In men with rising prostate-specific antigen (PSA) levels after radical therapy for prostate cancer, intermittent androgen suppression (IAS) was as effective as continuous androgen deprivation (CAD), with no overall difference in survival between the two treatments, and the potential for huge cost savings with IAS. Intermittent androgen suppression treatment was delivered for 8 months in each cycle and restarted only when PSA levels reached > 10 ng/mL off treatment, vs continuous delivery of treatment administered without breaks in therapy.

These results of an intergroup phase III randomized, controlled trial promise to be practice-changing, according to experts interviewed by The ASCO Post.1

"We showed that using IAS is not inferior to CAD, with a high level of confidence. We now have level 1A evidence from multiple trials that have consistently shown no difference in overall survival between IAS and CAD," said lead author Laurence Klotz, MD,  Professor of Surgery at the University of Toronto. "Intermittent androgen suppression should be the new standard of care for most patients with PSA recurrence after radical therapy," he stated.

The study also showed improved quality of life in patients treated with IAS when off therapy, and Dr. Klotz said there are putative benefits related to side effects associated with CAD, such as loss of bone mineral density and an increase in factors related to the metabolic syndrome. Moreover, the study has economic implications. Patients in the IAS arm were on therapy only 27% of the time, "reducing the cost of therapy on average by 73%," Dr. Klotz said.

Interim Analysis

The study presented at the Genitourinary Cancers Symposium was an interim analysis of 1,386 patients with rising PSA and nonmetastatic prostate cancer after radical therapy (either radical prostatectomy or radiation therapy) who were randomly assigned to IAS vs CAD. The two arms were well balanced for performance status, PSA level, prior radical prostatectomy, and time since radiation therapy. Median follow-up was 6.9 years. IAS patients completed a median of eight cycles of therapy.

Median survival was 8.8 years in the IAS arm vs 9.1 years in the CAD arm. Time to development of castration resistance was close to 10 years and favored IAS, but Dr. Klotz pointed out that the trial design was biased toward IAS. He noted that in order to achieve castration resistance status, patients had to be on treatment. Dr. Klotz added that some patients who had a rising PSA off treatment in fact may have had castration-resistant disease, but treatment had to be restarted and the PSA seen to continue to rise before this status could be defined.

More non-prostate cancer-related deaths were reported in the CAD arm (134 vs 146 deaths, respectively), whereas more prostate cancer deaths occurred in the IAS arm (122 vs 97 deaths, respectively). These differences were not statistically significant.

No difference in adverse events was reported between the two arms, including myocardial events and osteoporotic fractures, with the exception of more hot flashes in the CAD arm. ■

Financial Disclosure: Dr. Klotz reported no potential conflicts of interest.

Reference

1. Klotz L, O'Callaghan CJ, Ding K, et al. A phase III randomized trial comparing intermittent versus continuous androgen suppression for patients with PSA progression after radical therapy. Genitourinary Cancers Symposium. Abstract 3. Presented February 17, 2011.