Long-Term Outcomes in Patients with Prostate Cancer Managed with Intermittent Androgen Suppression

Abstract

Objectives: To assess the long-term outcomes of patients with prostate cancer managed with intermittent androgen suppression (IAS) following their enrolment in an open, non-randomised feasibility study initiated 10 years ago. Patients and Methods: Patients with prostate cancer who developed marked side effects following androgen deprivation were considered for entry into the study. All patients were required to have been managed with androgen deprivation for a minimum of 9 months and to have achieved PSA remissions to levels <4 ng/ml or falls to greater than 90% of pre-treatment levels. Patients remained off treatment until PSA values rose to >20 ng/ml or individuals became symptomatic – at which stage a 9-month cycle of androgen suppression was repeated. Such on-off cycling continued until hormone-resistant disease developed and patients proceeded (off trial) to second-line therapies. Results: 75 patients were recruited to the study following an initial referral with treatment-related side effects specifically associated with androgen deprivation. 86% of these remain alive at a median of 134 months (11 years) since initial histological diagnosis. Survival times and times to hormone resistance (from first cycle hormone deprivation) have also been calculated. Overall there is a median survival time of 95 months (8 years) from initial (first-cycle) androgen deprivation in those presenting with localised or locally advanced disease and a median survival time of 87 months (7 years) for those presenting with metastatic disease. There exists a median of 83 months to hormone resistance in the localised and locally advanced group and a median of 50 months in those presenting with metastatic disease. We have calculated a 100% 5-year actuarial survival rate for those presenting with localised or locally advanced disease (from time of first cycle hormone ablation) and a 70% 5-year actuarial survival rate for those presenting with metastatic. Conclusions: Long-term outcome figures and actuarial survival rates presented here provide further support for a pulsed or intermittent approach to androgen ablation in patients with prostate cancer. In addition, they serve as valuable extended outcome data for patients managed in this way. Likewise, data presented here suggests that apparent survival advantages appear related, at least in part, to a delay in the onset of androgen resistance and that such a management approach is both safe and effective in those presenting with both metastatic disease as well as those with more localised pathology.

Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer

“…Although a number of Phase II studies of intermittent androgen suppression have been undertaken previously, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] the current clinical trial is unique, in that it was designed as a prospective study focusing on a well defined group of patients. The trial spanned an interval of 6 years with a mean followup of 3.7 years and a median follow-up of 4.2 years.…”

“…The clinical trial focused on men in biochemical recurrence after they had received radiotherapy for locally advanced prostate cancer and has been used as a guideline for several subsequent large, Phase III, randomized studies. [30][31][32][33][34][35] …”

Rapid Androgen Cycling as Treatment for Patients with Prostate Cancer

“…The practice of cycling between androgen-depleted and androgen-repleted states is not new. Intermittent androgen suppression was introduced initially as a strategy both to delay the outgrowth of castration-resistant cells and to minimize toxicity (8,28). As currently used in an investigational setting, intermittent androgen suppression seeks to maintain a state of medical castration 2 to 3 months beyond the point of maximal PSA decline, at which time ADT is discontinued (29).…”

A Prospective Audit of Intermittent Anti-Androgen verses Pituitary Blockade Suggests a Bipolar Androgen Type Strategy May Be Safe in Untreated Prostate Cancer

“…Details of the initial management of these patients have been reported previously [11,12]. The first patient recruited began observation of treatment in 1994 after completion of a pilot study, which identified some of the parameters in need of standardisation [13].…”