John Anderson

Objective To compare the effect on the course of advanced prostate cancer of hormone treatment commenced on diagnosis with that deferred until clinically significant progression occurs. Patients and methods Nine hundred and thirty-eight patients with locally advanced or asymptomatic metastatic prostate cancer were randomized either to immediate treatment (orchidectomy or luteinizing hormone-releasing hormone analogue) or to the same treatment deferred until an indication occurred, Follow-up and management were otherwise according to the participating clinician's normal practice. Information was collected annually on survival, local and distant progression, and major complications (pathological fracture, spinal cord compression, ureteric obstruction and extra-skeletal metastases). Results Follow-up data were returned on 934 patients; 51 deferred patients died from causes other than prostate cancer before treatment was started (but only five of these presented at age <70 years) and 29 died from prostate cancer before treatment could be started, Treatment was commenced for local progression almost as frequently as for metastatic disease, Progression from M0 to M1 disease (P<0.001, two-tailed) and development of metastatic pain occurred more rapidly in deferred patients; 141 deferred patients needed transurethral resection for local progression compared with 65 treated immediately (P<0.001, two-tailed). Pathological fracture, spinal cord compression, ureteric obstruction and development of extra-skeletal metastases were twice as common in deferred patients. Of the patients who died, 67% did so from prostate cancer; 361 patients died in the deferred arm compared with 328 in the immediate arm (P=0.02, two-tailed), where 257 and 203 were deaths from prostate cancer, respectively (P=0.001 two-tailed). This difference was seen largely in M0 patients, with 119 and 81 deaths from prostate cancer, respectively (P<0.001 two-tailed). Conclusions The results consistently favour immediate treatment, although some of the data, especially on M0 patients, are immature. The implications for management of advanced prostate cancer are discussed.

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.