Changing the Standard of Care for Men with Recurrent Prostate Cancer

For men undergoing androgen deprivation therapy for metastatic prostate cancer, the side effects—including fatigue, hot flashes, mood swings and momentary memory loss—may be extremely taxing. Now, results of a large phase III randomized, controlled study conducted by the National Cancer Institute of Canada show that shorter, eight month cycles of intermittent androgen deprivation (IAD) therapy can deliver comparable clinical outcomes for some patients whose PSA levels rise following radical prostatectomy or radiation therapy.

Those who reviewed that study data at last month’s ASCO meeting agreed that this study represents a “practice changing” milestone with ASCO endorsing the concept that IAD now be presented to patients at the time of biochemical PSA recurrence in the absence of metastatic disease on scans (detectable lesions in bone or soft tissue).

“We have known since the mid-1990’s that androgen suppressive therapy could be used in an interrupted fashion, but we didn’t know until now that men were not sacrificing length of life in the hopes of having a better quality of life,” says Juanita M. Crook, MD, principal investigator and radiation oncologist with the British Columbia Cancer Agency. “The results of this trial will change the standard of care.”

The Canadian study, supported by a team of cross-border North American scientists,  administered intermittent androgen deprivation in patients for eight months then stopped and restarted only when their PSA levels reached >3 ng/ml when off the treatment, compared to men treated with continuous androgen deprivation (CAD). The data showed that intermittent antiandrogen treatment was equivalent to continuous antiandrogen treatment with similar overall survival and quality-of-life measures. Biostatiscally, intermittent therapy was called “a non-inferior” (in laymen’s terms, “comparable”) arm of the trial—disease specific death was 18% in the intermittent arm compared with 15% in the continuous arm.

Dr. Crook believes the IAD method will be widely accepted. “There is no detriment to survival, some men see quality-of-life benefit, and it also happens to be cheaper,” says Crook.

Summary
Intermittent androgen deprivation provides similar outcomes to continuous therapy with the potential for fewer side effects and less disruption to quality of life—good news for many men and their families. IAD patients complained of fewer hot flashes and 35% of them had full recovery of serum testosterone after completing IAD. Cardiac events and osteoporotic fracture events were equal in both arms. Further, intermittent androgen deprivation offers cost-savings to health systems as both patients and the systems pay only 27% of the cost of continuous treatment.

Patients about to start androgen deprivation therapy or currently undergoing continuous androgen deprivation treatment should ask their physician to see if they qualify for IAD.

Intermittent Androgen Deprivation Study Details
The patient group tested 1,386 men whose PSA recurred with no evidence of metastatic disease on scans—and after primary tumor treatment—either radiation therapy or radical prostatectomy. Eligible patients had a PSA of >3.0 ng/ml at more than 12 months following either surgery, radiation following surgery, or primary radiation therapy. The median follow up for all patients was 6.9 years and the intermittent androgen treated patients received between 1-9 cycles of treatment with the median number being 2 cycles of hormonal therapy between periods of discontinuation. Median survival was 8.8 years for the intermittent patients and 9.1 years for those patients who were treated continuously. The median age of the treated men was 74.2 years.