Using fewer—but higher—doses of radiation to treat men with prostate cancer who had their prostates removed does not increase long-term side effects or lower their quality of life compared to conventional radiation treatment, a new, multi-institutional clinical trial shows. Findings from the phase III NRG Oncology GU003 trial were presented October 25 at the American Society for Radiation Oncology (ASTRO) Annual Meeting in Chicago.
"Delivering post-prostatectomy radiation therapy with fewer treatments is a win when it comes to reducing the burden of prostate cancer on society. For patients, fewer treatments equate to a shorter time commitment that increases access to a potentially curative treatment, reduces expenses related to travel and co-pays, and involves less time away from work and other responsibilities," said lead author Mark K. Buyyounouski, MD, a professor of radiation oncology and director of genitourinary cancers in the Department of Radiation Oncology at Stanford University’s School of Medicine in Stanford, California. "Additionally, providers can improve their facility’s productivity and increase the overall capacity for all patients. And for payors, fewer treatments mean fewer expenses.”
Prostate cancer is the second most common cancer in men. About 1 in 8 men in the U.S. will be diagnosed with the disease during their lifetime. Prostate cancer is highly treatable; 98% of patients live 10 years or more after treatment. Given the high survival rate, quality of life and long-term side effects from treatment are important considerations. "Preserving quality of life was a major priority when testing the shorter treatment course. It is important for patients to know that accepting a more convenient treatment doesn’t mean they have to compromise on quality of life," said Dr. Buyyounouski.
The use of shorter radiation therapy courses is already a well-accepted practice standard for men who choose not to have prostatectomy surgery, based on the results of multiple randomized trials. This trial is the first to test whether an accelerated approach is also a viable option for men after undergoing prostatectomy. For men who choose to have initial surgery, radiation is indicated afterwards if rising prostate specific-antigen (PSA) levels indicate the cancer has returned.
Dr. Buyyounouski and his team compared patient-reported genitourinary (GU) and gastrointestinal (GI) side effects following hypofractionated, post-operative radiation therapy delivered over five weeks to those experienced by men treated with conventionally fractionated radiation delivered over seven weeks. Side effects were measured using the Expanded Prostate Cancer Index Composite (EPIC); patients reported how GU and GI symptoms affected their quality of life immediately after completing radiation therapy and again at six, 12 and 24 months after treatment. Researchers then compared changes in patients' EPIC scores over the study period.
Immediately after treatment, the average change to patients' GU scores did not differ between treatment groups, but patients treated with shortened radiation initially reported worse GI symptoms. By six months, however, there were no differences in GU or GI impacts reported by the two groups. Patients' quality of life as indicated by changes in GU or GI scores remained comparable until the end of the two-year follow-up period.
The trial was unique in its use of patient-reported outcomes as the primary endpoint. As Dr. Buyyounouski explained, "the ideal way of measuring quality of life is by asking the patient themselves."
Dr. Buyyounouski said the research team was not surprised that participants reported some discomfort initially following treatment. He said, “Short-term side effects of radiation therapy are well-established, and patients understand that. What patients ultimately want to know is whether the side effects will go away, and that's what we saw in our study. There was some increase in bowel side effects, more so with the shorter treatment, but, after six months, these side effects resolved—and patients didn’t report any further or additional bowel or bladder side effects one and two years later."
Dr. Buyyounouski said he believes side effects were minimal because of the way the study was designed and the high skill level of the radiation oncologists involved in the study. "Like many of the studies before ours, we designed this study to be scalable and deliverable by radiation oncologists everywhere.” The study was conducted at more than 90 centers in North America. “Knowing the results of the study, it may also be possible to make an adjustment to the treatment technique that lessens the bowel symptoms reported by patients at the end of treatment. Radiation oncology is process-oriented, and, consequently, feedback is commonly used to refine and improve our treatments,” said Dr Buyyounouski.
Senior author Howard M. Sandler, MD, FASTRO, said the findings can inform discussions between patients and their providers on the best course of treatment. "I think this is another option for radiation oncologists to be able to provide an effective treatment to patients who might otherwise not have access to treatment, due to restraints around needing seven weeks to complete their therapy," said Dr. Sandler, chair and professor of radiation oncology at Cedars-Sinai Medical Center in Los Angeles.
"The hypofractionated approach lowers the bar for getting someone a treatment they can benefit from following prostatectomy," he said. "It is yet another option for patients."
Abstract 3, American Society for Radiation Oncology (ASTRO) 2021 Annual Meeting
Primary Endpoint Analysis of a Randomized Phase III Trial of Hypofractionated vs. Conventional Post-Prostatectomy Radiotherapy: NRG Oncology GU003
Purpose/Objective(s): To determine if hypofractionated post-operative prostate bed radiotherapy (HYPORT) does not increase patient-reported genitourinary (GU) or gastrointestinal (GI) toxicity over conventionally fractionated post-operative radiotherapy (COPORT).
