Robot-Assisted Radical Cystectomy in Octogenarians

Abstract

Background and Purpose:

Radical cystectomy is the standard of care for muscle-invasive bladder cancer; however, few patients over age 75 undergo cystectomy. Morbidity and mortality rates in this age group approach 60% and 10%, respectively. We sought to determine if minimally invasive surgery, in the form of robot-assisted radical cystectomy (RARC), may reduce morbidity and mortality associated with this operation in elderly patients.

Patients and Methods:

After Institutional Review Board approval, all RARC performed between 2009 and 2012 from one institution were reviewed, and 23 cases in patients over the age of 80 were identified. Data analyzed included age, indication for cystectomy, American Society of Anesthesiologists score (ASA), Charlson Comorbidity Index, pathologic stage, estimated blood loss, transfusion rate, and 90-day morbidity and mortality rate.

Results:

Twenty-three patients over the age of 80 years underwent RARC by a single surgeon (IT) between April 2009 and October 2012. Average age was 83.7 years (range 80–88 years) with average Charlson Comorbidity Index score of 4.3 (age-weighted 8.3). Indication for cystectomy was oncologic in all cases (21 bladder malignancy, 2 hemorrhagic cystitis in the setting of prostate cancer). The average blood loss and operative times were 208 mL (range 50–650 mL) and 253 minutes (range 175–365 min). Seven (30.4%) patients needed blood transfusions. The average length of hospital stay was 8.2 days (range 6–24 days). The overall complication rate within 90 days was 34.8% (8 patients) with no mortality. Longest follow-up is 34 months.

Conclusions:

RARC should be strongly considered for patients over the age of 80 with clinical indications for cystectomy. The complication rate is acceptable even in complicated patients with multiple comorbidities and those with previous abdominal surgery or pelvic radiation. Hospital stay remains shorter than with open surgery, and complication rates appear to be lower than previously reported for this age group.

Introduction

Bladder cancer is often considered a disease of the elderly with a median age at diagnosis of 73 years and more than 40% of the diagnoses in patients over age 75 years. It is a leading cause of cancer-related mortality in patients over the age of 80 years. With life expectancy in the United States continuing to rise, it is expected that more octogenarians will present to urologists seeking surgical treatment. While superficial bladder cancer can be managed with low-morbidity endoscopic surgery, the standard of care for muscle-invasive bladder cancer is radical cystectomy (RC). This presents a treatment dilemma when considering elderly patients, because RC remains a complex procedure with a high morbidity and mortality rate, even in relatively young, healthy patients.

The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data have shown that only 14% of patients over the age of 80 years who have received a diagnosis of muscle-invasive bladder cancer undergo radical cystectomy.¹ Meanwhile, 49.4% of patients between the age of 65 and 79 years are treated with radical cystectomy.² Konety and associates³ showed that demographics, geographics, and disease-related variables all contribute to the decreasing number of patients who undergo RC as age increases above 80 years. The SEER data also demonstrate that in those who underwent RC over the age of 80 years, cancer-specific survival did improve.

Urologists have long been exploring minimally invasive surgical approaches to lessen the morbidity of open surgery, including the use of the da Vinci^® surgical system (Intuitive Surgical, Inc.), which has more recently been utilized in radical cystectomy. With greater surgeon experience, robot-assisted radical cystectomy (RARC) should be strongly considered for treatment of the elderly population. Our experience in a cohort of patients at a community hospital over the age of 80 years who underwent RARC demonstrates the feasibility and safety of this approach in this population of patients.

Patients and Methods

An Institutional Review Board-approved retrospective data analysis of all RARCs completed at one institution by a single surgeon (IT) was performed. This produced 113 RARCs performed over a 4-year period, from April 2009 to October 2012. Of these patients, 23 were over the age of 80 years. Demographic data included patient age, sex, comorbidities, body mass index (BMI), American Society of Anesthesiologists (ASA) grade, previous surgery or radiation, previous treatment for the diagnosed cancer, indication for cystectomy, and preoperative hematocrit and creatinine levels. From these data, the Charlson comorbidity score was derived, both age-weighted and non-age-weighted.

