From November 1978 to July 1984, 285 men with previously untreated, localized
prostate cancer were consecutively randomized in an open multicenter study. The main objective was to determine if early endocrine treatment prolongs the interval to
metastasis and/or
cancer related or overall survival. Patients were randomized to receive either 80 mg.
polyestradiol phosphate by
intramuscular injection every 4 weeks plus 50 micrograms ethinylestradiol 3 times daily or 280 mg.
estramustine phosphate 2 times daily, or for surveillance only but with deferred endocrine treatment at progression to metastatic disease. From 1983 further inclusion into the
polyestradiol phosphate plus ethinylestradiol group was closed because of a high frequency of cardiovascular complications and thereafter 13 patients were instead randomized to a new treatment group with 80 mg.
polyestradiol phosphate only by
intramuscular injection every 4 weeks. Mean age was 70 years for 228 evaluable patients: 66 in the
polyestradiol phosphate plus ethinylestradiol group, 74 in the
estramustine phosphate group and 88 in the deferred treatment group, respectively. Mean followup for 100 patients alive on August 31, 1993 was 144 months (range 111 to 180). During the observation period 51 patients had
metastasis. There was no difference in interval to
metastasis (p = 0.07) among the 3 groups, although there was a tendency for a higher probability of
metastases in the deferred treatment group. A total of 128 patients (56%) died during the observation period and
prostatic cancer was considered to be the cause of death in 46 (20%). There was a significant difference (p = 0.03) among the 3 groups in the probability of dying of
prostatic cancer, with the highest risk in the surveillance group but we found no significant difference in overall survival. The relevance of different prognostic factors and their interaction with treatment was also evaluated. These analyses were applied to the entire patient group as well as to the different subgroups. We found that patients with moderately well differentiated
cancer (stage greater than T0a) who received early treatment with
estramustine phosphate had the lowest risk of
metastases or death from
prostatic cancer, while those with well differentiated
cancer (stage greater than T0a) did best on early
polyestradiol phosphate plus ethinylestradiol treatment.