|Year : 2018 | Volume
| Issue : 10 | Page : 701-707
The impact of perioperative blood transfusion on survival and recurrence after radical prostatectomy for prostate cancer: A systematic review and meta-analysis
Zhang Pushan1, Chen Manbiao1, Liu Sulai2, Li Jun1, Zhang Ruidong1, Ye Hanshen1
1 Department of Blood Transfusion, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510150, China
2 Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan 410000, China
|Date of Web Publication||24-Sep-2018|
Department of Blood Transfusion, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510150
Source of Support: None, Conflict of Interest: None
Objective: Conflicting data have been reported regarding the association between perioperative blood transfusion (PBT) and clinical outcomes for prostate cancer patients. We conducted a systematic review and meta-analysis to evaluate the impact of PBT on cancer survival and recurrence for patients who underwent radical prostatectomy (RP).
Methods: A systematic review of PubMed, EMBASE, and Cochrane libraries was performed to identify all eligible studies that evaluate the association between PBT and clinical outcomes for prostate cancer patients undergoing RP. The analyzed outcomes were overall survival (OS) and recurrence-free survival (RFS) at 3, 5, and 10 years.
Results: A total of eight articles met our criteria. Meta-analysis indicated that prostate cancer patients with PBT had decreased OS (hazard ratio [HR] =1.51, 95% confidence interval [CI], 1.22–1.85, P < 0.01; HR = 1.57, 95% CI, 1.33–1.85, P < 0.01; HR = 1.55, 95% CI, 1.03–2.33, P = 0.04) and RFS (HR = 1.67, 95% CI, 1.37–2.04, P < 0.01; HR = 1.42, 95% CI, 1.23–1.63, P < 0.01; HR = 1.37, 95% CI, 1.03–1.83, P = 0.03) at 3, 5, and 10 years after surgery compared with those without PBT.
Conclusions: The findings from the current meta-analysis demonstrate that PBT was associated with adverse survival and recurrence outcomes for prostate cancer patients undergoing RP.
Keywords: Blood transfusion, radical prostatectomy, recurrence, survival
|How to cite this article:|
Pushan Z, Manbiao C, Sulai L, Jun L, Ruidong Z, Hanshen Y. The impact of perioperative blood transfusion on survival and recurrence after radical prostatectomy for prostate cancer: A systematic review and meta-analysis. J Can Res Ther 2018;14, Suppl S3:701-7
|How to cite this URL:|
Pushan Z, Manbiao C, Sulai L, Jun L, Ruidong Z, Hanshen Y. The impact of perioperative blood transfusion on survival and recurrence after radical prostatectomy for prostate cancer: A systematic review and meta-analysis. J Can Res Ther [serial online] 2018 [cited 2020 Feb 24];14:701-7. Available from: http://www.cancerjournal.net/text.asp?2018/14/10/701/193115
| > Introduction|| |
One major complication of radical prostatectomy (RP) is blood loss and blood transfusion. Clinical evidence suggests that immunosuppressive effects of red blood cell (RBC) transfusion may contribute to an increased incidence of tumor recurrence complications in surgical patients.,,,, This effect may alter the disease outcome of neoplasm, because patients with blood transfusion may demonstrate a poorer prognosis compared with patients without blood transfusion.
A great deal of attention over the past 40 years has centered on whether perioperative blood transfusion (PBT) in cancer patients impacts recurrence and survival. Conflicting data have been reported regarding the association between PBT and clinical outcomes. A large-scale study of more than 2000 patients undergoing radical cystectomy showed a significant association between PBT and increased risk of cancer recurrence and cancer-specific mortality. However, another study about 11,680 patients undergoing RP did not find an association between PBT and cancer recurrence. As these published results were based on retrospective cohort or prospective observational cases from a single center, they could contribute to this inconsistent phenomenon. It is necessary to undertake a systematic review and meta-analysis to evaluate the postoperative influence of PBT for patients with prostate cancer.
| > Methods|| |
Literature search and study selection
In accordance with the PRISMA guidelines, a systematic review of the literature was performed in March 2016 using Medline, EMBASE, and the Cochrane Central Search library. Review articles and bibliographies of other relevant studies identified were hand-searched to find additional studies. The following Medical Subject Heading terms and key words were used to identify relevant studies: “Blood transfusion,” “Recurrence,” “Survival,” “Prostatectomy,” and “Prostate Cancer.” Searches were restricted to publications in English.
