|Year : 2022 | Volume
| Issue : 3 | Page : 136-144
Does obesity affect the outcomes of clinically localized prostate cancer in the era of extraperitoneal robot-assisted radical prostatectomy?
Mu-Chiao Tung1, Chun-Hsien Wu2, Richard C Wu3, Wade Wei-Ting Kuo4, Hsing-Chia Mai5, Sih-Han Chen1, Chao-Yang Chiang1, Victor C Lin6
1 Department of Urology, E-DA Hospital, Taiwan
2 Department of Urology, E-DA Hospital; Department of Nursing; Institute of Biotechnology and Chemical Engineering; School of Medicine, College of Medicine, I-Shou University, Taiwan
3 Department of Urology, E-DA Hospital; Department of Nursing, I-Shou University, Taiwan
4 Department of Urology, E-DA Hospital; Institute of Biotechnology and Chemical Engineering; School of Medicine, College of Medicine, I-Shou University, Taiwan
5 Department of Urology, E-DA Cancer Hospital, Taiwan
6 Department of Urology, E-DA Hospital; School of Medicine, College of Medicine, I-Shou University, Taiwan
|Date of Submission||22-Sep-2021|
|Date of Decision||15-Dec-2021|
|Date of Acceptance||21-Dec-2021|
|Date of Web Publication||25-Aug-2022|
No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445
Victor C Lin
No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445
Source of Support: None, Conflict of Interest: None
Purpose: Obesity has been proven to affect the outcomes in open radical prostatectomy. However, the relationship between obesity and the outcomes of robot-assisted radical prostatectomy (RARP) was not conclusive. Herein, we aimed to investigate the impact of obesity on the clinical outcomes after RARP. Materials and Methods: From April 2016 to June 2020, 164 patients underwent RARP by a single experienced surgeon at our institute. Patients with previous transurethral resection of prostate (n = 30), hernioplasty (n = 13), and transperitoneal RARP (n = 26) were excluded. Finally, 105 patients were enrolled and divided into different groups according to their body mass index (BMI) and waist circumference (WC) using the definition of Taiwan National Health Institute. BMI was categorized into three groups (normal: BMI <24, overweight: BMI between 24 and 27, and obese: BMI ≥27 [kg/m2]). WC was categorized into two groups (normal: WC <90 and central obesity: WC ≥90 [cm]). Perioperative outcomes and functional outcomes including preoperative, postoperative erectile function, and postoperative continence status were evaluated. Results: Among BMI groups, 29 patients were normal, 43 patients were overweight, and 33 patients were obese. Console time and sum time showed a significant difference in different BMI groups (P = 0.034 and 0.016, respectively). Of the 101 patients with available magnetic resonance imaging, 74 patients' WC were normal, and 27 patients were central obese. Blood loss in central obesity group was significant more than normal WC group (300 ml vs. 200 ml, P = 0.04). No significant differences were observed in pathological and functional outcomes in both groups. Conclusion: Obesity and central obesity seemed to result in longer operation time and more blood loss in extraperitoneal RARP while functional outcomes can be maintained regardless of the obesity degree. Large-scale studies are necessary to further explore the relationship between obesity and the outcomes of RARP in future.
Keywords: Central obesity, obesity, robot-assisted radical prostatectomy
|How to cite this article:|
Tung MC, Wu CH, Wu RC, Kuo WW, Mai HC, Chen SH, Chiang CY, Lin VC. Does obesity affect the outcomes of clinically localized prostate cancer in the era of extraperitoneal robot-assisted radical prostatectomy?. Urol Sci 2022;33:136-44
|How to cite this URL:|
Tung MC, Wu CH, Wu RC, Kuo WW, Mai HC, Chen SH, Chiang CY, Lin VC. Does obesity affect the outcomes of clinically localized prostate cancer in the era of extraperitoneal robot-assisted radical prostatectomy?. Urol Sci [serial online] 2022 [cited 2022 Sep 30];33:136-44. Available from: https://www.e-urol-sci.com/text.asp?2022/33/3/136/354706
| Introduction|| |
Obesity has become one of the most common diseases in modern society. According to Taiwan National Health Institute, Taiwanese men had reached an average overweight status in body mass index (BMI) among all age groups. Public awareness raised concerns that obesity could lead to health deterioration. Consequently, many studies were conducted to research the relationship between obesity and specific disease or surgical outcomes, such as prostate cancer and robot-assisted radical prostatectomy (RARP). In Taiwan, prostate cancer is the sixth leading cause of cancer death and the fifth leading cause of cancer incidence in men. Additionally, there was an increasing trend in incidence and mortality rates in Taiwanese patients with prostate cancer. Hence, it had been wondered whether the broadening growing trend of obesity could be related to the rapid-rising overweight and poor surgical outcome in Taiwan.
