Elsevier

European Urology

Volume 63, Issue 5, May 2013, Pages 839-845
European Urology

Platinum Priority – Bladder Cancer
Editorial by George N. Thalmann on pp. 846–847 of this issue
The Impact of Perioperative Blood Transfusion on Cancer Recurrence and Survival Following Radical Cystectomy

https://doi.org/10.1016/j.eururo.2013.01.004Get rights and content

Abstract

Background

While the receipt of a perioperative blood transfusion (PBT) has been associated with an increased risk of mortality for a number of malignancies, the relationship between PBT and survival following radical cystectomy (RC) for bladder cancer (BCa) has not been well established.

Objective

To evaluate the association of PBT with disease recurrence and mortality following RC.

Design, setting, and participants

We identified 2060 patients who underwent RC at the Mayo Clinic between 1980 and 2005. PBT was defined as transfusion of allogenic red blood cells during RC or postoperative hospitalization.

Outcome measurements and statistical analysis

Survival was estimated using the Kaplan-Meier method and was compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of PBT with outcome, controlling for clinicopathologic variables.

Results and limitations

A total of 1279 patients (62%) received PBT. The median number of units transfused was 2 (interquartile range [IQR]: 2–4). Patients receiving PBT were significantly older (median: 69 yr vs 66 yr; p < 0.0001), had a worse Eastern Cooperative Oncology Group performance status (p < 0.0001), and were more likely to have muscle-invasive tumors (56% vs 49%; p = 0.004). Median postoperative follow-up was 10.9 yr (IQR: 7.9–15.7). Receipt of PBT was associated with significantly worse 5-yr recurrence-free survival (58% vs 64%; p = 0.01), cancer-specific survival (59% vs 72%; p < 0.001), and overall survival (45% vs 63%; p < 0.001). On multivariate analyses, PBT remained associated with significantly increased risks of postoperative tumor recurrence (hazard ratio [HR]: 1.20; p = 0.04), death from BCa (HR: 1.31; p = 0.003), and all-cause mortality (HR: 1.27; p = 0.0002). Among patients who received PBT, an increasing number of units transfused was independently associated with increased cancer-specific mortality (HR: 1.07; p < 0.0001) and all-cause mortality (HR: 1.05; p < 0.0001). Limitations include selection bias and lack of standardized transfusion criteria.

Conclusions

We found that PBT is associated with significantly increased risks of cancer recurrence and mortality following RC. While external validation is required, continued efforts to reduce the use of blood products in these patients are warranted.

Introduction

The potential immunosuppressive effect of red blood cell transfusion was first described by Opelz and Terasaki in 1974, in a report of enhanced renal allograft survival among patients receiving a transfusion [1]. Similarly, a later series noted lower recurrence rates in patients with Crohn's disease who received a perioperative blood transfusion (PBT) [2]. PBT has been associated with subsequent disease recurrence in a number of malignancies, including colon, esophageal, and hepatic carcinomas [3], [4], [5]. While multiple hypotheses regarding the biologic activity of PBT—including immunomodulation and growth factor delivery from red blood cells—have been offered, no definitive mechanistic link has been established [6], [7], [8].

Conflicting data have been reported regarding the association of PBT with recurrence rates for prostate cancer (PCa) patients undergoing radical prostatectomy [9], [10], [11], [12], as well for renal cell carcinoma patients following nephrectomy [13], [14]. With regard to bladder cancer (BCa), there has been a paucity of data regarding the association of PBT with postoperative outcomes after radical cystectomy (RC) [15], [16]. As RC remains associated with a relatively high rate of transfusion [16], [17], [18], [19], determining the association of PBT with postoperative cancer control and mortality remains important for optimizing patient management.

Using a large cohort of patients with long-term follow-up, we evaluated the association of PBT with disease recurrence and survival following RC, controlling for clinicopathologic variables.

Section snippets

Patients and methods

Following institutional review board approval, we reviewed the Mayo Clinic Cystectomy Registry and identified 2060 patients treated with RC for BCa at our institution between 1980 and 2005. RC with lymphadenectomy was performed using standard techniques by various surgeons over the time frame of the study. Given the time span of patients included, the extent of lymph node dissection varied but currently extends from the mid–common iliac artery proximally to the Cooper ligament distally,

Results

Of 2060 patients undergoing RC, 1279 patients (62%) received a PBT, with 2 U as the median number of units transfused (interquartile range [IQR]: 2–4 units). Clinicopathologic demographics for these patients, as well as for the cohort who did not receive a PBT, are provided in Table 1. As can be seen, patients receiving PBT were significantly older (p < 0.0001) and more likely to be female (p < 0.0001), with a worse ECOG performance status (p < 0.0001), a lower body mass index (p < 0.0001), and a lower

Discussion

We found in this study with a large cohort of patients undergoing RC with long-term postoperative follow-up that receipt of a PBT was associated with significantly increased risks of cancer recurrence, death from BCa, and all-cause mortality. Additionally, among patients who received a PBT, an increasing number of units transfused was associated with significantly increased risks of cancer-specific and all-cause mortality. These findings remained significant after controlling for

Conclusions

We found an association of PBT with significantly increased risks of tumor recurrence and mortality following RC. This association remained when accounting for potential confounding clinical and pathologic features. While these data require external validation, continued efforts to limit the use of blood products in these patients are warranted; these efforts include implementing restrictive transfusion criteria or alternative strategies for blood replacement and surgical techniques to minimize

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