The eligible studies had to meet the following selection criteria: (1) The studies had to evaluate the association between PBT and clinical outcomes (recurrence or mortality) for patients undergoing RP, (2) the report contained key information or can estimate hazard ratio [HR] by the shown data, (3) the papers focused on autogenic blood transfusion were excluded, and (4) conference abstracts, reviews, and letters to editors were not included in the study. Studies with overlapping or insufficient data were excluded from the study. [Table 1] illustrates the process of identifying and selecting articles.
Data extraction and study quality assessment
Two reviewers extracted the information from eligible studies to the inclusion criteria. Disagreement was resolved during a consensus with a third reviewer. The literature information, demographic and survival analysis, as well as methods of risk evaluation method were extracted individually. HR and its 95% confidence intervals (CIs) that elevated PBT and non-PBT for overall survival (OS) and recurrence-free survival (RFS) were used to measure the association for each study. The predefined time point was 3, 5, and 10 years after surgery. If available, the HRs with their 95% CIs and P values were collected from the original article. If not, we calculated HRs and their 95% CIs using the data of observed deaths/cancer recurrences, the data of samples in each group, or the data provided by the authors. If only survival curves were available, we extracted data from the graphical survival plots and estimated the HRs., We evaluated the quality of studies using the Newcastle–Ottawa Scale.
A meta-analysis was performed to assess the outcomes of PBT when compared with non-PBT. The PBT group was defined as patients who received any amount of allogeneic blood products (packed RBCs, plasma, platelets, or whole blood) during the 30 days before and after the surgery. Non-PBT group was patients who did not receive any blood products. Stratified analyses were performed on sample size, study quality, and publication year. Statistical heterogeneity was assessed using a formal Q-statistic as well as I2, with the statistical significance level set at 0.05. Publication bias was evaluated by Egger's and Begg's test, with the statistical significance level set at 0.05. All these analyses were implemented in STATA 11.0 statistical software (Stata Corp., College Station, TX, USA).
Characteristics of the individual studies
One hundred and sixty-eight studies were identified from the electronic database and hand search. We excluded 156 articles; full texts of 12 relevant articles were analyzed, two articles were excluded because they lacked of key information or made estimation of HR impossible,, resulting in eight articles for analysis.,,,,,,, The characteristics of the included studies are summarized in [Table 2]. According to the 9-star Newcastle–Ottawa Scale, five of the studies were defined as high-quality studies (score >7).
Statistical analysis and meta-analysis
Six studies reported 3-year OS, involving 9388 cases; seven studies reported 5-year OS, involving 11965 cases; and five studies reported 10-year OS, involving 9202 cases. There was no statistical heterogeneity between trials (I2 =6.9%; P = 0.37) about 3-year OS, fixed effects modeling was used to obtain pooled estimates. The pooled summary of the HR was 1.51 (95% CI: 1.22–1.85, P < 0.01) about 3-year OS [Figure 1]a. Measures of heterogeneity do not indicate a high degree of variability about 5-year OS (I2 = 50.5%, P = 0.06). Fixed effects modeling was used to obtain pooled estimates. The pooled summary of the HR was 1.57 (95% CI: 1.33–1.85, P < 0.01) about 5-year OS [Figure 1]b. Significant heterogeneity among studies about 10-year OS was present (I2 = 88.4%, P < 0.01). Random effects modeling was used to obtain pooled estimates. The pooled summary of the HR was 1.55 (95% CI: 1.03–2.33, P = 0.04) [Figure 1]c. Similar results were obtained in small sample size studies (HR: 1.51, 95% CI: 1.21–1.88, P < 0.01) and large sample size studies (HR: 1.65, 95% CI: 1.28–2.14, P < 0.01) on 5-year OS [Table 3]. Studies with high quality (HR: 1.63, 95% CI: 1.35–1.97, P < 0.01) demonstrated that PBT could decrease 5-year OS, while low-quality studies demonstrated that PBT has no effect on 5-year OS (HR: 1.36, 95% CI: 0.96–1.94, P = 0.08). When examining differences over time, we found that studies published before 2000 had a summary estimate with a pooled HR of 1.31 (95% CI: 1.01–1.70, P = 0.04) and studies published after 2000 had an overall estimate with a pooled HR of 2.17 (95% CI: 1.60–2.95, P < 0.01) [Table 3].
