Dignam JJ, et al. - Given that end points that reliably portend prognosis and treatment benefit (surrogate end points) can accelerate therapy development in prostate cancer, researchers investigated potential surrogates under long-term (24 month) androgen deprivation (AD) (LTAD), a proven therapy in high-risk localized disease. They found that time interval free of biochemical failure (IBF) not only satisfied surrogacy criteria but also identified the benefit of LTAD on disease-specific survival and overall survival (OS). Based on findings, the IBF could be a valid end point in clinical trials and may also aid in risk monitoring following initial treatment.

Methods

• Researchers assessed the time interval free of biochemical failure (IBF) in relation to clinical end points of prostate cancer–specific survival (PCSS) and overall survival (OS) in the NRG/RTOG 9202 randomized trial (N = 1,520) of short-term AD (4 months) vs long-term AD (LTAD; 28 months).
• They assessed LTAD benefit on IBF and clinical end points, link between IBF and clinical end points, and the mediating impact of IBF on LTAD clinical end point benefits, by applying survival modeling and landmark analysis methods.

Results

• For both biochemical failure (BF) and the clinical end points, the superiority of LTAD over short-term AD was demonstrated.
• For OS and PCSS, relative risk reductions of 39% and 73%, respectively, were observed in men remaining free of BF for 3 years.
• On accounting for 3-year IBF status, they noted an attenuation in the LTAD OS benefit from 12% (hazard ratio [HR], 0.88; 95% CI, 0.79 to 0.98) to 6% (HR, 0.94; 95% CI, 0.83 to 1.07).
• The attenuation in the LTAD benefit for PCSS was from 30% (HR, 0.70; 95% CI, 0.52 to 0.82) to 6% (HR, 0.94; 95% CI, 0.72 to 1.22).
• Prostate cancer was identified as the cause of 50% of subsequent deaths among men with BF and 9% deaths among men free of BF through 3 years.