前列腺癌早期行前列腺切除术与观察治疗的随访研究。

Follow-up of Prostatectomy versus Observation for Early Prostate Cancer.

机构信息

From the Minneapolis Veterans Affairs (VA) Health Care System and Center for Chronic Disease Outcomes Research and the Section of General Medicine, University of Minnesota School of Medicine, Minneapolis (T.J.W.); the VA Cooperative Studies Program Coordinating Center, Perry Point, MD (K.M.J.); the General Medicine Division, Massachusetts General Hospital, Boston (M.J.B.); the Division of Urology, Washington University School of Medicine, St. Louis (G.L.A.); the Department of Urology, University of Oklahoma College of Medicine, Oklahoma City (D.C.); the Department of Pathology and Immunology, Baylor College of Medicine, Houston (T.W.); VA Medical Center, Greater Los Angeles Healthcare System, Los Angeles (W.J.A.); and Myriad Genetics Laboratories, Salt Lake City (M.K.B.).

出版信息

N Engl J Med. 2017 Jul 13;377(2):132-142. doi: 10.1056/NEJMoa1615869.

DOI:10.1056/NEJMoa1615869

PMID:28700844

Abstract

BACKGROUND

We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality.

METHODS

From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up).

RESULTS

During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], -1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, -0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, -10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, -11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years.

CONCLUSIONS

After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression. (Funded by the Department of Veterans Affairs and others; PIVOT ClinicalTrials.gov number, NCT00007644 .).

摘要

背景

我们之前发现，接受局部前列腺癌手术治疗的男性与仅接受观察治疗的男性在死亡率方面没有显著差异。关于非致命性健康结果和长期死亡率仍然存在不确定性。

方法

从 1994 年 11 月到 2002 年 1 月，我们随机将 731 名患有局限性前列腺癌的男性分为前列腺切除术组或观察组。我们通过 2014 年 8 月延长了主要结局（全因死亡率）和主要次要结局（前列腺癌死亡率）的随访时间。我们通过 2010 年 1 月（原始随访）描述了疾病进展、接受的治疗和患者报告的结果。

结果

在 19.5 年的随访期间（中位数为 12.7 年），手术组 364 名男性中有 223 名（61.3%）死亡，观察组 367 名男性中有 245 名（66.8%）死亡（风险差异绝对值为 5.5 个百分点；95%置信区间为 -1.5 至 12.4；风险比为 0.84；95%置信区间为 0.70 至 1.01；P=0.06）。手术组 27 名（7.4%）男性归因于前列腺癌或治疗的死亡，观察组 42 名（11.4%）男性归因于前列腺癌或治疗的死亡（风险差异绝对值为 4.0 个百分点；95%置信区间为 -0.2 至 8.3；风险比为 0.63；95%置信区间为 0.39 至 1.02；P=0.06）。对于中危疾病的男性，手术可能比观察具有更低的全因死亡率（绝对差异为 14.5 个百分点；95%置信区间为 2.8 至 25.6），但对于低危疾病（绝对差异为 0.7 个百分点；95%置信区间为 -10.5 至 11.8）或高危疾病（绝对差异为 2.3 个百分点；95%置信区间为 -11.5 至 16.1）则并非如此（交互作用 P=0.08）。与观察组相比，手术组治疗疾病进展的频率较低（绝对差异为 26.2 个百分点；95%置信区间为 19.0 至 32.9）；治疗主要是针对无症状、局部或生化（前列腺特异性抗原）进展。尿失禁和勃起及性功能障碍在 10 年内通过手术比通过观察更常见。与观察组相比，2 年内与疾病相关或治疗相关的日常生活活动受限通过手术更为常见。

结论

在 731 名局限性前列腺癌男性接受近 20 年的随访后，手术与观察相比并未显著降低全因死亡率或前列腺癌死亡率。手术与观察组相比，不良事件的发生率更高，但治疗疾病进展的频率较低，主要是针对无症状、局部或生化进展。（由美国退伍军人事务部和其他机构资助；PIVOT 临床试验。gov 编号，NCT00007644）。