Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer

Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer

EURURO-7929; No. of Pages 4 E U R O P E A N U R O L O G Y X X X ( 2 018 ) X X X – X X X available at www.sciencedirect.com journal homepage: www.euro...

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EURURO-7929; No. of Pages 4 E U R O P E A N U R O L O G Y X X X ( 2 018 ) X X X – X X X

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Brief Correspondence

Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer Felix Preisser a,b,c,d,*, Elio Mazzone a,b,c,e,f, Sebastiano Nazzani a,b,c,g, Marco Bandini a,b,c,e,f, Zhe Tian a, Michele Marchioni a,h, Thomas Steuber d, Fred Saad a,b,c, Francesco Montorsi e,f, Shahrokh F. Shariat i, Hartwig Huland d, Markus Graefen d, Derya Tilki d,j, Pierre I. Karakiewicz a,b,c a

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada; b Centre de Recherche du Centre Hospitalier

de l’Université de Montréal (CR-CHUM), Montréal, Québec, Canada; c Institut du Cancer de Montréal, Montréal, Québec, Canada; d Martini-Klinik, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; e Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; f Vita-Salute San Raffaele University, Milan, Italy; g Academic Department of Urology, IRCCS Policlinico San Donato, University of Milan, Milan, Italy;

h

Department of

Urology, SS Annunziata Hospital, “G. D’Annunzio” University of Chieti, Chieti, Italy; i Department of Urology, Medical University of Vienna, Vienna, Austria; j

Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Article info

Abstract

Article history: Accepted July 7, 2018

Cytoreductive radical prostatectomy (CRP) may offer a survival advantage, according to several retrospective analyses. However, few data are available regarding the morbidity of radical prostatectomy in the metastatic setting. We addressed intra- and postoperative complications of CRP relative to radical prostatectomy for nonmetastatic prostate cancer (nmRP). Within the National Inpatient Sample database (2008–2013), we identified patients who underwent CRP versus nmRP. Propensity score matching to reduce the effect of inherent differences between CRP and nmRP patients, multivariable logistic regression models, Poisson regression models, and linear regression models were used. Of 76 378 patients, 1.2% (n = 953) underwent CRP. CRP resulted in higher rates of overall (odds ratio [OR]: 1.34, p = 0.01), intraoperative (OR: 2.61, p = 0.005), and miscellaneous surgical complications (OR: 1.69, p = 0.02). Moreover, CRP was associated with longer stay (OR: 1.07, p = 0.01) and higher total hospital charges ($810 more per surgery, p = 0.0004). Intra- and postoperative complications associated with CRP are higher than those of nmRP. Similarly, an increase in total hospital charges is associated with CRP. Nonetheless, CRP complication profile validates its safety and feasibility. Patient summary: In this population-based study, we recorded higher intra- and postoperative complications rates for CRP versus nmRP. Nonetheless, CRP complication rates appear manageable but require explicit discussion at counseling.

Associate Editor: Giacomo Novara Keywords: Prostatectomy Metastatic National Inpatient Sample Complications Cytoreductive Prostate cancer

* Corresponding author. Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Martinistrae 52, Hamburg 20246, Germany. Tel. +49 (0)40 7410 51300; Fax: +49 (0)40 7410 51323. E-mail address: [email protected] (F. Preisser).

https://doi.org/10.1016/j.eururo.2018.07.006 0302-2838/© 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Please cite this article in press as: Preisser F, et al. Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer. Eur Urol (2018), https://doi.org/10.1016/j. eururo.2018.07.006

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Cytoreductive radical prostatectomy (CRP) may result in survival benefits relative to no local therapy in highly selected patients with metastatic prostate cancer (mPCa) [1–6]. Prospective studies are ongoing (NCT01751438, NCT02454543, NCT02458716, ISRCTN15704862). These trials will provide CRP complication rates, but not a direct comparison between complications associated with CRP and radical prostatectomy for nonmetastatic prostate cancer (nmRP). To date, the best available evidence, focusing on CRP complications, originates from a 106patient CRP study within six centers of excellence [7]. To address this limitation, we examined the effect of CRP on perioperative outcomes, length of stay (LOS), and total hospital charges compared with nmRP. In the National Inpatient Sample (NIS; Supplementary material) database (2008–2013), we focused on patients with primary diagnosis of prostate cancer (PCa). Patients with secondary diagnosis of metastatic disease were defined to have mPCa. Outcomes of interest consisted of: intraoperative, cardiac, respiratory, vascular, wound, genitourinary, miscellaneous medical, and miscellaneous surgical complications, as well as of blood transfusions, parenteral nutrition, bowel obstruction, LOS, total hospital charges, and in-hospital mortality [8]. Covariates consisted of patient age, year of surgery, race, Charlson comorbidity index, insurance status, hospital region, income, approach, hospital bed size, hospital teaching status, and annual hospital volume [9]. Propensity score matching (PSM) reduced inherent differences between CRP and nmRP patients. Statistical tests were two sided with a significance level of p < 0.05 for multivariable logistic regression (MLR) models, Poisson regression (MPR) models, and linear regression models. This study was approved by the institutional review board. Among 76 378 patients (Supplementary Table 1), 953 (1.2%) underwent CRP. CRP rates increased from 0.96% to 1.37% (2008–2013) in a nonsignificant fashion (p = 0.2). CRP patients more frequently experienced overall (14.9% vs 12.3%, p = 0.02), intraoperative (1.6% vs 0.8%, p = 0.02), genitourinary (1.9% vs 1.0%, p = 0.01), and miscellaneous surgical complications (3.4% vs 2.0%, p = 0.01) versus nmRP.

