Open radical cystectomy is a reliable surgery with acceptable complication rates in elderly male patients: a retrospective, tertiary hospital-based study

Abstract

Objective: This study aims to evaluate safety of radical cystectomy (RS)+pelvic lymph node dissection (PLND)+ileal conduit urinary diversion (ICUD) in male patients aged >65 years versus ≤65 years.

Materials and Methods: Eighty-five male patients who underwent RS + PLND + ICUD for bladder cancer were retrospectively analyzed. The patients were divided into two groups according to age: ≤65 years (Group 1, n = 40) versus >65 years (Group 2, n = 45). Data including baseline demographic and clinical characteristics of the patients, length of hospital stay, and complications within 90 days of surgery, and Grade ≤ II and Grade ≥ III complications according to the Clavien-Dindo (C-D) classification were recorded. Groups were compared in terms of demographic features and development of complications within 90 day after surgery statistically.

Results: The median length of hospital stay was statistically significantly longer in Group 2 than Group 1 [10 (7–17) days vs. 9 (6–14) days, respectively; p < .05]. There was no statistically significant difference in the rehospitalization rate within 90 days of surgery between the groups (p > .05).

Conclusion: Our study results suggest that RS + PLND + ICUD is a safe procedure in male patients aged ≥65 years.

Keywords:

• Aging male
• bladder cancer
• Clavien–Dindo classification
• elderly
• open radical cystectomy
• postoperative complication

Introduction

Bladder cancer is the fourth leading cause of cancer malignancy among men and its incidence is about fourfold higher in men than women [1,2]. The risk of bladder cancer increases with age and peaks around the seventh decade of life [3–6]. Due to the aging population, its incidence is expected to increase among elderly in the future [7].

With the introduction of advanced therapeutic modalities in recent years, several chronic diseases can be controlled and managed, leading to an increase in the aging population. Therefore, the life expectancy has risen in developed countries [8]. According to the 2015 United Nations estimates, the number of individuals aged >60 years is expected to more than double globally, reaching up to 2.1 billion in the next 35 years [9]. Thus, as in all other oncological diseases, it is likely to become a serious concern to manage muscle invasive bladder cancer (MIBC) and non-MIBC (NMIBC) in elderly in the practice of urology in future years [3].

Standard treatment of nonmetastatic MIBC and high-risk NMIBC in selected cases includes radical cystectomy (RS)+pelvic lymph node dissection (PLND)+ileal conduit urinary diversion (ICUD) [6]. However, RS is associated with high morbidity and mortality rates due to an increasing number of comorbidities in elderly [7]. Previous studies have reported increased morbidity and mortality rates following RS in patients aged ≥75 years [10]. In addition, the complication rate has been estimated as up to 70% in this patient population and complications of the surgical wounds, genitourinary system infections, pulmonary complications, and ICUD-related complications have been reported similar to younger patients [3,11].

In recent years, the concept of biological age has been used more frequently rather than chronological age for the assessment of health status of the patients. In this context, it is recommended that age alone should not be considered a contraindication for radical uro-oncological procedures and that all elderly patients with malignancy should be evaluated to avoid undertreatment or overtreatment [6,12–14].

In the present study, we aimed to evaluate the safety of RS + PLND + ICUD in male patients aged >65 years versus ≤65 years.

Materials and methods

This retrospective study was conducted at University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Department of Urology between January 2011 and January 2019. A total of 114 patients who underwent RS for bladder cancer were screened. Those having no PLND or those having orthotopic bladder or ureterocutaneostomy as an urinary diversion procedure; patients with missing data; and female patients were excluded from the study. Finally, a total of 85 male patients who underwent RS + PLND + ICUD for bladder cancer were included. The study protocol was approved by the Ethics Committee of Haydarpasa Numune Training and Research Hospital. The study was conducted in accordance with the principles of the Declaration of Helsinki.

The patients were divided into two groups according to age: ≤65 years (Group 1, n = 40) versus >65 years (Group 2, n = 45). Data including baseline demographic and clinical characteristics of the patients, comorbidities, duration of surgery, requirement for intraoperative erythrocyte suspension (ES) transfusion, length of hospital stay, postoperative complications (within 90 days), rehospitalization rate within 90 days, pathological examination results, and Grade ≤ II and Grade ≥ III complications according to the Clavien–Dindo (C–D) classification were recorded [15].

