Acute Toxicity Following Single-Dose Radiation Therapy in the Management of Intermediate Risk Prostate Cancer: Results from a Phase 2 Randomized Trial

Abstract

to evaluate acute treatment-related toxicity and patient-reported quality of life (QoL) after 24Gy SDRT derived from a randomized Phase II study in patients with histologically proven intermediate-risk adenocarcinoma of the prostate (NCCN definition). since November 2015, 30 patients were enrolled in an IRB approved prospectively randomized study to receive either 45Gy in 5 daily fractions (Hypo-SBRT) or 24Gy SDRT. Patients with a baseline IPSS score >15, a previous transurethral prostate resection, or a gland size >100 cc were not eligible. Treatment protocols were based on VMAT-IGRT techniques with urethral sparing and real-time motion management with beacon transponders, and the CTV included the prostate gland and seminal vesicles, and a 2 mm margin for PTV expansion. Accurate anatomical reproducibility was achieved via the placement of an endorectal balloon filled with air (150 cc) and a Foley catheter loaded with the becon trasponders. This setup conferred excellent organ motion mitigation and online tracking ensured treatment delivery was always within the 2 mm PTV/CTV margin. Acute toxicity within the first three months was defined as a primary endpoint. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were graded according to the NCI CTCAE v.4 and QoL was assessed by EPIC and IPSS questionnaires. a total of 15 patients were accrued to each protocol arm, and a minimum follow-up of 3 months was achieved in all patients (range, 3-15). Treatment acceptance and protocol compliance were complete. No grade ≥2 acute GI or GU toxicities were observed in either group. G1 GU and GI toxicities in the hypo arm were 18% and 0%, respectively and 41% and 8%, respectively in the SDRT arm. There were no significant differences in mean EPIC scores in all domains between the two groups. At one-month post treatment, a 6% and 8% drop in the EPIC urinary domain scores occurred in the hypo and SDRT arm, respectively. The scores returned to baseline at the 3 months in both groups. Similarly, at 1-month median IPSS values in the hypo and SDRT arm increased from 7 to 11 and from 7 to 10, respectively, but returned to the baseline value of 7 at 3-months. These observations recapitulated the acute toxicity profiles observed in a phase I/II single arm hypofractionated study (5x9Gy daily, in 200 cases) and a phase I pilot study of 24Gy SDRT in radiation- surgery-naïve prostates failing androgen ablation (28 patients) using the same technique as described above, both completed before initiation of the presently reported trial. These early trial endpoints indicate that 24Gy SDRT with urethral sparing and real-time motion management can be consistently and safely delivered and is associated with acceptable treatment-related symptoms. QoL profiles are consistent with the low rates of mild GU and GI toxicities. Other primary endpoints (i.e. late toxicity, biochemical outcomes and 24 months post-treatment biopsy) have not been reached.