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Intraoperative cell salvage during radical prostatectomy is not associated with greater biochemical recurrence rate
ADULT UROLOGY
INTRAOPERATIVE CELL SALVAGE DURING RADICAL PROSTATECTOMY IS NOT ASSOCIATED WITH GREATER BIOCHEMICAL RECURRENCE RATE ALAN M. NIEDER, ADRIENNE J. K. CARMACK, PAUL D. SVED, SANDY S. KIM, MURUGESAN MANOHARAN, AND MARK S. SOLOWAY
ABSTRACT Objectives. To evaluate the risk of long-term biochemical recurrence for patients who receive cell-salvaged blood. Radical retropubic prostatectomy (RRP) is historically associated with the potential for significant blood loss. Different blood management strategies include blood donation, hemodilution, preoperative erythropoietin, and intraoperative cell salvage (IOCS). Oncologic surgeons have been reluctant to use IOCS because of the potential risk of tumor dissemination. Methods. We retrospectively analyzed an RRP database and compared those who did and did not receive cell-salvaged blood by baseline parameters, pathologic outcomes, and biochemical recurrence. We also stratified our patients according to the risk of recurrence. Results. A total of 1038 patients underwent RRP between 1992 and 2003. Of these, 265 (25.5%) received cell-salvaged blood and 773 (74.5%) did not. The two groups had similar baseline characteristics. No differences were found between the two groups when compared by risk of seminal vesicle invasion or positive surgical margins. Those who received cell-salvaged blood had a lower risk of extraprostatic extension. The median follow-up for all patients was 40.2 months. The overall risk of biochemical recurrence at 5 years for those who did and did not receive cell-salvaged blood was 15% and 18%, respectively (P ⫽ 0.76). No significant differences were found in the risk of biochemical recurrence when patients were stratified according to low, intermediate, and high risk. Conclusions. IOCS is a safe and effective blood management strategy for patients undergoing RRP. The risk of biochemical recurrence was not increased for those who received cell-salvaged blood. Concerns about spreading tumor cells by way of IOCS would seem unwarranted. UROLOGY 65: 730–734, 2005. © 2005 Elsevier Inc.
R
adical retropubic prostatectomy (RRP) is an operation that may be associated with significant blood loss. Variability in anatomy, difficulty in controlling the dorsal venous complex, nerve sparing versus non-nerve sparing, obesity, and surgeon experience may all affect the estimated blood loss (EBL). The mean EBL during RRP has been reported as up to 1800 mL in previous series.1 Even in contemporary series, the EBL ranges from 770 mL2 to 1575 mL.3 Some patients may require blood transfusion, either allogeneic or autologous. Blood
From the Department of Urology, University of Miami School of Medicine, Miami, Florida Reprint requests: Mark S. Soloway, M.D., Department of Urology, University of Miami School of Medicine, P.O. Box 016960 (M814), Miami, FL 33101. E-mail: [email protected] Submitted: August 5, 2004, accepted (with revisions): October 27, 2004 © 2005 ELSEVIER INC. 730
ALL RIGHTS RESERVED
volume management is thus an important issue in the care of patients undergoing RRP. The different means of managing blood loss include preoperative donation of autologous blood,4 preoperative recombinant erythropoietin injection,5 intraoperative hemodilution,6 and intraoperative cell salvage (IOCS).7 IOCS is an attractive blood management strategy, because it is relatively inexpensive, obviates a trip to the blood bank, and prevents the risks associated with allogeneic blood transfusion such as viral infection. The risk of contracting human immunodeficiency virus or hepatitis C virus from a blood transfusion has been estimated to be greater than 1 in 200,000 and 1 in 30,000, respectively.8 Even though the risks are low, the consequences are potentially life-threatening. Many oncologic surgeons have been reluctant to use IOCS because of the theoretical risk of tumor 0090-4295/05/$30.00 doi:10.1016/j.urology.2004.10.062
TABLE I. Baseline and pathologic characteristics of study patients Received Cell Salvaged Blood Characteristic Patients (n) Mean age ⫾ SD (yr) Mean Gleason score Mean initial PSA ⫾ SD (ng/mL) Pathologic Gleason score Seminal vesicle invasion (n) Extraprostatic extension (n) Positive margins (n)
Yes
No
P Value
265 (25.5) 61.5 ⫾ 7.2 6.1 9.4 ⫾ 20.7 6.6 24 (9.1) 38 (14.3) 83 (31.3)
773 (74.5) 60.8 ⫾ 7.4 6.2 9.2 ⫾ 10.5 6.6 78 (10.1) 159 (21.0) 257 (33.2)
— 0.14 0.34 0.86 0.39 0.71 0.03 0.62
KEY: PSA ⫽ prostate-specific antigen. Data in parentheses are percentages.
