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Keywords:

  • prostate;
  • cancer;
  • prostatectomy;
  • transfusion

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Objective

To assess whether there is a difference in the biochemical recurrence rate in patients who had radical retropubic prostatectomy (RRP) with or without cell salvage transfusion.

Patients and methods

The records of 769 consecutive patients undergoing RRP between 1992 and 1998 were retrospectively reviewed. Patients having adjuvant hormonal treatment, postoperative external beam radiotherapy, or a follow-up of < 1 year were excluded from the analysis. The remaining 408 patients were categorized into three groups: 87 who received cell-salvaged blood using a commercial cell saver; 264 receiving only autologous transfusion; and 57 with no transfusion. Disease recurrence was defined as a prostate-specific antigen (PSA) level of> 0.2 ng/mL. Bivariate and multivariate logistic regression analyses were used to assess and compare the risk of cancer recurrence in the three groups. Covariates used in the multivariate analyses included Gleason score, preoperative PSA level, seminal vesicle involvement and surgical margins.

Results

The mean (range) follow-up was 40.2  (12–104) months; there were no significant differences among the groups in initial PSA level and Gleason score. In the multivariate logistic regression analysis, the initial PSA, Gleason score, seminal vesicle involvement and surgical margins, but not transfusion group, were independent predictors of recurrence.

Conclusion

Cell salvage during RRP does not influence the recurrence of prostate cancer. Cell salvage is a safe method of transfusion during RRP.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Blood volume management is an important issue in the care of patients undergoing radical retropubic prostatectomy (RRP). The use of various techniques for RRP has led to a dramatic decrease in the use of homologous blood. Autologous pre-donation is frequently suggested and is a reasonable alternative to homologous blood transfusion. Other blood-volume management techniques have been investigated but have not gained popularity despite their use in other surgical procedures. One of these techniques is intraoperative cell salvage (IOCS). Although there are data on the use of IOCS in various urological malignancies, there are no data on its use and effect on recurrence of prostate cancer for a large group of patients. Because this technology is readily available, and the mean intraoperative blood loss during RRP is 500–1000 mL, the use of IOCS merits investigation [1].

The need for a viable alternative to homologous blood transfusion has been investigated by different groups. The reluctance of clinicians to use, and of patients to receive, homologous blood stems from the complications associated with the use of this type of blood replacement. A study of the risks of the screened blood supply indicated that the risks of HIV infection per screened unit is ≈ 1 in 493 000, of human T cell leukaemia virus 1 in 641 000, of hepatitis C virus 1 in 103 000 and of hepatitis B, 1 in 63 000 [2]. Furthermore, various investigators have reported an increased risk of tumour recurrence and postoperative infection when large amounts of homologous blood are given to patients before, during or after surgery [3,4]. This relationship of homologous blood products to infection and cancer recurrence has led to theories of how these transfusions might alter immune function. It has been proposed that this immune dysregulation may be synergistic to reactivated latent or active viral infections.

Autologous pre-donation for RRP has been used as an alternative to homologous blood by many surgeons performing RRP. The advantage of autologous pre-donation is that the risks associated with homologous blood are removed or reduced, but some effects may remain. The primary problems are the cost of donation and the wastage of many of these donated units [5–7]. Patients may also have preoperative anaemia if the pre-donation period is inadequate to allow for regeneration of the red cell mass.

IOCS has been available for over two decades; it is commonly used in cardiothoracic and vascular surgery. The use of IOCS during oncological surgery has the theoretical risk of introducing tumour cells from the operative field to the patient's vasculature. The reluctance of surgeons to use this method of blood salvage has diminished, as reports found no increase in local recurrence or metastatic disease when compared with standard survival data [8]. There are few data on the use of IOCS during RRP. The availability of a sensitive marker for recurrence, i.e. PSA, provides an opportunity to accurately detect any recurrence of prostate cancer. The aim of the present study was to investigate if the use of IOCS influenced the PSA recurrence rate.

