Is Robot-Assisted Radical Cystectomy Justified in the Elderly? A Comparison of Robotic Versus Open Radical Cystectomy for Bladder Cancer in Elderly ≥75 Years Old

Abstract

Background and Purpose:

Open radical cystectomy (ORC) or minimally invasive radical cystectomy with pelvic lymph node (LN) dissection carries significant morbidity to the elderly because they often have several medical comorbidities that make a surgical approach more challenging. The objective of this study is to compare robot-assisted radical cystectomy (RARC) and ORC in elderly patients.

Patients and Methods:

A prospective bladder cancer cystectomy database was queried to identify all patients age ≥75 years. A total of 20 patients were identified for each of the RARC and ORC cohorts. A retrospective analysis was performed on these 40 patients undergoing radical cystectomy for curative intent.

Results:

Patients in both groups had comparable preoperative characteristics and demographics. Patients had significant medical comorbidities with 80% in each cohort having American Society of anesthesiologists classification of 3 and 50% having had previous abdominal surgery. Complete median operative times for RARC was 461 (interquartile range [IQR] 331, 554) vs 370 minutes for ORC (IQR 294, 460) (P=0.056); however, median blood loss for RARC was 275 mL (IQR 150, 450) vs 600 mL for ORC (IQR 500, 1925). The median hospital stay for RARC was 7 days (IQR 5, 8) vs 14.5 days for ORC (IQR 8, 22) (P<0.001). The major complication (Clavien≥III) rate for RARC was 10% compared with 35% for ORC (P=0.024). There were two positive margins in the ORC group compared with one in the RARC group with median LN yields of 15 nodes (IQR 11, 22) and 17 nodes (IQR 10, 25) (P=0.560) respectively.

Conclusions:

In a comparable cohort of elderly patients, RARC can achieve similar perioperative outcomes without compromising pathologic outcomes, with less blood loss and shorter hospital stays. For an experienced robotic team, RARC should be considered in elderly patients because it may offer significant advantage with respect to perioperative morbidity over ORC.

Introduction

A ge is now recognized as the single most important risk factor for the development of cancer; therefore, cancer is considered primarily a disease of the elderly.¹ Interestingly, the fastest growing segment of the population is the 85 and older age group, which is projected to increase in number from 3.7 million in 1996, 5.7 million in 2010, and 18.2 million by 2050.¹ Because of this strong link between age and cancer, the challenge rests for physicians to optimize outcomes in elderly patients. Bladder cancer also is a disease of the elderly as evidenced by a recent analysis of the Surveillance, Epidemiology, and End Result (SEER) database demonstrating a peak incidence at aged 85 years.² Thus, there is expected to be an increased incidence of bladder cancer in elderly patients who have a reasonable life expectancy.

Radical cystectomy, pelvic lymph node (LN) dissection, and urinary diversion remain the standard treatment for patients with muscle-invasive bladder cancer in the United States³; however, it carries with it a high complication rate, reported as high as 64%.⁴ The elderly patient poses several challenges to the operative surgeon because not only the number but also the complexity of comorbidities increase with age,⁵ thus putting these patients at an even greater risk of complications that they are not able to tolerate as well as younger patients who possess more physiologic reserve. Therefore, elderly patients are less likely to receive potentially curative surgery when compared with their younger counterparts. Prout and colleagues⁶ demonstrated from SEER data that only 25% of patients with muscle-invasive bladder cancer ages 70 to 79 years were treated with radical cystectomy compared with 55% of those aged 55 to 59 years.