Statistical analysis

Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were expressed in mean ± standard deviation (SD), median (min–max), and number and frequency. The Kolmogorov–Smirnov test was used to check the normality of data for quantitative variables. The Mann–Whitney U-test was used to compare two groups of quantitative variables showing abnormal distribution and the Student's T-test was used to compare two groups of quantitative variables showing normal distribution. The Pearson chi-square test was used to compare qualitative data. The Pearson correlation analysis was used to examine the relationship between the age, body mass index (BMI) and complications. The Spearman correlation analysis was used to examine the relationship between the complication and other parameters. A p values of <.05 was considered statistically significant.

Results

A total of 85 male patients who underwent RS + PLND + ICUD were included in this study. Of the patients, 47.1% were in Group 1 and 52.9% were in Group 2. Baseline demographic and clinical characteristics of the patients are shown in Table 1. Accordingly, there was no statistically significant difference in the BMI, hypertension, diabetes mellitus, ischemic heart disease, American Society of Anesthesiologists (ASA) class, duration of surgery, pathological examination results, complication rate, and C-D complication grades between the groups (p > .05, each). However, the median length of hospital stay was statistically significantly longer in Group 2 than Group 1 (10 [range, 7 to 17] days vs. 9 [range, 6 to 14] days, respectively; p < .05). There was no statistically significant difference in the rehospitalization rate within 90 days of surgery between the groups (p > .05) (Table 2).

Table 1. Baseline demographic and clinical characteristics of patients.

	≤65 years (n, %=40, 47.1%)		>65 years (n, %=45, 52.9%)
	n, %	Median (min–max)	n, %	Median (min–max)	p
Age, year (mean ± SD)		57 ± 6		72 ± 4	^a<.001*
BMI, kg/m^2 (mean ± SD)		27.89 ± 4.39		29.44 ± 4.33	^a.106
HT
No	14 (35%)		15 (33.3%)		^b.871
Yes	26 (65.0%)		30 (66.7%)
DM
No	22 (55.0%)		23 (51.1%)		^b.720
Yes	18 (45.0%)		22 (48.9%)
IHD
No	16 (40.0%)		21 (46.7%)		^b.536
Yes	24 (60.0%)		24 (53.3%)
COPD
No	24 (60.0%)		18 (40.0%)		^b.066
Yes	16 (40.0%)		27 (60.0%)
ASA Class
Class 2	17 (42.5%)		10 (22.2%)		^b.070
Class 3	23 (57.5%)		33 (73.3%)
Class 4	0 (0%)		2 (4.4%)

^aStudent’s t-test.

^bChi-square test.

*p<.05.

ASA: American Society of Anesthesiologists; BMI: body mass index; COPD: chronic obstructive pulmonary disease; DM: diabetes mellitus; HT: hypertension; IHD: ischemic heart disease.

Table 2. Operative data.

	≤65 years (n, %=40, 47.1%)		>65 years (n, %=45, 52.9%)
	n, %	Median (min–max)	n, %	Median (min–max)	p
Duration of surgery (minutes)		300 (250–360)		300 (260–420)	^a.569
Pathology
pT0	2 (5.0%)		5 (11.1%)
pTa	1 (2.5%)		6 (13.3%)
pT1	5 (12.5%)		2 (4.4%)
pT2	9 (22.5%)		11 (24.4%)		^b.655
pT3	12 (30.0%)		17 (37.8%)		^b.353
pT4	11 (27.5%)		4 (9.8%)		^b.071
Complications (within 90 days)
No	23 (57.5%)		24 (53.3%)		^b.700
Yes	17 (42.5%)		21 (46.7%)
Multiple complications (within 90 days)
No	33 (82.5%)		39 (86.7%)		^b.594
Yes	7 (17.5%)		6 (13.3%)
Clavien-Dindo classification (within 90 days)
No	23 (57.5%)		24 (53.3%)		^b.881
Grade ≤2	9 (22.5%)		10 (22.2%)
Grade ≥3	8 (20.0%)		11 (24.4%)
Length of hospital stay (day)		9 (6–14)		10 (7–17)	^a.007*
Rehospitalization (within 90 days)
No	28 (70.0%)		31 (68.9%)		^b.912
Yes	12 (30.0%)		14 (31.1%)

^aMann–Whitney U-test.

^bChi-square test.

*p<.05.

