Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer

Abstract

Importance Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

Once‐a‐week or every‐other‐day urethra‐sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow‐up results

“…In the last years, phase I to III trials of prostate SBRT have consistently reported excellent disease control rates with very mostly mild‐to‐moderate toxicity and minimal impact on patient's QoL . Based on these studies, prostate SBRT can be considered nowadays as an appropriate definitive treatment modality for low‐ and intermediate‐risk prostate cancer.…”

“…Several extreme hypofractionated schedules have been reported so far differing in fractionation as well as in overall treatment time (OTT). Most frequently, 5 fractions of 7 or 7.25 Gy have been delivered for an assumed total equivalent dose to the tumor of 90 Gy in 2 Gy/fraction and a 5‐year biochemical relapse‐free (bRFS) survival rates exceeding 90% . Results from the Scandinavian HYPO‐RT‐PC phase III trial have recently confirmed the noninferiority of extreme hypofractionation vs standard fractionated RT in terms of bRFS and late toxicity …”

Ultrahypofractionation Should be a Standard of Care Option for Intermediate-Risk Prostate Cancer

“…In the Japanese HDR monotherapy series (between two and nine fractions of HDR), the 5-year bDFS was 94% for intermediate-risk patients (it is noted that 70% of patients also received ADT). The Kishan et al [15] series reported even lower rates of grade 3 þ gastrointestinal and genitourinary toxicities than the ASCO series: 0.1% and 0.6% acutely, 0.4% and 2.4% in late term, respectively. In sum, UHF EBRT (SABR) seemed to have similar biochemical control and toxicities compared with brachytherapy boost or brachytherapy monotherapy for intermediate-risk patients.…”

“…It is reasonable to ask what the oncological outcomes are for intermediate-risk patients. Published after the ASTRO/ASCO/AUA guidelines, Kishan et al [15] summarised the medium-term outcomes of 2142 patients treated with SABR (69% robotic arm-mounted and 31% gantry-mounted linear accelerator) from 10 single-institutional phase II prospective studies and two multi-institutional prospective studies [15]. The median follow-up in this series was 83 months, with 297 patients having over 9 years of follow-up.…”

Planning feasibility of extremely hypofractionated prostate radiotherapy on a 1.5 T magnetic resonance imaging guided linear accelerator

“…For prostate radiotherapy, extreme hypofractionation (≥5.0 Gy/fraction), or stereotactic body radiotherapy (SBRT), is increasingly used, as the shortened treatment schedule is more convenient to the patient and potentially cost effective [2,3]. Multiple single arm phase I and II extreme hypofractionation trials, and a recent publication from the HYPO-RT-OC randomized phase II trial using SBRT, showed low rates of severe toxicity and excellent biochemical control for low and intermediate risk prostate cancer patients [4][5][6][7][8].…”