Stereotactic Ablative Radiation Therapy for Prostate Cancer

Overview

This single arm trial will investigate a novel way to plan and deliver SABR for prostate cancer. Prostate-directed SABR will be high-dose SABR (40 Gy in 5 fractions) with central sparing of the urethra and peripheral sparing of the rectum and pudendal arteries (SUPR-SABR). This study tests the hypothesis that genitourinary (GU) and gastrointestinal (GI) toxicity rates following SUPR-SABR are comparable to (or possibly lower than) historical GU and GI toxicity rates following standard SABR (stSABR) with 36.25 Gy in the treatment of low- and intermediate-risk prostate cancer.

It is estimated that there will be 268,000 prostate cancer diagnoses and nearly 35,000 deaths due to prostate cancer in the United States in 2022 \[1\]. Most men diagnosed with prostate cancer present with localized or organ confined disease which is most commonly managed with active surveillance, prostatectomy, brachytherapy, and external beam radiotherapy (EBRT). Conventionally fractionated (1.8-2.0 Gy per fraction for nine weeks) EBRT is of historical and clinical importance in localized prostate cancer, however, moderately hypofractionated (≥2.5 Gy per fraction for four to six weeks) EBRT and SABR have also emerged as standards of care in appropriately selected patients. The increased precision associated with image guided stereotactic techniques now permits safe delivery of large doses per fraction, also known as hypofractionation. SABR is a specific type of hypofractionated RT. Hallmarks of the SABR technique, also commonly known as stereotactic body radiotherapy (SBRT), include doses of at least 5 Gy per fraction, five or fewer fractions, motion management, noncoplanar beam or arc therapy, body immobilization, and ablative prescription doses. There is growing interest in the use of SABR in men with low- and intermediate- risk prostate cancer due to their lower risk of extra prostatic disease including pelvic lymph node micrometastases and the low alpha/beta ratio of prostate cancer. Several series with follow up times exceeding five years have demonstrated excellent biochemical control for SABR approaching 95% for low risk and 80-90% for intermediate risk disease with low rates of clinically significant late GU and GI toxicity. Most published clinical experiences of SABR for prostate cancer have employed 35 to 36.25 Gy in 7- to 7.25 Gy fractions (i.e., standard SABR or stSABR). Importantly, it has never been established whether this represents the optimal dose level for SABR and, nationally, there is not only a single standard of care for SABR prescription dose and fractionation. What is more, contemporary literature with prostate SABR suggests a benefit with dose escalation, however, there is interest in avoiding a parallel increase in GU, GI, and sexual side effects of treatment. The proposed trial concept would offer men with low- and intermediate-risk prostate cancer a dose-escalated SABR regimen (SUPR-SABR) of 40 Gy in 5 fractions with a safety profile already supported by medical literature and which is expectedly more efficacious than stSABR. This dose and fractionation is already being used in some radiation oncology practices. However, to further improve the therapeutic index of curative RT, the protocol will employ all available methods to spare the urethra, pudendal artery, and rectum (SUPR-SABR): foley catheter placement during planning, rectal spacer gel placement, endorectal balloon during planning and treatment, prostatic immobilization, strict contouring and dose constraints, and the most highly conformal photon planning available. This protocol will offer men a clinical study with highly important endpoints and lower anticipated treatment related morbidity. If the primary analysis demonstrates favorable healthcare related quality of life (HRQOL) with SUPR-SABR when compared to prospectively collected historic controls of stSABR, then this would serve as the basis for a randomized trial between SUPR-SABR and stSABR.