A previous literature had reported that obesity could increase surgical difficulty, influence the outcomes, and increase the biochemical recurrence (BCR) rate in open radical prostatectomy. Furthermore, another study has suggested that obesity was an independent risk factor for higher complication rates, more adverse pathological features, and worse functional outcomes.
However, RARP provided a minimally invasive approach, a precise dissection, and a delicate reconstruction under broad magnification that open surgery could not do. Is the above concern of obesity on the surgical outcomes of prostate cancer still true in the era of RARP? Some evidence regarding this issue was limited and inconclusive. Therefore, this study aimed to investigate the impact of obesity on the outcomes of RARP in the Taiwanese population.
| Materials and Methods|| |
From April 2016 to June 2020, a total of 164 patients who underwent RARP under the diagnosis of localized prostate cancer were retrospectively included in our institute. All surgeries were conducted by a single experienced surgeon and a committed robotic surgical team. Among the 164 patients, 30 patients had transurethral resection of the prostate surgical history, and 13 patients had hernioplasty history. These patients were omitted as these procedures could impact our perioperative, oncological, and functional outcomes. Additionally, 26 patients who underwent transperitoneal RARP were omitted as patients with extraperitoneal RARP were targeted. Finally, 105 patients were enrolled in this study for further analysis. The flow diagram is shown in [Figure 1].
|Figure 1: The flow diagram of the study design, including the exclusion criteria and grouping characteristic|
Click here to view
All clinical information, including demographic information, perioperative data, and postoperative functional outcomes, were archived and retrospectively reviewed and analyzed following the regulation of the Institutional Review Board in our hospital (Project name: Analysis of prognostic factor for the oncological outcome and complications of prostate cancer patients in Taiwan, number: EMRP-102-093, approval date: July 01, 2021). Patients' consent was waived by our Institutional Review Board owing to the retrospective aspect of our study.
Operative technique and principle
We conducted the RARP with the da Vinci Xi surgical system via the extraperitoneal approach with pelvic lymph node dissection (PLND). Bilateral standard or extended PLND was conducted for all patients depending on the National Comprehensive Cancer Network prostate cancer risk classification. For the high-risk group, we conducted the extended PLND. For the low and intermediate groups, we conducted the standard PLND.
The brief surgical procedures were described as the following as previously described. Under the general anesthesia and Trendelenburg position, the patient was prepared under Trendelenburg position. A 20 French urinary catheter was inserted into the bladder. The five-port technique was introduced. A 2-cm transverse incision was made infraumbilically, and the anterior sheath of the rectus muscle was detected and then subsequently deepened into the exposed posterior sheath. The preperitoneal space was created with the assistance of Spacemaker™ Dissection Balloon (Medtronic, Minneapolis, MN, USA), and then, two 8-mm robotic trocars were inserted under the finger guidance. After the establishment of pneumopreperitoneum, the space of Retzius was further dissected using traditional laparoscopic instruments, and the last two trocars (one 8 mm and one 12 mm) were inserted after bilateral lateral aspects of the pelvic cavity.