dissemination. Prostate cancer is unique, because a sensitive and specific marker, prostate-specific antigen (PSA), is available to detect recurrence. Davis et al.9 previously published our institutional experience with IOCS between 1992 and 1998 and reported no short-term increased risk of biochemical recurrence among 408 patients. We have since reviewed our RRP database and evaluated the longterm risk of biochemical recurrence for patients who did and did not receive cell-salvaged blood. We now report on all patients who underwent RRP since 1992 who were at least 1 year from surgery. MATERIAL AND METHODS Between January 1992 and February 2003, 1114 men underwent RRP by a single surgeon (M.S.S.) at the University of Miami School of Medicine. The data of all patients were entered in an RRP database. The University of Miami School of Medicine Institutional Review Board granted approval for a retrospective analysis of our patient population. The following patients were excluded from the analyses: patients with incomplete preoperative or operative data (n ⫽ 19); patients without any postoperative follow-up (n ⫽ 5); and patients who received adjuvant androgen deprivation (n ⫽ 52). No patient received adjuvant radiotherapy. The remaining 1038 patients formed the basis of our study. Of these 1038, 211 (20.3%) received neoadjuvant hormonal therapy; these patients were included in the analysis because previous data had demonstrated no difference in the biochemical or clinical recurrence rate for those who did or did not receive neoadjuvant hormonal therapy.10 Our study population was categorized into two groups: group 1 consisted of the 265 patients who received cell-salvaged blood and group 2 consisted of the 773 patients who did not. The patients were evaluated by baseline characteristics and pathologic outcomes. We stratified our analyses of PSA recurrence using three subgroups of patients: low risk (PSA 0 to 10 ng/mL with Gleason score 2 to 6); intermediate risk (PSA 0 to 10 ng/mL with Gleason score 7 or greater or PSA 10 to 20 ng/mL with Gleason score 2 to 7); and high risk (PSA 10 to 20 ng/mL with Gleason score 8 to 10 or PSA greater than 20 ng/mL with any Gleason score).11 Patients were followed postoperatively quarterly for 2 years and then semiannually indefinitely. Biochemical recurrence was defined as a PSA level of 0.4 ng/mL or greater.12 Statistical analyses were conducted with commercially available software. Student’s t test and chisquare tests were used to compare the two groups. The logUROLOGY 65 (4), 2005
rank test was used to compare the Kaplan-Meier estimates of biochemical recurrence-free survival between the two groups. Our policy has been to avoid allogeneic blood transfusion by giving patients the opportunity to donate 1 U autologous blood before RRP and using IOCS. Some patients did not donate blood for various reasons (eg, insurance limitations, inability to travel to donation center). IOCS was available for all patients; however, we would occasionally have the machine on “stand-by” to reduce costs. We often place IOCS on stand-by if the patient meets the following criteria: preoperative hematocrit greater than 45%, the presence of predonated autologous blood, and thin body habitus. In brief, the technique of IOCS involves the collection of intraoperative blood that is then stored until a decision is made to transfuse or discard it. If a decision is made to transfuse the cell-salvaged blood, the blood is washed, rinsed, and spun through a filter to isolate the red blood cells. To obtain a 250-mL unit of cellsalvaged blood, approximately 500 mL of blood must be collected. Leukocyte depletion filters were not used. The decision to transfuse either autologous or cell-salvaged blood is a collaborative decision between the surgeon and anesthesiologist. The decision is dependent on the patient’s age, comorbidities, preoperative hematocrit, and EBL. We did not routinely check the intraoperative or postoperative hematocrit. If the EBL was greater than 700 mL, either autologous or cell-salvaged blood was transfused. If IOCS was used, but the EBL was low, there was no transfusion indication and thus the cell-salvaged blood was discarded.
RESULTS Of the 1038 patients, 265 (25.5%) received cellsalvaged blood and 773 (74.5%) did not. No significant differences were found between the two groups in mean age, preoperative Gleason score, or preoperative PSA level (Table I). The risks of seminal vesicle invasion and positive surgical margins were not significantly different between the two groups (Table I). The risk of extraprostatic extension between those who received cell-salvaged blood and those who did not, 14% and 21%, respectively, was statistically significant (P ⫽ 0.03). No differences were noted in the transfusion of cell-salvaged blood between the two groups when bilateral nerve-sparing RRP was performed (P ⫽ 0.26). During the entire series, the transfusion of cell-salvaged blood remained relatively constant, 731
FIGURE 1. Kaplan-Meier curve comparing PSA recurrence for all patients.
