Heterogeneous Dose-Escalated Prostate Stereotactic Body Radiation Therapy for All Risk Prostate Cancer: Quality of Life and Clinical Outcomes of an Institutional Phase 2 Study

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Most published prostate SBRT studies treated low to intermediate-risk prostate cancer (CaP) with uniform doses of 35-40 Gy/ 5 fx. Previous attempts at uniform dose escalation to 50 Gy caused high rates of GI toxicity. We hypothesized heterogeneous dose escalation to 50 Gy to regions of the prostate not adjacent to the urethra, rectum and bladder is safe and efficacious. We report outcomes of an institutional phase II protocol. Thirty-five patients were enrolled on an institutional review board approved phase II study. Treatment involved LINAC based VMAT or IMRT with a rectal balloon. The contoured prostate was expanded by 3 mm (0 mm posteriorly). A prescription target of 50 Gy/ 5 fx was delivered to >50% of the portion of PTV >3 mm from sensitive structures (urethra, rectum, bladder), while the seminal vesicles and PTV <3mm from sensitive structures were treated to 36.25 Gy/ 5 fx. Study patients completed the EPIC-26 questionnaire at baseline and 1.5, 4, 8 and 12 months post SBRT. Clinically significant changes in quality of life (QOL) over time were determined using a minimally clinically important difference (MCID), defined as a change of >1/2 the standard deviation of the baseline QOL value. One patient had low, 12 intermediate (4 with multiple risk factors), and 16 high-risk CaP. Median and mean iPSAs were 9.0 and 16.6 ng/ml. Androgen deprivation therapy (median 6 months) was given to 17 patients (59%). Median age was 70 yrs. At median follow-up of 46 months, treatment was well-tolerated. Urinary irritation/obstructive and urinary bother scores declined by MCID threshold from baseline assessment to the first visit at six weeks post SBRT, but subsequently recovered by 4 months. No differences were observed for urinary incontinence, bowel domain, bloody stools, or sexual domain. One patient developed acute grade 2 GU toxicity and 2 patients developed acute grade 2 or higher GI toxicity. One patient developed late grade 2 GU toxicity and 4 patients developed late grade 2 or higher GI toxicity. This includes one patient with a very large prostate (270 cc) and implanted radiofrequency transponders who developed prostatic infection 3 weeks post SBRT, requiring surgical debridement resulting in acute and late grade 4 GI toxicities. Freedom from biochemical failure (nadir +2) at 3 years was 88.9%. Heterogeneous dose-escalated prostate SBRT was well-tolerated in patients with predominantly intermediate and high-risk CaP, with the exception of a single high grade toxicity of likely of infectious etiology. Urinary irritation/obstructive scores and urinary bother scores declined from baseline to six weeks post SBRT, but recovered by fourth months. There was no change in bloody stools or bowel domain scores with SBRT. Further investigation and follow-up is needed to establish the role of heterogeneous dose-escalated SBRT in CaP.