Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 1 of 24
1 Running title EP-RARP in the morbidly obese- outcomes Source of funding: None
Author’s names and affiliation 1st Author: Vineet Agrawal MD, FRCSEd (Urol.), FEBU Address: Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642 USA Tel: 585 354 0911 e-mail address: [email protected]
2nd Author: Changyong Feng, PhD Address: University of Rochester, Department of Biostatistics and Computational Biology, 601 Elmwood Avenue Box 630, Rochester, New York 14642 Tel: 585 275 4263 e-mail address: [email protected]
Senior author: Jean Joseph, MD, MBA Head-Section of Laparoscopic and Robotic Surgery, Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642 USA. Tel: (585) 275 8762 e-mail address: [email protected] Corresponding author: Vineet Agrawal
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 2 of 24
2 ABSTRACT Introduction An increasing number of obese patients (BMI >30 kg/m 2]) with localized prostate cancer are presenting as candidates for RARP, which can be carried out using the transperitoneal (TP) or the extraperitoneal (EP) approach. Morbidly obese (BMI > 40 kg/m2) patients present as an especially challenging surgical cohort. We sought to evaluate the perioperative and pathological outcomes associated with EP-RARP in morbidly obese men. Methods In this institutional review board approved study, our prospectively collected database (CAISIS) was reviewed. 1663 patients underwent EP-RARP for localized prostate cancer at our institution between July 2003 and December 2013, by a single surgeon. 40 patients were considered morbidly obese. A propensity score-matched analysis was performed using multivariate analysis incorporating 10 co-variates to identify comparable group of patients with a BMI of >40 kg/m2 and 0.05). Despite a higher total operating time and estimated blood loss in the morbidly obese (238 vs. 176 mins, p 30 kg/m2] is regarded as an epidemic with almost one third of the US adult population classified as obese 1. It is associated with chronic diseases such as diabetes, coronary artery disease, sleep apnea, and some cancers2. The association between prostate cancer, the most common solid organ malignancy in men, and obesity is complex with obese men shown to have more aggressive prostate cancer than non-obese men3-4. Radical prostatectomy is the gold standard treatment for localized prostate cancer5. With the high prevalence of both obesity and prostate cancer, as well as the wide acceptance of the robot-assisted approach to performing a prostatectomy (RARP) among the urological community and patients6, an increasing number of obese and morbidly obese patients (BMI ≥ 40 kg/m2) are presenting as candidates for RARP. The procedure can be carried out using a transperitoneal (TP) or an extraperitoneal (EP) approach. Several studies have compared the outcomes of obese and non-obese patients undergoing a RARP7-18. However, only two studies have focused specifically on outcome in the morbidly obese16-17. These studies only utilized the TP approach. The outcome of EP-RARP in the morbidly obese was studied in a previous report as part of a larger cohort, but the number of morbidly obese patients was limited to three18. Therefore, the outcomes of EP-RARP in a morbidly obese patient population have not been previously examined to a significant extent.
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 4 of 24
4
Herein, we report the perioperative, postoperative, and pathological outcomes, and
complications associated with EP-RARP in the morbidly obese, compared to a
propensity score-matched group of non-morbidly obese men.
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 5 of 24
5 METHODS Institutional review board approval was obtained for this study. We reviewed data from our prospectively collected database (Cancer Information Systems-CAISIS) maintained from the beginning of our experience with RARP. All surgeries were performed by one surgeon (JJ) at a tertiary academic center between July 2003 and December 2013. 2763 RARP (1663 EP, 1000 TP) were performed during this time period. A total of 40 morbidly obese (BMI > 40 kg/m2) males who had undergone EP-RARP were identified. Propensity score matching was used to identify a comparative group of 40 non-morbidly obese patients (BMI < 40 kg/m2) who had also undergone EP-RARP in the same time period. This was done in order to minimize the bias inherent in comparing a nonmatched cohort of non-morbidly obese men, who may have a different risk profile, and different cancer characteristics, such as a lower comorbidity status or less aggressive cancer respectively. The following patient and tumor characteristics were extracted: age, BMI, ASA score, co-morbidities, previous abdominal surgeries, PSA, biopsy Gleason score sum, and clinical T-Stage. The operative and perioperative outcome variables measured were total operative time (creation of pneumoperitoneum, trocar placement, specimen retrieval, closure, and console times), estimated blood loss, transfusion rates, length of stay, whether a pelvic lymphadenectomy was carried out, and the nerve-sparing status. Postoperative pathological variables measured were prostate specimen weight, Gleason score sum, T-Stage and surgical margin status. Intraoperative or postoperative complications were classified according to the modified Clavien-Dindo classification19.
