There has been an ongoing debate about which type of radiation therapy is preferable in the treatment of localized prostate cancer: hypofractionation (larger fractions given over 4–5 weeks) or conventional radiotherapy (given over 8–9 weeks). A new study presented at the 2016 ASCO Annual Meeting may help to resolve that debate.1
The large, randomized trial found that hypofractionation was not inferior to conventional radiation therapy in terms of efficacy or safety in men with localized intermediate-risk prostate cancer. This is the third large, randomized, contemporary study to demonstrate that both techniques have equivalent efficacy and safety.
Taking into consideration patient convenience and cost, shorter radiation therapy should be considered a new standard of care for prostate cancer.— Charles Catton, MD
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“Shorter radiation therapy with hypofractionation is noninferior to conventional radiotherapy for disease control, at a median follow-up of 6 years. Both acute and late grade 3 toxicities were not increased in the hypofractionated arm. Survival is similar in both arms and quality of life is similar. Taking into consideration patient convenience and cost, shorter radiation therapy should be considered a new standard of care for prostate cancer,” stated presenting author Charles Catton, MD, of the Department of Radiation Oncology, Princess Margaret Cancer Center, Toronto, Ontario, Canada, speaking on behalf of the Ontario Clinical Oncology Group.
Study Details
The randomized, controlled trial enrolled 1,206 men with intermediate-risk prostate cancer, as defined by the Canadian consensus guidelines: stage T1–2, Gleason score of 6, and prostate-specific antigen (PSA) 10–20 ng/mL; T2bc, Gleason score of 6, and PSA < 20 ng/mL; or T1–2, Gleason score of 7 and PSA < 20 ng/mL Participants were enrolled at 27 sites in Canada, Australia, and France between May 2006 and November 2011.
Patients were randomized to receive hypofractionated radiation therapy given at 60 Gy in 20 fractions 5 days a week over 4 weeks (shorter radiation therapy group, n = 608) or at 78 Gy in 39 fractions 5 days a week over 8 weeks (conventional group, n = 598). Participants were stratified by preradiation therapy, risk of seminal vesicle involvement, and treatment center. Androgen-deprivation therapy was permitted for a maximum of 90 days before entering the trial, but patients could not receive this therapy during or post radiation as part of primary therapy.
The primary outcome was a composite that included evidence of biochemical failure (ie, PSA > 2 ng/mL above nadir), or local/distant recurrence, or implementation of androgen-deprivation therapy or death from any cause. Median follow-up was 6 years (range, 4.5–10 years).
Baseline demographic and disease characteristics were similar in both arms. Median age was about 72 years, approximately 50% had a PSA value between 5 and 10 ng/mL, approximately 63% had a Gleason score of 3 + 4, and about 53% were clinical stage T1c.
Results and Toxicity
At a median follow-up of 6 years, 166 events were reported in the shorter radiation therapy arm vs 170 events in the conventional arm. The most common first event was biochemical failure: 97 with shorter radiation therapy and 100 with conventional therapy.
“Local recurrence, distant recurrence, and initiating androgen-deprivation therapy as a first event were infrequent in both arms,” Dr. Catton told the audience.
At 5 years, 79% of both arms were alive and free from failure, and the survival curves did not diverge after 5 years. The number of deaths reported was 76 with shorter radiation therapy and 78 with conventional therapy.
Hypofractionated Therapy vs Conventional Therapy
- For the past decade, the merits of hypofractionated radiation therapy vs conventional radiation therapy have been debated for the treatment of prostate cancer.
- Now three large randomized trials have established noninferiority of hypofractionation vs conventional radiotherapy for disease control and safety.
- Hypofractionation is more convenient and cost-effective for patients and appears ready to become a new standard of care.
The toxicity profiles of the two arms were similar for both acute and late side effects. No difference in grade 3 or higher genitourinary or gastrointestinal acute toxicity was seen during the first 14 weeks post randomization. From 6 months post therapy and beyond, no difference between treatment arms was observed for late grade 3 or higher genitourinary or gastrointestinal toxicity, but a trend was observed toward fewer events in the arm receiving shorter radiation therapy.
No significant differences were observed between the two arms for grade 2 or greater acute or late genitourinary toxicity. For gastrointestinal toxicity significantly more acute events were reported with shorter radiation therapy (all grade 2): 16% vs 10%, respectively. However, significantly fewer grade 2 or greater late gastrointestinal events were observed in the short treatment arm.
Quality of life was assessed at baseline in 87% of patients, at 24 months in 75%, and at 48 months in 70%. No significant difference in quality of life was found between the two treatment arms at any time point assessed. “There was a significant functional decline over time for the entire cohort, as one would expect,” Dr. Catton concluded. ■
Disclosure: Dr. Catton has received honoraria from AbbVie, Bayer, Ferring, Janssen, and Sanofi and has been a consultant for AbbVie.
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