We collected operative characteristics including estimated blood loss (EBL), operative time in minutes, type of lymph node dissection, and type of urinary diversion. Pathologic data reviewed included pathologic grade, margin status, lymphovascular invasion, concomitant diagnosis of prostate cancer on pathology evaluation, and number of lymph nodes obtained. Postoperative data collected included length of hospital stay, transfusion rate, complications within 90 days, and discharge hematocrit and creatinine values. Mortality since surgery was also documented. The longest follow-up interval is 3 years.

Results

Twenty-three patients over 80 years of age underwent RARC in the study period (April 2009 to October 2012). All operations analyzed were performed by IT with similar operative technique as that described by Richards and colleagues.⁴ All patients had ileal loop urinary diversion created extracorporeally. Eighty-three percent of the patients were men (n=19). The average patient age was 83.7 years (range 80–88 years) with average Charlson Comorbidity Index of 4.3 and age-weighted Charlson Comorbidity Index of 8.3 (ranges 2–6 and 6–10) (Table 1). Ten-year life expectancy based on Charlson score ranged from 0% to 2%. It is also important to note that five (22%) patients had radiation to the pelvis before cystectomy. Ten (43%) patients had received intravesical chemotherapy before cystectomy. One patient also had coil embolization of the bladder before cystectomy for hemorrhagic cystitis, and one had received intravesical alum for the same. Twelve (52%) patients had previous abdominal surgery.

Table 1.

Patient Characteristics

Total patients=23
	Average	Range
Age (years)	83.7	80–88
ASA	2.6	2–4
BMI	26.4	18–39
Preoperative hematocrit (%)	36	27.1–47.9
Preoperative creatinine (mg/dL)	1.4	0.7–2.9
Charlson Comorbidity Index (age-weighted)	8.3	6–10

ASA=American Society of Anesthesiologists; BMI=body mass index.

All patients had oncologic diagnoses before cystectomy (21 bladder carcinoma, 1 metastatic prostate cancer with hemorrhagic cystitis, and 1 hemorrhagic cystitis in the setting of previous external beam radiation for prostate cancer—see Table 2: Indications for cystectomy). Average ASA score was 2.6 (range 2–4). Patient BMI ranged from 18 to 39 with an average BMI of 26.4 (Table 1).

Table 2.

Indications for Cystectomy

Indication	Number of patients
Muscle-invasive bladder cancer	15
CIS/recurrent high grade superficial	3
Squamous-cell bladder cancer	2
Hematuria	2
Defunctionalized bladder	1

CIS=carcinoma in situ.

The average EBL was 208 mL (range 50–650 mL), and average operative time was 253 minutes (range 175–365 min). All but three patients also underwent extended bilateral pelvic lymph node dissection that included presacral, external, internal, and common iliac and obturator lymph node packets, performed robotically. Of the three patients who did not have extended lymph node dissection, one had superficial bladder cancer status post bacillus Calmette-Guérin therapy with a resultant defunctionalized bladder, and the other two had clinically significant hemorrhagic cystitis secondary to external beam radiation for prostate cancer, because such lymph node dissection was deemed oncologically unnecessary.

Pathologic evaluation confirmed muscle-invasive disease in all but 4 patients (19 patients, 84%). These patients without muscle-invasive carcinoma (T₂ or greater) either had downgrading of their disease (T₁), carcinoma in situ (T_is), or no evidence of urothelial cancer (1 patient). Pathologic evaluation revealed T₃ or T₄ disease in 70% of this patient group (16 patients). In 74% of the cases (17 patients), negative surgical margins were achieved. Of the patients with positive margins (6 patients, 26%), 5 of the 6 had T₄ disease diagnosed on final pathologic determination. Lymphovascular invasion was seen in 16 (70%) patients. Fifty-three percent of the men undergoing cystectomy (10 patients) also had prostate cancer diagnosed on pathologic specimen. Of the patients undergoing lymph node dissection, an average of 19 nodes were recovered, ranging from 8 to 29 nodes.

Our current cystectomy protocol paces patients to discharge on postoperative day 6 barring any complications, patient concerns, or disposition issues. The average length of hospital stay for this cohort was 8.2 days with a range of 6 to 24 days. Seven (30.4%) patients needed blood transfusions during the postoperative course.

