Lundgren R, Nordle O, Josefsson K
Department of Urology, University Hospital, Lund, Sweden.
J Urol. 1995 May;153(5):1580-6.
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.
1978年11月至1984年7月，285例既往未经治疗的局限性前列腺癌男性患者在一项开放性多中心研究中被连续随机分组。主要目的是确定早期内分泌治疗是否能延长至转移和/或癌症相关或总生存期的间隔时间。患者被随机分为三组，分别接受：每4周肌肉注射80毫克聚磷酸雌二醇，每日3次，每次50微克炔雌醇；或每日2次，每次280毫克磷酸雌莫司汀；或仅进行监测，但在疾病进展至转移性疾病时进行延迟内分泌治疗。从1983年起，由于心血管并发症发生率高，停止将患者纳入聚磷酸雌二醇加炔雌醇组，此后13例患者被随机分配到一个新的治疗组，仅每4周肌肉注射80毫克聚磷酸雌二醇。228例可评估患者的平均年龄为70岁：聚磷酸雌二醇加炔雌醇组66例，磷酸雌莫司汀组74例，延迟治疗组88例。对1993年8月31日仍存活的100例患者的平均随访时间为144个月（范围111至180个月）。在观察期内，51例患者发生转移。三组之间转移间隔时间无差异（p = 0.07），尽管延迟治疗组转移概率有升高趋势。在观察期内，共有128例患者（56%）死亡，46例（20%）被认为死于前列腺癌。三组之间死于前列腺癌的概率有显著差异（p = 0.03），监测组风险最高，但我们发现总生存期无显著差异。还评估了不同预后因素的相关性及其与治疗的相互作用。这些分析应用于整个患者组以及不同亚组。我们发现，接受早期磷酸雌莫司汀治疗的中度分化癌（分期大于T0a）患者发生转移或死于前列腺癌的风险最低，而高分化癌（分期大于T0a）患者在早期聚磷酸雌二醇加炔雌醇治疗中效果最佳。