After docking the robot, bilateral PLND was first conducted. The bilateral endopelvic fascia was incised, and the dorsal vein complex (DVC) was controlled with suture ligation by computed tomography-1 needle, 1-0 Vicryl (Ethicon, Somerville, NJ, USA). We transected the bladder neck with monopolar scissors and then pulled up vas segments and seminal vesicles. Bilateral lateral pedicles were controlled with Hem-O-Lok (Teleflex Medical, Durham, NC, USA). Nerve-sparing technique may be introduced to preserve both neurovascular bundles depending on the preoperative biopsy results, erection function, and intraoperative status. We routinely introduced bilateral nerve sparing to our RARP patients unless the following circumstances. Firstly, the patient had a biopsy Gleason score >8. Secondly, the patient had high clinical and magnetic resonance imaging (MRI) staging beyond T3a. Thirdly, the patient was impotent and sexually inactive before RARP. Fourthly, the patient requested nonnerve sparing for a better oncological outcome. Lastly, strict adhesion or suspected surgical margin involvement was noted near the neurovascular bundles that could compromise the pathological results. In addition to the abovementioned circumstances, the nerve-sparing technique was routinely employed.
The DVC and prostate apex were cut from the urethra using cold scissors. Then, the prostate with both seminal vesicles was captured into an Endobag and placed at the right preperitoneal space cranially. The bladder neck was everted with 3-0 Chromic Catgut (Ethicon) interruptedly, and the rhabdosphincter was reconstructed with two combined RB-1 needles, 3-0 Monocryl (Ethicon). The vesicourethral anastomosis was performed using continuous sutures with two combined RB-1 needles, 3-0 Monocryl (Ethicon). A 100-ml normal saline was infused into to inflate the bladder for leakage test. If no leak or minor leak was noted, Foley's catheter would be removed on postoperative day 6 or 7 without a cystogram. Otherwise, cytogram would be conducted on postoperative day 7, and the Foley's catheter was removed when no severe contrast medium extravasation. If the leak was still noted, delaying Foley's catheter removal for 2 days was our policy.
Definition of obesity and central obesity
Obesity was evaluated by two parameters, BMI and waist circumference (WC). BMI was calculated by measuring the patient's admission body height and weight. With the standard of Taiwan National Health Institute, patients were grouped as normal, overweight, and obese following their BMI value. The normal group had a BMI of <24 kg/m2. The overweight group had a BMI between 24 and 27 kg/m2. The obese group had a BMI larger than or equal to 27 kg/m2. WC was acquired by measuring the circumference at the umbilicus level on the patient's preoperative MRI [Figure 2]. Patients were categorized into two groups based on their WC: normal group had WC <90 cm and central obesity group had WC larger than or equal to 90 cm.
|Figure 2: An example using curve-measuring tool to measure the diameter of the waist circumference at the umbilicus level on a patient's preoperative MRI image|
Click here to view
The preoperative profile including age, body weight, body height, prostate-specific antigen (PSA), clinical stage, biopsy grade groups, and risk groups was recorded. The clinical stage was further stratified into T1, T2, and T3. Perioperative data including port time, docking time, console time, nerve-sparing status, estimated blood loss, and blood transfusion amount are documented Foley indwelled days and hospital stay days were also recorded. Additionally, the sum of port time, docking time, and console time was added to the sum time. Pathological T stage, pathological Gleason's score, grade groups, regional lymph node status and lymph node yield, specimen weight, surgical margins, lymphovascular invasion, extraprostatic extension, seminal vesical invasion, and perineural invasion were recorded based on the final pathology report. The number of patients receiving adjuvant androgen deprivation therapy (ADT), due to either regional lymph node metastasis or BCR, and the days to BCR were all recorded.
Functional result assessment was composed of erectile function and urinary continence. Erectile function was assessed by erectile function score (EHS) preoperatively and postoperatively during outpatient department. An EHS of one and two was considered erectile dysfunction; an EHS of three and four was potent. Erectile function was traced until 1 year after RARP as an outcome. Urinary continence, which was defined as the daily use of not more than one protective safety pad, was evaluated 3 months after the RARP as we pursued early recovery on urinary continence. In contrast, the use of more than one pad per day was considered incontinence.
