Perioperative and early oncological outcomes after robot-assisted radical prostatectomy (RARP) in morbidly obese patients: a propensity score-matched study

Authors


Abstract

Objective

  • To evaluate the perioperative and pathological outcomes associated with robot-assisted radical prostatectomy (RARP) in morbidly obese men.

Patients and Methods

  • Between January 2008 and March 2012, 3041 patients underwent RARP at our institution by a single surgeon (V.P.).
  • In all, 44 patients were considered morbidly obese with a body mass index (BMI) of ≥40 kg/m2.
  • A propensity score-matched analysis was conducted using multivariable analysis to identify comparable groups of patients with a BMI of ≥40 and <40 kg/m2.
  • Perioperative, pathological outcomes and complications were compared between the two matched groups.

Results

  • There was no significant difference in operative time. However, the mean estimated blood loss was higher in morbidly obese patients, at a mean (sd) of 113 (41) vs 130 (27) mL (P = 0.049).
  • Anastomosis was more difficult in morbidly obese patients (P = 0.001).
  • There were no significant differences in laterality, ease of nerve sparing, or transfusion rate between the groups.
  • There were no intraoperative complications in either group. Postoperative pathological outcomes were similar between the groups.
  • Differences in positive surgical margins and ease of nerve sparing approached statistical significance (P = 0.097, P = 0.075 respectively). Postoperative complication rates, pain scores, length of stay and indwelling catheter duration were similar in the groups.

Conclusions

  • RARP in morbidly obese patients is technically demanding. However, it can be accomplished with acceptable morbidity and resource use.
  • In the hands of an experienced surgeon, it is a safe procedure and offers beneficial clinical outcomes.
Abbreviations
BMI

body mass index

EBL

estimated blood loss

MRSA

methicillin-resistant Staphylococcus aureus

OT

operation time

PSM

positive surgical margin

(RA)(L)RP

(robot-assisted) (laparoscopic) radical prostatectomy

RPP

radical perineal prostatectomy

Introduction

Obesity represents a major healthcare problem that is significantly affecting people of all ages in developed countries. It is considered the second most common preventable cause of death in the USA. In 2009 and 2010, the National Health and Nutrition Examination Survey (NHANES) reported the overall prevalence of obesity as 35.7% among adults in the USA. When stratified by age and gender, the data showed a prevalence of 37.2% for men aged 40–60 years and 36.6% for those aged ≥60 years [1].

Obesity is measured and classified using BMI. The WHO classifies obesity into class I (BMI of 30–34.99 kg/m2), class II (BMI of 35–39.99 kg/m2) and class III (BMI of ≥40 kg/m2). This classification system emanates from observational and epidemiological studies, which relate BMI to risk of morbidity and mortality [2].

It has been found that obesity can result in adverse postoperative outcomes based on the technical difficulty encountered in the procedure or its effect on haemodynamic and respiratory parameters. In addition, obesity increases the risk of multiple diseases including hypertension, diabetes mellitus and dyslipidaemia [2]. These diseases have been shown to increase the risk of postoperative complications. As a result, obese patients represent an increased risk for any surgical procedure.

Localised prostate cancer is effectively managed surgically using robot-assisted technology. During the past decade, the application of robot-assisted technology has evolved and its advantages and disadvantages in obese patients have been examined. Many studies have compared the clinical, pathological and functional outcomes of robot-assisted radical prostatectomy (RARP) in obese and non-obese patients [3-13]. However, to date, only one study with a small sample size has reported outcomes for morbidly obese men undergoing RARP [14].

The impact of morbid obesity and the technical challenges it presents in performing RARP have not been well defined. The focus of the present study was to discern the perioperative and pathological outcomes in a cohort of morbidly obese patients undergoing RARP.

Patients and Methods

The Global Robotic Institute database for RARP (N = 3041) was reviewed for patients operated between January 2008 and March 2012. There were 27 cases classified as salvage and were excluded from the study population. In all, 44 patients in the database were identified as morbidly obese with a BMI of ≥40 kg/m2 (morbidly obese group). Morbidly obese patients were then computer-matched to those with a BMI of <40 kg/m2 (n = 2970). The final two cohorts, morbidly obese (n = 44) and non-morbidly obese (n = 44) constitute the clinical material for this comparative study.

