Prof. Kouhen Fadila
It is currently acknowledged that hypofractionated radiotherapy, an increasingly favored approach in prostate cancer treatment, delivers higher radiation doses over fewer sessions compared with conventional fractionation schedules. This approach is supported by the recognition that prostate cancer has a low alpha/beta ratio, which enhances its responsiveness to such treatment strategies.
Large randomized studies have validated the safety and effectiveness of moderate hypofractionated radiotherapy for patients diagnosed with low-, intermediate-, or high-risk prostate cancer.
In the NRG-GU003 phase III randomized trial, reported in JAMA Oncology by Mark K. Buyyounouski, MD, MS, and colleagues, it was concluded that hypofractionated postprostatectomy radiotherapy (HYPORT) is comparable to conventionally fractionated postprostatectomy radiotherapy (COPORT) in terms of patient-reported late toxic effects, establishing it as an acceptable new standard practice in patients primarily treated with prostatectomy.
Mark K. Buyyounouski, MD, MS
Study Details
In this clinical trial, conducted between June 2017 and July 2018, 296 patients meeting specific criteria were randomly assigned from 93 medical sites across the United States and Canada. The trial aimed to determine whether HYPORT could be deemed noninferior to COPORT concerning patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at the 2-year follow-up.
Secondary objectives included comparing freedom from biochemical failure, time to disease progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer–specific survival, overall survival, and adverse events between the two treatment arms.
Patients eligible for inclusion in the study had either a detectable prostate-specific antigen level (PSA; ≥ 0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA level (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin. They were randomly assigned to receive either 62.5 Gy administered in 25 fractions (HYPORT) or 66.6 Gy administered in 37 fractions (COPORT).
Key Findings
With a median patient age of 65 (age range = 44–81 years), 144 patients received HYPORT and 152 received COPORT. At the end of radiotherapy, the mean GU change scores in both the HYPORT and COPORT groups were not clinically significant and did not show statistical differences, a pattern that persisted at 6 and 12 months after radiotherapy. However, the mean GI change scores for both groups were clinically significant and statistically different at the end of radiotherapy (HYPORT: –15.52 [18.43], COPORT: –7.06 [12.78], P < .001). Nonetheless, these differences in GI change scores were no longer clinically or statistically significant at 6 and 12 months.
When the investigators assessed outcomes at 24 months, the differences in mean GU and GI change scores for HYPORT were noninferior to those for COPORT, rejecting the null hypothesis of inferiority (mean GU score: HYPORT: –5.01 [15.10], COPORT: –4.07 [14.67], P = .005; mean GI score: HYPORT: –4.17 [10.97], COPORT: –1.41 [8.32], P = .02). With a median follow-up of 2.1 years for censored patients, there was no significant difference between HYPORT and COPORT in terms of biochemical failure, defined as a PSA level of 0.4 ng/mL or higher and rising (2-year rate: HYPORT 12% vs COPORT 8%, P = .28).
The investigators concluded: “HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy.”
Disclosure: This study was supported by 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 jamanetwork.com.