Materials/Methods: Eligibility criteria were: 1) an undetectable PSA (< 0.1 ng/mL) with either margin negative pT3pN0/X or margin positive pT2pN0/X adenocarcinoma of the prostate or 2) a detectable PSA (≥ 0.1 ng/mL) and pT2/3pN0/X disease. HYPORT was 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT was 66.6 Gy in 37 fractions of 1.8 Gy. Lymph node RT was not allowed. Androgen deprivation therapy (ADT) ≤ 6 months was allowed. Patients were stratified according to baseline Expanded Prostate cancer Index Composite (EPIC) score (four tiers based on GU and GI scores) and ADT use (yes vs. no) then randomized 1:1. The co-primary endpoints were based on change scores (24-month score minus baseline score) from the GU and GI domains of the EPIC. The hypothesis is that the mean change scores at 24 months are no worse for HYPORT than it is for COPORT. The non-inferiority margins were based on 0.5*standard error from NRG Oncology/RTOG 0415: -5 for GU and -6 for GI. Two hundred eighty-two patients provide ≥ 90% power with a one-sided alpha = 0.025 for each domain while inflating for non-compliance/loss to follow-up.
Results: Between July 2017 and July 2018, 298 patients were screened and 296 were randomized: 144 to HYPORT and 152 to COPORT. Compliance with the EPIC was 100% at baseline, 83% at the end of RT, 77% at 6 months, 78% at 12 months, and 73% at 24 months. At the end of RT, the HYPORT and COPORT mean GU change scores were neither clinically significant nor significantly different and remained so at 6 and 12 months. The mean GI change scores for HYPORT and COPORT were both clinically significant and significantly different at the end of RT (HYPORT mean GI = -15.0 vs COPORT mean GI = -6.8 p ≤ 0.01). However, both the HYPORT and COPORT mean GI change scores clinically and statistically significant differences were resolved at 6 and 12 months. The 24-month mean GU and GI change scores for HYPORT and COPORT remained neither clinically nor
statistically significant (HYPORT mean GU = -5.2 vs COPORT mean GU = -3.0, p = 0.81; HYPORT mean GI = -2.2 vs COPORT mean GI = -1.5, p = 0.12). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT versus COPORT for biochemical failure defined as a PSA ≥ 0.4 ng/mL followed by a value higher than the first by any amount (2-yr actuarial, 12% vs 8%, p = 0.29) or local failure (2-yr actuarial, 0.7% vs 0.8%, p = 0.35).
Conclusion: HYPORT is non-inferior to COPORT in terms of late patient-reported GU or GI toxicity. More follow-up is needed to appropriately assess disease control endpoints. In some clinic scenarios, HYPORT may be considered an acceptable practice standard.
Author Disclosure: M.K. Buyyounouski: Research Grant; Varian. Honoraria; Wolters Kluwer, Elsevier. S. Pugh: None. R.C. Chen: Consultant; Accuray Inc, Abbvie. Advisory Board; Myovant. M. Mann: None. R. Kudchadker: None. A.A. Konski: Stock; General Electric Stock. ; American College of Radiology. Leadership; American Radium Society. O.Y. Mian: None. J.M. Michalski: Independent Contractor; Sheila Michalski and Associates. Research Grant; NCI. Honoraria; Genome Dx, Inc. Advisory Board; Boston Scientific, Inc, Merck inc. oversight of clinical trial proposals related to GU cancers.; NCI. Board member; National Children's Cancer Society. ; NRG Oncology. E. Vigneault: Independent Contractor; CHUQ L'Hotel Dieu de Québec. Research Grant; Philips. Honoraria; Abbvie. Advisory Board; Abbvie, Ferring, Tersera, Sanofi, Bayer. R.K. Valicenti: None. M. Barkati: None. C.A. Lawton: None. L. Potters: None. D.C. Monitto: Consultant; Decipher Biosciences. J. Kittel: Employee; Advocate Aurora Health. Partner; Radiation Oncology Associates. T.M. Schroeder: Research Grant; The University of New Mexico Cancer Center. Part of a team of fiduciaries who steer the organization by adopting sound, ethical, legal governance and financial management policies, advance the cancer research mission.; New Mexico Cancer Care Alliance. R. Hannan: Research Grant; Dendreon Corporation, Prometheus Laboratories. C.E. Duncan: None. J. Rodgers: None. H.M. Sandler: Consultant; Janssen, Caribou Publishing. Stock; Advanced Medical Isotope Corporation.Back To Top
Shorter RT Course Offers Similar Long-Term Side Effects Following Prostate Removal Surgery. Appl Rad Oncol.