Perioperative Blood Transfusion Promotes Worse Outcomes of Bladder Cancer after Radical Cystectomy: A Systematic Review and Meta-Analysis

RESEARCH ARTICLE Perioperative Blood Transfusion Promotes Worse Outcomes of Bladder Cancer after Radical Cystectomy: A Systematic Review and Meta-Analysis You-Lin Wang1, Bo Jiang1, Fu-Fen Yin3, Hao-Qing Shi4, Xiao-Dong Xu4, ShuaiShuai Zheng1, Shuai Wu1*, Si-Chuan Hou1,2* 1 Department of Urology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China, 2 Department of Urology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China, 3 Department of Obstetrics and Gynecology, Affiliate Hospital of Qingdao University, Qingdao, China, 4 Department of Urology, Affiliate Hospital of Qingdao University, Qingdao, China * (SW); (SCH) Abstract OPEN ACCESS Citation: Wang Y-L, Jiang B, Yin F-F, Shi H-Q, Xu XD, Zheng S-S, et al. (2015) Perioperative Blood Transfusion Promotes Worse Outcomes of Bladder Cancer after Radical Cystectomy: A Systematic Review and Meta-Analysis. PLoS ONE 10(6): e0130122. doi:10.1371/journal.pone.0130122 Academic Editor: Zheng Su, Genentech Inc., UNITED STATES Received: January 31, 2015 Accepted: May 18, 2015 Published: June 16, 2015 Copyright: © 2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81301968). Competing Interests: The authors have declared that no competing interests exist. Background Multiple studies have investigated the effect of perioperative blood transfusion (PBT) for patients with radical cystectomy (RC), but the results have been inconsistent. We conducted a systematic review and meta-analysis to investigate the relationship between PBT and the clinical outcomes of RC patients. Methods We searched MEDLINE, EMBASE, the Cochrane library and BIOSIS previews to identify relevant literature for studies that focused on the relationship of PBT and outcomes of patients undergoing RC. A fixed or random effects model was used in this meta-analysis to calculate the pooled hazard ratio (HR) with 95% confidence intervals (CIs). Results A total of 7080 patients in 6 studies matched the selection criteria. Aggregation of the data suggested that PBT in patients who underwent RC correlated with increased allcause mortality, cancer-specific mortality and cancer recurrence. The combined HRs were 1.19 (n = 6 studies, 95% CI: 1.11–1.27, Z = 4.71, P<0.00001), 1.17 (n = 4 studies, 95% CI: 1.06–1.30, Z = 3.06, P = 0.002), 1.14 (n = 3 studies, 95% CI: 1.03–1.27, Z = 2.50, P = 0.01), respectively. The all-cause mortality associated with PBT did not vary by the characteristics of the study, including number of study participants, follow-up period and the median blood transfusion ratio of the study. PLOS ONE | DOI:10.1371/journal.pone.0130122 June 16, 2015 1 / 11 PBT and Outcomes of Patients Underwent RC- A Meta-Analysis Conclusion Our data showed that PBT significantly increased the risks of all-cause mortality, cancerspecific mortality and cancer recurrence in patients undergoing RC for bladder cancer. Introduction Bladder cancer is the fifth most common cancer in Western countries and the highest cause of death among urinary malignancies in China [1]. RC remains the gold standard for treatment of muscle-invasive bladder cancer. This procedure is associated with significant blood loss and a common transfusion requirement. Substantial improvements in surgical techniques and perioperative management in the past two decades have markedly reduced operative and hospital mortality rates for patients with bladder carcinoma undergoing cystectomy [2, 3]. However, a large number of patients still require perioperative BTs (PBTs). Recently, many investigators have focused on the underlying association between PBT and outcomes in various operations, such as lung cancer [4, 5], hepatocellular carcinoma [6, 7], colorectal cancer [8, 9], and prostate cancer [10], but their results were highly contradictory. A previous meta-analysis performed by Liu et al [11] demonstrated that allogeneic blood transfusion (ABT) was associated with adverse clinical outcomes for hepatocellular carcinoma patients undergoing surgery, including increased death, recurrence and complications. PBT in patients with bladder cancer was associated with increased morbidity and mortality after RC in several observational studies [12, 13], but other studies [14, 15] did not show this association in multivariable analysis. Some studies indicated that the disease characteristics (e.g., older age, higher pathological stage, longer surgical time and greater estimated blood loss) of patients who received PBT, rather than PBT itself, lead to worse outcomes [14, 15]. However, no metaanalysis has focused on the association between PBT and outcomes after RC for bladder cancer. We performed a meta-analysis of eligible studies to investigate the relationship between PBT and the clinical outcomes of RC and clarify the exact impact of PBT in patients who have undergone RC. Methods 2.1 Data sources We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane library and BIOSIS databases for studies that were published from the time of inception to October 2014 using terms such as ‘‘bladder and transfusion” and “cystectomy and transfusion” combined with Boolean operators where appropriate. We also searched the reference lists of relevant studies and previous meta-analyses for additional studies. Unpublished conference papers were screened from the ISI Web of Knowledge Conference Proceedings to ensure the search was as comprehensive as possible, and these data were also included when possible. 2.2 Study selection Two investigators (Y-L.W. and F-F.Y) independently extracted data from eligible studies. Disagreements were resolved by discussion and consensus. Two investigators reviewed all studies that met the inclusion and exclusion criteria. The following information was recorded for each study: (1) the study had to report the correlation between perioperative allogeneic blood transfusion and outcomes in patients undergoing RC; and (2) data were available on clinical PLOS ONE | DOI:10.1371/journal.pone.0130122 June 16, 2015 2 / 11 PBT and Outcomes of Patients Underwent RC- A Meta-Analysis outcomes (e.g., all-cause mortality, cancer-specific mortality, or disease recurrence). We excluded reviews, letters without original data and editorials. For duplicate publications reported by the same authors, either the higher quality or most recent publication was selected. 2.3 Data extraction and quality assessment Two investigators independently reviewed each eligible article and extracted information from all of the publications that met the inclusion c (...truncated)