Chronologic age seems to be less important than Karnofsky performance status (KPS). A KPS of 90 to 100 was associated with a 9-month survival advantage compared with a KPS <80 in a series of 114 consecutive patients aged >70 years with nonmetastatic bladder cancer who underwent radical cystectomy.⁷ Most elderly patients with muscle-invasive bladder cancer can tolerate curative therapy; Clark and associates noted similar operative mortality in 1054 patients stratified by age (<60, 60–69, 70–79, and >80 years) but a higher rate of early complications in the >70 age group.⁸

Despite the morbidity and mortality associated with radical cystectomy, there is a growing body of literature supporting radical cystectomy in the elderly because it provides a disease-specific survival benefit compared with alternative treatments.⁹ Since the initial report in 2003,¹⁰ robot-assisted radical cystectomy (RARC) has been increasingly used around the world as a minimally invasive treatment option for the management of muscle-invasive bladder cancer. A single-institution prospective study showed that patients undergoing RARC compared with open radical cystectomy (ORC) experienced fewer postoperative complications and that RARC was an independent predictor of fewer overall and major complications.¹¹

The elderly patient poses several unique challenges to robotic surgery including decreased elasticity of the lungs and a decreased forced expiratory volume.¹² To assess the impact of RARC in the elderly on perioperative morbidity and mortality, we compared our initial RARC series in the elderly with a group of historical ORC elderly controls.

Patients and Methods

Before initiating this analysis, we obtained approval from our Institutional Review Board in recognition of and compliance with the United States Health Insurance Portability and Accountability Act of 1996 guidelines. From May 2008 through August 2010, a total of 20 patients aged ≥75 years with clinically localized bladder cancer underwent RARC with bilateral pelvic LN dissection at Wake Forest University Baptist Medical Center and were included in this analysis. Data were prospectively compiled in our bladder cancer database including patient demographics, preoperative disease characteristics, intraoperative variables, postoperative variables, and pathologic outcomes.

For control data, we queried our institutional cystectomy database to identify a contemporaneous cohort of 20 patients aged ≥75 years with clinically localized bladder cancer who underwent ORC. These were the 20 most recent consecutive elderly patients whounderwent ORC at our institution. The decision to perform ORC was at the discretion of the treating surgeon and patient preferences. All of the surgeons (AKH, AKK, JJS, and JAP) are fellowship trained, dedicated urologic oncologists. Two of the surgeons in this series performed both open and robotic surgery (AKK and JAP), one of the surgeons performed only robotic surgery (AKH), while the other one performed only open surgery (JJS).

Since the initiation of our robotic program in 2008, we have performed 150 RARC. Over the same period, we have performed 63 ORC, 10 of which were in elderly patients. The RARC and pelvic lymphadenectomy were performed with da Vinci^® S or Si (Intuitive Surgical, Sunnydale, CA) robotic assistance and extracorporeal urinary diversion. Patients were counseled on different options for extracorporeal urinary diversion that included ileal conduit, continent cutaneous, or orthotopic neobladder. Most patients at our institution are referred to medical oncology for consideration of neoadjuvant chemotherapy. Treatment is at the discretion of the medical oncology team involving the patient and family in the decision-making process. Our surgical technique, patient preparation, and surgical approach have been described in detail elsewhere as have the boundaries and technique of our LN dissection.¹³

We used standard descriptive methods to characterize the two cohorts. For comparisons, we used the Student t test for parametric and Mann-Whitney U test for nonparametric comparisons of continuous data. We used the Fisher exact test to compare categorical data between the two groups. All statistics were performed using JMP^® 8 (SAS Institute Inc, Cary, NC).

Results

The patients' clinical and demographic characteristics are shown in Table 1. There was no significant difference between the two groups with regards to patient sex, age, body mass index (BMI), American Society of Anesthesiologists (ASA) class, and previous abdominal surgical history. A majority of patients had significant medical comorbidities with 80% being ASA class III in each cohort, and one-half the patients in each cohort had undergone previous abdominal surgery. A total of four patients had undergone previous therapy for prostate cancer in the RARC group compared with only one patient in the ORC cohort.

Table 1.