Additionally, CRP patients more frequently underwent blood transfusions (6.3% vs 4.9%; p = 0.048). No differences in in-hospital mortality were recorded (0.1% vs 0.03%, p = 0.7; Table 1). After PSM, no differences in baseline characteristics were recorded between nmRP and CRP (Supplementary Table 2). Here, in MLR models, overall (odds ratio [OR]: 1.34, p = 0.01), intraoperative (OR: 2.61, p = 0.005), and miscellaneous surgical complications (OR: 1.69, p = 0.02) were higher at CRP (Table 2). In MPR models, CRP (OR: 1.07, p = 0.01) represented an independent predictor for longer LOS (Table 2). Linear regression models revealed higher total hospital charges: $810 (p = 0.0004) for each CRP than nmRP (Table 2). Moreover, low hospital volume was an independent predictor of overall, miscellaneous medical, miscellaneous surgical complications, bowel obstructions, blood transfusions, LOS, and total hospital charges (–$1500) versus high volume. Medium hospital volume was also an independent predictor of pulmonary complications and total hospital charges (–$600) versus high volume. The proportion of CRPs relative to all RPs is low (1.2%). Nonetheless, this rate increased by 41% during the study span, albeit in a nonsignificant fashion (p = 0.2). Despite a lack of statistical significance, such 41% increase is clinically meaningful and may be related to greater confidence in cytoreductive effects of RP in the metastatic setting, in accordance with retrospective data that have been reported previously on that topic [1–3,5]. Nonetheless, the overall marginal rate of CRP is also indicative of its use in exceptional patients. Based on the absence of prospective data supporting the survival advantage of CRP, it should ideally be exclusively offered within protocol settings. The overall complication rates recorded for CRP in our cohort (14.9%) are lower than the overall complication rates recorded by Sooriakumaran et al [7] (20.8%). These differences could be related to NIS database limitations, where readmission information is unavailable. This rate accounted for 3.8% of overall complications in the Sooriakumaran et al study. This consideration indicates an overall complication rate of approximately 17.0% in the Sooriakumaran et al study, if readmision rates were not considered. In

Table 1 – Complication rates of cytoreductive prostatectomy and radical prostatectomy for nonmetastatic prostate cancer patients, n (%), within the National Inpatient Sample (2008–2013) CRP (n = 953, 1.2%) Overall complication In-hospital mortality Intraoperative complication Genitourinary complication Blood transfusion Miscellaneous surgical complication Cardiac complication Pulmonary complication Vascular complication Wound complication Bowel obstruction Miscellaneous medical complication Parenteral nutrition

142 1 15 18 60 32 13 16 5 4 39 57 0

nmRP (n = 75 425, 98.8%)

(14.9) (0.1) (1.6) (1.9) (6.3) (3.4) (1.4) (1.7) (0.5) (0.4) (4.1) (6.0) (0)

9247 23 639 735 3660 1512 770 989 292 175 2736 3803 109

(12.3) (0.03) (0.8) (1.0) (4.9) (2.0) (1.0) (1.3) (0.4) (0.2) (3.6) (5.0) (0.1)

p value

a

0.02 0.7 0.02 0.01 0.048 0.01 0.4 0.4 0.7 0.4 0.5 0.2 0.5

CRP = cytoreductive prostatectomy; nmRP = radical prostatectomy for nonmetastatic prostate cancer. Derived from chi-square test.

a

Please cite this article in press as: Preisser F, et al. Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer. Eur Urol (2018), https://doi.org/10.1016/j. eururo.2018.07.006