Perioperative data were entered prospectively into an approved Institutional Review Board database and analysed retrospectively. Data were collected by prospective review of the patient's record including positive biopsy results, PSA determination, DRE, etc.

All cases were performed by a single surgeon (V.P.) at our institution using the transperitoneal six-port technique previously described [15]. In morbidly obese patients several measures were undertaken to maintain similar perioperative outcomes. Long bariatric trocars were used whenever the anterior abdominal wall was expected to be thick enough to present a difficulty in reaching the deep pelvic structures. Access ports were inserted in a more cephalic position to maintain a more favourable angle during the procedure and to prevent interposition of the pubic bone. The da Vinci Si Surgical System (Intuitive Surgical, Sunnyvale, CA, USA), allows the use of longer robotic instruments and is preferred in obese patients.

To maximise the vision in the operative field, the following manoeuvres were performed. Trendelenburg position is increased and this modification mandates extra caution during positioning to prevent sliding of the patient and to avoid pressure points by the usage of the beanbag, extra padding and securing with adhesive tape. If difficulty is encountered with pubic bone interposition, the scope is changed from 30 to 0 ° for dissection of the apex and anastomosis. Moreover, if visualising the bladder fat is difficult, a switch is performed from 30 to 0 ° for dissection of the bladder neck, seminal vesicles and posterior sphincter complex. Two instruments to retract the fat and bladder are used to prevent the fat from falling into the operative field.

Pathological analyses were performed and confirmed at our institution and specimens were processed according to the recommendations of the American Society of Clinical Pathologists [16]. The apex and bladder neck cones were amputated and sectioned in the sagittal plane. The remaining specimen was sectioned transversely at intervals of 4 mm. Positive surgical margins (PSMs) were defined as the presence of tumour tissue on the inked surface of the specimen. Pathological staging was performed according to the 2002 TNM system [17]. Nerve sparing and anastomosis was subjectively evaluated by the surgeon as being ‘not difficult’, ‘somewhat difficult’ or ‘very difficult’. Postoperative complications were classified using the Dindo modification of the Clavien Grading System [18].

Descriptive demographic and clinical data are reported as frequency distributions and simple percentages for categorical variables. Continuous variables are expressed as the mean (sd) and the median. Univariate analysis of discrete variables was accomplished by chi-square analysis or the Fisher'sexact test (if the expected value in any cell was <5) with the appropriate degrees of freedom. Comparisons of continuous variables were conducted using a two-tailed Student's t-test. Pearson's product-moment correlation coefficient analysis was used to discern the degree of relationship between selected parameters.

Multivariable logistic regression was used to generate a propensity score based on 10 covariates as independent variables: age, diabetes mellitus, hypertension, dyslipidaemia, coronary artery disease, prior abdominal surgery, preoperative overall Gleason score, PSA level, sexual health inventory for men score (SHIM), AUA Symptom Score (AUA-SS) and group membership as a binary dependent variable. This process generated a score between 0 and 1, which was then used to summarise a collection of covariates and integrated the likelihood of patient membership into a particular cohort. Morbidly obese patients were then matched to patients who were notmorbidly obese in a 1:1 ratio using an optimal matching algorithm. This approach minimised the overall distance between observations and was conducted using Mahalanobis distance within propensity score callipers (no matches outside the callipers). This statistical methodology was used to ensure the homogeneity of the study groups on the variables measured.

All P values were reported as two-sided and were not adjusted for multiple testing. A significant difference between measurements was defined as P ≤ 0.050.

Results

The demographic and baseline clinical characteristics are shown in Table 1. The mean (sd) BMI for the morbidly obese group was 43.2 (3.9) kg/m2 and 28.9 (3.5) kg/m2for the non-morbidly obese group (P < 0.001). The two study groups demonstrated no significant differences, thus confirming their homogeneity on the variables measured. Within the non-morbidly obese, 28 patients (63.6%) had a BMI of <30 kg/m2 and 16 patients (36.4%) had a BMI of >30 kg/m2.

