This is a multicenter, Phase I/II study of hypofractionated (HypoFX) prostate bed radiation therapy (RT) as salvage or adjuvant therapy. The Phase I portion of this study aimed to identify the shortest dose-fractionation schedule with acceptable toxicity. The Phase II portion aimed to assess the health-related quality of life (QoL) of utilizing this HypoFx regimen.
Eligibility included standard adjuvant or salvage prostate bed RT indications. Patients were assigned to receive one of three daily RT schedules: 56.6 Gy in 20 Fx, 50.4 Gy in 15 Fx, or 42.6 Gy in 10 Fx. Regional nodal irradiation and ADT were not allowed. Participants were followed for 2 years after treatment with outcome measures based on PSA levels, toxicity assessments (CTCAE v4.0), QoL measures (EPIC, EQ-5D), and out-of-pocket costs.
There were 32 evaluable participants, and median follow-up was 3.53 years. The shortest dose-fractionation schedule with acceptable toxicity was determined to be 42.6 Gy in 10 FX, with most patients (n=23) treated with this schedule. Grade 3 GU and GI toxicities occurred in three patients and one patient, respectively. There was one grade 4 sepsis event. Higher dose to the hottest 25% of the rectum was associated with increased risk of grade 2+ GI toxicity; no dosimetric factors were found to predict for GU toxicity. There was a significant decrease in the mean bowel, but not bladder, QoL score at 1 year compared to baseline. PSA failure occurred in 34.3% using a nadir plus 2 ng/mL definition. Metastases were more likely to occur in regional lymph nodes (5/7) than in bones (2/7). Mean out of pocket costs for patients during treatment, were $223.90.
We identified 42.6 Gy in 10 fractions as the shortest dose-fractionation schedule with acceptable toxicity in this Phase I/II study. There was a higher than expected rate of grade 2-3 GU and GI toxicity and a decreased EPIC bowel QoL domain with this regimen. Future studies are needed to explore alternative adjuvant/salvage HypoFx RT schedules following radical prostatectomy.
International journal of radiation oncology, biology, physics. 2020 Nov 20 [Epub ahead of print]
Nolan A Wages, Jason C Sanders, Amy Smith, Songserea Wood, Mitchell S Anscher, Nikole Varhegyi, Tracey L Krupski, Timothy J Harris, Timothy N Showalter
Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA. Electronic address: ., Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA., Department of Radiation Oncology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA., Department of Urology, University of Virginia School of Medicine, Charlottesville, VA, USA.