Clinical Characteristics

	ORC		RARC		P value
Sex (n, %)
Male	12	(60)	11	(55)	0.750
Female	8	(40)	9	(45)
Age
Median (IQR)	77	(75, 83)	79	(78, 82)	0.100
BMI
Median (IQR)	26.3	(24, 31)	26	(24, 30)	0.570
ASA Class (n, %)
1	0		0		0.0887
2	4	(20)	2	(10)
3	16	(80)	16	(80)
4	0		2	(10)
Number of previous (n, %)
Abdominal surgery	10	(50)	11	(55)	0.750
Prostate cancer	1	(5)	4	(20)	0.150
Abdominal radiation	1	(5)	2	(10)	0.550
Systemic chemotherapy	1	(5)	0		0.310

ORC=open radical cystectomy; RARC=robot-assisted radical cystectomy; IQR=interquartile range; BMI=body mass index; ASA=American Society of Anesthesiologists.

The patient's operative and postoperative characteristics are shown in Table 2. Operative duration (including patient repositioning and redraping) was defined as initial incision to final closure of skin. Median operative duration for RARC was 461 minutes (IQR 331, 554) vs 370 minutes (IQR 294, 460) for ORC (P=0.056). Median estimated blood loss, however, was 275 mL (IQR 150, 450) for RARC and 600 mL (IQR 500, 1925) for ORC (P=0.0001); thus, fewer patients needed blood transfusions in RARC (20%) vs ORC (60%) (P=0.009). Median hospital stay was 7 days (IQR 5, 8) for RARC vs 14.5 days (IQR 8, 22) for ORC (P=0.0001).

Table 2.

Operative And Postoperative Characteristics

	ORC		RARC		P value
Operative duration (min)
Median (IQR)	370	(294, 460)	461	(331, 554)	0.056
Diversion (n, %)
Ileal conduit	20	(100)	20	(100)	1.0
Continent cutaneous	0		0
Orthotopic neobladder	0		0
EBL (mL)
Median (IQR)	600	(500, 1925)	275	(150, 450)	0.0001^*
Required transfusion (n, %)	12	(60)	4	(20)	0.009^*
Hospital stay, days
Median (IQR)	14.5	(8, 22)	7	(5, 8)	0.0001^*
Total complications, Clavien
0	3	(15)	11	(55)
I	4	(20)	0
II	6	(30)	7	(35)
III	3	(15)	1	(5)
IV	3	(15)	1	(5)
V	1	(5)	0	(0)
Total	17	(85)	9	(45)	0.0067^*
Major complications	7	(35)	2	(10)	0.0240^*

ORC=open radical cystectomy; RARC=robot-assisted radical cystectomy; IQR=interquartile range; EBL=estimated blood loss.

Statistically significant.

Using the Clavien complication system to classify all complications within 90 days of surgery (Table 3), 45% of RARC patients and 85% of ORC patients sustained any complication (P=0.007). Major complications were defined as Clavien≥III, and 10% of RARC patients compared with 35% of ORC patients sustained a major complication (P=0.024). There was one perioperative mortality in the ORC cohort from sepsis compared with none in the RARC group.

Table 3.

Total Complications

	ORC	RARC
Clavien, # of patients
I
Dehydration	1	0
II
Prolonged ileus/TPN	3	2
UTI	2	4
DVT/PE	1	0
Surgical site infection	3	0
Clostridium difficile infection	0	1
III
Urine leak	1	1
Enteric anastamotic leak	1	0
Fascial dehiscence	1	0
IV
Acute renal failure	1	0
Intraoperative air embolus	0	1
Enterotomy	1	0
Respiratory failure	1	0
V
Death from Sepsis	1	0
Total	17	9

ORC=open radical cystectomy; RARC=robot-assisted radical cystectomy; TPN=total parenteral nutrition; UTI=urinary tract infection; DVT=deep vein hrombosis; PE=pulmonary embolus.

The patient pathologic data are shown in Table 4. The tumor stage was similar between the two groups with 50% of the patients in the ORC group and 40% of the patients in the RARC group having pT₃/pT₄ disease. LN-positive disease was noted in 15% of ORC compared with 35% of RARC (P=0.14). The median total LN yield was also similar between the two groups with a median LN yield of 15 (IQR 11, 22) in the ORC group and 17 (IQR 10, 25) in the RARC group (P=0.56). Only one patient in the RARC group had a positive margin, whereas two patients in the ORC group had positive margins (P=0.54).

