SBRT improves multiple quality of life domains but not DFS vs MH-IMRT

Stereotactic body radiation therapy (SBRT) was associated with superior patient-reported bowel quality of life (HRQOL) and lower rates of grade 3 or higher genitourinary adverse events compared with moderately hypofractionated intensity-modulated radiation therapy (MH-IMRT) in patients with favorable intermediate-risk prostate cancer, according to results from the phase 3 NRG-GU005 trial (NCT03367702).¹

However, SBRT was not superior for urinary irritative/obstructive health-related quality of life (HRQOL) or disease-free survival (DFS). The findings were published in JAMA, adding insight on the relative risks and benefits of shortened treatment courses for prostate radiotherapy.

About the study

NRG-GU005 was an international, open-label, randomized phase 3 trial conducted at 136 centers in the US, Canada, Europe, and Asia. The study enrolled 698 patients with previously untreated, localized intermediate-risk prostate cancer. Eligible patients had clinical stage T1-T2b disease with either Gleason score 3+4 (grade group 2) and a prostate-specific antigen (PSA) level below 20 ng/mL or Gleason score 3+3 (grade group 1) and a PSA level of 10 ng/mL to 20 ng/mL.

Patients were randomly assigned 1:1 to SBRT consisting of 36.25 Gy in 5 fractions (n = 353) or MH-IMRT consisting of either 70 Gy in 28 fractions or 60 Gy in 20 fractions (n = 345). The trial used the Expanded Prostate Cancer Index Composite-26 (EPIC-26) to evaluate patient-reported urinary irritative/obstructive and bowel HRQOL. The primary HRQOL outcomes were the proportions of patients experiencing a minimal clinically important decline (MCID) in those domains at 2 years, and the oncologic primary outcome was DFS at 3 years.

At 2 years, 35.4% of patients receiving SBRT and 33.7% receiving MH-IMRT experienced an MCID in urinary irritative/obstructive HRQOL, a difference that was not statistically significant (P = .68). In contrast, fewer patients treated with SBRT experienced an MCID in bowel HRQOL, at 34.9% vs 43.8% with MH-IMRT (P = .03). In both cohorts, rectal spacing was associated with improved patient-reported bowel function.

Urinary incontinence at 1 and 2 years and sexual function at 1 year favored SBRT. Grade 3 or 4 genitourinary adverse events occurred in 0.6% of patients receiving SBRT compared with 2.5% of those receiving MH-IMRT (P = .04).

At 3 years, DFS was 88.6% (95% CI, 85.2 to 92.1) with SBRT and 92.1% (95% CI, 88.9 to 95.2) with MH-IMRT (1-sided log-rank P < .001). The rate of biochemical DFS failure by PSA testing was significantly higher with SBRT, with rates of 7.8% vs 4.2%, respectively, at 3 years (P = .04; adjusted HR, 1.82; 95% CI, 1.01 to 3.27; P = .046).

Clinical context

Prior randomized data have supported SBRT as an option for selected patients with localized prostate cancer. In the phase 3 PACE-B trial (NCT01584258), 874 men with T1 or T2 disease were randomly assigned 1:1 to SBRT or conventional/moderately hypofractionated radiotherapy. At a median follow-up of 74.0 months, SBRT was noninferior to standard radiotherapy for biochemical or clinical failure (95.8% vs 94.6%; HR, 0.73; 90% CI, 0.48 to 1.12; P-value for non-inferiority = .004), although late grade 2 or higher genitourinary toxicity was more common with SBRT (26.9% vs 18.3%; P < .001).²

Notably, PACE-B allowed a higher-dose regimen permitted per trial protocol. The NRG-GU005 investigators noted that the higher dose used in PACE-B likely contributed to more favorable PSA control with SBRT, although the trial also showed increased urinary adverse events.

“The NRG GU-005 trial shows that SBRT can be offered as a standard of care for most low- or intermediate-risk prostate cancer patients. [The study also] shows SBRT can result in lower toxicity than standard treatment,” said lead author Rodney J. Ellis, MD, in correspondence with Urology Times®. “This trial adds to the PACE-B phase 3 trial that shows SBRT is non-inferior to standard IMRT.”

However, he also added, “An increase in PSA failure was noted prior to the planned 5-year end point for reporting. Thus, further follow-up and more studies are [needed] to determine if the dose to the whole gland needs to match PACE-B, or if advanced imaging may be used for a focal boost to be given to higher risk regions to assure equivalent outcomes while maintaining lower toxicity.”

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