We used the licensed PASW Statistic version 18 provided by I-Shou University for statistical analysis. Perioperative outcomes collected as continuous variables were analyzed by the Kruskal–Wallis test and Mann–Whitney U-test. Other perioperative and functional outcomes were collected as categorical variables and analyzed using the Chi-square test.
| Results|| |
Patient's characteristics are summarized in [Table 1]. Of the 105 patients included in this study, 29 (27.6%) patients had normal BMI; 43 (41.0%) patients were overweight; and 33 (31.4%) patients were obese. One hundred and one patients had available MRI images at our hospital with WC data obtained, 74 (73.3%) patients had normal WC, and 27 (26.7%) patients had central obesity. Age at surgery, preoperative PSA level, biopsy grade groups, clinical staging, and risk groups showed no significant difference among BMI and WC groups.
|Table 1: The patient's characteristics of different groups. Age at surgery, preoperative prostatespecific antigen level, biopsy grade group, clinical staging, and risk group showed no significant difference among different body mass index and waist circumference groups|
Click here to view
Perioperative outcomes are summarized in [Table 2]. There was a significant difference in console time and the sum of port time, docking time, and console time in different BMI groups. Median console time and sum time in normal, overweight, and obese groups were 184.5 and 219.5, 209 and 254, and 210 and 268 min, respectively. The other perioperative outcomes, including port time, docking time, estimated blood loss, Clavien–Dindo complication rates, Foley inserted days, and hospital days, exhibited no significant difference in different BMI groups. When we stratified patients into various WC groups, estimated blood loss was significantly different as the central obesity group had a median blood loss of 300 ml compared with 200 ml in the normal WC group (P = 0.04). Other perioperative outcomes showed no significant difference between the normal WC group and the central obesity group.
|Table 2: The perioperative outcomes of different groups. Operating times including console time and sum time were significantly longer in obese group. Estimated blood loss was significantly higher in centralobese group|
Click here to view
Pathological outcomes are summarized in [Table 3]. There was no difference in pathological staging, positive surgical margins, lymphovascular invasion, extracapsular extension, seminal vesicle invasion, and perineural invasion among the three BMI groups. Neither did WC groups reveal any significant differences in pathological features. Out of the 44 patients who received adjuvant ADT, 22 of them were regional prostate cancer, and 19 of them were due to BCR. Additionally, three patients received ADT due to progressive pathological features. There was no considerable difference in BMI or WC groups (P = 0.556 and 0.851). The median day to BCR was 205 days in patients with BCR. No significant difference was found in days to BCR in BMI or WC groups (P = 0.435 and 0.219).
|Table 3: The pathological outcomes of different groups. No significant difference was found in pathological features among different body mass index and waist circumference groups|
Click here to view
Functional outcomes are summarized in [Table 4]. The potency rate of preoperative erectile function showed no significant difference in BMI (60/105, P = 0.471) or WC (57/101, P = 0.364) groups. In patients who were potent preoperative, 1-year postoperative erectile function status showed no significant difference as 4 of 12 patients (33.3%) in the normal BMI group, 11 of 28 patients (39.3%) in the overweight group, and 7 of 20 patients (35.0%) in the obese group were potent (P = 0.938). In WC groups, 12 of 38 patients (31.6%) were potent in the normal WC group, and 7 of 19 patients (36.8%) in the central obesity group. For 3-month postoperative continence status, only two patients were urinary incontinent after the RARP. There was no significant difference when compared with different BMI (P = 0.405) or WC (P = 0.527) groups.
|Table 4: The functional outcomes of different groups. No significant difference was found in erectile function and continence rate among different body mass index and waist circumference groups|
Click here to view
| Discussion|| |
With the increasing number of obese population, obesity-related malignancies have become a public health concern. Recent studies have discovered that obesity is associated with an increased risk of cancer of at least 13 anatomic sites, including endometrial, esophageal, renal, and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; and colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancers. Microscopically, obesity also played a potential role in the pathogenesis of prostate cancer. Various explanations had been suggested in the current literature, such as deregulation of the insulin/insulin-like growth factor-1 axis alterations in sex hormone secretion that might decrease serum testosterone and dihydrotestosterone, alteration of adipokine signaling, and higher oxidative stress. These mechanisms explained how excess adipose tissue could result in advanced prostate cancer in the obese population. Additionally, a Canadian study by Boehm et al. suggested that abdominal obesity in the overweight and obese BMI population is associated with high-grade prostate cancer risk. In our study, there was no significant difference in the grade of prostate cancer among different BMI or WC groups. Although there appeared to be a trend noted in the biopsy grade group (P = 0.097) in different WC groups, the grade group in the final pathological specimen showed no difference. With the rather small case number, different BMI standards (BMI of >25 kg/m2 for overweight and >30 kg/m2 for obese by Boehm et al. vs. our cutoff value 24 and 27 according to Taiwanese standard), different WC standards (102 vs. 90 cm), and different targeted races (Canadians vs. Taiwanese) from this study, we believed that larger studies were needed to further research the relationship of obesity and whether it would lead to more aggressive prostate cancer in the Taiwanese population.