ranging from 25.4% to 25.7% when evaluated by quartiles. The median follow-up for all patients was 40.2 months. The median follow-up for groups 1 and 2 was 40.3 months (range 0.36 to 141.2) and 44.4 months (range 0.13 to 142.4), respectively. The overall biochemical recurrence rate for groups 1 and 2 was 15% and 18%, respectively, at 5 years (P ⫽ 0.76). Figure 1 shows a Kaplan-Meier survival curve comparing the PSA recurrence for all patients (P ⫽ 0.76, log rank ⫽ 0.09). We stratified our patients according to a low, intermediate, and high risk of recurrence. The distribution of patients in groups 1 and 2 was not significantly different among the low-risk, intermediate-risk, and high-risk groups (P ⫽ 0.35). Figure 2 shows Kaplan-Meier survival curves comparing the PSA recurrence for low-risk (P ⫽ 0.77, log rank ⫽ 0.09), intermediate-risk (P ⫽ 0.78, log rank ⫽ 0.08), and high-risk (P ⫽ 0.58, log rank ⫽ 0.31) patients. The time to biochemical recurrence was not significantly different for patients who did and did not receive cell-salvaged blood at 27.9 ⫾ 30.3 months and 32.1 ⫾ 29.5 months (P ⫽ 0.49). Only 9 patients (0.9%) in our series received an allogeneic blood transfusion. Four of these patients also received cell-salvaged blood. COMMENT The transfusion rates during RRP have decreased steadily during the past several years as the expe732
rience with RRP for the treatment of prostate cancer has increased. As surgeon skill and familiarity with the operation has increased, the EBL has decreased. The indications for transfusion have also decreased as more information has been gained regarding tolerable hemoglobin levels. An analysis of the Department of Defense Center for Prostate Disease Research Multicenter National Research Database for 2918 patients undergoing radical prostatectomy showed statistically significant decreases in the median EBL (from 1800 to 800 mL), rates of preoperative blood donation (from 81.7% to 10.9%), and transfusion rates (from 93.2% to 13.7%) from 1985 to 2000.1 Other modern studies have reported homologous blood transfusion rates of 4.6%,13 7.1%,14 and 9.7%.15 Thus, although the likelihood of a patient receiving blood is relatively low, the risk is still present. In our current series, only 0.9% received allogeneic transfusion, and 1.5% of those who received cell-salvaged blood also received an allogeneic transfusion. Thus, the use of IOCS minimizes the need for an allogeneic transfusion. Oncologic surgeons have been hesitant to embrace IOCS primarily because of a theoretical risk of tumor dissemination. Ward et al.16 demonstrated that malignant prostatic cells could be identified in cytologic washings during RRP. However, several studies have demonstrated the safety of IOCS during urologic oncology procedures. In 1986, Klimberg et al.17 reported on their use of IOCS in 49 patients with urologic cancer, including 10 who underwent RRP. Five of the patients (10.2%) developed metastases during a follow-up of 12 to 23 months, and 43 (87.8%) remained with no evidence of disease. Theirs was a small noncomparative study with a short follow-up period. In an updated retrospective study from the same center, Hart et al.18 reported on 49 patients who underwent radical cystectomy with the use of IOCS. At a minimum of 1 year of follow-up, no patient had metastasis. These investigators concluded that the use of IOCS is safe in genitourinary cancer and that the fears of tumor dissemination are unwarranted. Akchurin et al.19 reported on their combined use of IOCS and cardiopulmonary bypass for 8 patients with malignant tumors who also required cardiac surgery. Six of these patients had either renal cell carcinoma or retroperitoneal sarcoma with invasion of the supradiaphragmatic inferior vena cava. At 1 year of follow-up, no patient had metastatic disease. Gray et al.7 retrospectively compared 62 patients who underwent RRP with IOCS as the sole blood management technique with 101 patients who underwent RRP with autologous blood predonation. A statistically significant difference was found between the preoperative and postoperative hematoUROLOGY 65 (4), 2005
FIGURE 2. Kaplan-Meier curve comparing PSA recurrence by risk group.
crit levels between the two groups. Those who were in the cell salvage cohort had a preoperative and postoperative hematocrit of 42.7% and 31.3%, respectively, compared with the autologous predonation patients whose levels were 39.6% and 27.9%, respectively. Furthermore, only 3% of patients who had IOCS received an allogeneic transfusion compared with 14% in the autologous predonation cohort. Using a progression-free survival PSA cutoff of 0.4 ng/mL, these investigators found no difference in progression between the two groups, although the IOCS group only had a mean follow-up of 7 months. They concluded that IOCS is not associated with an increased risk of early biochemical recurrence. We do not believe that a significant, if any, risk of tumor dissemination exists from IOCS. Davis et al.9 previously demonstrated no difference in the risk of biochemical recurrence with the use of IOCS in a smaller subset of 408 patients undergoing RRP at our institution. They compared 87 patients who received cell-salvaged blood, 264 who received only autologous transfusion, and 57 who received no transfusion. Biochemical recurrence was detected in 67 patients (16%) and was not significantly associated with the method of transfusion (chi-square P ⫽ 0.784). In our current updated report, we evaluated 1038 patients with complete operative data and compared the PSA recurrence rate between those who did and did not receive cell-salvaged blood. Additional stratification of our patients according to low, intermediate, and high risk did not demonstrate any significant differences in PSA recurrence among the cohorts. Our study had a few limitations. The most important was that it was not a prospective, randomized study. Although we believe that our two cohorts were similar, as demonstrated by the baseline characteristics and pathologic outcomes, those UROLOGY 65 (4), 2005