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 6 of 24
6 The WHO definition of BMI was used (40 kg/m2 - class 3 or morbid obesity). Blood loss was estimated by subtracting the irrigation fluid, and estimated urine output from the blood in the suction canister at the end of the procedure. Length of stay was calculated from the time of the admission until patient discharge. Patients with intermediate and high-risk disease according to the D’Amico risk classification underwent bilateral pelvic lymphadenectomy Nerve sparing was scored as none, partial or complete, and noted if unilateral or bilateral. It was deemed to be complete only if carried out bilaterally. Histology was confirmed at our institution in cases of outside referral. The pathological assessment of the prostatectomy specimens was performed according to the Stanford protocol. Presence of cancer cells at the inked margin was regarded as evidence of positive surgical margin. We used the successive generations of the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) as they became available. In the beginning of our experience, we used a 3-arm daVinci system. The procedures were carried out using our standardized extraperitoneal technique of a “W” configuration using 6-trocars20. Patients are placed in Trendelenburg position after bladder drainage. The extraperitoneal space is created under direct vision using a 0-degree laparoscope, placed through the balloon dilator (OMS-XB2 ExtraviewTM, Covidien, Mansfield, MA) inserted in a 1-cm paraumbilical fascial incision. Postoperative care was standardized for all patients with the removal of the drain when the output was
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 7 of 24
7 less than 40-60 ccs in an 8-hr shift. The Foley catheter was removed in 8-10 days. Unless there were contraindications, mechanical and chemical prophylaxes for prevention of DVT/PE were used postoperatively until discharge from the hospital. Statistical analysis Group 1 and 2 included patients with a BMI >40 kg/m 2 and < 40 kg/m2 respectively. The mean and standard deviation of continuous variables, and the frequency of categorical variables were calculated. Two-sample t-test was used to compare the mean values of continuous variables, and the Pearson’s chi-squared or Fisher’s exact test was used to compare the distributions of categorical variables in both groups. All p-values are twosided, with the significance level of each comparison set at 0.05. The analysis was implemented with SAS 9.3 (SAS Institute Inc., Cary, NC). Since the data is not from a randomized clinical trial, we used the propensity score method to select patients for group 2, so that patients in the two groups were comparable. To generate the propensity score matching, multiple logistic regression was used based on 10 co-variates as independent variables: age, diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, ASA score, prior abdominal surgery, overall Gleason score, PSA level, clinical T-staging, and group membership (BMI >40 kg/m2 and < 40 kg/m2) as binary dependent variables. A score of 0 to 1 was generated. A 1:1 propensity score matching was performed to identify comparable group of patients with a BMI of >40 kg/m2 and 40 kg/m2
Mean (SD; median): BMI 42.9 (5.4; 41.8) Age*, years 58.2 (7; 59) PSA* level, ng/ml 5.5 (0.9; 5.1) N (%) Diabetes* 14 (35) Dyslipidemia* 19 (47.5) Coronary artery disease* 4 (10) Hypertension* 33 (82.5) Prior abdominal surgery* 10 (25) ASA* 2.6 (0;3) Preoperative Gleason score sum* 6 27 (67.5) 7 9 (22.5) ≥8 3 (7.5) Clinical stage* T1 33 (82.5) T2 7 (17.5) T3 0 *: variables used for propensity score matching
Not morbidly obese BMI < 40 kg/m2
p-value
29.39 (1.2; 31.8) 59 (4.2; 60) 5.6 (0.5; 4.2)
40 kg/m2
Mean (SD; median): OT, min 238(70.5; 224) Console time 175 (49.8; 199) EBL 235 (70.7; 250) N (%) Nerve sparing None 14 (35) Unilateral 11 (27.5) Bilateral 15 (37.5) PLND Performed 18 (45) Not performed 22 (55) Mean (SD; median) Prostate weight 61.2 (12.0; 61) N (%) PSM 4 (10) Pathological Stage pT2 29 (72.5) pT3 11 (27.5) Postoperative Gleason score sum 6 19 (47.5) 7 19 (47.5) ≥8 2 (5) Mean (median) LOS, days 1.2 (1) N (%) Intraoperative complications None 39 (97.5) Transfusion 0 Transient hypotension 1 (2.5) Clavien-classified complications Grades 1-2 1 (2.5) Grades 3-4 0 Postoperative complications None 35 (87.5) Transfusion 1 (2.5) UTI 1 (2.5) Lower limb cellulitis 1 (2.5) Wound infection 1 (2.5) Bladderneck contracture1(2.5)
Not morbidly obese BMI < 40 kg/m2
p-value
176.4(46.8; 167.5) 138 (40.9; 132.5) 192.4 (56.5; 160)
Page 1 of 24
1 Running title EP-RARP in the morbidly obese- outcomes Source of funding: None
Author’s names and affiliation 1st Author: Vineet Agrawal MD, FRCSEd (Urol.), FEBU Address: Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642 USA Tel: 585 354 0911 e-mail address: [email protected]
