Intermittent androgen suppression in prostate cancer: an update of the Vancouver experience

This report will review the long-term follow-up of a prospective Phase II evaluation of intermittent androgen suppression in the treatment of prostate cancer. Specifically, this analysis will address completed cycle characteristics, the concept of prolonged off-treatment cycles, the time to cancer progression, cancer-specific survival and the association between PSA and bone scan changes.

A total of 102 patients have been entered into this protocol. Treatment was initiated with combined androgen blockade and continued for 6 months or longer to reach a serum PSA nadir. Medication was then withheld until the serum PSA increased to predetermined trigger points based on initial parameters. Each cycle of treatment and no-treatment was repeated until the regulation of PSA became biochemically androgen independent.

One hundred two patients have been commenced on IAS with an average follow-up time of 219 weeks (range: 14.5 to 588). Ninety-one patients have completed at least one therapeutic cycle with a total of 188 completed cycles available for analysis. The average time off therapy (percentage time off therapy) for cycles 1, 2, 3 and 4 was 13 months (53%), 11 months (51%), 10 months (47%) and 8 months (45%), respectively. A prolonged off-treatment time of greater than 72 weeks was observed in 33 (18%) of all completed cycles, and was most common in the men being treated for radiation failure stage C. Progression and survival data was calculated for the entire trial cohort (n=102). The average time to androgen independent progression in the 29 (28%) patients who progressed was 194 weeks. Death from prostate cancer occurred in 19 (18%) patients at an average of 258 weeks following treatment initiation. A review of bone scans revealed 22 events of newly detected lesions, all but 2 of which were preceded by a rise in serum PSA.

Longer duration follow-up of a single cohort continues to support IAS as a viable treatment option for men with prostate cancer. This approach affords an improved quality of life when the patient is off therapy, with reduced toxicity and costs. There is a trend toward extended times to progression and death compared to contemporary studies of continuous androgen suppression. Randomized, prospective protocols are currently underway to determine whether survival is affected in a beneficial or adverse way in men with locally recurrent or metastatic cancer.