BOSTON – The combination of radiation and hormonal therapy for locally advanced prostate cancer results in significantly better overall and disease-specific survival outcomes than hormonal therapy alone, according to the final results of a long-term study.
At a median follow-up of 8 years, the addition of radiation therapy (RT) to androgen deprivation therapy (ADT) was associated with significantly better overall survival (hazard ratio 0.70, P = .0003) and disease-specific survival (HR 0.46, P less than .0001) compared with ADT alone, Dr. Padraig Warde reported at the annual meeting of the American Society for Radiation Oncology.
Dr. Padraig Warde
"We believe our study results support the recommendation that for patients with locally advanced prostate cancer who are suitable for a curative treatment approach, combined-modality treatment should be considered the standard of care," said Dr. Warde, a professor of radiation oncology at Princess Margaret Hospital and the University of Toronto.
"Clearly the optimal duration of androgen deprivation therapy needs to be defined. However, the benefit of radiation therapy may be greater in the modern era with dose escalation," he added.
The findings of the study are consistent with those of a similarly designed study, the randomized Scandinavian Prostate Cancer Group (SPCG) 7 study, noted Dr. Jason A. Efstathiou, a radiation oncologist at Massachusetts General Hospital in Boston, the invited discussant.
"External-beam radiation and hormonal therapy should now be the gold standard against which interventions for high-risk and locally advanced prostate cancer are compared, including radical prostatectomy," he said.
The Final Word
Dr. Warde presented final data from the NCIC Clinical Trials Group (NCIC CTG) PR.3/Medical Research Council (MRC) UK PR07 trial. Results of an interim analysis of the trial published last year showed a similar benefit for adding RT to ADT at 7 years.
From 1995 through 2005, investigators enrolled a total of 1,205 patients, most of whom (1,057) had locally advanced (T3, T4, N0/NX stage) prostate cancer. A smaller number had organ-confined disease (T2, N0/NX) with either a prostate-specific antigen (PSA) level greater than 40 mcg/L or a PSA greater than 20 mcg/L and a Gleason score of 8 or higher.
The patients were randomly assigned to receive lifelong therapy with either a bilateral orchiectomy or a luteinizing hormone releasing hormone agonist with or without 65- to 69-Gy RT to the prostate (with or without a dose to the seminal vesicles), and with or without 45 Gy to pelvic lymph nodes. In all, 602 patients were assigned to ADT only, and 603 to both ADT and RT.
Dr. Jason A. Efstathiou
At a median follow-up of 8 years, 260 patients on ADT alone and 205 on the combined therapy had died. Of these patients, 199 (43%) died from disease and/or treatment; 134 had been treated with ADT alone, and 65 with ADT plus radiation.
The 10-year overall survival rates were 55% for the combined therapy, and 49% for RT alone.
Treatment Well Tolerated
Although the radiation group had a moderate worsening of bowel scores at 6 months, "consistent with clinical expectations," the men who received radiotherapy generally tolerated it well, Dr. Warde said.
By 24 months there were no significant between-group differences in bowel or rectum domain on the EORTC (European Organisation for Research and Treatment of Cancer) quality-of-life questionnaire. Results in the urinary function quality-of-life domain were similar, Dr. Warde said. He did not provide specifics.
An exploratory analysis within the radiation arm showed that there were no significant differences in either overall or disease-specific survival with the addition of pelvic radiation to prostate radiation; in this analysis the hazard ratio was adjusted for geographic region of treatment, PSA, Gleason score, nodal staging, and prior hormonal therapy.
The study was supported by grants from the U.S. National Cancer Institute, U.K. Medical Research Council, and U.K. National Cancer Research Network. Dr. Warde and Dr. Efstathiou reported having no conflicts of interest.