Patients and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Records of 769 consecutive patients undergoing RRP by the same surgeon between 1992 and 1998 were retrospectively reviewed. Patients having adjuvant hormonal treatment, postoperative external beam radiotherapy or an incomplete follow-up were excluded. The remaining 408 patients were categorized into three groups: group 1, 87 who received cell salvaged blood during RRP, using the Haemonetics cell saver (Braintree, MA, USA); group 2, 264 who received only autologous transfusion; and group 3, 57 receiving no blood transfusion. Disease recurrence was defined as a PSA level of> 0.2 ng/mL.

The cell saver was used on all patients receiving a cell salvage transfusion; the machine functions using anticoagulant (heparin or citrate) delivered through a double-lumen catheter to the tip of the suction apparatus. The blood anticoagulant mixture is drawn into a cardiotomy reservoir that contains a 40 µm filter. The operator of the machine adjusts a series of valves that control the delivery of blood to a 225-mL or a 375-mL bowl rotating at 4800 rpm. Red blood cells align to the outside of the bowl because of their greater density; they are then washed with isotonic saline, and the plasma and most of the platelets removed. The final product is a saline suspension of red blood cells with a haematocrit of 55–60%. The red blood cells are pumped into a reinfusion bag and are available for immediate transfusion to the patient through a 20 µm filter. The entire cycle takes 7–10 min [9].

Our policy has been to give all patients an opportunity to donate one unit of blood for their surgery. We transfuse the autodonated blood if the blood loss is> 700 mL. Some patients did not donate blood. A similar policy was used for the cell-saver blood; if there was no autologous blood, cell-saver blood was given if the estimated blood loss was> 700–900 mL. Other variables included the patient's age and comorbidity, e.g. cardiac disease. If the patient donated blood this was used before a decision was made to use the cell-salvaged blood. Thus, no autologous unit was wasted if it was needed during or after RRP.

The three transfusion groups were compared using a one-way anova for continuous variables with normal or approximately normal distributions, and the Kruskal–Wallis test for variables with skewed distributions. Chi-square analyses were used for nominal and ordinal variables. Bivariate and multivariate logistic regression analyses were used to assess and compare the risk of biochemical recurrence, including in the model the following independent variables: transfusion method, Gleason score, preoperative PSA level, seminal vesicle involvement (SVI) and surgical margin status.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

There were no significant differences (P > 0.05) among the three transfusion groups in initial PSA and Gleason sum. Recurrence was detected in 67 patients (16%) and was not significantly associated with the method of transfusion (chi-square P = 0.784). Recurrence rates were 15%, 16% and 19%, respectively, for groups 1, 2 and 3. Compared with patients having no recurrence, those with recurrence were significantly (P < 0.01) older, had a higher initial PSA level and a higher Gleason sum (Table 1). The rate of recurrence was significantly higher for patients with than with no SVI and for those with than with no surgical margin involvement (Table 1). In multivariate logistic regression analysis, the variables initial PSA, Gleason sum, SVI and surgical margin status, but not transfusion group, were independent significant predictors of recurrence. After adjusting for the remaining variables in the model, patients in group 1 were less likely to have recurrence than those in group 2 (odds ratio, 0.81; 95% CI, 0.33–2.00) or group 3 (0.66, 95% CI 0.21–2.08). No patient in this consecutive review of 769 RRPs received an homologous blood transfusion.

Table 1.  Statistically significant independent predictors of recurrence
PredictorRecurrenceNo recurrenceP
Mean (sd):
 age, years64.1 (5.7)61.2 (7.8)< 0.01
 PSA, ng/mL18.7 (16.2)  8.1 (7)< 0.01
 Gleason score  7.4 (1.2)  6.4 (1.1)< 0.01
SVI, %55.311.4< 0.001
+ve surgical margin, %36.8  8.2< 0.001
Capsular invasion, %62.721.7< 0.001
Extraprostatic extension, %20.9  9.70.0086

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References

Cell salvage has been viewed by many surgeons as having a theoretical risk of tumour cell dissemination when used during surgery for cancer. The use of cell salvage in urological oncology has been assessed for various urological malignancies [8,10,11]; it has been assessed during RRP but the number of patients and follow-up were limited.