Only one patient (1.2%) had C–D Grade I wound site complication. In terms of C–D Grade II complications, epididymitis was seen in one patient (1.2%) which was successfully managed through antibiotherapy, while 32 patients (37.6%) required ES transfusion. C–D Grade IIIa complications were managed through lymphocele drainage in three patients (3.5%), pelvic hematoma drainage in one patient (1.2%), bilateral nephrostomy tube insertion in one patient (1.2%), and Pleuracan® (B. Braun Melsungen AG, Germany) insertion in one patient (1.2%). Five patients (5.9%) had Grade IIIb complications. Three of them (3.5%) underwent laparotomy for abscess drainage (n = 1, 1.2%) and conduit revision (n = 2, 2.4%), while one (1.2%) received wound site revision, and the other one (1.2%) received hematoma drainage. Four patients (4.7%) with C–D Grade IVa complications underwent hemodialysis. One of the patients (1.2%) had C–D Grade IVb “multiple organ dysfunction syndrome” complication. This patient then died in intensive care unit. Three patients (3.5%) with C–D Grade V complications died within the early postoperative period (≤30 days) (Table 2).

Correlation analysis showed a significant correlation between duration of surgery and development of postoperative complications (r:0.301, p < .05). However, there was no significant correlation between demographic and clinical characteristics of patients including age, BMI, ASA class and development of postoperative complications (p > .05, each). Although the duration of surgery, length of hospital stay, multiple complications and rehospitalization within 90 days were significantly correlated with development of complications (p < .05, each) (Table 3).

Table 3. Correlation analysis results.

	Complications (r/p)
Age (year)	^a0.038/.733
BMI (kg/m^2)	^a0.091/.408
ASA Class	^b0.186/.088
Duration of surgery (minutes)	^b0.301**/.005
Multiple complications (within 90 days)	^b0.473**/<.001
Clavien-Dindo classification (within 90 days)	^b0.958**/<.001
Length of hospital stay (day)	^b0.430**/<.001
Rehospitalization (within 90 days)	^b0.225*/.039

^aPearson Correlation Analysis.

^bSpearman Correlation Analysis.

*Correlation is significant at the .05 level.

**Correlation is significant at the .01 level.

ASA: American Society of Anesthesiologists; BMI: body mass index; COPD: chronic obstructive pulmonary disease; DM: diabetes mellitus; HT: hypertension; IHD: ischemic heart disease.

Discussion

In the present study, we evaluated the safety of RS + PLND + ICUD in male patients aged >65 years versus ≤65 years. Our study results showed similar complication and rehospitalization rates within 90 days of surgery between the patients aged >65 years and ≤65 years. However, the length of stay was significantly longer in the patients aged >65 years. These findings indicate that RS is a safe procedure in male patients aged ≥65 years with similar complication rates to younger males.

The C–D classification is a useful grading system of postoperative complications [15]. It is mainly used to evaluate whether the patient require a surgical intervention or monitoring in the intensive care unit. The C–D classification consists of seven grades including I, II, IIIa, IIIb, IVa, IVb, and V. Grade ≥ III complications require surgical, endoscopic or radiological intervention, while Grade IV complications are life-threatening complications requiring intensive care unit management and Grade V complications are death events [15]. Accordingly, we evaluated postoperative complications under two main groups as Grade ≤ II and Grade ≥ III.

Patients undergoing RS are at high risk for per-operative morbidities. Previous studies have demonstrated that nearly 60% of patients undergoing RS experience at least one complication within 90 days of surgery [16,17]. In addition, there are several studies showing the effect of aging on urological surgeries in the literature [18–20]. In a study comparing two age groups (75–84 years vs. ≥85 years) undergoing RS, Compoj et al. [10] found no significant difference in the complication, 30-day mortality, and overall and cancer-specific survival rates between the groups, while the 90-day mortality rate was significantly higher in the patients aged ≥85 years. In addition, postoperative complications were graded according to the C–D classification, similar to our study, and the authors reported an overall complication rate of 55.4%. In our study, however, we were unable to evaluate early (within 30 days) and late complications (within 90 days) separately. Based on complications within 90 days, 25 patients (29.4%) had only one complication, while 13 patients (15.3%) had multiple complications. Of note, our institute is a tertiary referral hospital for oncological diseases in the region where the study was conducted and radical oncological surgeries such as RS, radical retropubic prostatectomy, and radical nephrectomy can be successfully performed by separate surgical teams with a high level of experience. In addition, nursing training has been implemented on a regular basis for postoperative care of patients undergoing specialized procedures such as RS. The relatively low complication rates in our study compared to the previous studies can be explained by highly experienced surgeons, high-quality nursing training, and available institutional facilities and relatively young age of our patients (median 66 [range, 40 to 82] years).