who received cell-salvaged blood did have a lower risk of extraprostatic extension. We never purposefully decided to transfuse or not transfuse the cell-salvaged blood on the basis of the preoperative risk stratification or surgical findings. The risk of receiving cell-salvaged blood was constant during the period of our series, when evaluated by risk stratification, and whether a nerve-sparing procedure was or was not performed. The concern regarding the risks of an allogeneic transfusion (eg, human immunodeficiency virus and hepatitis) are not insignificant, and, given the previously reported safety of IOCS and its availability in our institution, we believed it was to our patients’ benefit to begin using IOCS without initiating a randomized study in which some patients would likely receive allogeneic blood. However, because selection bias may have had an unknown effect on our outcomes, only a prospective, blinded, randomized study would provide the most valid answers as to the safety of IOCS. CONCLUSIONS The use of IOCS is a safe and valuable technique of blood management for patients undergoing RRP. Long-term follow-up showed no apparent increased risk of metastatic disease. The biochemical recurrence rates were not significantly different between those who did and did not receive cell-salvaged blood, even among patients with a high risk of recurrence. We have IOCS available for RRP and other urologic oncology operations in which a potential for significant blood loss exists. ACKNOWLEDGMENT. To Harvey Chaplin, Mel Dick, Jay Weiss, and Jackson Memorial Hospital Foundation for support of this project. 733
REFERENCES 1. Moul JW, Sun L, Wu H, et al: Factors associated with blood loss during radical prostatectomy for localized prostate cancer in the prostate-specific antigen (PSA) era: an overview of the Department of Defense (DOD) Center for Prostate Disease Research (CPDR) national database. Urol Oncol 21: 447– 455, 2003. 2. Goh M, Kleer CG, Kielczewski P, et al: Autologous blood donation prior to anatomical radical retropubic prostatectomy: is it necessary? Urology 49: 569 –574, 1997. 3. Lance RS, Freidrichs PA, Kane C, et al: A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group. BJU Int 87: 61– 65, 2001. 4. Goodnough LM, Grishaber JE, Birkmeyer JD, et al: Efficacy and cost-effectiveness of autologous blood predeposit in patients undergoing radical prostatectomy procedures. Urology 44: 226 –231, 1994. 5. Rosenblum N, Levine MA, Handler T, et al: The role of preoperative epoetin alfa in men undergoing radical retropubic prostatectomy. J Urol 163: 829 – 833, 2000. 6. Monk TG, Goodnough LT, Brecher ME, et al: Acute normovolemic hemodilution can replace preoperative autologous blood donation as a standard of care for autologous blood procurement in radical prostatectomy. Anesth Analg 85: 953– 958, 1997. 7. Gray CL, Amling CL, Polston GR, et al: Intraoperative cell salvage in radical retropubic prostatectomy. Urology 58: 740 –745, 2001. 8. Goodnough LT, Brecher ME, Kanter MH, et al: Transfusion medicine: first of two parts— blood transfusion. N Engl J Med 340: 438 – 447, 1999. 9. Davis M, Sofer M, Gomez-Marin O, et al: The use of cell salvage during radical retropubic prostatectomy: does it influence cancer recurrence? BJU Int 91: 474 – 476, 2003.
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10. Soloway MS, Pareek K, Sharifi R, et al: Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. J Urol 167: 112–116, 2002. 11. Sofer M, Hamilton-Nelson KL, Schlesselman JJ, et al: Risk of positive margins and biochemical recurrence in relation to nerve-sparing radical prostatectomy. J Clin Oncol 20: 1853–1858, 2002. 12. Amling CL, Blute ML, Bergstralh EJ, et al: Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol 164: 101–105, 2000. 13. Lepor H, and Kaci L: Contemporary evaluation of operative parameters and complications related to open radical retropubic prostatectomy. Urology 62: 702–706, 2003. 14. Nuttall GA, Cragun MD, Hill DL, et al: Radical retropubic prostatectomy and blood transfusion. Mayo Clin Proc 77: 1301–1305, 2002. 15. Lepor H, Nieder AM, and Ferrandino MN: Intraoperative and postoperative complications of radical retropubic prostatectomy in a consecutive series of 1,000 cases. J Urol 166: 1729 –1733, 2001. 16. Ward JF, Nowacki M, Sands JP, et al: Malignant cytological washings from radical prostatectomy specimens: a possible mechanism for local recurrence of prostate cancer following surgical treatment of organ confined disease. J Urol 156: 1381–1385, 1996. 17. Klimberg I, Sirois R, Wajsman Z, et al: Intraoperative autotransfusion in urologic oncology. Arch Surg 121: 1326 – 1329, 1986. 18. Hart OJ III, Klimberg IW, Wajsman Z, et al: Intraoperative autotransfusion in radical cystectomy for carcinoma of the bladder. Surg Gynecol Obstet 168: 302–306, 1989. 19. Akchurin RS, Davidov MI, Partigulov SA, et al: Cardiopulmonary bypass and cell-saver technique in combined oncologic and cardiovascular surgery. Artif Organs 21: 763–765, 1997.