Table 1. Comparison of preoperative variables for patients undergoing RARP stratified by BMI
VariableMorbidly obese BMI ≥40 kg/m2Not morbidly obese BMI <40 kg/m2P
  1. Categorical data are presented as n (%).
Total patients, n (%)44 (100.0)44 (100.0) 
Mean (sd; median):   
BMI, kg/m243.2 (3.9; 42.0)28.9 (3.5; 28.8)<0.001
Age, years58.7 (6.3; 60.0)57.9 (8.1; 57.5)0.639
PSA level, ng/mL6.0 (3.0; 5.3)5.9 (4.1; 5.0)0.926
N (%):   
Diabetes14 (31.8)12 (27.3)0.640
Hypertension32 (72.7)32 (72.7)1.000
Coronary artery disease4 (9.1)7 (15.9)0.334
Dyslipidaemia16 (36.4)12 (27.3)0.360
Prior abdominal surgery17 (36.4)16 (36.4)0.826
Preoperative Gleason score sum:  0.695
624 (54.5)20 (45.5) 
715 (34.1)18 (40.9) 
≥85 (11.4)6 (13.6) 
Clinical stage:  0.242
T129 (65.1)35 (79.5) 
T215 (34.1)8 (18.2) 
T301 (2.3) 
Sexual Health in Men Inventory score:  0.658
≤2129 (65.9)27 (61.4) 
>2115 (34.1)17 (38.6) 
AUAS ymptom Score:  0.455
1–723 (52.3)20 (45.5) 
8–1917 (38.6)16 (36.4) 
20–354 (9.1)8 (18.2) 

The clinical stage distribution was 29 patients (65.9%) in stage T1, 15 (34.1%) in stage T2 and none in stage T3 in the morbidly obese group. In the group that was notmorbidly obese, there were 35 patients (79.5%) in stage T1, eight (18.2%) in stage T2 and one (2.3%) in stage T3. This distribution did not achieve statistical significance.

Two patients (4.5%) had a history of prostate treatment in the morbidly obese group compared with three (6.8%) in the non-morbidly obese. The risk class according to the D'Amico classification for the morbidly obese group was distributed as follows: low risk, 21 patients (47.7%); intermediate risk, 17 patients (38.6%); and high risk, six patients (13.6%). In the non-morbidly obese, the distribution was as follows: low risk, 20 patients (45.5%); intermediate risk, 17 patients (38.6%); and high risk, seven patients (15.9%). There was no significant difference in the distribution of D'Amico class between the study groups. Almost half of the patients in both groups were classified as D'Amico class low risk.

Intraoperative Data

Bilateral nerve sparing was performed in 17 patients (38.6%) in the morbidly obese group and 23 patients (52.3%) in the non-morbidly obese. The ease of nerve sparing was found to be ‘very difficult’ in 10 patients (30.3%) in the morbidly obese group and in six patients (14.6%) in the non-morbidly obese. The anastomosis was considered to be ‘very difficult’ in 18 patients (40.9%) in the morbidly obese group and in one patient (2.3%) in the non-morbidly obese (P ≤ 0.001).

The mean (sd) estimated blood loss (EBL) was greater in morbidly obese patients, at 129.8 (40.7) vs 112.5 (40.8) mL in those who were non-morbidly obese (P = 0.049). The mean operationtime (OT; skin-to-skin) was longer for morbidly obese patients, at 84.0 (27.2) vs 76.9 (11.0) min for those who were non-morbidly obese. This comparison did not achieve statistical significance. An analysis was conducted to discern the association between BMI, EBL and OT for the study groups and no significant relationship was identified. There were no intraoperative complications, open conversions, or blood transfusions in either group. The information on intraoperative variables by group is summarised in Table 2.

Table 2. Comparison of intraoperative outcomes for patients undergoing RARP stratified by BMI
VariableMorbidly obese BMI ≥40 kg/m2Not morbidly obese BMI <40 kg/m2P
  1. Categorical data are presented as n (%).
Total patients, n (%)44 (100.0)44 (100.0) 
Mean (sd; median):   
OT, min84.0 (27.2; 77.5)76.9 (11.0; 75.0)0.117
EBL, mL129.8 (40.7; 100.0)112.5 (40.8; 100.0)0.049
N (%):   
Nerve sparing:  0.061
None11 (25.0)3 (6.8) 
Unilateral16 (36.4)18 (40.9) 
Bilateral17 (38.6)23 (52.3) 
Ease of nerve sparing:  0.075
‘No difficulty’2 (6.1)9 (22.0) 
‘Somewhat difficult’21 (63.7)26 (63.4) 
‘Very difficult’10 (30.3)6 (14.6) 
Difficulty of anastomosis:  0.001
‘No difficulty’3 (6.8)6 (13.6) 
‘Somewhat difficult’23 (52.3)37 (84.1) 
‘Very difficult’18 (40.9)1 (2.3) 