Table 4.

Pathologic Characteristics

	ORC		RARC
	N	(%)	N	(%)	P value
P stage
pT₀,T_a, T_is, T₁, T₂	10	(50)	12	(60)	0.740
pT₃, T₄	10	(50)	8	(40)
Pathologic+nodes (pN+)	3	(15)	7	(35)	0.140
Total lymph nodes
Median (IQR)	15	(11, 22)	17	(10, 25)	0.560
Positive margin (n, %)	2	(10)	1	(5)	0.540

ORC=open radical cystectomy; RARC=robot-assisted radical cystectomy; IQR=ingterquartile range.

Discussion

Because of the close link between advancing age and the incidence of bladder cancer, it can be expected that bladder cancer will continue to be an enormous challenge with the growth of our aging population in the years ahead.¹ To meet this challenge, it has become even more critical to analyze minimally invasive surgical techniques that are being used in the elderly as RARC is being performed increasingly around the world. This study compared the impact of RARC vs ORC on perioperative outcomes including morbidity and mortality in patients ≥75 years at a single medical center with an experienced robotic and open surgical team.

ORC has been shown to be safe in high-risk, elderly patients at bladder cancer centers of excellence^8,9,14
–16; however, population data reveal that a large number of elderly patients with bladder cancer are not being treated with radical cystectomy in the United States.⁶ RARC in the elderly was recently shown to be feasible in a retrospective single institution study by Coward and colleagues.¹⁷ Of the 99 patients who underwent RARC and who were included in the analysis, 38 were aged ≥70 years, and there was no difference between the older and younger groups with regard to perioperative or pathologic outcomes. There have been no other reports, to the best of our knowledge, in the English literature evaluating the outcomes of RARC compared with ORC in the elderly.

In theory, RARC in the elderly presents several unique challenges including increased operative times, the effects of the pneumoperitoneum and steep Trendelenburg position, the increased likelihood of intra-abdominal adhesions from previous abdominal surgeries, and increased complexity of medical comorbidities. All of these factors need to be addressed to ensure patient safety and optimal patient outcomes.

The elderly patients in our series had significant medical comorbidities with 80% in the ORC and RARC cohorts having ASA classification of III and two patients in the RARC group with ASA IV. Furthermore, 50% of the ORC patients and 55% of the RARC patients had previous abdominal surgery. Despite this, RARC was completed in all 20 of the patients with no need for conversion to open surgery. Aging is accompanied by a decrease in the lung tissue elasticity and a decreased response to hypoxemia and/or hypercapnia¹; yet, despite these physiologic changes, the pneumoperitoneum, as well as the steep Trendelenburg position required, in our experience, RARC was well tolerated.

In addition, the elderly patients who underwent RARC in our series had longer operative times compared with ORC and, despite this, did not suffer any additional perioperative complication. Perhaps the longer operative duration for RARC is less critical because of the decrease in blood loss and decrease in fluid shifts afforded by the robotic approach; blood loss and transfusions have been associated with worse outcomes and increased complications in patients undergoing radical cystectomy.^18,19

Several studies have documented the feasibility of ORC in the elderly but have revealed an increase in morbidity compared with their younger cohorts. For instance, Clark and colleagues⁸ used a nonstandardized reporting system and noted an increase in early complications (within 90 days of surgery) in elderly patients ≥70 years but not an increase in perioperative mortality. Most studies, however, report a wide variety and incidence of complications after radical cystectomy in the elderly because very few studies follow any standardized reporting system of complications.

