRT. SBRT does result in similar kinetics to HDR treatment, and is approaching PSA nadirs of HDR treatments in historical series, illustrating its biological equivalence to HDR.