Pathological Outcomes

On postoperative pathological examination, both groups were similar in prostate weight, pathological stage distribution, postoperative Gleason sum score, seminal vesicle invasion, extracapsular extension, tumour volume and dimension. The presence of PSMs was identified in 11 patients (25.0%) in the morbidly obese group and in five (11.4%) in the non-morbidly obese group. This difference approached statistical significance (P = 0.097). Moreover, there was no significant relationship between BMI and prostate weight in either of the study groups. The distribution of pathological stage for the groups was also similar. The information in Table 3 provides a comparison of the pathological outcomes in the propensityscore-matched groups.

Table 3. Comparison of pathological outcomes for patients undergoing RARP stratified by BMI
VariableMorbidly obese BMI ≥40 kg/m2Not morbidly obese BMI <40 kg/m2P
  1. Categorical data are presented as n (%).
Total patients, n (%)44 (100.0)44 (100.0) 
Mean (sd; median):   
Prostate weight, g53.6 (14.7; 52.0)50.9 (17.2; 47.0)0.429
Tumour volume, %22.5 (14.6; 20.0)20.7 (16.9; 15.0)0.672
Tumour dimension, cm2.0 (0.9; 2.0)1.7 (0.8; 1.6)0.197
N (%):   
PSM11 (25.0)5 (11.4)0.097
Pathologicalstage:  0.632
pT231 (70.5)33 (75.0) 
pT313 (29.5)11 (25.0) 
Postoperative Gleason score sum:  0.385
613 (29.5)13 (29.5) 
728 (63.6)24 (54.5) 
≥83 (6.8)7 (15.9) 

Postoperative Events

Overall, the incidence of postoperative morbidity for the propensity score-matched groups was low. There were 39 patients (88.6%) in the morbidly obese group and 41 (93.2%) in the non-morbidly obese group who did not incur any postoperative complication. Six patients (13.6%) in the morbidly obese group and three (6.8%) in the non-morbidly obese group had complications. In the morbidly obese group there were four patients (9.1%) with urinary leaks, one with wound dehiscence (2.3%) and one with a methicillin-resistant Staphylococcus aureus (MRSA) infection (2.3%). In the non-morbidly obese group there was one patient (2.3%) with deep venous thrombosis, one (2.3%) with hepatitis and one (2.3%) with an incident of pneumonia. The overall rate of postoperative complications for the groups was similar. The occurrence rate based on the Clavien-classified complications did not differ significantly between the groups.

Hospital length of stay and indwelling Foley catheter days were also similar for the groups. There was no significant relationship between the patient's BMI and hospital length of stay and indwelling Foley catheter days in either of the study groups. The information for postoperative events by group is summarised in Table 4.

Table 4. Comparison of postoperative hospital events for patients undergoing RARP stratified by BMI
VariableMorbidly obese BMI ≥40 kg/m2Not morbidly obese BMI <40 kg/m2P
  1. Categorical data are presented as n (%).
Total patients, n (%)44 (100.0)44 (100.0) 
N (%):   
Postoperative complications:  0.713
None39 (88.6)41 (93.2) 
Deep venous thrombosis01 (2.3) 
Hepatitis01 (2.3) 
Pneumonia01 (2.3) 
Wound dehiscence1 (2.3)0 
MRSA1 (2.3)0 
Urine leak4 (9.1)0 
Clavien-classified complications:  0.484
Grades 1–25 (11.4)3 (6.8) 
Grades 3–41 (2.3)0 
Mean (sd; median):   
Pain scores:   
First pain score2.7 (2.3; 2.0)3.3 (3.0; 3.0)0.342
Second pain score3.0 (2.0; 3.0)3.3 (2.1; 3.0)0.381
Third pain score1.8 (1.5; 2.0)2.2(1.8; 2.0)0.340
Length of hospital stay, days1.2 (0.8; 1.0)1.2 (0.7; 1.0)1.000
Indwelling Foley catheter time, days5.8 (3.1; 5.0)5.1 (1.3; 5.0)0.187
Range4–84–8 

Discussion

The number of obese individuals continues to increase worldwide at an unprecedented rate. With the advent of PSA screening and early detection of prostate cancer, more men many who are obese will require surgical management to cure their disease. Surgery has been found to achieve preferable cancer control rates in men presenting with localised prostate cancer [19]. Among the surgical approaches, RARP has been found to reduce pain and discomfort, has fewer complications, decreased hospital stay and provides the patient with a more rapid return to the activities of daily living [20].