It is likely that studies that fail to use standardized reporting systems underestimate complications as demonstrated by a large retrospective review of a prospectively compiled database, which identified a complication rate of 64% within 90 days of ORC when using strict reporting guidelines.⁴ Furthermore, in this same large database, there was a trend toward increased overall complications in octogenarians (n=117) compared with younger patients (72% vs 64%, P=0.08), but the rates of major complications were similar (17% vs 13%, P=0.3).¹⁶

In our study, the Clavien system was used to compare complications after cystectomy. While there were more overall and major complications in our ORC patients compared with the data reported by Froehner and colleagues,¹⁶ 80% of the elderly patients in our series who underwent ORC had ASA scores III to IV compared with 43% of the patients in the aforementioned series.^4,16 Perhaps the increased comorbidity explains the rise in complication rate in the ORC elderly patients in our series. In addition, there were fewer complications at 90 days in the RARC compared with the ORC group and fewer major complications (Clavien≥III) as well.

Certainly unmeasured selection bias can impact the results of a nonrandomized series, but RARC at our institution was associated with fewer complications than ORC in the elderly perhaps related to less fluid shifts, decreased operative blood loss, and lower rate of transfusions in our RARC patients. Of the major complications that occurred in the RARC group, one patient sustained a small injury to the external iliac vein during the robotic LN dissection, which resulted in a postulated air embolus. This patient sustained no long-term effects and was discharged to home on postoperative day 7.

Elderly patients have less physiologic reserve to deal with postoperative complications, and studies have shown that complications in the elderly after radical cystectomy are associated with an increased hospital stay.²⁰ Likewise, in our study, the robotic approach was associated with a significant reduction in hospital stay compared with the open approach. It is likely that the increased incidence in complications in the ORC group was the driving force behind the increased length of stay because all patients in this series regardless of treatment approach followed the same institutional postoperative pathways.

Bladder cancer is a potentially lethal malignancy, and adherence to sound oncologic principles is critical to optimizing patient outcomes. SEER data suggest that radical cystectomy provides the greatest overall and cancer-specific survival benefit to those elderly patients with muscle-invasive bladder cancer.⁹ Furthermore, these data suggest that elderly patients undergoing radical cystectomy had a survival advantage if a standard lymphadenectomy was performed compared with elderly patients who underwent cystectomy without LN dissection.²¹

The RARC was developed to emulate the same steps and LN dissection of the ORC. When adhering to these principles, RARC can achieve similar short-term oncologic outcomes in terms of LN yields and positive margin rates compared with ORC.^22
–24 Therefore, in terms of pathologic outcomes, the elderly patients in our series undergoing RARC had equivalent LN yields and positive margins (10% for ORC vs 5% for RARC) compared with ORC. Certainly, these patients will need to be followed long term to ensure oncologic equivalence, but short- to intermediate-term follow-up in one RARC series has reported bladder cancer-specific survival rates of 82% and 72% at 12 and 36 months, respectively, in 59 patients with mean follow-up of 25 months, which is comparable to other ORC series.²⁵

Our initial experience with RARC suggests that this is a safe and feasible procedure for elderly, comorbid patients, many of whom had multiple previous abdominal surgeries. Despite longer operative times for RARC, perioperative and pathologic outcomes were not compromised. RARC in the elderly was associated with fewer complications, less blood loss, and shorter hospital stay compared with ORC. While these findings are provocative, definitive conclusions are limited because of the inherent selection bias present in a nonrandomized study and the small sample size. Furthermore, these results were obtained at a robotic and bladder cancer center of excellence and may not be extrapolated to every hospital around the world. Future research should focus on the care of the elderly patient with bladder cancer as well as the development of tools to help risk stratify patients before surgery, because patient selection remains a critical factor in achieving an optimal outcome.

Conclusions

With a growing population of elderly patients and concurrent increasing prevalence of bladder cancer, it is imperative to find ways to optimize perioperative morbidity and mortality in elderly patients with significant comorbidities. RARC is a reasonable option in caring for the elderly patient with bladder cancer who is thought to benefit from surgical extirpation; it may offer several benefits including decreased blood loss, fewer postoperative complications, and a shorter hospitalization when performed by an experienced team.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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