When conducting the RARP, excess adipose tissue may increase surgical difficulty in target identification and dissection, which could cause more blood loss, longer surgical time, and more surgical complication. Research for robotic surgery over other anatomic sites, such as robotic gynecologic surgery and colorectal surgery, had pointed out that obesity could lead to prolonged operation time despite the excellent execution under robotic manipulation. Our study suggested similar results as prolonged operating times are essential in obese and overweight BMI groups. In WC groups, a trend for prolonged operation time in central obesity patients was also discovered. Additionally, we had noted a significant increase in roughly estimated blood loss in the central obesity group. In a report from Porcaro et al., BMI is an independent predictor of the risk of Clavien–Dindo grade 3 complications. The higher patient's BMI is, the greater risk of a grade 3, and higher complications could occur. However, this phenomenon was not true in our study, and we did not find that there was any significant difference in Clavien–Dindo grade 3 and higher complications among all groups. Although there appeared to be a trend (P = 0.057), our few grade 3 complications made it unsuitable for statistical analysis. Moreover, most grade 3 complications in our study were pelvic lymphoceles that needed percutaneous drainage. We thought that the difference could be associated with different surgical approaches (transperitoneal approach by Porcaro et al. versus extraperitoneal approach by Lin et al.).
Since obese fat could cause surgical complications, would it transform into unfavorable results, such as worse pathological results, higher BCR rates, or even poorer functional results? Back to the period of open radical prostatectomy, it certainly would. Research from Mandel et al. suggested that BMI was an independent risk factor for most analyzed pathologic and functional results after radical prostatectomy, including negative surgical margin, potency rate, time of surgery, and intraoperative blood loss. Additionally, according to Agnes et al., microenvironmental changes in obese patients would increase the BCR rate and cancer-specific mortality after radical prostatectomy. The significantly higher intraoperative blood loss and longer operating time by our series showed that some degree of surgical complications remained even with the da Vinci surgical system but did not result in inferior pathological and functional results. In other words, the higher the magnifying degree under the da Vinci surgical system could overcome the obstacles proposed by obesity without compromising the patient's prognosis.
Obesity was considered to prompt erectile dysfunction through vascular and endocrinological mechanisms. However, no significant differences were noticed regarding preoperative or postoperative erectile function rate in our series. Since most of our patients were senile with age older than 65 years, we speculated that the vascular and endocrinological effects of obesity were diminished as other complex confounding factors, such as diabetes mellitus, neurological conditions, mood and depression, or psychology, could implicate erectile functions.
BMI, as a simple and straightforward evaluation tool for obesity, has been associated with mortality in big meta-analyses. Therefore, it is widely used as the current standard of measurement of obesity in clinical practice. However, BMI does not discriminate between fat and lean mass. Nor does it address body fat distribution. Central obesity, with the measurement of WC, was shown to reflect a more precise body fat distribution. Additionally, it confers a higher degree of cardiovascular risk due to higher atherothrombotic events. Therefore, central obesity is regarded as a more precise indicator of body fat distribution than BMI.
However, measuring WC takes more effort than measuring BMI. The most standard measurement of WC should be taken with a measuring tape in the central level between the lowest rib border and the upper pelvic rim while standing in easy position. We here suggested a different procedure for measuring WC at the umbilicus level on MRI images in supine position. Although it had not been widely used, we sought it as a possible alternative method to represent patients' central obesity.
With a small sample size in our study (27 cases in the central obesity group), the central obesity group had significantly more roughly estimated blood loss during RARP. The microenvironmental adipose change in the pelvic region could be attributed to this phenomenon. In future, we look forward to large-scale studies that will further examine central obesity or even body fat percentage in the Taiwanese prostate cancer population.