Traditionally, many urologists have recommended alternative forms of treatment for morbidly obese men presenting with prostate cancer or postponed surgical intervention until after weight loss. The technical difficulty inherent in operating on morbidly obese patients has led many investigators to explore the potential benefits of other alternatives. Radical perineal prostatectomy (RPP) avoids operating through the anterior abdominal wall fat and has been suggested to result in enhanced outcomes when compared with conventional open RP. Dahm et al. [21]. studied the feasibility of RPP in 18 morbidly obese patients and recommended this approach in those with localised prostate cancer seeking surgical management. They reported an OT of 183 min and an EBL of 573 mL. There were four complications in the series: two neuropraxia, a minor bleeding and an early sepsis. No patient required a transfusion. PSMs were identified in five patients (27.8%). The length of stay was 3.5 days and in-dwelling catheter days were 10–21 days. Outcomes were compared in relation to the level of experience of the operator. However, outcomes were not compared with other approaches or to different BMI categories [21]. It should be noted that RPP is limited by its inability to perform nerve-sparing in potent men or lymph node dissection in high-risk patients and this may greatly limit its application.

Laparoscopic radical prostatectomy (LRP) has been suggested as an alternative approach for obese patients. Several reports have documented its safety and efficacy [22, 23]. However, no study has documented the application of LRP in morbidly obese patients.

In an effort to examine the potential advantages of RARP in morbidly obese patients, the present study conducted a comparative analysis of two cohorts of patients stratified by BMI. To our knowledge, the only report of RARP outcomes in morbidly obese patients was published by Yates et al. [14]. They reported their results in 15 patients and concluded that RARP is feasible in morbidly obese patients. Their OT was 163 min and the EBL was 210 mL. No major complications were reported and the length of stay was 1.3 days. The presence of PSM was found in two of the 15 patients. They did not compare their outcomes with patients who were not morbidly obese.

The present study was designed to control for all possible confounders by matching morbidly obese patients to a general cohort of patients with BMI of <40 kg/m2 in order to eliminate their potential effects on outcomes. The two study groups in the present investigation showed significant differences in baseline characteristics prior to optimal matching. A series of demographic, clinical and pathological factors that may affect perioperative outcomes were included in the propensity score-matching procedure (Table 1).

Intraoperatively, the groups showed similar OTs, intraoperative complications, as well as ease and laterality of nerve sparing. Anastomosis was assessed as being ‘very difficult’ in 18 patients (40.9%) in morbidly obese group compared with one (2.3%) in the non-morbidly obese group (P = 0.001). The EBL was significantly different; 112 vs 129 mL (P = 0.049). This finding did not influence the transfusion rate. Moreover, no relationship existed between OT, EBL and BMI in the two study groups. Other studies have reported statistically significant differences in EBL, although all involve losses of <100 mL, which would be of questionable clinical significance [4, 7, 8, 10].

Ease of nerve sparing was assessed in the present study as being ‘very difficult’ in 10 patients (22.7%) in the morbidly obese group and six (13.6%) in the not morbidly obese group. A similar observation was noted for the nerve sparing: where it was not performed in 11 morbidly obese patients (25.0%) compared with three who were non-morbidly obese (6.8%). These intraoperative findings confirm that RARP in morbidly obese patients may be technically demanding but in the hands of an experienced surgeon can be accomplished with acceptable results. We think that surgical experience may play an important role in ameliorating the technical difficulties encountered in operating on morbidly obese patients.

