Wallis Christopher J D, Mahar Alyson L, Choo Richard, Herschorn Sender, Kodama Ronald T, Shah Prakesh S, Danjoux Cyril, Narod Steven A, Nam Robert K
Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada Institute of Health Policy, Management and Evaluation, University of Toronto, Suite 425, 155 College Street, Toronto, ON M5T 3M6, Canada.
Division of Urology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Room MG-406, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
BMJ. 2016 Mar 2;352:i851. doi: 10.1136/bmj.i851.
To determine the association between exposure to radiotherapy for the treatment of prostate cancer and subsequent second malignancies (second primary cancers).
Systematic review and meta-analysis of observational studies.
Medline and Embase up to 6 April 2015 with no restrictions on year or language.
Comparative studies assessing the risk of second malignancies in patients exposed or unexposed to radiotherapy in the course of treatment for prostate cancer were selected by two reviewers independently with any disagreement resolved by consensus.
Two reviewers independently extracted study characteristics and outcomes. Risk of bias was assessed with the Newcastle-Ottawa scale. Outcomes were synthesized with random effects models and Mantel-Haenszel weighting. Unadjusted odds ratios and multivariable adjusted hazard ratios, when available, were pooled.
Second cancers of the bladder, colorectal tract, rectum, lung, and hematologic system.
Of 3056 references retrieved, 21 studies were selected for analysis. Most included studies were large multi-institutional reports but had moderate risk of bias. The most common type of radiotherapy was external beam; 13 studies used patients treated with surgery as controls and eight used patients who did not undergo radiotherapy as controls. The length of follow-up among studies varied. There was increased risk of cancers of the bladder (four studies; adjusted hazard ratio 1.67, 95% confidence interval 1.55 to 1.80), colorectum (three studies; 1.79, 1.34 to 2.38), and rectum (three studies; 1.79, 1.34 to 2.38), but not cancers of the hematologic system (one study; 1.64, 0.90 to 2.99) or lung (two studies; 1.45, 0.70 to 3.01), after radiotherapy compared with the risk in those unexposed to radiotherapy. The odds of a second cancer varied depending on type of radiotherapy: treatment with external beam radiotherapy was consistently associated with increased odds while brachytherapy was not. Among the patients who underwent radiotherapy, from individual studies, the highest absolute rates reported for bladder, colorectal, and rectal cancers were 3.8%, 4.2%, and 1.2%, respectively, while the lowest reported rates were 0.1%, 0.3%, and 0.3%.
Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low. Further studies with longer follow-up are required to confirm these findings.
确定前列腺癌放射治疗暴露与后续第二原发恶性肿瘤（第二原发性癌症）之间的关联。
观察性研究的系统评价和荟萃分析。
截至2015年4月6日的Medline和Embase，对年份和语言无限制。
由两名评审员独立选择评估前列腺癌治疗过程中接受或未接受放射治疗的患者发生第二原发恶性肿瘤风险的比较研究，任何分歧通过共识解决。
两名评审员独立提取研究特征和结果。采用纽卡斯尔-渥太华量表评估偏倚风险。结果采用随机效应模型和Mantel-Haenszel加权法进行综合分析。合并未调整的比值比和多变量调整的风险比（如可得）。
膀胱、结肠、直肠、肺和血液系统的第二原发性癌症。
在检索到的3056篇参考文献中，选择了21项研究进行分析。大多数纳入研究是大型多机构报告，但偏倚风险为中度。最常见的放射治疗类型是外照射；13项研究将接受手术治疗的患者作为对照，8项研究将未接受放射治疗的患者作为对照。各研究的随访时间不同。与未接受放射治疗的患者相比，放射治疗后膀胱（4项研究；调整后风险比1.67，95%置信区间1.
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