UROLOGY 65 (4), 2005
INTRAOPERATIVE CELL SALVAGE DURING RADICAL PROSTATECTOMY IS NOT ASSOCIATED WITH GREATER BIOCHEMICAL RECURRENCE RATE ALAN M. NIEDER, ADRIENNE J. K. CARMACK, PAUL D. SVED, SANDY S. KIM, MURUGESAN MANOHARAN, AND MARK S. SOLOWAY
ABSTRACT Objectives. To evaluate the risk of long-term biochemical recurrence for patients who receive cell-salvaged blood. Radical retropubic prostatectomy (RRP) is historically associated with the potential for significant blood loss. Different blood management strategies include blood donation, hemodilution, preoperative erythropoietin, and intraoperative cell salvage (IOCS). Oncologic surgeons have been reluctant to use IOCS because of the potential risk of tumor dissemination. Methods. We retrospectively analyzed an RRP database and compared those who did and did not receive cell-salvaged blood by baseline parameters, pathologic outcomes, and biochemical recurrence. We also stratified our patients according to the risk of recurrence. Results. A total of 1038 patients underwent RRP between 1992 and 2003. Of these, 265 (25.5%) received cell-salvaged blood and 773 (74.5%) did not. The two groups had similar baseline characteristics. No differences were found between the two groups when compared by risk of seminal vesicle invasion or positive surgical margins. Those who received cell-salvaged blood had a lower risk of extraprostatic extension. The median follow-up for all patients was 40.2 months. The overall risk of biochemical recurrence at 5 years for those who did and did not receive cell-salvaged blood was 15% and 18%, respectively (P ⫽ 0.76). No significant differences were found in the risk of biochemical recurrence when patients were stratified according to low, intermediate, and high risk. Conclusions. IOCS is a safe and effective blood management strategy for patients undergoing RRP. The risk of biochemical recurrence was not increased for those who received cell-salvaged blood. Concerns about spreading tumor cells by way of IOCS would seem unwarranted. UROLOGY 65: 730–734, 2005. © 2005 Elsevier Inc.
R
adical retropubic prostatectomy (RRP) is an operation that may be associated with significant blood loss. Variability in anatomy, difficulty in controlling the dorsal venous complex, nerve sparing versus non-nerve sparing, obesity, and surgeon experience may all affect the estimated blood loss (EBL). The mean EBL during RRP has been reported as up to 1800 mL in previous series.1 Even in contemporary series, the EBL ranges from 770 mL2 to 1575 mL.3 Some patients may require blood transfusion, either allogeneic or autologous. Blood
From the Department of Urology, University of Miami School of Medicine, Miami, Florida Reprint requests: Mark S. Soloway, M.D., Department of Urology, University of Miami School of Medicine, P.O. Box 016960 (M814), Miami, FL 33101. E-mail: [email protected] Submitted: August 5, 2004, accepted (with revisions): October 27, 2004 © 2005 ELSEVIER INC. 730
ALL RIGHTS RESERVED
volume management is thus an important issue in the care of patients undergoing RRP. The different means of managing blood loss include preoperative donation of autologous blood,4 preoperative recombinant erythropoietin injection,5 intraoperative hemodilution,6 and intraoperative cell salvage (IOCS).7 IOCS is an attractive blood management strategy, because it is relatively inexpensive, obviates a trip to the blood bank, and prevents the risks associated with allogeneic blood transfusion such as viral infection. The risk of contracting human immunodeficiency virus or hepatitis C virus from a blood transfusion has been estimated to be greater than 1 in 200,000 and 1 in 30,000, respectively.8 Even though the risks are low, the consequences are potentially life-threatening. Many oncologic surgeons have been reluctant to use IOCS because of the theoretical risk of tumor 0090-4295/05/$30.00 doi:10.1016/j.urology.2004.10.062
TABLE I. Baseline and pathologic characteristics of study patients Received Cell Salvaged Blood Characteristic Patients (n) Mean age ⫾ SD (yr) Mean Gleason score Mean initial PSA ⫾ SD (ng/mL) Pathologic Gleason score Seminal vesicle invasion (n) Extraprostatic extension (n) Positive margins (n)
Yes
No
P Value
265 (25.5) 61.5 ⫾ 7.2 6.1 9.4 ⫾ 20.7 6.6 24 (9.1) 38 (14.3) 83 (31.3)
773 (74.5) 60.8 ⫾ 7.4 6.2 9.2 ⫾ 10.5 6.6 78 (10.1) 159 (21.0) 257 (33.2)
— 0.14 0.34 0.86 0.39 0.71 0.03 0.62
KEY: PSA ⫽ prostate-specific antigen. Data in parentheses are percentages.