Complications are expected to be higher in morbidly obese patients where multiple adverse events can result from the combination of pneumoperitoneum and high BMI combined with the need for a steep Trendelenburg position and prolonged OT. Ahlering et al. [4] showed that obese patients have a higher rate of complications, whereas no other study confirmed this relationship. They found a complication rate of 26.3% (five of 19) vs 4.9% (four of 81) in obese and non-obese patients, respectively (P = 0.01). However, complications in their series were not graded by the Clavien grading system but were defined by the need for increased hospital stay, the need for a secondary procedure or re-hospitalisation within 30 days. Other studies have reported that obesity was not associated with a higher rate of complications but did affect the conversion rate [8, 9].

Postoperative outcomes in the present study showed no significant difference in the complication rate, pain scores, length of hospital stay or indwelling catheter duration. There were nine complications in eight patients in the present series. There were six complications (13.6%) in the morbidly obese group and three (6.8%) in the non-morbidly obese group. When classified by Clavien grading system all complications were grade II except wound dehiscence (grade IIIb), which occurred in the morbidly obese group. This finding confirms published data where no differences in complication rates were found between obese and non-obese patients [5-13].

Obesity seems to correlate with higher grade and more aggressive disease, as well as increased likelihood of death from prostate cancer [24-27]. There were no differences in any pathological outcomes between the present study groups. However, PSM did approach statistical significance (P = 0.097). Hermann et al. [8] reported fewer PSMs in patients of normal weight than in overweight and obese patients. Their obese patients had a significantly higher percentage of clinical T1c and lower percentage of T2 cancers compared with overweight and normal-weight patients [8]. Similarly, Castle et al. [7] found a higher PSM rate in obese patients when compared with patients who were not obese who had comparable Gleason scores and pathological stages. Their results were still valid after testing for the risk of PSM and laterality of nerve sparing. In the present study, PSM approached but did not reach statistical significance and no differences could be identified in seminal vesicle invasion, extracapsular extension, tumour volume or tumour dimension.

For the learning curve in obese patients, Wiltz et al. [9] showed that EBL and OT were not significantly different between obese patients and those who were not obese. This was not the case in their earlier report [10]. When these two variables were studied in relation to surgical experience (case volume) they noted that the rate of improvement in EBL and OT is rapid in obese patients, especially when compared with the first 100 cases. Moreover, complications were similar between the two groups despite a general trend toward a higher grade of complications in the patients who were not obese. They concluded this finding was a function of having selected healthier patients when comparing obese patients with non-obese counterparts. They reported that technical difficulty associated with obese patients is an important factor early in the learning curve and that RARP in obese patients should be reserved until a high degree of proficiency with the procedure has been achieved. Conversely, Chalasani et al. [5] in a study designed to assess the effect of the learning curve on RARP in obese patients found that the only difference was in hospital length of stay, when they compared their first 50 patients with the remainder of their cohort of 153 patients.

The present study provides valuable information concerning the application of RARP in a technically challenging cohort of patients. However, it has some inherent limitations that must be considered in evaluating the results. As a single centre, single surgeon experience, the findings may represent technical subtleties that might preclude equivalent success in the widespread application of RARP in morbidly obese patients. Despite the application of sophisticated statistical algorithms to control for bias in group membership, the study design has some inherent limitations. It was conceived as an observational, nonrandomised investigation conducted by a retrospective analysis of prospectively collected data. Propensity analysis can only control for those confounders that are included in the database. Other factors that may contribute to a surgeon's decision to apply a particular surgical technique may not be controlled in the analysis and may influence the results. A further limitation of propensity matching is that a variable that may affect group membership but not outcomes is analysed the same as one with a similar effect on group assignment. Notwithstanding these limitations the two study groups were comparable based on the preoperative variables measured in the study (Table 1). This research initiative does represent the largest study to date of perioperative outcomes in morbidly obese patients undergoing RARP. Moreover, observational, nonrandomised studies have the advantage that they are representative of what actually occurs in a community-based practice and are therefore more open to generalization.

In conclusion, despite its inherent limitations, the present study provides convincing evidence that RARP can be performed in morbidly obese patients with acceptable clinical outcomes. These preliminary results are encouraging. Morbidly obese patients should not be denied RARP because of their overweight status. With the availability of an experienced robotic surgeon, these patients no longer have to wait for surgical intervention. Further follow-up with an increased sample size is warranted to validate these findings and assess the long-term functional and oncological benefits in this challenging group of patients.

Conflict of Interest

None declared.

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