2nd Author: Changyong Feng, PhD Address: University of Rochester, Department of Biostatistics and Computational Biology, 601 Elmwood Avenue Box 630, Rochester, New York 14642 Tel: 585 275 4263 e-mail address: [email protected]
Senior author: Jean Joseph, MD, MBA Head-Section of Laparoscopic and Robotic Surgery, Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 656, Rochester, NY 14642 USA. Tel: (585) 275 8762 e-mail address: [email protected] Corresponding author: Vineet Agrawal
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 2 of 24
2 ABSTRACT Introduction An increasing number of obese patients (BMI >30 kg/m 2]) with localized prostate cancer are presenting as candidates for RARP, which can be carried out using the transperitoneal (TP) or the extraperitoneal (EP) approach. Morbidly obese (BMI > 40 kg/m2) patients present as an especially challenging surgical cohort. We sought to evaluate the perioperative and pathological outcomes associated with EP-RARP in morbidly obese men. Methods In this institutional review board approved study, our prospectively collected database (CAISIS) was reviewed. 1663 patients underwent EP-RARP for localized prostate cancer at our institution between July 2003 and December 2013, by a single surgeon. 40 patients were considered morbidly obese. A propensity score-matched analysis was performed using multivariate analysis incorporating 10 co-variates to identify comparable group of patients with a BMI of >40 kg/m2 and 0.05). Despite a higher total operating time and estimated blood loss in the morbidly obese (238 vs. 176 mins, p 30 kg/m2] is regarded as an epidemic with almost one third of the US adult population classified as obese 1. It is associated with chronic diseases such as diabetes, coronary artery disease, sleep apnea, and some cancers2. The association between prostate cancer, the most common solid organ malignancy in men, and obesity is complex with obese men shown to have more aggressive prostate cancer than non-obese men3-4. Radical prostatectomy is the gold standard treatment for localized prostate cancer5. With the high prevalence of both obesity and prostate cancer, as well as the wide acceptance of the robot-assisted approach to performing a prostatectomy (RARP) among the urological community and patients6, an increasing number of obese and morbidly obese patients (BMI ≥ 40 kg/m2) are presenting as candidates for RARP. The procedure can be carried out using a transperitoneal (TP) or an extraperitoneal (EP) approach. Several studies have compared the outcomes of obese and non-obese patients undergoing a RARP7-18. However, only two studies have focused specifically on outcome in the morbidly obese16-17. These studies only utilized the TP approach. The outcome of EP-RARP in the morbidly obese was studied in a previous report as part of a larger cohort, but the number of morbidly obese patients was limited to three18. Therefore, the outcomes of EP-RARP in a morbidly obese patient population have not been previously examined to a significant extent.
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 4 of 24
4
Herein, we report the perioperative, postoperative, and pathological outcomes, and
complications associated with EP-RARP in the morbidly obese, compared to a
propensity score-matched group of non-morbidly obese men.
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 5 of 24
5 METHODS Institutional review board approval was obtained for this study. We reviewed data from our prospectively collected database (Cancer Information Systems-CAISIS) maintained from the beginning of our experience with RARP. All surgeries were performed by one surgeon (JJ) at a tertiary academic center between July 2003 and December 2013. 2763 RARP (1663 EP, 1000 TP) were performed during this time period. A total of 40 morbidly obese (BMI > 40 kg/m2) males who had undergone EP-RARP were identified. Propensity score matching was used to identify a comparative group of 40 non-morbidly obese patients (BMI < 40 kg/m2) who had also undergone EP-RARP in the same time period. This was done in order to minimize the bias inherent in comparing a nonmatched cohort of non-morbidly obese men, who may have a different risk profile, and different cancer characteristics, such as a lower comorbidity status or less aggressive cancer respectively. The following patient and tumor characteristics were extracted: age, BMI, ASA score, co-morbidities, previous abdominal surgeries, PSA, biopsy Gleason score sum, and clinical T-Stage. The operative and perioperative outcome variables measured were total operative time (creation of pneumoperitoneum, trocar placement, specimen retrieval, closure, and console times), estimated blood loss, transfusion rates, length of stay, whether a pelvic lymphadenectomy was carried out, and the nerve-sparing status. Postoperative pathological variables measured were prostate specimen weight, Gleason score sum, T-Stage and surgical margin status. Intraoperative or postoperative complications were classified according to the modified Clavien-Dindo classification19.
