British Journalof Urology (1991), 67, 184-187 01991 British Journal of Urology
Orchiectomy versus Oestrogen in the Treatment of Advanced Prostatic Cancer R. HAAPIAINEN, S. RANNIKKO, M. RUUTU, M. ALA-OPAS, E. HANSSON, H. JUUSELA, J. PERMI, M. SAARIALHO, J. VllTANEN and 0. ALFTHAN Second Department of Surgery, Urological Unit, Helsinki University Central Hospital, Helsinki, Finland
Summary-The primary clinical efficacy of orchiectomy and the combination therapy of intramuscular polyoestradiol phosphate 80 mg monthly and oral ethinyl oestradiolO.15 mg daily was evaluated by progression and cancer mortality rates in a series of 277 prostatic cancer patients representing part of the Finnprostate study. After a follow-up of 5 years there was a significant difference between the groups in terms of progression rate and prostatic cancer deaths. The oestrogen combination was more effective in delaying progression of the disease. The overall mortality rate was similar in both groups. About one-third of the patients were alive after 5 years.
The safety and reliability of orchiectomy in the treatment of advanced prostatic carcinoma have been well established (Merril, 1988) and the procedure is widely used in Finland. It is usually performed as subcapsular orchiectomy and its acceptance by patients is not a problem. The oestrogen treatment commonly used in Scandinavia includes polyoestradiol phosphate, either alone or in combination with ethinyloestradiol (Jonsson, 1971). The purpose of the present study was to compare the primary clinical efficacy of orchiectomy and intramuscular polyoestradiol phosphate (PEP) in combination with oral ethinyloestradiol (EE) in the treatment of locally advanced or metastatic prostatic cancer.
Patients and Methods The present series of 277 prostatic cancer patients formed part of the 404 prostatic cancer patients included in a Finnish multicentre study (Finnprostate) and diagnosed between February 1979 and December 1982. The diagnoses, exclusion criteria, randomisation design and progression criteria have already been described (Haapiainen et al., 1986). The current oestrogen group consisted of 146 Accepted for publication 1 May 1990
patients (mean age 72.7 years) and the orchiectomy group included 131 patients (mean age 71.8 years). At the time of diagnosis there were no significant differences between the groups in terms of local extent of tumour (T classification), presence of distant metastases (M classification) or differentiation grade of the malignancy (G classification). The oestrogen therapy consisted of intramuscular polyoestradiol phosphate (PEP, Estradurin), 160 mg as an initial dose followed by 80 mg monthly. In addition, ethinyloestradiol (EE, Etivex), 1 mg, was given orally for 2 weeks, followed by 150 pg daily. Bilateral castration included either total or subcapsular orchiectomy. Statistical analysis of proportions was achieved using the x2 test and the test for linear trend. Survival analyses were performed by the conventional product limit method and the Cox proportional hazard method. The primary clinical efficacy of oestrogen therapy and orchiectomy was evaluated by progression rates (non-progression was defined as disease-free interval), cancer mortality and cardiovascular mortality after a minimum follow-up of 5 years.
Results During the first 5 years, 49 of 131 orchiectomised patients (37%) showed evidence of progression and
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another 12 (9%) had such aggressive disease that they died of disseminated prostatic cancer during the evaluation phase. In the oestrogen group, 25 of 146 patients (17%) showed progression and 22 (1 5%)died from prostatic carcinoma (Fig. 1). There was a statistically significant difference ( P < 0.05) between the groups overall, the oestrogen combination being more effective in delaying progression of the disease. Some differences were observed between the groups in respect of M categories. In both MO and M 1 patients the oestrogen therapy delayed progression more effectively than orchiectomy ( P
Orchiectomy versus Oestrogen in the Treatment of Advanced Prostatic Cancer R. HAAPIAINEN, S. RANNIKKO, M. RUUTU, M. ALA-OPAS, E. HANSSON, H. JUUSELA, J. PERMI, M. SAARIALHO, J. VllTANEN and 0. ALFTHAN Second Department of Surgery, Urological Unit, Helsinki University Central Hospital, Helsinki, Finland
Summary-The primary clinical efficacy of orchiectomy and the combination therapy of intramuscular polyoestradiol phosphate 80 mg monthly and oral ethinyl oestradiolO.15 mg daily was evaluated by progression and cancer mortality rates in a series of 277 prostatic cancer patients representing part of the Finnprostate study. After a follow-up of 5 years there was a significant difference between the groups in terms of progression rate and prostatic cancer deaths. The oestrogen combination was more effective in delaying progression of the disease. The overall mortality rate was similar in both groups. About one-third of the patients were alive after 5 years.
The safety and reliability of orchiectomy in the treatment of advanced prostatic carcinoma have been well established (Merril, 1988) and the procedure is widely used in Finland. It is usually performed as subcapsular orchiectomy and its acceptance by patients is not a problem. The oestrogen treatment commonly used in Scandinavia includes polyoestradiol phosphate, either alone or in combination with ethinyloestradiol (Jonsson, 1971). The purpose of the present study was to compare the primary clinical efficacy of orchiectomy and intramuscular polyoestradiol phosphate (PEP) in combination with oral ethinyloestradiol (EE) in the treatment of locally advanced or metastatic prostatic cancer.
Patients and Methods The present series of 277 prostatic cancer patients formed part of the 404 prostatic cancer patients included in a Finnish multicentre study (Finnprostate) and diagnosed between February 1979 and December 1982. The diagnoses, exclusion criteria, randomisation design and progression criteria have already been described (Haapiainen et al., 1986). The current oestrogen group consisted of 146 Accepted for publication 1 May 1990
patients (mean age 72.7 years) and the orchiectomy group included 131 patients (mean age 71.8 years). At the time of diagnosis there were no significant differences between the groups in terms of local extent of tumour (T classification), presence of distant metastases (M classification) or differentiation grade of the malignancy (G classification). The oestrogen therapy consisted of intramuscular polyoestradiol phosphate (PEP, Estradurin), 160 mg as an initial dose followed by 80 mg monthly. In addition, ethinyloestradiol (EE, Etivex), 1 mg, was given orally for 2 weeks, followed by 150 pg daily. Bilateral castration included either total or subcapsular orchiectomy. Statistical analysis of proportions was achieved using the x2 test and the test for linear trend. Survival analyses were performed by the conventional product limit method and the Cox proportional hazard method. The primary clinical efficacy of oestrogen therapy and orchiectomy was evaluated by progression rates (non-progression was defined as disease-free interval), cancer mortality and cardiovascular mortality after a minimum follow-up of 5 years.
Results During the first 5 years, 49 of 131 orchiectomised patients (37%) showed evidence of progression and
184
185
ORCHIECTOMY V. OESTROGEN IN TREATMENT OF ADVANCED PROSTATIC CANCER
another 12 (9%) had such aggressive disease that they died of disseminated prostatic cancer during the evaluation phase. In the oestrogen group, 25 of 146 patients (17%) showed progression and 22 (1 5%)died from prostatic carcinoma (Fig. 1). There was a statistically significant difference ( P < 0.05) between the groups overall, the oestrogen combination being more effective in delaying progression of the disease. Some differences were observed between the groups in respect of M categories. In both MO and M 1 patients the oestrogen therapy delayed progression more effectively than orchiectomy ( P
