Formal discussant for the presentation of SWOG S9921 results, Susan F. Slovin, MD, PhD, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, said there were some important points to understand about this “vintage” trial.
“The trial was designed 20 years ago, and the view is different now. ‘High risk’ can be a variable category, and high-risk patients are routinely referred for hormonal therapy. The role of adjuvant therapy is not widely accepted in high-risk patients,” she said.
“It is still unclear whether 2 years of androgen-deprivation therapy is too much or too little. Large trials in this space have been fraught by being cut off in the middle and not reaching accrual. Thus, the trials that have been conducted in this area lack the statistical power to demonstrate a survival difference,” she told the audience.
Two Large Trials
“The main goal of adjuvant therapy is to eradicate micrometastasis in high-risk patients. Let’s put our retrospective glasses on to address this,” Dr. Slovin told listeners.
She mentioned two large studies of adjuvant chemotherapy in high-risk patients: TAX 35011 and the VA Cooperative Study 553.2 The first study evaluated hormone therapy with or without docetaxel, and the second study compared observation vs docetaxel plus prednisone. Both studies were terminated prematurely and were underpowered to detect progression-free survival differences, she said. Neither study showed a difference in progression-free survival for either arm.
However, the VA Cooperative Study 553 found a potential advantage in progression-free survival for adjuvant docetaxel in two subgroups: those with higher-risk pathology (ie, stage T3b) and/or African American men. These findings suggest there may be some benefit in specific subgroups, she noted.
Going forward, Dr. Slovin suggested that studies in the modern era can incorporate new tools for better patient selection as well as newer agents that might show a benefit for adjuvant therapy in high-risk patients. In addition to more modern chemotherapy, incorporating a new grading system for prostate tumors, genomic-profiling assays to separate out patients with low- vs high-risk disease, and new radiolabeled tracers for imaging can provide useful information so that the patients selected for these trials are truly at high risk.
“If we can identify the right patient population, this would facilitate studies. We should continue to conduct these trials and take advantage of new genomic-profiling assays and radiotracers. We can enrich the study population for trials that will pay off,” Dr. Slovin commented. ■
Disclosure: Dr. Slovin reported no potential conflicts of interest.
1. Netto GJ, Eisenberger M, Epstein JI, et al: Interobserver variability in histologic evaluation of radical prostatectomy between central and local pathologists: Findings of TAX 3501 multinational clinical trial. Urology 77:1155-1160, 2011.
An older trial designed to evaluate the benefits of adjuvant therapy following radical prostatectomy in patients with high-risk prostate cancer showed no difference in overall or disease-free survival between 2 years of androgen-deprivation therapy and 2 years of androgen-deprivation therapy plus...