dissemination. Prostate cancer is unique, because a sensitive and specific marker, prostate-specific antigen (PSA), is available to detect recurrence. Davis et al.9 previously published our institutional experience with IOCS between 1992 and 1998 and reported no short-term increased risk of biochemical recurrence among 408 patients. We have since reviewed our RRP database and evaluated the longterm risk of biochemical recurrence for patients who did and did not receive cell-salvaged blood. We now report on all patients who underwent RRP since 1992 who were at least 1 year from surgery. MATERIAL AND METHODS Between January 1992 and February 2003, 1114 men underwent RRP by a single surgeon (M.S.S.) at the University of Miami School of Medicine. The data of all patients were entered in an RRP database. The University of Miami School of Medicine Institutional Review Board granted approval for a retrospective analysis of our patient population. The following patients were excluded from the analyses: patients with incomplete preoperative or operative data (n ⫽ 19); patients without any postoperative follow-up (n ⫽ 5); and patients who received adjuvant androgen deprivation (n ⫽ 52). No patient received adjuvant radiotherapy. The remaining 1038 patients formed the basis of our study. Of these 1038, 211 (20.3%) received neoadjuvant hormonal therapy; these patients were included in the analysis because previous data had demonstrated no difference in the biochemical or clinical recurrence rate for those who did or did not receive neoadjuvant hormonal therapy.10 Our study population was categorized into two groups: group 1 consisted of the 265 patients who received cell-salvaged blood and group 2 consisted of the 773 patients who did not. The patients were evaluated by baseline characteristics and pathologic outcomes. We stratified our analyses of PSA recurrence using three subgroups of patients: low risk (PSA 0 to 10 ng/mL with Gleason score 2 to 6); intermediate risk (PSA 0 to 10 ng/mL with Gleason score 7 or greater or PSA 10 to 20 ng/mL with Gleason score 2 to 7); and high risk (PSA 10 to 20 ng/mL with Gleason score 8 to 10 or PSA greater than 20 ng/mL with any Gleason score).11 Patients were followed postoperatively quarterly for 2 years and then semiannually indefinitely. Biochemical recurrence was defined as a PSA level of 0.4 ng/mL or greater.12 Statistical analyses were conducted with commercially available software. Student’s t test and chisquare tests were used to compare the two groups. The logUROLOGY 65 (4), 2005
rank test was used to compare the Kaplan-Meier estimates of biochemical recurrence-free survival between the two groups. Our policy has been to avoid allogeneic blood transfusion by giving patients the opportunity to donate 1 U autologous blood before RRP and using IOCS. Some patients did not donate blood for various reasons (eg, insurance limitations, inability to travel to donation center). IOCS was available for all patients; however, we would occasionally have the machine on “stand-by” to reduce costs. We often place IOCS on stand-by if the patient meets the following criteria: preoperative hematocrit greater than 45%, the presence of predonated autologous blood, and thin body habitus. In brief, the technique of IOCS involves the collection of intraoperative blood that is then stored until a decision is made to transfuse or discard it. If a decision is made to transfuse the cell-salvaged blood, the blood is washed, rinsed, and spun through a filter to isolate the red blood cells. To obtain a 250-mL unit of cellsalvaged blood, approximately 500 mL of blood must be collected. Leukocyte depletion filters were not used. The decision to transfuse either autologous or cell-salvaged blood is a collaborative decision between the surgeon and anesthesiologist. The decision is dependent on the patient’s age, comorbidities, preoperative hematocrit, and EBL. We did not routinely check the intraoperative or postoperative hematocrit. If the EBL was greater than 700 mL, either autologous or cell-salvaged blood was transfused. If IOCS was used, but the EBL was low, there was no transfusion indication and thus the cell-salvaged blood was discarded.
RESULTS Of the 1038 patients, 265 (25.5%) received cellsalvaged blood and 773 (74.5%) did not. No significant differences were found between the two groups in mean age, preoperative Gleason score, or preoperative PSA level (Table I). The risks of seminal vesicle invasion and positive surgical margins were not significantly different between the two groups (Table I). The risk of extraprostatic extension between those who received cell-salvaged blood and those who did not, 14% and 21%, respectively, was statistically significant (P ⫽ 0.03). No differences were noted in the transfusion of cell-salvaged blood between the two groups when bilateral nerve-sparing RRP was performed (P ⫽ 0.26). During the entire series, the transfusion of cell-salvaged blood remained relatively constant, 731
FIGURE 1. Kaplan-Meier curve comparing PSA recurrence for all patients.
