At the American Society for Clinical Oncology’s (ASCO) meeting there was an upsetting plenary presentation made on June 3. Data was presented by principal investigator, Maha Hussain, M.D., F.A.C.P., from the University of Michigan Comprehensive Cancer Center. Dr. Hussain discussed the findings from the phase III clinical trial SWOG-9346, the largest such study to date in men with metastatic, hormone-sensitive prostate cancer who were on hormone therapy (ADT).
The study demonstrated that intermittent androgen-deprivation (IAD) therapy is not as good as continuous hormone therapy with regard to a man’s longevity! This finding flies in the face of prior research that has shown that continuous ADT and intermittent ADT are equal to each other.
This study was a seventeen year study led by SWOG, a cancer research cooperative group funded by the National Cancer Institute (NCI). The SWOG network, with funding from the NCI, led an international team in conducting this study at more than 500 sites, enrolling 3,040 men with hormone-sensitive, metastatic prostate cancer between 1995 and 2008
“Based on these results,” Dr. Hussain said, “we can conclude that intermittent ADT is not as effective as continuous ADT in men with metastatic prostate cancer.”
How the Trial Was Conducted:
All men participating in the trial received an initial course of androgen-deprivation treatment for seven months. The 1,535 eligible men whose prostate-specific antigen (PSA) level dropped to 4 ng/mL or less by the end of those seven months were then assigned at random to stop therapy (the intermittent therapy group) or continue therapy (the continuous therapy group).
Those randomized to the intermittent therapy arm had their treatment suspended until their PSA rose to a predetermined level, at which time they started another seven-month course of androgen-deprivation therapy, cycling on and off therapy in this way as long as their PSA levels continued to respond appropriately during the “on” cycle.
Men on continuous therapy had a median overall survival time of 5.8 years from the time of randomization, with 29 percent of these men surviving at least 10 years. Those on intermittent therapy had a median overall survival time of 5.1 years, with 23 percent surviving at least 10 years from the time they were randomly assigned to a treatment arm.
The researchers found, in additional analyses, that men with “minimal disease” (disease that had not spread beyond the lymph nodes or the bones of the spine or pelvis) did significantly better on continuous therapy, while men with “extensive disease” (disease that had spread beyond the spine, pelvis, and lymph nodes or to the lungs or liver) seemed to do about as well using either treatment approach.
Additional analyses indicated that the median overall survival time for those with minimal disease was 7.1 years on continuous androgen-deprivation therapy compared to only 5.2 years on intermittent treatment. Patients with extensive disease had median overall survival times of 4.4 years on continuous therapy and 5.0 years on intermittent therapy.
Trial researchers also compared quality-of-life measures across the two study arms during the first 15 months following patient randomization, including measures of sexual function (impotence and libido), physical and emotional function, and energy level. They found improved sexual function in men who received intermittent therapy as compared to those on continuous therapy.
“Though we see potential quality-of-life benefits with IAD,” Hussain says, “from a medical perspective, the primary findings of the study demonstrating that IAD is inferior with regard to overall survival should be the primary consideration in counseling all patients who are interested in intermittent therapy and particularly those with minimal disease.”
•1,535 men with metastatic, hormone-sensitive prostate cancer were randomized to intermittent androgen-deprivation (AD) therapy or continuous AD therapy after seven months of androgen deprivation.
• When overall survival times were compared, intermittent ADT was inferior to continuous ADT.
• For the subset of patients with minimal disease, continuous ADT was superior to intermittent ADT.
• For patients with extensive disease, overall survival was comparable between intermittent and continuous ADT.
• A number of quality-of-life measures got higher scores in the intermittent ADT arm than the continuous ADT arm.
Where does this leave us? This is an excellent question. Each of us with minimal advanced prostate cancer will need to evaluate the value of the increased QOL vs. or longevity. This is a very personal decision that those of us with minimal disease will need to wrestle with as we go forward.
Joel T Nowak, M.A., M.S.W.