Does failure of single hormone therapy delineate hormone refractoriness for prostate cancer?

The results of two randomized phase III trials have shown benefit with docetaxel-based chemotherapy in advanced prostate cancer patients who had disease progression following primary androgen ablation therapy. In these trials, 50% and 45% of patients, respectively had at least a 50% reduction in prostate-specific antigen (PSA) levels, with median survival times of 17.5 and 18.9 months, respectively. Because the definition of hormone-refractory disease is very loose, it is important that all benefit from hormones has been achieved in these hormone-sensitive tumours. This led us to review our prostate cancer patients treated with secondary hormone manipulations.

Advanced prostate cancer patients treated with two or more modalities of hormone therapy, i.e. anti-androgens, luteinizing hormone-releasing hormone and estrogens, were identified and the treatment response in terms of reduction in PSA levels was assessed.

Overall, 65 patients were included in the study. The majority of patients responded to second- (81.9%) or third-line (77.8%) hormone manipulations, irrespective of whether they had localized or advanced prostate disease. Patients who showed any degree of PSA response to second-line hormone manipulation had a median PSA response duration of 6.1 months (range 0.6-27.0 months). Similarly, the median duration of PSA response to third-line hormone therapy was 6.35 months (range 1.9-15.4 months). The duration of PSA control appears to be better among patients with a > 50% PSA response to both second- and third-line hormone manipulation. However, patients with a lower degree of PSA response to the hormone manipulations also demonstrate PSA control of significant duration.

Most patients with a PSA response after primary hormone therapy show a further response to hormones before becoming truly hormone-refractory. There is a concern that the rush to use novel agents will reduce the period of successful palliation in these patients rather than being additive. Patients should show complete hormone refractoriness before newer agents are added to prostate cancer treatment.