A prospective multicenter trial in Canada has shown positive results with hypofractionated image-guided radiotherapy (H-IGRT) using widely available standard linear accelerators.
Other hypofractionated protocols have used stereotactic body radiotherapy machines that may not be widely available.
"For the patient who lives a distance from the cancer center, this kind of schedule is a real boon," said lead author Andrew Loblaw, MD, MSc, a radiation oncologist at Sunnybrook Health Sciences Centre, Toronto.
The typical course of external beam radiotherapy for localized prostate cancer takes between 39 and 49 visits, Dr. Loblaw noted. Fractionating the total radiation dose can reduce the number of visits from between 20 and 25 (mild fractionation) to as few as five visits (extreme hypofractionation).
Stereotactic irradiation has become a popular option for H-IGRT because skilled surgeons can deliver highly precise radiation doses using multiple beams with a sharp dose gradient that minimizes radiation outside the target tumor. But stereotactic procedures are not widely available outside major medical centers, usually located in major metropolitan areas. Patients who live some distance from these centers are at a treatment disadvantage due to the time and cost of repeated travel for treatment.
Researchers in Toronto and Winnipeg, Manitoba designed a five-course hypofractionated regimen to deliver a 35-Gy dose in five weekly fractions over 29 days using intensity-modulated radiotherapy on standard linear accelerators. The physicians implanted gold seed fiducials for daily image guidance with a 4-mm margin around the target prostate.
A prospective phase I/II study was launched in 2006. All patients had stage T1-2b prostate cancers, Gleason scores of 6 or lower, and PSA of 10.0 ng/mL or lower at the beginning of treatment. None of the patients received hormone therapy.
Acute toxicities were assessed using Cancer Terminology for Adverse Events version 3 and late toxicities using Radiation Therapy Oncology Group measures. Quality of life was assessed using the Expanded Prostate Index Composite score. Biochemical failure was defined as the nadir PSA level plus 2.0 ng/mL. Results were also assessed using the positive biopsy rate at 3 years.
By September 2011, 83 patients had completed treatment with a median follow-up of 42 months. The median patient age was 66.8 years, and all of the patients had Gleason scores of 6. The median pre-treatment PSA was 5.3 and Eastern Cooperative Oncology Group status was 0.
Few significant side effects
Significant side effects were extremely low, Dr. Loblaw said. Just one patient was catheterized, and there were no grade 3 or higher acute gastrointestinal toxicities.
"We biopsied nearly all of the patients who went through the program, a 97% biopsy negative rate," Dr. Loblaw said. "We did not have any patients who required a second-line treatment for prostate cancer."
There was just one biochemical failure in the group. That patient had a history of prostatitis and also had a negative biopsy. Quality of life scores were generally good after 3 years of follow-up. Bowel scores and hormonal scores were unchanged at 96% and 95%. Urinary scores declined from 95% to 93% and sexual scores from 65% to 51%.
This technique, using standard linear accelerators to delivery an extreme hypofractionated radiotherapy schedule, is feasible, well tolerated, and shows excellent pathologic and biochemical control, Dr. Loblaw said. The authors recommended a randomized prospective study to compare this extreme schedule to standard fractionation for localized prostate cancer.