One reason for the lack of enthusiasm for this method of blood volume management is the risk of tumour spread. Are cancerous cells from the operative field being transfused back to the patient? In vitro studies showed that standard red blood cell filters can remove most but not all the other blood cells. A leukocyte-depletion filter will decrease this risk [12]. Although there is a theoretical risk of re-introducing neoplastic cells, in vivo data suggest that there is no increased risk. The present results suggest that cell salvage during surgery for prostate cancer is safe.

The greatest risk of transfusion from the homologous blood supply is the risk of acquiring a blood-borne pathogen. Other risks include transfusion reaction and, as noted, the immune changes that can occur. The standard alternative to this blood volume management is autologous pre-donation, which carries little risk. A problem with auto-donation is the time involved and the time to normalize the haematocrit before surgery, which may take up to 4 weeks. Also, many studies have shown that autologous donation is not cost-effective, attributable to the increased wastage of units. Cell salvage is a reasonable alternative or additional method of volume management in a patient undergoing RRP. The surgeon may choose to only use cell salvage as the method of volume management, or to have the patient donate less blood before RRP. Using this method can help to reduce the time expended before surgery for pre-donation, decrease the need for homologous blood and its associated risks, and decrease the cost of wasted units associated with autologous pre-donation. No patient in the present series received a homologous blood transfusion, with the availability of cell salvage and pre-donation in over 760 consecutive RRPs.

In conclusion, the use of cell salvage during RRP does not appear to influence the recurrence of prostate cancer. To date this is the largest series of patients who have received cell-salvaged blood during RRP. Cell salvage decreases the need for autologous blood donation and eliminates the risk of hepatitis and HIV transmission through homologous transfusion; it is a safe method of transfusion during RRP.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and methods
  5. Results
  6. Discussion
  7. References
  • 1
    Walsh PC. Radical retropubic prostatectomy. In WalshPC, RetikAB, StameyTA eds, Campbell's Urology, 6th edn, Vol. 3. Chapter 78. Philadelphia: WB Saunders, 1992: 286528
  • 2
    Schreiber GB, Busch MP, Klienman SH et al. The risk of transfusion-transmitted viral infections. N Engl J Med 1996; 334: 168590
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    Francis DM. Relationship between blood transfusion and tumour behaviour. Br J Surg 1991; 78: 14208
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    Blumberg N, Heal JM. Effects of transfusion of immune function. Arch Pathol Laboratory Med 1994; 118: 3719
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    O'Hara JF Jr, Sprung J, Klein EA, Dilger JA, Domen RE, Piedmonte MR. Use of preoperative autologous blood donation in patients undergoing radical retropubic prostatectomy. Urology 1999; 54: 1314
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    Goad JR, Eastham JA, Fitzgerald KB et al. Radical retropubic prostatectomy. limited benefit of autologous blood donation. J Urol 1995; 154: 21039
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    Goh M, Kleer CG, Kielczewski P, Wojno KJ, Kim K, Oesterling JE. Autologous blood donation prior to anatomical radical retropubic prostatectomy: is it necessary? Urology 1997; 49: 56973
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    Klimberg I, Sirois R, Wajsman Z, Baker J. Intraoperative autotransfusion in urologic oncology. Arch Surg 1986; 121: 13269
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    Popovsky MA, Devine PA, Taswell HF. Intraoperative autologous transfusion. Mayo Clin Proc 1985; 60: 12534
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    Hart OJ, Klimberg IW, Wajsman Z, Baker J. Intraoperative autotransfusion in radical cystectomy for carcinoma of the bladder. Surg Gynecol Obstet 1989; 168: 3026
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    Pisters LL, Wajsman Z. Use of predeposit autologous blood and intraoperative autotransfusion in urologic cancer surgery. Urology 1992; 40: 2115
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    Edelman MJ, Potter P, Mahaffey KG, Frink R, Leidich RB. The potential for reintroduction of tumor cells during intraoperative blood salvage: reduction of risk with the RC-400 leukocyte depletion filter. Urology 1996; 47: 17981
Abbreviations
RRP

radical retropubic prostatectomy

IOCS

intraoperative cell salvage

SVI

seminal vesicle involvement.