Dosimetric Comparison and Toxicity Analysis of Stereotactic Radiotherapy for High-Risk Prostate Cancer

FASTR was designed to provide a compact treatment course for high risk prostate cancer patients but was discontinued because of excess toxicity.(1) FASTR-2 employed a lower dose to the prostate (35Gy vs. 40Gy), smaller PTV margins and omitted nodal radiation in order to lower the volumes of rectum receiving high and intermediate doses compared to FASTR. Here we compare the acute toxicity and rectal dosimetry between our FASTR and FASTR-2 patients. Eligibility for FASTR-2 included high-risk prostate cancer (cT3/4, PSA>20 or Gleason Score ≥ 8), age ≥ 70 or refused standard treatment, no evidence of extra-prostatic disease. Patients received 18 months of ADT starting 2 months prior to radiation. CTV was defined as prostate plus proximal 1cm seminal vesicles. PTV was a non-uniform expansion around CTV (4mm posteriorly, 5mm in all other directions). Volumetric arc therapy was used for treatment delivery (1 fraction/week x 5 weeks) and cone beam CT with soft tissue matching (no fiducial placement) was used for daily image guidance. Toxicity was assessed at 6 weeks, 6 months, and 1 year according to Common Toxicity Criteria. 15 patients were enrolled in the original FASTR study; 30 patients were enrolled in FASTR-2 between 2015 and 2017. Two patients were withdrawn due to ineligibility following enrollment. One patient (3.7%) reported grade 2 GI toxicity at 6 weeks. There were no reported grade ≥ 2 GI toxicity at 6 months or 1 year. There were no reported episodes of rectal bleeding. Four patients (14.8%), 5 patients (17.9%) and 5 patients (21.7%) reported grade 2 GU toxicity at 6 weeks, 6 months and 1 year, respectively. The most common toxicities were nocturia and urinary frequency/urgency. Rectal maximum point dose, D20 and D50 decreased from 40.7Gy, 29.6Gy and 20.8Gy in FASTR to 35.0Gy, 22.2Gy and 11.1Gy in FASTR-2 (p<0.001). Bladder point dose, D20 and D50 decreased from 40.9Gy, 28.1Gy and 21.5Gy in FASTR to 35.7Gy, 15.7Gy and 6.3Gy in FASTR-2 (p<0.001). FASTR-2 was more tolerable than FASTR, with no grade ≥ 3 toxicities reported, in keeping with expectations based on our previous FASTR analysis.(2) Advantages to FASTR-2 include image guidance without fiducials and a weekly treatment schedule which is more convenient for some patients. Trade-offs with FASTR-2 include a lower dose to the prostate (but still in keeping with ASTRO guidelines) and elimination of pelvic nodal irradiation (but need for routine pelvic radiotherapy still remains debated). Long-term follow-up is necessary to ensure disease control is comparable to conventional high risk treatment paradigms.