|Figure 1: (a) Forest plot of 3-year overall survival associated with perioperative blood transfusion for prostate cancer. (b) Forest plot of 5-year overall survival associated with perioperative blood transfusion for prostate cancer. (c) Forest plot of 10-year overall survival associated with perioperative blood transfusion for prostate cancer|
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We used Egger's test and Begg's test to evaluate the publication bias. P values for Begg's adjusted rank correlation test about 3-, 5-, 10-year OS were 0.85, 0.88, and 0.46, respectively. The Egger's regression asymmetry test about 3-, 5-, 10-year OS was 0.48, 0.95, and 0.37, respectively.
Five studies reported the data of 3-year RFS in PBT and non-PBT patients, involving 9345 cases; six studies reported 5-year RFS, involving 11,563 cases; and four studies reported 10-year RFS, involving 8986 cases. There was no statistical heterogeneity between trials (I2 =0%; P = 0.769), but for 3-year RFS, fixed effects modeling was used to obtain pooled estimates. The pooled summary of the HR was 1.67 (95% CI: 1.37–2.04, P < 0.01) [Figure 2]a. Measures of heterogeneity do not indicate a high degree of variability about 5-year RFS (I2 = 0%, P = 0.56). Fixed effects modeling was used to obtain pooled estimates. The pooled summary of the HR was 1.42 (95% CI: 1.23–1.63, P < 0.01) about 5-year RFS [Figure 2]b. Significant heterogeneity among studies about 10-year RFS was present (I2 = 68%, P = 0.03). Random effect modeling was used to obtain pooled estimates. The pooled summary of the HR was 1.37 (95% CI: 1.03–1.83, P = 0.03) [Figure 2]c. Similar results were obtained in either large (HR: 1.39, 95% CI: 1.20–1.60, P < 0.01) or small (HR: 1.83, 95% CI: 1.13–2.95, P < 0.01) sample size studies. PBT was associated with decreased RFS in low-quality studies (HR: 1.83, 95% CI: 1.13–2.95, P < 0.01) and high-quality studies (HR: 1.39, 95% CI: 1.20–1.60, P < 0.01). When examining differences over time, we found that studies published before 2000 had a summary estimate with a pooled HR of 1.31 (95% CI: 1.04–1.66, P = 0.02) and studies published after 2000 had an overall estimate with a pooled HR of 1.48 (95% CI: 1.24–1.76, P < 0.01) [Table 3].
|Figure 2: (a) Forest plot of 3-year recurrence-free survival associated with perioperative blood transfusion for prostate cancer. (b) Forest plot of 5-year recurrence-free survival associated with perioperative blood transfusion for prostate cancer. (c) Forest plot of 10-year recurrence-free survival associated with perioperative blood transfusion for prostate cancer|
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P values for Begg's adjusted rank correlation test about 3-, 5-, 10-year OS were 1.0, 0.85, and 1.0, respectively. The Egger's regression asymmetry test about 3-, 5-, 10-year OS was 0.54, 0.35, and 0.73, respectively.