The overall 90-day complication rate was 34.8%; complications were experienced in eight patients. All complications were Clavien classification score II, except one, which was Clavien classification score III. The complications are summarized in Table 3. Two patients with Clostridium difficile infections were treated with antibiotics. There were two incidents of wound dehiscence; one was managed with local wound care and the other was managed with surgical debridement and closure. Three patients had postoperative ileus necessitating total parenteral nutrition for less than 1 week. One patient was readmitted for dehydration and was also treated for urinary tract infection (UTI). One patient was treated for UTI as well as pulmonary embolism and deep vein thrombosis. Three patients had more than one complication. At this time, there have been no deaths in this cohort. The longest follow-up interval is 34 months.

Table 3.

Complications by Patient

Patient	Complication
1	Clostridium difficile colitis, ileus
2	Wound dehiscence
3	Ileus
4	Clostridium difficile colitis
5	Readmission, dehydration, UTI
6	Ileus
7	UTI, PE, DVT
8	Wound dehiscence

UTI=urinary tract infection; PE=pulmonary embolism; DVT=deep vein thrombosis.

Pre- and postoperative hematocrit averaged 36% and 33.4% (range 27.1–47.9% and 30.2–38.1%, respectively) (Table 4). Pre- and postoperative creatinine level average was 1.4 mg/dL and 1.2 mg/dL (range 0.7–2.9 mg/dL and 0.7–1.9 mg/dL, respectively). Interestingly, all but three patients had a discharge creatinine value that was the same or lower than the preoperative creatinine level (85%). Nine (45%) patients had a reduction of creatinine greater than 0.3 mg/dL.

Table 4.

Postoperative Results

	Average	Range
Operative time (min)	253	175–365
EBL (mL)	208	50–650
Length of stay	8.2 days	6–24 days
Discharge hematocrit (%)	33.4	30.2–38.1
Discharge creatinine (mg/dL)	1.2	0.7–1.9
Need for transfusion	7 patients	-
Complications within 90 days	8 patients	-

EBL=estimated blood loss.

Discussion

The treatment of bladder cancer in elderly patients remains a difficult management issue for primary care physicians, oncologists, and urologists. Although multiple reports advocate consideration of cystectomy in the elderly,^5

–10 SEER data suggest that avoidance of cystectomy because of age continues. Significant comorbidities and shortened life expectancy often drive patients and physicians away from surgical management. Indeed, the overall complication rate of elderly patients undergoing open RC has been reported by several authors ranging up to 60%,^11

–15 with mortality rates sometimes exceeding 10%.¹⁶ As demonstrated in our series, however, the complication rate can be much lower, more consistent with complication rates across all age groups.^17,18

Similar to the majority of patients over age 80 years, our patients all had at least one significant comorbidity contributing to their overall state of health.¹⁹ This was reflected in the Charlson Comorbidity Index. More than half of our patients also had a history of abdominal surgery, and 22% had previous radiation to the pelvis. Despite this history, all cystectomies and extended lymph node dissections were completed robotically, without the need to convert to an open procedure.

As a referral center, it is possible that the poorest surgical candidates were never referred to our facility, which does inject selection bias into our cohort; however, our inclusion criteria for surgery were broad. As noted, patients with significant comorbid conditions or the so-called “hostile pelvis” were not excluded. Our data demonstrate that chronologic age should not be used as a determinant for whether or not to consider surgery, and that robotic surgery can be successfully performed even in the setting of previous surgery and radiation.

It seems that use of minimally invasive techniques may temper morbidity of the surgery, and this may be most important in the geriatric population. Clinical investigators have found a significant decrease in blood loss and transfusion requirements as well as time to resumption of regular diet and length of hospital stay in their analysis of open vs robotic cystectomy at any age.²⁰ They also noted similar complication rates (24% open, 21% robotic) without sacrificing oncologic outcome. These benefits may be most appreciated in geriatric patients with lower reserve for dramatic fluid shifts and intolerance for long hospitalizations. In one study, delirium affected 29% of patients undergoing cystectomy, with advanced age being an independent risk factor for delirium.²¹ Shorter hospitalization may reduce this risk in the elderly. Indeed, our patients were stable for discharge in most cases within a week of the surgery, thus avoiding significant complications from extended hospital stay including delirium.

In addition, while urinary diversion was performed extracorporeally in this cohort, totally intracorporeal urinary diversion has been described.²² Intracorporeal creation of urinary diversion may well decrease wound-associated complications such as dehiscence. It is unknown, however, what additional complications may be encountered during the development of new surgical techniques. As with all complicated operations, experience of the surgeon is of great importance.