ranging from 25.4% to 25.7% when evaluated by quartiles. The median follow-up for all patients was 40.2 months. The median follow-up for groups 1 and 2 was 40.3 months (range 0.36 to 141.2) and 44.4 months (range 0.13 to 142.4), respectively. The overall biochemical recurrence rate for groups 1 and 2 was 15% and 18%, respectively, at 5 years (P ⫽ 0.76). Figure 1 shows a Kaplan-Meier survival curve comparing the PSA recurrence for all patients (P ⫽ 0.76, log rank ⫽ 0.09). We stratified our patients according to a low, intermediate, and high risk of recurrence. The distribution of patients in groups 1 and 2 was not significantly different among the low-risk, intermediate-risk, and high-risk groups (P ⫽ 0.35). Figure 2 shows Kaplan-Meier survival curves comparing the PSA recurrence for low-risk (P ⫽ 0.77, log rank ⫽ 0.09), intermediate-risk (P ⫽ 0.78, log rank ⫽ 0.08), and high-risk (P ⫽ 0.58, log rank ⫽ 0.31) patients. The time to biochemical recurrence was not significantly different for patients who did and did not receive cell-salvaged blood at 27.9 ⫾ 30.3 months and 32.1 ⫾ 29.5 months (P ⫽ 0.49). Only 9 patients (0.9%) in our series received an allogeneic blood transfusion. Four of these patients also received cell-salvaged blood. COMMENT The transfusion rates during RRP have decreased steadily during the past several years as the expe732
rience with RRP for the treatment of prostate cancer has increased. As surgeon skill and familiarity with the operation has increased, the EBL has decreased. The indications for transfusion have also decreased as more information has been gained regarding tolerable hemoglobin levels. An analysis of the Department of Defense Center for Prostate Disease Research Multicenter National Research Database for 2918 patients undergoing radical prostatectomy showed statistically significant decreases in the median EBL (from 1800 to 800 mL), rates of preoperative blood donation (from 81.7% to 10.9%), and transfusion rates (from 93.2% to 13.7%) from 1985 to 2000.1 Other modern studies have reported homologous blood transfusion rates of 4.6%,13 7.1%,14 and 9.7%.15 Thus, although the likelihood of a patient receiving blood is relatively low, the risk is still present. In our current series, only 0.9% received allogeneic transfusion, and 1.5% of those who received cell-salvaged blood also received an allogeneic transfusion. Thus, the use of IOCS minimizes the need for an allogeneic transfusion. Oncologic surgeons have been hesitant to embrace IOCS primarily because of a theoretical risk of tumor dissemination. Ward et al.16 demonstrated that malignant prostatic cells could be identified in cytologic washings during RRP. However, several studies have demonstrated the safety of IOCS during urologic oncology procedures. In 1986, Klimberg et al.17 reported on their use of IOCS in 49 patients with urologic cancer, including 10 who underwent RRP. Five of the patients (10.2%) developed metastases during a follow-up of 12 to 23 months, and 43 (87.8%) remained with no evidence of disease. Theirs was a small noncomparative study with a short follow-up period. In an updated retrospective study from the same center, Hart et al.18 reported on 49 patients who underwent radical cystectomy with the use of IOCS. At a minimum of 1 year of follow-up, no patient had metastasis. These investigators concluded that the use of IOCS is safe in genitourinary cancer and that the fears of tumor dissemination are unwarranted. Akchurin et al.19 reported on their combined use of IOCS and cardiopulmonary bypass for 8 patients with malignant tumors who also required cardiac surgery. Six of these patients had either renal cell carcinoma or retroperitoneal sarcoma with invasion of the supradiaphragmatic inferior vena cava. At 1 year of follow-up, no patient had metastatic disease. Gray et al.7 retrospectively compared 62 patients who underwent RRP with IOCS as the sole blood management technique with 101 patients who underwent RRP with autologous blood predonation. A statistically significant difference was found between the preoperative and postoperative hematoUROLOGY 65 (4), 2005
FIGURE 2. Kaplan-Meier curve comparing PSA recurrence by risk group.
crit levels between the two groups. Those who were in the cell salvage cohort had a preoperative and postoperative hematocrit of 42.7% and 31.3%, respectively, compared with the autologous predonation patients whose levels were 39.6% and 27.9%, respectively. Furthermore, only 3% of patients who had IOCS received an allogeneic transfusion compared with 14% in the autologous predonation cohort. Using a progression-free survival PSA cutoff of 0.4 ng/mL, these investigators found no difference in progression between the two groups, although the IOCS group only had a mean follow-up of 7 months. They concluded that IOCS is not associated with an increased risk of early biochemical recurrence. We do not believe that a significant, if any, risk of tumor dissemination exists from IOCS. Davis et al.9 previously demonstrated no difference in the risk of biochemical recurrence with the use of IOCS in a smaller subset of 408 patients undergoing RRP at our institution. They compared 87 patients who received cell-salvaged blood, 264 who received only autologous transfusion, and 57 who received no transfusion. Biochemical recurrence was detected in 67 patients (16%) and was not significantly associated with the method of transfusion (chi-square P ⫽ 0.784). In our current updated report, we evaluated 1038 patients with complete operative data and compared the PSA recurrence rate between those who did and did not receive cell-salvaged blood. Additional stratification of our patients according to low, intermediate, and high risk did not demonstrate any significant differences in PSA recurrence among the cohorts. Our study had a few limitations. The most important was that it was not a prospective, randomized study. Although we believe that our two cohorts were similar, as demonstrated by the baseline characteristics and pathologic outcomes, those UROLOGY 65 (4), 2005