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 6 of 24
6 The WHO definition of BMI was used (40 kg/m2 - class 3 or morbid obesity). Blood loss was estimated by subtracting the irrigation fluid, and estimated urine output from the blood in the suction canister at the end of the procedure. Length of stay was calculated from the time of the admission until patient discharge. Patients with intermediate and high-risk disease according to the D’Amico risk classification underwent bilateral pelvic lymphadenectomy Nerve sparing was scored as none, partial or complete, and noted if unilateral or bilateral. It was deemed to be complete only if carried out bilaterally. Histology was confirmed at our institution in cases of outside referral. The pathological assessment of the prostatectomy specimens was performed according to the Stanford protocol. Presence of cancer cells at the inked margin was regarded as evidence of positive surgical margin. We used the successive generations of the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) as they became available. In the beginning of our experience, we used a 3-arm daVinci system. The procedures were carried out using our standardized extraperitoneal technique of a “W” configuration using 6-trocars20. Patients are placed in Trendelenburg position after bladder drainage. The extraperitoneal space is created under direct vision using a 0-degree laparoscope, placed through the balloon dilator (OMS-XB2 ExtraviewTM, Covidien, Mansfield, MA) inserted in a 1-cm paraumbilical fascial incision. Postoperative care was standardized for all patients with the removal of the drain when the output was
Journal of Endourology Outcomes of Extraperitoneal Robot-assisted Radical Prostatectomy in the Morbidly Obese: A Propensity Score Matched Study (doi: 10.1089/end.2014.0661) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 7 of 24
7 less than 40-60 ccs in an 8-hr shift. The Foley catheter was removed in 8-10 days. Unless there were contraindications, mechanical and chemical prophylaxes for prevention of DVT/PE were used postoperatively until discharge from the hospital. Statistical analysis Group 1 and 2 included patients with a BMI >40 kg/m 2 and < 40 kg/m2 respectively. The mean and standard deviation of continuous variables, and the frequency of categorical variables were calculated. Two-sample t-test was used to compare the mean values of continuous variables, and the Pearson’s chi-squared or Fisher’s exact test was used to compare the distributions of categorical variables in both groups. All p-values are twosided, with the significance level of each comparison set at 0.05. The analysis was implemented with SAS 9.3 (SAS Institute Inc., Cary, NC). Since the data is not from a randomized clinical trial, we used the propensity score method to select patients for group 2, so that patients in the two groups were comparable. To generate the propensity score matching, multiple logistic regression was used based on 10 co-variates as independent variables: age, diabetes mellitus, hypertension, dyslipidemia, coronary artery disease, ASA score, prior abdominal surgery, overall Gleason score, PSA level, clinical T-staging, and group membership (BMI >40 kg/m2 and < 40 kg/m2) as binary dependent variables. A score of 0 to 1 was generated. A 1:1 propensity score matching was performed to identify comparable group of patients with a BMI of >40 kg/m2 and 40 kg/m2
Mean (SD; median): BMI 42.9 (5.4; 41.8) Age*, years 58.2 (7; 59) PSA* level, ng/ml 5.5 (0.9; 5.1) N (%) Diabetes* 14 (35) Dyslipidemia* 19 (47.5) Coronary artery disease* 4 (10) Hypertension* 33 (82.5) Prior abdominal surgery* 10 (25) ASA* 2.6 (0;3) Preoperative Gleason score sum* 6 27 (67.5) 7 9 (22.5) ≥8 3 (7.5) Clinical stage* T1 33 (82.5) T2 7 (17.5) T3 0 *: variables used for propensity score matching
Not morbidly obese BMI < 40 kg/m2
p-value
29.39 (1.2; 31.8) 59 (4.2; 60) 5.6 (0.5; 4.2)
40 kg/m2
Mean (SD; median): OT, min 238(70.5; 224) Console time 175 (49.8; 199) EBL 235 (70.7; 250) N (%) Nerve sparing None 14 (35) Unilateral 11 (27.5) Bilateral 15 (37.5) PLND Performed 18 (45) Not performed 22 (55) Mean (SD; median) Prostate weight 61.2 (12.0; 61) N (%) PSM 4 (10) Pathological Stage pT2 29 (72.5) pT3 11 (27.5) Postoperative Gleason score sum 6 19 (47.5) 7 19 (47.5) ≥8 2 (5) Mean (median) LOS, days 1.2 (1) N (%) Intraoperative complications None 39 (97.5) Transfusion 0 Transient hypotension 1 (2.5) Clavien-classified complications Grades 1-2 1 (2.5) Grades 3-4 0 Postoperative complications None 35 (87.5) Transfusion 1 (2.5) UTI 1 (2.5) Lower limb cellulitis 1 (2.5) Wound infection 1 (2.5) Bladderneck contracture1(2.5)
Not morbidly obese BMI < 40 kg/m2
p-value
176.4(46.8; 167.5) 138 (40.9; 132.5) 192.4 (56.5; 160)
