Safety and Efficacy of Virtual Prostatectomy With Single-Dose Radiotherapy in Patients With Intermediate-Risk Prostate Cancer: Results From the PROSINT Phase 2 Randomized Clinical Trial

Abstract

Importance: Ultra-high single-dose radiotherapy (SDRT) represents a potential alternative to curative extreme hypofractionated stereotactic body radiotherapy (SBRT) in organ-confined prostate cancer.

Objective: To compare toxic effect profiles, prostate-specific antigen (PSA) responses, and quality-of-life end points of SDRT vs extreme hypofractionated SBRT.

Design, setting, and participants: The PROSINT single-institution phase 2 randomized clinical trial accrued, between September 2015 and January 2017, 30 participants with intermediate-risk prostate cancer to receive SDRT or extreme hypofractionated SBRT. Androgen deprivation therapy was not permitted. Data were analyzed from March to May 2020.

Interventions: Patients were randomized in a 1:1 ratio to receive 5 × 9 Gy SBRT (control arm) or 24 Gy SDRT (test arm).

Main outcomes and measures: The primary end point was toxic effects; the secondary end points were PSA response, PSA relapse-free survival, and patient-reported quality of life measured with the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaires.

Results: A total of 30 men were randomized; median (interquartile range) age was 66.3 (61.2-69.9) and 73.6 (64.7-75.9) years for the SBRT and SDRT arms, respectively. Time to appearance and duration of acute and late toxic effects were similar in the 2 trial arms. Cumulative late actuarial urinary toxic effects did not differ for grade 1 (hazard ratio [HR], 0.41; 90% CI, 0.13-1.27) and grade 2 or greater (HR, 1.07; 90% CI, 0.21-5.57). Actuarial grade 1 late gastrointestinal (GI) toxic effects were comparable (HR, 0.37; 90% CI, 0.07-1.94) and there were no grade 2 or greater late GI toxic effects. Declines in PSA level to less than 0.5 ng/mL occurred by 36 months in both study arms. No PSA relapses occurred in favorable intermediate-risk disease, while in the unfavorable category, the actuarial 4-year PSA relapse-free survival values were 75.0% vs 64.0% (HR, 0.76; 90% CI, 0.17-3.31) for SBRT vs SDRT, respectively. The EPIC-26 median summary scores for the genitourinary and GI domains dropped transiently at 1 month and returned to pretreatment scores by 3 months in both arms. The IPSS-derived transient late urinary flare symptoms occurred at 9 to 18 months in 20% (90% CI, 3%-37%) of patients receiving SDRT.

Conclusions and relevance: In this randomized clinical trial among patients with intermediate-risk prostate cancer, SDRT was safe and associated with low toxicity, and the tumor control and quality-of-life end points closely match the SBRT arm outcomes. Further studies are encouraged to explore indications for SDRT in the cure of prostate cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT02570919.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Greco and Fuks are founders of Ceramedix Inc and also reported patent application number PTC/PT2020/050027 related to this work. Dr Fuks also reported patents unrelated to this work (US10413533B2, US20170333413A1, US20180015183A1). No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

SBRT indicates stereotactic body radiotherapy; SDRT, single-dose radiotherapy.

Figure 2.. Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) vs Single-Dose Radiotherapy (SDRT) Stratified by Treatment Arm

A, Cumulative incidence of bowel grade 1 gastrointestinal (GI) toxic effects. B, Cumulative incidence of genitourinary (GU) grade 1 toxic effects. C, Cumulative incidence of urinary grade ≥2 toxic effects. D, Percentage volume reductions compared to baseline measured by magnetic resonance imaging. Error bars indicate SE; HR, hazard ratio.

Figure 3.. Prostate-Specific Antigen (PSA) Response With Stereotactic Body Radiotherapy (SBRT) vs Single-Dose Radiotherapy (SDRT)

A, Median PSA over time stratified by treatment arm; error bars indicate interquartile range. B, Actuarial PSA relapse-free survival (bRFS) stratified by treatment arm. C, Actuarial bRFS stratified by favorable intermediate-risk (FIR) vs unfavorable intermediate-risk (UIR) categories. D, UIR actuarial bRFS stratified by treatment arm. HR indicates hazard ratio.

Figure 4.. EPIC-26 Patient-Reported Outcomes of Stereotactic Body Radiotherapy (SBRT) vs Single-Dose Radiotherapy (SDRT) Over Time Stratified by Treatment Arm

Mean summary scores for the genitourinary (GU) domain (A), gastrointestinal (GI) domain (B), and sexual domain (C). Error bars indicate SEM. EPIC indicates Expanded Prostate Cancer Index Composite.