| > Discussion|| |
Blood transfusion is a common intervention with uncertain long-term consequences, especially in the setting of oncologic surgery. Since the initial report of immunosuppression in transplant patients, there have been several reports of deleterious outcomes in patients undergoing potentially curative surgery for cancer., Whereas, a number of other authors reported no effect of PBT on survival or recurrence after cancer surgery.,,,, Liu et al. did a meta-analysis of literature published between 1967 and November 2012, including 22 clinical studies in the final analysis. The findings from their meta-analysis demonstrated that allogeneic blood transfusion was associated with increased death and recurrence for hepatocellular carcinoma patients undergoing surgery. There is a lack of systematic evaluation focused on PBT for patients with prostate cancer. We, therefore, undertook a systematic review and meta-analysis of the literature to find the supporting evidence of PBT use in RP for patients with prostate cancer.
Our meta-analysis illustrated that PBT in patients undergoing surgery for prostate cancer was associated with significantly worse outcomes after 3, 5, and 10 years, including OS and RFS. Subgroup analysis by different published years and sample sizes displayed the similar survival and recurrence disadvantage. Low-quality studies showed no effect of PBT on OS.
The reason why PBT can cause adverse clinical outcomes in patients with cancer remains uncertain. The suppressive effects of transfusion on the immune system have been assumed as a main possible reason. A potential mechanism for the immunologic activity of PBT is transfusion-induced energy due to the presentation of large amounts of antigen in the transfused blood products. Animal studies have showed that at least some of the immunosuppressive effects are mediated by donor leukocytes, and the tumor-promoting properties of allogeneic blood can be abrogated by leukoreduction of the donor blood. In the clinical setting, packed allogeneic RBC transfusion has been shown to enhance both inflammatory and immunosuppressive systemic responses in patients who underwent colorectal cancer resection.
Several limitations should be noted in our study. First, none of the studies analyzed here were randomized controlled trials. Because of practical and ethical constraints, randomized trials have not yet been done in this area, as there is no choice for patients with substantial hemorrhage but transfusion. The designs of the studies used for our analysis are relatively weak due to their retrospective nature, and significant clinical heterogeneity exists between them. Second, the characteristics of patients are different between the studies. As we do not have direct access to the original data, detailed statistical analyses are not possible. Patients who need blood transfusion are always severity case or have bad general health condition, which may cause patient selection bias and influence the long-term outcomes. Thus, the conclusions drawn from our study should be interpreted cautiously. Third, some small sample size studies included in our analysis was also a limitation. However, we also included adequately powered prospective studies and some large sample sizes retrospective studies which involve more than 1000 cases.,,, Fourth, several HRs were calculated based on the data extracted from the survival curve, and this may bring errors although tiny. Finally, restriction of the literature search to English language may result in the loss of eligible researches published in other languages.
| > Conclusions|| |
The findings from the current meta-analysis demonstrate that PBT was associated with adverse survival and recurrence outcomes for prostate cancer patients undergoing RP. However, conclusions drawn from our study should be interpreted cautiously. Multicenter prospective study with a longer follow-up period and more clearly defined parameters would be the best way to study this issue in the future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Gantt CL. Red blood cells for cancer patients. Lancet 1981;2:363.
Swisher SG, Holmes EC, Hunt KK, Gornbein JA, Zinner MJ, McFadden DW. Perioperative blood transfusions and decreased long-term survival in esophageal cancer. J Thorac Cardiovasc Surg 1996;112:341-8.
Fujimoto J, Okamoto E, Yamanaka N, Tanaka T, Tanaka W. Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma. Hepatogastroenterology 1997;44:1390-6.
Kaneko M, Sasaki S, Ishimaru K, Terai E, Nakayama H, Watanabe T. The impact of perioperative allogeneic blood transfusion on survival in elderly patients with colorectal cancer. Anticancer Res 2015;35:3553-8.
Wang YL, Jiang B, Yin FF, Shi HQ, Xu XD, Zheng SS, et al.
