ORLANDO, Fla.—Physicians treating men with high-risk prostate cancer can safely reduce the duration of androgen blockade given in combination with pelvic radiation from 36 months to 18 months without compromising outcomes, including survival, according to the phase III results of the PCS IV multicenter, randomized study presented at the 2013 Genitourinary Cancers Symposium.
The trial randomly assigned 630 men with node-negative prostate cancer to treatment with pelvic radiation plus 18 or 36 months of androgen blockade. Results indicated that after a median follow-up of 77 months, men assigned to 18 months treatment had an overall survival hazard ratio (HR) of 1.15 (95% CI, 0.83–1.59; P = .398).
Abdenour Nabid, MD, associate professor at Sherbrooke University Hospital Center in Sherbrooke, Quebec, who presented the results said that based on these results, it is possible that androgen blockade delivered during 18 months could represent a threshold effect where patients receive no further gain after that duration.
“The job is done,” Nabid said.
However, in his discussant presentation, Anthony V. D’Amico, MD, PhD, chief of genitourinary radiation oncology at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital, qualified the results of this study with a statistical examination.
“A noninferiority trial requires in advance that a clinical decision is made on the upper limit of the 95% CI that you will accept as not inferior to the standard of care,” D’Amico said. “If we accept 18 months as noninferior to 36, we are saying that we accept up to a 59% increased risk for death in men getting 18 months vs 36 months with the data presented at this time.”
D’Amico, who added that he is not a believer in long-term hormonal therapy, said that, at this time, physicians can say rigorously that “36 months is not superior to 18 months; however, 18 months may still be inferior to 36.”
To put the new data in perspective, D’Amico compared the results of the PCS IV study to the EORTC study by Bolla et al published in the New England Journal of Medicine in 2009 that compared 6 months of androgen suppression to 36 months of androgen suppression. In this study, the researchers selected 1.35 as the upper limit of the acceptable HR for short-term therapy vs long-term therapy. The result was an overall survival HR of 1.42 with an upper 95% confidence interval of 1.79, which rejected noninferiority of 6 months androgen suppression compared with standard of care.
However, in the study by Nabid and colleagues, given that the HR was 1.15, D’Amico said that he believes that “in time, this study is likely going to be able to ascertain whether 18 months can substitute for 36 if we use the same benchmark of 1.35 that the Bolla study of 36 vs 6 months used.”
According to D’Amico, it would require 275 deaths to assess noninferiority with a 1.35 upper limit. Currently, 147 patients have died on the PCS IV trial; 71 in the 36-month group and 76 in the 18-month group.
Five-year overall survival for patients in the 18-month group was 86.8% compared with 92.1% for patients in the 36-month group (P = .052). At 10 years the overall survival was 63.2% for patients in the 18-month group vs 63.6% for patients in the 36-month group (P = .429).
Multivariable Cox regression analysis indicated that there was no statistically significant difference between the two groups other than age, meaning that older patients died more rapidly, Nabid said.
Treatment effect of 18-months therapy vs 36-months therapy on quality of life is now under analysis with 9,683 questionnaires answered during more than 12 years.