Several limitations of this study should be taken into considerations. Firstly, the retrospective study design may introduce selection bias. Secondly, the small case number of this study may lead to inadequate power during analysis. Lastly, the targeted population was the Taiwanese population. Different obesity standards should be applied when compared with different races. We only evaluated BMI and WC values at a single time point before RARP. Changes in obesity status over time after RARP could alter the functional outcome.
| Conclusion|| |
Our results suggested that obesity could contribute to longer operation time and more evaluated blood loss in central-obese patients who underwent RARP. However, oncological outcomes in different obesity groups were similar under the high magnifying scale using the da Vinci system. Additionally, functional outcomes can be maintained regardless of the body weight status if the surgeries were conducted by experienced hands. Large-scale studies are necessary to further investigate the relationship between obesity and central obesity as well as the outcome of RARP in the Taiwanese population.
Financial support and sponsorship
Conflicts of interest
Prof. Victor C. Lin, an editorial board member at Urological Science, had no role in the peer review process of or decision to publish this article. The other authors decalared no conflicts of interest in writing this paper.
| References|| |
Cao Y, Ma J. Body mass index, prostate cancer-specific mortality, and biochemical recurrence: A systematic review and meta-analysis. Cancer Prev Res (Phila) 2011;4:486-501.
Mandel P, Kretschmer A, Chandrasekar T, Nguyen HG, Buchner A, Stief CG, et al.
The effect of BMI on clinicopathologic and functional outcomes after open radical prostatectomy. Urol Oncol 2014;32:297-302.
Li H, Zhao C, Liu P, Hu J, Yi Z, Chen J, et al.
Radical prostatectomy after previous transurethral resection of the prostate: A systematic review and meta-analysis. Transl Androl Urol 2019;8:712-27.
Chen SH, Wu CH, Wu RC, Kuo WW, Lee YH, Li RC, et al
. Surgical and functional outcomes of robotic-assisted radical prostatectomy in patients with previous transurethral resection of the prostate. Urol Sci 2020;31:267-72. [Full text]
Avgerinos KI, Spyrou N, Mantzoros CS, Dalamaga M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism 2019;92:121-35.
Divella R, De Luca R, Abbate I, Naglieri E, Daniele A. Obesity and cancer: The role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer 2016;7:2346-59.
Boehm K, Sun M, Larcher A, Blanc-Lapierre A, Schiffmann J, Graefen M, et al.
Waist circumference, waist-hip ratio, body mass index, and prostate cancer risk: Results from the North-American case-control study Prostate Cancer & Environment Study. Urol Oncol 2015;33:494.e1-7.
Eddib A, Danakas A, Hughes S, Erk M, Michalik C, Narayanan MS, et al.
Influence of morbid obesity on surgical outcomes in robotic-assisted gynecologic surgery. J Gynecol Surg 2014;30:81-6.
Shiomi A, Kinugasa Y, Yamaguchi T, Kagawa H, Yamakawa Y. Robot-assisted versus laparoscopic surgery for lower rectal cancer: The impact of visceral obesity on surgical outcomes. Int J Colorectal Dis 2016;31:1701-10.
Porcaro AB, Sebben M, Tafuri A, de Luyk N, Corsi P, Processali T, et al.
Body mass index is an independent predictor of Clavien-Dindo grade 3 complications in patients undergoing robot assisted radical prostatectomy with extensive pelvic lymph node dissection. J Robot Surg 2019;13:83-9.
Maj-Hes AB, Mathieu R, Özsoy M, Soria F, Moschini M, Abufaraj M, et al.
Obesity is associated with biochemical recurrence after radical prostatectomy: A multi-institutional extended validation study. Urol Oncol 2017;35:460.e1-8.
Pizzol D, Smith L, Fontana L, Caruso MG, Bertoldo A, Demurtas J, et al.
Associations between body mass index, waist circumference and erectile dysfunction: A systematic review and META-analysis. Rev Endocr Metab Disord 2020;21:657-66.
Kubin M, Wagner G, Fugl-Meyer AR. Epidemiology of erectile dysfunction. Int J Impot Res 2003;15:63-71.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]