Perioperative blood transfusion promotes worse outcomes of bladder cancer after radical cystectomy: A systematic review and meta-analysis. PLoS One 2015;10:e0130122.
Linder BJ, Frank I, Cheville JC, Tollefson MK, Thompson RH, Tarrell RF, et al.
The impact of perioperative blood transfusion on cancer recurrence and survival following radical cystectomy. Eur Urol 2013;63:839-45.
Chalfin HJ, Frank SM, Feng Z, Trock BJ, Drake CG, Partin AW, et al.
Allogeneic versus autologous blood transfusion and survival after radical prostatectomy. Transfusion 2014;54:2168-74.
Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.
Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998;17:2815-34.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007;8:16.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088-101.
Paul R, Schmid R, Busch R, van Randenborgh H, Alschibaja M, Schöler S, et al.
Influence of blood transfusions during radical retropubic prostatectomy on disease outcome. Urology 2006;67:137-41.
Boehm K, Beyer B, Tennstedt P, Schiffmann J, Budaeus L, Haese A, et al.
No impact of blood transfusion on oncological outcome after radical prostatectomy in patients with prostate cancer. World J Urol 2015;33:801-6.
Ford BS, Sharma S, Rezaishiraz H, Huben RS, Mohler JL. Effect of perioperative blood transfusion on prostate cancer recurrence. Urol Oncol 2008;26:364-7.
Yeoh TY, Scavonetto F, Weingarten TN, Karnes RJ, van Buskirk CM, Hanson AC, et al
. Perioperative allogeneic nonleukoreduced blood transfusion and prostate cancer outcomes after radical prostatectomy. Transfusion 2014;24:12595.
McClinton S, Moffat LE, Scott S, Urbaniak SJ, Kerridge DF. Blood transfusion and survival following surgery for prostatic carcinoma. Br J Surg 1990;77:140-2.
Eickhoff JH, Göte H, Baeck J. Peri-operative blood transfusion in relation to tumour recurrence and death after surgery for prostatic cancer. Br J Urol 1991;68:608-11.
Heal JM, Chuang C, Blumberg N. Perioperative blood transfusions and prostate cancer recurrence and survival. Am J Surg 1988;156:374-80.
Velagapudi SR, Frydenberg M, Oesterling JE, Bergstralh EJ, Moore SB, Ruckle HC, et al
. Homologous blood transfusion in patients with prostate cancer: No effect on tumor progression or survival. Urology 1994;43:821-7.
Kim JK, Kim HS, Park J, Jeong CW, Ku JH, Kim HH, et al.
Perioperative blood transfusion as a significant predictor of biochemical recurrence and survival after radical prostatectomy in patients with prostate cancer. PLoS One 2016;11:e0154918.
Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc 1973;5:253-9.
Liu L, Wang Z, Jiang S, Shao B, Liu J, Zhang S, et al.
Perioperative allogeneic blood transfusion is associated with worse clinical outcomes for hepatocellular carcinoma: A meta-analysis. PLoS One 2013;8:e64261.
Blumberg N, Heal JM. Effects of transfusion on immune function. Cancer recurrence and infection. Arch Pathol Lab Med 1994;118:371-9.
Blajchman MA, Bardossy L, Carmen R, Sastry A, Singal DP. Allogeneic blood transfusion-induced enhancement of tumor growth: Two animal models showing amelioration by leukodepletion and passive transfer using spleen cells. Blood 1993;81:1880-2.
Ydy LR, Slhessarenko N, de Aguilar-Nascimento JE. Effect of perioperative allogeneic red blood cell transfusion on the immune-inflammatory response after colorectal cancer resection. World J Surg 2007;31:2044-51.
Velagapudi SR, Frydenberg M, Oesterling JE, Bergstralh EJ, Moore SB, Ruckle HC, et al.
Homologous blood transfusion in patients with prostate cancer: No effect on tumor progression or survival. Urology 1994;43:821-7.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]