EURURO-7929; No. of Pages 4 E U R O P E A N U R O L O G Y X X X ( 2 0 18 ) X X X – X X X

Table 2 – Multivariable regression models predicting risk of complications, length of stay, and total hospital charges for cytoreductive prostatectomy patients relative to radical prostatectomy for nonmetastatic prostate cancer, after 4:1 propensity score matching within the National Inpatient Sample (2008–2013)

Overall complications Intraoperative complications Genitourinary complications Cardiac complications Miscellaneous medical complications Miscellaneous surgical complications Pulmonary complications Blood transfusion Vascular complications Wound complications Bowel obstruction Length of stay (Poisson regression model) a Total hospital charges (linear regression model) c

OR

95% CI

1.34 2.61 1.69 1.19 1.22 1.69 1.77 1.31 1.31 1.40 1.18 1.07b

1.08–1.67 1.35–5.07 0.96–2.98 0.62–2.30 0.88–1.70 1.08–2.63 0.95–3.30 0.96–1.81 0.46–3.72 0.43–4.49 0.80–1.75 1.02–1.12

0.01 0.005 0.07 0.6 0.2 0.02 0.1 0.09 0.6 0.6 0.4 0.01

$810d

$358–1261

0.0004

p value

CI = confidence interval; OR = odds ratio. All models were adjusted for approach, year of diagnosis, age, Charlson comorbidity index, insurance status, race, teaching status, lymph node dissection, hospital volume, region, hospital bed size, and income. a Model additionally adjusted for all complications. b Relative risk. c Model additionally adjusted for all complications and length of stay. d Change in total hospital charges in dollars per unit.

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nmRP further corroborates a lack of meaningful short-term outcome differences. The main study limitations are the retrospective nature and missing information about tumor characteristics. Moreover, PSM and multivariable adjustments were unable to account for potential differences in tumor characteristics between CRP and nmRP patients. Complications could not be rated according to prospective Clavien-Dindo method. Unfortunately, individual surgeon volume was unavailable; ideally, surgeon volume and hospital volume, predictors for complication rates, should be considered in all analyses. Additionally, we were unable to adjust for patient characteristics, such as performance status, as well as presence or absence of exposure to neoadjuvant chemotherapy, androgen deprivation therapy, and radiotherapy. In conclusion, intra- and postoperative complications associated with CRP are higher than those of nmRP. Nonetheless, CRP complication rates appear manageable but require explicit discussion at counseling. Author contributions: Felix Preisser had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Tilki, Karakiewicz, Preisser, Bandini. Acquisition of data: Tian, Mazzone, Nazzani. Analysis and interpretation of data: Marchioni, Preisser, Mazzone, Bandini, Shariat.

consequence, Sooriakumaran et al study and our study appear to be in very close agreement. Last but not least, the readmission rate of 3.8% in the Sooriakumaran et al study focusing on CRP is highly comparable with readmissions of patients treated with nmRP, with 3.9% readmissions, as reported by Gandaglia et al [10]. Taken together, our data, as well as those of others, indicate highly comparable findings. Our study provides not only a crude comparison between perioperative complications according to CRP versus nmRP, but also a fully adjusted comparison between the two populations (mPCa vs nonmetastatic PCa). After PSM and multivariable adjustments, CRP was associated with a 1.3fold increase in overall, 1.7-fold increase in miscellaneous surgical, and 2.6-fold increase in intraoperative complications. Conversely, for the remaining eight endpoints (namely, genitourinary, cardiac, miscellaneous medical, pulmonary, vascular, and wound complications; blood transfusions; and bowel obstructions), no significant differences were identified. These observations corroborate absence of critically higher adverse complication rates after CRP that could be interpreted as an absolute safety contraindication to CRP. It is of utmost importance to note that this finding originates from a population-based cohort and not from centers of excellence data, where better intraand postoperative complication profiles might be expected. Moreover, a significant increase in LOS was recorded for CRP. However, this difference was of questionable clinical pertinence (OR: 1.07). Additionally, CRP was associated with a marginally higher average of total hospital charges ($810 per surgery) relative to nmRP. Last but not least, absence of differences in mortality rates between CRP and

Drafting of the manuscript: Preisser, Karakiewicz, Steuber, Montorsi. Critical revision of the manuscript for important intellectual content: Graefen, Huland, Steuber, Saad, Montorsi. Statistical analysis: Marchioni, Preisser, Bandini. Obtaining funding: None. Administrative, technical, or material support: Tian, Nazzani, Saad. Supervision: Tilki, Karakiewicz, Graefen. Other: None. Financial disclosures: Felix Preisser certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.

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Please cite this article in press as: Preisser F, et al. Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer. Eur Urol (2018), https://doi.org/10.1016/j. eururo.2018.07.006