who received cell-salvaged blood did have a lower risk of extraprostatic extension. We never purposefully decided to transfuse or not transfuse the cell-salvaged blood on the basis of the preoperative risk stratification or surgical findings. The risk of receiving cell-salvaged blood was constant during the period of our series, when evaluated by risk stratification, and whether a nerve-sparing procedure was or was not performed. The concern regarding the risks of an allogeneic transfusion (eg, human immunodeficiency virus and hepatitis) are not insignificant, and, given the previously reported safety of IOCS and its availability in our institution, we believed it was to our patients’ benefit to begin using IOCS without initiating a randomized study in which some patients would likely receive allogeneic blood. However, because selection bias may have had an unknown effect on our outcomes, only a prospective, blinded, randomized study would provide the most valid answers as to the safety of IOCS. CONCLUSIONS The use of IOCS is a safe and valuable technique of blood management for patients undergoing RRP. Long-term follow-up showed no apparent increased risk of metastatic disease. The biochemical recurrence rates were not significantly different between those who did and did not receive cell-salvaged blood, even among patients with a high risk of recurrence. We have IOCS available for RRP and other urologic oncology operations in which a potential for significant blood loss exists. ACKNOWLEDGMENT. To Harvey Chaplin, Mel Dick, Jay Weiss, and Jackson Memorial Hospital Foundation for support of this project. 733
REFERENCES 1. Moul JW, Sun L, Wu H, et al: Factors associated with blood loss during radical prostatectomy for localized prostate cancer in the prostate-specific antigen (PSA) era: an overview of the Department of Defense (DOD) Center for Prostate Disease Research (CPDR) national database. Urol Oncol 21: 447– 455, 2003. 2. Goh M, Kleer CG, Kielczewski P, et al: Autologous blood donation prior to anatomical radical retropubic prostatectomy: is it necessary? Urology 49: 569 –574, 1997. 3. Lance RS, Freidrichs PA, Kane C, et al: A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group. BJU Int 87: 61– 65, 2001. 4. Goodnough LM, Grishaber JE, Birkmeyer JD, et al: Efficacy and cost-effectiveness of autologous blood predeposit in patients undergoing radical prostatectomy procedures. Urology 44: 226 –231, 1994. 5. Rosenblum N, Levine MA, Handler T, et al: The role of preoperative epoetin alfa in men undergoing radical retropubic prostatectomy. J Urol 163: 829 – 833, 2000. 6. Monk TG, Goodnough LT, Brecher ME, et al: Acute normovolemic hemodilution can replace preoperative autologous blood donation as a standard of care for autologous blood procurement in radical prostatectomy. Anesth Analg 85: 953– 958, 1997. 7. Gray CL, Amling CL, Polston GR, et al: Intraoperative cell salvage in radical retropubic prostatectomy. Urology 58: 740 –745, 2001. 8. Goodnough LT, Brecher ME, Kanter MH, et al: Transfusion medicine: first of two parts— blood transfusion. N Engl J Med 340: 438 – 447, 1999. 9. Davis M, Sofer M, Gomez-Marin O, et al: The use of cell salvage during radical retropubic prostatectomy: does it influence cancer recurrence? BJU Int 91: 474 – 476, 2003.
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10. Soloway MS, Pareek K, Sharifi R, et al: Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. J Urol 167: 112–116, 2002. 11. Sofer M, Hamilton-Nelson KL, Schlesselman JJ, et al: Risk of positive margins and biochemical recurrence in relation to nerve-sparing radical prostatectomy. J Clin Oncol 20: 1853–1858, 2002. 12. Amling CL, Blute ML, Bergstralh EJ, et al: Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol 164: 101–105, 2000. 13. Lepor H, and Kaci L: Contemporary evaluation of operative parameters and complications related to open radical retropubic prostatectomy. Urology 62: 702–706, 2003. 14. Nuttall GA, Cragun MD, Hill DL, et al: Radical retropubic prostatectomy and blood transfusion. Mayo Clin Proc 77: 1301–1305, 2002. 15. Lepor H, Nieder AM, and Ferrandino MN: Intraoperative and postoperative complications of radical retropubic prostatectomy in a consecutive series of 1,000 cases. J Urol 166: 1729 –1733, 2001. 16. Ward JF, Nowacki M, Sands JP, et al: Malignant cytological washings from radical prostatectomy specimens: a possible mechanism for local recurrence of prostate cancer following surgical treatment of organ confined disease. J Urol 156: 1381–1385, 1996. 17. Klimberg I, Sirois R, Wajsman Z, et al: Intraoperative autotransfusion in urologic oncology. Arch Surg 121: 1326 – 1329, 1986. 18. Hart OJ III, Klimberg IW, Wajsman Z, et al: Intraoperative autotransfusion in radical cystectomy for carcinoma of the bladder. Surg Gynecol Obstet 168: 302–306, 1989. 19. Akchurin RS, Davidov MI, Partigulov SA, et al: Cardiopulmonary bypass and cell-saver technique in combined oncologic and cardiovascular surgery. Artif Organs 21: 763–765, 1997.
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