From the oncologic standpoint, our cohort did demonstrate a higher incidence of positive margins on pathologic examination than other recent series. While reports from Lau and coworkers²³ and Wang and colleagues²⁰ reveal positive margin rates of 8% and 6%, respectively, ours was 26%. We postulate that this high positive surgical margin rate has more to do with the advanced nature of the disease in these patients than surgical technique. Elderly patients are known to present with more advanced disease, on average, than younger patients, and this was consistently true in our cohort. The patients with positive surgical margins all had advanced cancer. All but one patient had T₄ disease. In addition, of the seven (30%) patients with T₄ disease, only two had negative surgical margins.

The population in the study by Wang and associates²⁰ was not strictly elderly and therefore not entirely similar to ours; however, they did notice a trend toward more extravesical disease in the open group, which also had more positive surgical margins, when compared with the robotic group. In addition, they also noted that all three patients in the open group with positive surgical margins had T₄ disease. The two patients in the robotic group with positive margins had T₃ node-positive disease with microscopic extension into extravesical fat. Overall, in the robotic group, Wang and colleagues²⁰ had only two (6%) patients with T₄ disease. In comparison, 30.4% of our patients had T₄ disease. Similarly, Lau and coworkers²³ noted three patients with positive surgical margins and had only two patients with T₄ disease. It is not mentioned whether these are the same patients, but this would be consistent with our data.

Because of reduced life expectancy and aggressive pathology, some clinicians have questioned the benefit of cystectomy in the elderly population. In a review of SEER data, however, Chamie and associates²⁴ found an increase in cancer-specific survival of 6 months with radical cystectomy and lymph node dissection. Of note, this difference was not present if lymph node dissection was not performed, which underscores the importance of node dissection in the elderly, because they seem to derive little to no oncologic benefit from RC alone. Hollenbeck and colleagues²⁵ also used analysis of SEER data to conclude that RC in octogenarians reduced their death from disease as well as death from any cause by a significant amount. This was also noted by Horovitz and colleagues and Guillotreau and coworkers.^9,26 Donat et al.²⁷ determined that disease control and survival outcomes in the elderly were similar to those enjoyed in younger cohorts of patients. In addition, complication rates were not significantly different between groups.²⁶

Of course, as Farnham et al. pointed out,⁹ certain persons may benefit more from a palliative point of view than from an oncologic standpoint. In our series, a subset of patients underwent cystectomy because of hematuria and/or defunctionalized bladder. These patients were simply seeking improvement in their quality of life. While we did not use a tool for assessment of this, it is reasonable to believe that resolution of pain and hematuria after cystectomy would improve patient quality of life, reduce the cost of treatment, and reduce repeated admissions. These outcomes have not been addressed by the SEER data; hence, research in this area would be of great interest to clinicians.

A cohort of patients over age 80 years undergoing RARC was recently published reporting complication rates of 78% and mortality approaching 9%.²³ In comparison, we have seen fewer complications and no mortality in our group of similar patients. A limitation of this study clearly includes the small study size. It is possible that with a larger cohort, we may see different results. In addition, follow-up intervals are inconsistent because many of our patients return to referring urologists. It is noted that we may be underreporting complications that were managed by referring urologists and were not disclosed to us, which is another limitation of the study. With increasing interest in minimally invasive procedures for geriatric populations and with current data revealing dissimilar results, this is an area that needs further research with larger cohorts.

There is no doubt that experience of the surgeon plays a role in the outcome of complicated surgery. This cohort of patients likely benefits from the fact that the surgeon has surpassed his initial “learning curve.” Direct comparison between open and laparoscopic techniques in age-matched cohorts would also be valuable. Many facilities have moved toward exclusively minimally invasive techniques, making this comparison difficult today.

As the population ages and the percentage of people over age 65 years doubles in the next 30 years, surgical treatment of the elderly should be studied further, and urologists will need to redefine criteria for surgical candidacy.

Conclusions

Even in patients with significant comorbidities, previous radiation, or pelvic pathology, patients over age 80 years can safely undergo RARC. RARC affords these patients the standard of care for their disease and extends survival without significantly increasing complication rates when performed by experienced robotic surgeons.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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