Post-prostatectomy radiation therapy with fewer treatments does not increase long-term side effects or lower quality of life when compared to conventional radiation treatment for patients after undergoing prostate removal, according to research from a large Phase III clinical trial presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 3).
Mark K. Buyyounouski, MD, Professor of Radiation Oncology and Director of Genitourinary Cancers in the Department of Radiation Oncology at Stanford University's School of Medicine, presented findings from the multi-institutional Phase III NRG Oncology GU003 trial-the first trial of its kind to test whether an accelerated approach is a viable option for men after undergoing prostatectomy.
"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," Buyyounouski noted.
He and his colleagues compared patient-reported genitourinary (GU) and gastrointestinal (GI) side effects following hypofractionated, postoperative radiation therapy, delivered over 5 weeks, to those experienced by men treated with conventionally fractionated radiation delivered over 7 weeks.
The trial was unique in its use of patient-reported outcomes as the primary endpoint. As Buyyounouski explained, "the ideal way of measuring quality of life is by asking the patient themselves."
Study Details
A total of 298 patients were screened and 296 were randomized, with 144 patients receiving hypofractionated therapy and 152 treated with conventional post-prostatectomy radiotherapy. The researchers then measured side effects 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 6, 12, and 24 months after treatment. The team then compared changes in patients' EPIC scores over the study period.
The average change to patients' GU scores did not differ between treatment groups immediately after treatment, but subjects who received a shortened radiation initially reported worse GI symptoms, Buyyounouski said. However, after 6 months, there were no differences in GU or GI problems between the two groups. Moreover, quality of life, as indicated by changes in GU or GI scores, remained comparable until the end of the 2-year follow-up period.
Post-prostatectomy radiation therapy with fewer treatments for such patients has additional benefits, he noted. "Providers can improve their facility's productivity and increase the overall capacity for all patients and, for payors, fewer treatments mean fewer expenses.
"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," Buyyounouski explained.
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. For men who choose to have initial surgery, radiation is indicated afterwards if rising prostate specific-antigen (PSA) levels indicate the cancer has returned.
In the trial, 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.
Buyyounouski said the research team was not surprised that participants reported some discomfort initially following treatment.
"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 6 months, these side effects resolved-and patients didn't report any further or additional bowel or bladder side effects 1 and 2 years later."
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, 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," Buyyounouski stated.
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 7 weeks to complete their therapy," said 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. It is yet another option for patients."
Although more follow-up is needed to appropriately assess disease control endpoints, in some clinic scenarios, HYPORT may be considered an acceptable practice standard, the researchers concluded.
Kurt Samson is a contributing writer.