SAN ANTONIO – Patients who have locally advanced prostate cancer should receive androgen deprivation therapy (ADT) for at least 2 years after radiotherapy according to the long-term findings of the Radiation Therapy Oncology Group (RTOG) 9202 phase III trial.
“Compared to short-term androgen deprivation therapy, long-term androgen-deprivation therapy improves disease-free survival (DFS), local progression, distant metastases, bNED- and disease-specific survival,” reported Dr. Colleen Lawton at the annual scientific meeting of the American Society for Radiation Oncology.
Courtesy ASTRO/Adam Donohue
Dr. Colleen Lawton
At a median follow-up of 20 years, DFS was 16% and 10% in men given long- and short-term ADT, respectively, with a hazard ratio of 0.72 (95% confidence interval, 0.64-0.80; P less than .0001).
Local progression occurred in 13% and 23% (HR, 0.53; 95% CI, 0.41–0.67; P less than .0001), distant metastases in 17% and 26% (HR, 0.61; 95% CI, 0.49-0.76; P less than .001), and disease-specific survival was 84% and 78% (HR, 0.67; 95% CI, 0.53-0.84; P = .0007), respectively.
The cumulative incidence of biochemical failure was also lower in the long-term versus short-term ADT group (45% vs. 61%, HR, 0.57; 95% CI, 0.50-0.66; P less than .0001). Dr. Lawton of the Medical College of Wisconsin in Milwaukee observed that the benefits of long- over short-term ADT were even greater in higher-risk patients with a Gleason score of 8-10. The respective HRs for DFS, distant metastases, disease-specific survival, and biochemical failure were 0.67, 0.52, 0.55, and 0.51, and all were highly significant.
The RTOG 9202 findings add further to the evidence showing that men undergoing radiotherapy for localized disease should receive ADT for much longer after radiotherapy than may be currently practiced. Whether 2 years is the right duration or not is to be determined, perhaps a shorter course could be as effective, Dr. Lawton said in an interview.
Three other major trials have looked at this question, with results of the EORTC 22961 study showing that 3 years of ADT is better than 6 months (N Engl J Med. 2009;360:2516–27), the PCS IV trial showing that 18 months and 3 years of ADT are as effective, and the DART01/05 GICOR trial finding that just over 2 years of ADT betters 4 months of ADT (Lancet Oncol. 2015;16:320-7).
The RTOG 9202 trial (J Clin Oncol. 2008;26:2497-504) recruited more than 1,500 men with stage T2c-T4 prostate cancer between June 1992 and April 1995. All men were treated with a combination of goserelin (3.6 mg by monthly subcutaneous injection) and flutamide (250 mg three times a day orally) for 2 months before and 2 months during radiotherapy. Conventional radiotherapy of the pelvis was given at a dose of 44-46 Gy followed by a ‘cone down’ to the prostate with 65-75 Gy being given. Men were then randomized to either no further ADT or to continue ADT for 2 years. Men who continued ADT were treated with goserelin only.
Overall survival did not reach statistical significance, with approximately a 3% absolute and 10% reduction in risk, comparing long- with short-term ADT.
“The good news is that both in the short-term and long-term hormone therapy arms there was no difference in other-cause death or things that would really be traumatic for the patient,” Dr. Lawton said in an interview. “That said, there certainly are side effects that need to be mitigated with exercise and diet, because weight gain, muscle mass loss, bone loss, are realities of longer term therapy,” she added.
There was no difference in short- or late toxicities occurring 90 days after the start of radiotherapy generally, but patients in the long-term ADT arm did experience a higher rate of grade 3 or higher gastrointestinal events (3.0% vs. 1.5%, respectively, P = .04).
“I think the most important thing that patients want to know is ‘Doctor, am I going to die of my prostate cancer?,’ and we can tell them honestly, with very good science, that if they get the longer-term hormone therapy, we can really decrease that risk,” Dr. Lawton said.
The RTOG 9202 study was supported by grants from the National Cancer Institute. Dr. Lawton had nothing to disclose.