The mainstay of care for men with locally advanced prostate cancer has been hormonal therapy alone, but data from a recent randomized, controlled trial comparing hormonal therapy alone with radiation added to hormonal therapy should challenge this dogma.
Chicago-The mainstay of care for men with locally advanced prostate cancer has been hormonal therapy alone, but data from a recent randomized, controlled trial comparing hormonal therapy alone with radiation added to hormonal therapy should challenge this dogma.
"Radiotherapy could easily be part of the package discussed with the patient," said Padraig Warde, MBChB, deputy head of the radiation medicine program at the University of Toronto's Princess Margaret Hospital, and lead investigator of the study.
As presented at the American Society of Clinical Oncology annual meeting in Chicago, the study included 1,205 men with high-risk prostate cancer, defined as stage T3-T4 or T2 with a PSA level greater than 40.0 µg/L or T2 or a PSA level greater than 20.0 µg/L with a Gleason score of 8 or greater. The men were randomized to lifelong androgen deprivation therapy (orchiectomy or treatment with luteinizing hormone-releasing hormone analogs) or ADT together with radiation (45 Gy delivered in 25 fractions over 5 weeks to the pelvis plus 20 Gy to 24 Gy delivered in 10 to 12 fractions over 2.0 to 2.5 weeks to the prostate).
There were 175 deaths in the ADT-alone arm versus 145 deaths in the group that also received radiation therapy, a 23% reduction in the risk of death with combined treatment over the course of the study (p=.0331). At 7 years, 74% of the combination arm was still alive compared to 66% of the hormone therapy-alone arm.
Prostate cancer-specific death was also less likely in the combination arm. At 7 years, 10% in the combined treatment group had a prostate cancer-specific death compared to 21% in the hormone monotherapy arm, a hazard ratio of 0.57 in favor of combination therapy (p=.001).
Patients randomized to ADT plus radiation lived an average of 6 months longer than those who received ADT alone. The projected 10-year incidence of prostate cancer-specific death was 15% for men receiving both therapies versus 23% of men receiving only hormonal therapy.
The incidence of grade 3 toxicity was similar in both treatment arms, Dr. Warde said. In terms of grade 2 toxicity, an excess of rectal bleeding was observed in the men who received radiation therapy.
"It's possible that we have underestimated the value of radiation therapy," said Dr. Warde. "In the last 10 years, major improvements in technology have enabled radiation oncologists to deliver higher doses of radiation as compared to those used in this trial."
The radiation regimen was based on a protocol from the mid-1990s, he noted. The results of this study, therefore, may not fully capture the efficacy of radiation as it is applied today.
"The message from this randomized trial is that it is clear that radiation is an indispensable element in the treatment of patients with high-risk prostate cancer," said Jennifer Obel, MD, attending physician at Northshore University Health System, Evanston, IL, who moderated the news conference during which this study's findings were presented.