Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Bristol Medical School, University of Bristol, Bristol, UK.
Health Technol Assess. 2020 Aug;24(37):1-176. doi: 10.3310/hta24370.
Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments.
To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years.
A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up.
Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK.
Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring ( = 545), radical prostatectomy ( = 553) or radical radiotherapy ( = 545) and 997 chose a treatment.
The interventions were active monitoring, radical prostatectomy and radical radiotherapy.
Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants.
Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes.
There were no statistically significant differences between the groups for 17 prostate cancer-specific ( = 0.48) and 169 all-cause ( = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring ( = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy ( = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy ( = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy).
A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed.
At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years.
Current Controlled Trials ISRCTN20141297.
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.
前列腺癌是英国男性中最常见的癌症。前列腺特异性抗原检测后行活检导致过度诊断、过度治疗和治疗不足。由于缺乏比较常规治疗的随机对照试验，因此缺乏治疗效果的证据。
评估 50-69 岁局限性前列腺癌（主动监测、根治性前列腺切除术和根治性放疗）的常规治疗效果。
一项前瞻性、多中心前列腺特异性抗原检测方案，随后进行治疗随机试验，并进行全面的队列随访。
英国初级保健中的前列腺特异性抗原检测和九家泌尿科的治疗。
2001 年至 2009 年，228966 名 50-69 岁男性收到参加 ProtecT 研究和治疗（前列腺癌检测和治疗）的信息预约和前列腺特异性抗原检测的邀请；82429 名男性接受了检测，2664 名被诊断为局限性前列腺癌，1643 名同意随机分配至主动监测（545 名）、根治性前列腺切除术（553 名）或根治性放疗（545 名），997 名选择治疗。
干预措施为主动监测、根治性前列腺切除术和根治性放疗。
随机分组参与者 10 年中位随访时的明确或可能的疾病特异性死亡率。
总死亡率、转移、疾病进展、治疗并发症、资源利用和患者报告的结局。
各组之间在 17 例前列腺癌特异性死亡（=0.48）和 169 例全因死亡（=0.87）方面无统计学差异。主动监测组 8 例男性死于前列腺癌（每 1000 人年 1.5 例，95%置信区间 0.7 至 3.0）；根治性前列腺切除术组 5 例（0.9 例，95%置信区间 0.4 至 2.2）；根治性放疗组 4 例（0.7 例，95%置信区间 0.3 至 2.0）。主动监测组发生转移的男性多于根治性前列腺切除术和根治性放疗组：主动监测组 33 例（每 1000 人年 6.3 例，95%置信区间 4.5 至 8.8）；根治性前列腺切除术组 13 例（2.4 例，95%置信区间 1.4 至 4.2）；根治性放疗组 16 例（3.0 例，95%置信区间 1.9 至 4.9）（=0.004）。主动监测组疾病进展率高于根治性前列腺切除术和根治性放疗组：主动监测组 112 例（22.9 例，95%置信区间 19.0 至 27.5）；根治性前列腺切除术组 46 例（8.9 例，95%置信区间 6.7 至 11.9）；根治性放疗组 46 例（9.0 例，95%置信区间 6.7 至 12.0）（<0.001）。根治性前列腺切除术对性功能/尿控的影响最大，且仍比根治性放疗和主动监测差。根治性放疗对性功能的影响在 6 个月时最大，但在大多数参与者中有所恢复。主动监测组的性功能和尿控逐渐下降。根治性放疗组在 6 个月时的肠道功能较差，但除了血便外，其余均有恢复。根治性放疗组在 6 个月时的排尿和夜间尿频加重，但随后恢复。疾病特异性生存质量的变化与功能变化一致。焦虑/抑郁或一般或癌症相关的生存质量没有差异。在国家卫生与保健卓越研究所（National Institute for Health and Care Excellence）设定的 20000 英镑/质量调整生命年阈值下，每个治疗组最具成本效益的概率分别为 58%（根治性放疗）、32%（主动监测）和 10%（根治性前列腺切除术）。
仅使用了单次前列腺特异性抗原检测和经直肠超声活检。试验中几乎没有非白人男性。大多数男性患有低危和中危疾病。需要更长的随访时间。
在 10 年的中位随访点，前列腺癌特异性死亡率较低，无论分配的治疗方式如何。根治性前列腺切除术和根治性放疗可降低疾病进展和转移的风险，但会产生副作用。需要进一步的工作来随访中位随访 15 年的参与者。
当前对照试验 ISRCTN2460563。
该项目由英国国家卫生研究院卫生技术评估计划资助，全文将在 ; 第 24 卷，第 37 期发布。欲了解更多项目信息，请访问英国国家卫生研究院期刊图书馆网站。