Several scoring systems have been developed to predict postoperative complications. These include ASA, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group (ECOG) performance status. All these scoring systems have been shown to be useful in predicting postoperative complications before RS [21,22]. In our study, we found a statistically significant difference in the ASA scores and postoperative complications. Although it seems to be consistent with the literature, we found no significant correlation between the ASA scores and development of complications. This can be attributed to the small sample size and a high number of patients with ASA Class 3.

In a study, Roghmann et al. [22] showed that BMI was a helpful variable in predicting high-grade (C–D Grade ≥3) complications following RS. In our study, we found no statistically significant difference in the BMI values between Group 1 and Group 2 with similar complication rates, consistent with the literature. When the patients were evaluated according to the C–D grade of complications (Grade ≤2, n = 19 vs. Grade ≥3, n = 19), there was no statistically significant difference in the BMI values (p = .343). This can be explained by small sample size and low complication rate in our study. However, we believe that such scoring systems and BMI values before surgery may be useful in predicting postoperative complications and in identifying elderly patients most likely to benefit from surgical treatment. Furthermore, the use of such scoring systems and BMI values may be helpful in identifying patients who are ineligible for surgery, preventing overtreatment.

In the present study, we found a statistically significantly longer length of hospital stay in the patients aged >65 years compared to younger patients. Similarly, Clark et al. [23] reported longer length of hospital stay in elderly patients following RS. In addition, prolonged hospitalization and increased complication rates following RS have been shown to be associated with increased total health-related cost [24,25]. In a study evaluating treatment-related costs of bladder cancer between 1998 and 2008, Sloan et al. [26] reported that patients who were diagnosed with bladder cancer became elderly day by day with a high comorbidity rate. In this study, the rate of bladder cancer increased from 37% to 44%, while the overall survival rate increased from 10.7% to 21.1% among octogenarians. The authors concluded that aging population was also associated with increased treatment-related cost in elderly patients with bladder cancer. In our study, on the other hand, we were unable to perform a cost-effectiveness analysis, as our primary objective was to compare complication rates of RS among older male and younger patients. However, we believe that prolonged hospitalization requires possible additional medical and surgical interventions which are associated with an increased burden of treatment-related cost.

Furthermore, increased life expectancy and aging population worldwide, particularly in developed countries, bring a concern for the management of both benign and malignant urological diseases in elderly. In the literature, there are several studies investigating the effectiveness and safety of laparoscopic and endourological surgeries in elderly [27,28]. In their study, Besiroglu et al. [27] showed that percutaneous nephrolithotomy, which is known to be associated with high morbidity and complication rates, was safe and effective in aging male patients (>70 years). In addition, Sahin et al. [28] reported that laparoscopic ureterolithotomy for proximal ureteral calculi was safe with high success and low complication rates in patients aged ≥60 years. The authors also highlighted that it could be used in the first-line setting for the treatment of impacted and large ureteral calculi in geriatric patients.

Nonetheless, there are some limitations to this study. First, it has a retrospective design with a relatively small sample size and its inherent retrospective and nonrandomized nature may have led to selection bias. Second, we were unable to evaluate early and late complications separately and all complications observed within 90 days were evaluated. Third, we were unable to compare CCI, ECOG, and G8 scores in predicting postoperative complications. Therefore, further well-designed, large-scale, multi-center, prospective studies are required to confirm these findings.

In conclusion, our study results suggest that RS + PLND + ICUD is a safe procedure in male patients aged ≥65 years through a meticulous peroperative planning with similar complication rates to younger males in the tertiary setting.

Ethical statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

An informed consent was obtained from each patient included in the study.

Author contributions

Emre Karabay and Ramazan Topaktaş are responsible for concept of the study. Data collection and processing were done by Kemal Kayar. Analysis and/or interpretation of data was performed by Emre Karabay, Nejdet Karşıyakalı and Çağatay Tosun. Literature search was done by Kemal Kayar and Nejdet Karşıyakalı. Manuscript was written by Emre Karabay, Ramazan Topaktaş and Çağatay Tosun. Critical reiew was done by Metin İshak Öztürk.

Disclosure statement

No potential conflict of interest was reported by the authors.