Men with intermediate-risk prostate cancer can safely undergo radiation administered in larger fractions for 4 weeks (moderate hypofractionation) as an alternative to conventional radiation administered for 8 weeks, according to the results of a randomized, controlled, noninferiority clinical trial presented at ASCO 2016.
“A shorter, hypofractionated schedule of radiation is noninferior to conventional radiation for disease control in men with intermediate-risk prostate cancer at a median follow-up of 6 years,” said lead investigator Charles N. Catton, MD, FRCPC, Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, who presented the study results.
“The hypofractionated schedule used in this trial did not increase acute or late toxicity compared with conventional radiation. Survival is similar and quality of life is similar with both schedules. Considering patient convenience and cost, shorter radiation should be considered a new standard of care for intermediate-risk prostate cancer,” he stated.
The discussion about moderate hypofractionated versus conventional radiation has often been contentious, with some naysayers and others strongly in favor of it. The study presented by Dr Catton is the third large randomized clinical trial to show noninferiority of moderate hypofractionation to conventional radiation, and the time has come to make moderate hypofractionation the standard of care, agreed formal discussant of this study, W. Robert Lee, MD, MS, MEd, Professor of Radiation Oncology, Duke University School of Medicine, Durham, NC.
“Three noninferiority trials in more than 5000 men have shown consistent results. The efficacy of moderate hypofractionation is noninferior to conventional radiation and toxicity is not greater. Practitioners interested in better use of resources and patients’ convenience can confidently recommend [moderate] hypofractionation. In my view, it has been tested and proved,” Dr Lee said.
The randomized, controlled clinical trial enrolled 1206 men from 27 sites in Canada, Australia, and France between May 2006 and November 2011. The patients were randomized to receive moderate hypofractionation administered at 60 Gy in 20 fractions 5 days weekly for 4 weeks versus conventional radiation administered at 78 Gy in 39 fractions 5 days weekly for 8 weeks. All the patients had intermediate-risk prostate cancer, defined as stage T1-2 disease, Gleason score 6, and prostate-specific antigen (PSA) levels 10 ng/mL to 20 ng/mL; or stage T2b-c disease, Gleason score 6, and PSA levels <20 ng/mL; or stage T1-2 disease, Gleason score 7, and PSA levels <20 ng/mL.
The patients were allowed to receive androgen-deprivation therapy for up to 90 days before randomization, but not as primary therapy after radiation.
No difference was observed between the 2 treatment arms in baseline demographic and disease characteristics. Approximately 50% of the patients had PSA levels 5 ng/mL to 10 ng/mL, 63% had Gleason score 3 + 4, and 53% had clinical stage T1c disease.
At a median follow-up of 6 years, 166 biochemical or clinical failure events occurred in the moderate hypofractionation arm versus 170 failure events in the conventional radiation arm. PSA failure was the most common first biochemical or clinical failure event in both treatment arms, with 97 events in the moderate hypofractionation arm and 100 events in the conventional radiation arm, followed by death from any cause (61 deaths vs 57 deaths, respectively).
At 5 years, 79% of the patients in each treatment arm were free from local failure. After 5 years, the survival curves remained the same.
“We met the criteria for noninferiority of hypofractionated radiation,” Dr Catton said.
No significant difference in overall survival was observed between the 2 treatment arms. Furthermore, no difference was observed between the 2 treatment arms for acute grade ≥3 gastrointestinal (GI) or genitourinary toxicity in the first 14 weeks after treatment randomization. No difference in late (≥6 months) grade ≥3 GI or genitourinary toxicity was observed, although the trend favored moderate hypofractionation.
No differences were reported for grade ≥2 toxicities, except for acute grade ≥2 GI events observed more frequently with moderate hypofractionation compared with conventional radiation—16% versus 10%, respectively. Quality of life was similar in both treatment arms through 48 months.
After the presentation, Dr Lee explained that hypofractionation is an imprecise term. Moderate hypofractionation refers to radiation schedules delivered for 4 to 5 weeks and extreme hypofractionation is delivered for 1 to 2 weeks. Although moderate hypofractionation is a tested therapy in intermediate-risk prostate cancer, ongoing randomized clinical trials are comparing extreme hypofractionation with moderate hypofractionation and conventional radiotherapy.
“Ask the person what he/she means by hypofractionation. Moderate hypofractionation is a tested and proven [treatment]. Extreme hypofractionation is being tested and has yet to be proved,” Dr Lee told attendees.