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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Kishan reported receiving honoraria from Varian Medical Systems Inc and ViewRay Inc and serving on an advisory board for Janssen Pharmaceuticals Inc. Dr Collins reported receiving grants from and being a paid consultant to Accuray Inc. Dr Aghdam reported receiving grants from Accuray Inc. Dr Fuller reported receiving grants and personal fees from Accuray Inc and owning stock in Accuray Inc, Varian Medical Systems Inc, and ViewRay Inc. Dr Meier reported receiving grants and honoraria for speaking engagements (later donated to charity) from Accuray Inc. Dr Spratt reported serving on advisory boards for Blue Earth Diagnostics and Janssen Pharmaceuticals Inc. Dr Nickols reported receiving grants from Bayer, Gene Sciences Inc, Janssen Pharmaceuticals Inc, the Prostate Cancer Foundation, and Varian Medical Systems; serving as a paid consultant to Gene Sciences Inc, Nanobiotix, and Progenics; and owning stock in Gene Sciences Inc. Dr Steinberg reported receiving honoraria from ViewRay Inc. Dr Kupelian reported serving on the scientific advisory board for ViewRay Inc. No other disclosures were reported.

Figures

Figure 1.. Study Outcomes

A, Cumulative incidence of biochemical recurrence (P < .001). B, Cumulative incidence of distant metastases (P = .03). C, Kaplan-Meier curve of biochemical recurrence–free survival (P < .001). D, Kaplan-Meier curve of overall survival (P = .01). Fav-Int indicates favorable intermediate-risk disease; Low, low-risk disease; and Unfav-Int, unfavorable intermediate-risk disease.

Figure 2.. Comparative Rates of Grade 3 or Higher Toxic Events Across Various Radiotherapy Modalities

A, Rate of grade 3 or higher genitourinary (GU) toxic events. B, Rate of grade 3 or higher late gastrointestinal (GI) toxic events. Additional details in eTable 9 in the Supplement. ASCENDE-RT indicates Androgen Suppression Combined With Elective Nodal and Dose Escalated Radiation Therapy; CHHiP, conventional vs hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer; HDR, high-dose-rate brachytherapy; LDR, low dose-rate brachytherapy; MDACC, MD Anderson Cancer Center; PROFIT, Prostate Fractionated Irradiation Trial; and RTOG, Radiation Therapy Oncology Group.