A primary endpoint analysis of the NRG Oncology phase III NRG-GU003 clinical trial, which compared hypofractionated postoperative prostate bed radiotherapy (HYPORT) to conventional postprostatectomy radiotherapy (COPORT) for men with prostate cancer, determined that treatment with HYPORT yielded no increase in patient-reported genitourinary or gastrointestinal toxicity for trial participants. However, the trial failed to reject the null hypothesis that dose-escalated radiation therapy was not superior to conventional radiotherapy. These results were presented by Buyyounouski et al during the Plenary Session of the 2021 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 3).
“Radiotherapy is a curative treatment alternative to surgery for men with prostate cancer, and short courses are used all the time. Radiotherapy may also be indicated after surgery, but a short course has not been tested. NRG-GU003 is the first trial comparing a short course to a well-established practice standard of 7 weeks. After 2 years, patients reported no increase in urinary or bowel side effects with the shorter course, and its effectiveness was comparable,” stated lead study author Mark Buyyounouski, MD, of Stanford University.
More on NRG-GU003
Researchers working on NRG-GU003 accrued and randomly assigned 296 men: 144 men were included in the HYPORT treatment arm, and 152 men were included in the COPORT treatment arm. The HYPORT dosage was 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy vs the COPORT dosage of 66.6 Gy in 37 fractions of 1.8 Gy.
Researchers used Expanded Prostate Cancer Index Composite (EPIC) scoring to determine inferiority or noninferiority at 2-years following treatment. Secondary endpoints for the trial included comparing patient-reported genitourinary and gastrointestinal symptoms at 6, 12, 24, and 60 months from the end of treatment; time to disease progression, freedom from biochemical failure, local failure, regional failure, salvage therapy, distant metastasis, and death from prostate cancer; overall survival rates; and adverse events between treatment arms.
“Radiotherapy is a highly effective treatment after surgery if an elevated prostate-specific antigen (PSA) indicates recurrence of disease. However, a small minority of men receive treatment. We hope these results will better allow patients access to treatment and ultimately reduce the burden of prostate cancer because a safe and shorter treatment is available,” added Dr. Buyyounouski.
Primary Endpoint Analysis Results
Compliance with EPIC was 100% at baseline, 83% at the end of radiotherapy, 77% at 6 months, 78% at 12 months, and 73% at 24 months. At the end of radiotherapy, HYPORT and COPORT mean genitourinary change scores were neither clinically significant nor statistically significantly different and remained this way at 6 and 12 months following treatment. HYPORT and COPORT mean gastrointestinal change scores were both clinically significant and statistically significantly different at the end of radiotherapy (HYPORT mean GI = 15.0 vs COPORT mean GI = 6.8, P ≤ .01); however, these differences were resolved by 6 and 12 months following treatment.
The 24-month mean genitourinary and gastrointestinal change scores for HYPORT and COPORT remained neither clinically nor statistically significant (HYPORT mean GU = –5.2 vs COPORT mean GU = –3.0, P = .81; HYPORT mean GI = –2.2 vs COPORT mean GI = –1.5, P = .12). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure defined as a PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount (2-year rate: 12% vs 8%, P = .29) or local failure (2-year rate = 0.7% vs 0.8%, P = .35).
The study authors concluded, “HYPORT is noninferior to COPORT in terms of late patient-reported genitourinary or gastrointestinal toxicity. More follow-up is needed to appropriately assess disease control endpoints. In some clinic scenarios, HYPORT may be considered an acceptable practice standard.”
Disclosure: This project was supported the National Cancer Institute (NCI), and it was led by NRG Oncology with participation of other NCI-funded network groups. For full disclosures of the study authors, visit redjournal.org.
