Prescrire Int. 2013 Jan;22(134):18-20, 22-3.
Locally advanced prostate tumours, i.e. those that extend beyond the prostate gland but are not metastatic, often carry a poor prognosis: between 10% and 40% of patients die within 5 years after diagnosis. Various treatments are proposed to improve their prognosis. Which treatments have a proven survival benefit, and what are their adverse effects? To answer these questions, we reviewed the literature using the standard Prescrire methodology. Prostatectomy has not been evaluated in controlled trials versus either watchful waiting or radiation therapy alone. Prostatectomy is mainly proposed to patients who are in good general health. Five years after prostatectomy, mortality from prostate cancer is between 2% and 16%, depending on the study.Three-quarters of patients who have surgery at this stage experience erectile dysfunction, and at least 20% of patients develop urinary incontinence. External beam radiation therapy alone has not been compared with watchful waiting or prostatectomy. External beam radiation therapy has documented benefits in patients with locally advanced prostate cancer treated with gonadorelin agonists, preventing 8 to 10 deaths from all causes after 7 to 10 years of follow-up among 100 treated patients. However, about 60% of patients experience erectile dysfunction, about 15% symptomatic radiation proctitis, and about 5% urinary incontinence. When combined with prostatectomy, radiation therapy did not affect the 5-year survival rate but prolonged survival by about 2 years in a trial with more than 10 years of follow-up. When used without concomitant androgen suppression, antiandrogens have no proven impact on overall survival in patients with locally advanced prostate cancer. In the absence of radical prostatectomy or radiation therapy, androgen suppression, by means of orchiectomy or gonadorelin agonist, has a minimal impact on overall survival among patients with locally advanced cancer. In one randomised trial, androgen suppression in combination with prostatectomy prolonged median survival by about 2.5 years among patients with lymph node involvement. In another randomised trial, treatment with a gonadorelin agonist and flutamide for 6 months, started before radiation therapy, reduced the 10-year overall mortality rate to 29%, versus 43% after radiation therapy alone. Androgen suppression for at least 3 years after radiation therapy prevented 10 to 18 deaths from all causes per 100 patients during 10 to 15 years of follow-up in three randomised trials that provided similar results. Shorter durations of treatment appeared to be less effective in 3 other randomised controlled trials. The adverse effects of gonadorelin agonists often undermine patients' quality of life, due to hot flushes, loss of libido, erectile dysfunction, gynaecomastia, osteoporosis, weight gain, cardiovascular events, and diabetes. In mid-2012, European clinical practice guidelines recommend a combination of radiation therapy and androgen suppression for 2 to 3 years for most patients with locally advanced prostate cancer. Before choosing between therapeutic options, it is crucial to take into account the patient's priorities in terms of treatment efficacy and adverse effects, and reversibility of adverse effects.
局部晚期前列腺肿瘤，即那些超出前列腺腺体但未发生转移的肿瘤，往往预后较差：10%至40%的患者在确诊后5年内死亡。人们提出了各种治疗方法来改善其预后。哪些治疗方法具有已证实的生存获益，其不良反应又有哪些？为回答这些问题，我们采用标准的Prescrire方法对文献进行了综述。前列腺切除术尚未在与单纯观察等待或放射治疗的对照试验中进行评估。前列腺切除术主要推荐给一般健康状况良好的患者。前列腺切除术后5年，前列腺癌死亡率在2%至16%之间，具体取决于研究。在这个阶段接受手术的患者中有四分之三会出现勃起功能障碍，至少20%的患者会出现尿失禁。单纯外照射放疗尚未与观察等待或前列腺切除术进行比较。外照射放疗已证明对接受促性腺激素释放激素激动剂治疗的局部晚期前列腺癌患者有益，在100例接受治疗的患者中，经过7至10年的随访，可预防8至10例各种原因导致的死亡。然而，约60%的患者会出现勃起功能障碍，约15%出现有症状的放射性直肠炎，约5%出现尿失禁。与前列腺切除术联合使用时，放疗在一项超过10年随访的试验中并未影响5年生存率，但使生存期延长了约2年。在没有同时进行雄激素抑制的情况下，抗雄激素药物对局部晚期前列腺癌患者的总生存期没有已证实的影响。在没有进行根治性前列腺切除术或放疗的情况下，通过睾丸切除术或促性腺激素释放激素激动剂进行雄激素抑制，对局部晚期癌症患者的总生存期影响极小。在一项随机试验中，雄激素抑制与前列腺切除术联合使用可使有淋巴结受累的患者中位生存期延长约2.5年。在另一项随机试验中，在放疗前开始使用促性腺激素释放激素激动剂和氟他胺治疗6个月，可将10年总死亡率降至29%，而单纯放疗后为43%。在三项提供类似结果的随机试验中，放疗后至少3年的雄激素抑制可在10至15年的随访期间预防每100例患者中有10至18例各种原因导致的死亡。在另外三项随机对照试验中，较短的治疗时间似乎效果较差。促性腺激素释放激素激动剂的不良反应常常损害患者的生活质量，原因包括潮热、性欲减退、勃起功能障碍、男性乳房发育、骨质疏松、体重增加、心血管事件和糖尿病。2012年年中，欧洲临床实践指南建议，对于大多数局部晚期前列腺癌患者，采用放疗和雄激素抑制联合治疗2至3年。在选择治疗方案之前，至关重要的是要考虑患者在治疗效果、不良反应以及不良反应可逆性方面的优先事项。
