Journal of Surgical Oncology 2015;111:917–922
Radical Cystectomy in Patients Over 80 Years Old in Quebec: A Population-Based Study of Outcomes AHMED S. ZAKARIA, MD, MSc,1 FABIANO SANTOS, PhD,2 SIMON TANGUAY, MD, FRCSC,1 WASSIM KASSOUF, MD, FRCSC,1 AND ARMEN G. APRIKIAN, MD, FRCSC1* 1 Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, Canada Department of Oncology, Division of Cancer Epidemiology, McGill University, Montreal, Canada
2
Objectives: To document radical cystectomy (RC) outcomes in patients over 80 years old across Quebec during the years 2000–2009 and to examine potentially related factors. Methods: Within Quebec health insurance medical services database, we identified patients over 80 years who underwent RC. The outcomes analyzed were post-operative complications, mortality rates at 30, 60 and 90 days and overall survival. Results: A total of 275 patients over 80 years old had RC performed in 38 hospitals across Quebec. Among them, 33% had major post-operative complications with 16% having more than one complication. Mortality rates at 30, 60 and 90 days were 5.8%, 9.8% and 13% respectively. 44.3% of RCs were performed in seven academic hospitals with mortality rates of 2.5%, 6.5% and 9% respectively. Community hospitals had mortality of 8.5%, 12.4% and 16.3% respectively (P < 0.001). The cohort 5-year overall survival rate was 27%. The presence of post-operative complications and the number of complications negatively affected overall survival (P < 0.001) Conclusion: Patients over 80 years of age have high post-RC mortality rates, especially at 90 days. In addition, it appears that they have lower postoperative mortality if their RCs were performed in academic centers. Mortality rates and complications can be used when obtaining informed consent.
J. Surg. Oncol. 2015;111:917–922. ß 2015 Wiley Periodicals, Inc.
KEY WORDS: radical cystectomy; elderly; complications; mortality; survival; Quebec
INTRODUCTION Urinary bladder cancer (BC) in Canada is the second most frequent genitourinary tract tumor in terms of incidence and mortality. In 2013, Quebec ranked first among all Canadian provinces regarding estimated new cases of BC in both males and females and ranked second in estimated deaths [1]. Worldwide BC in the elderly is expected to be a major health issue in the near future. It is estimated that BC has the highest per-patient lifetime costs (from diagnosis to death) of all cancers [2–4]. Canadian seniors (aged 65 years and over) represent the fastest-growing age group in the community and will continue to increase to represent 25% of the population by 2036 compared to 14% in 2009. The population aged 80 years and over would be 2.6 times higher in 2036 compared to 2009, possibly reaching 3.3 million persons [5]. Radical cystectomy (RC) in the elderly is a challenging surgical procedure associated with significant complications, including death. The reported rates vary widely with post-RC complication rates reaching 60% [6–9], and mortality rates sometimes exceeding 10% [10]. However, multiple reports have advocated RC in the elderly and demonstrated that in selected older patients the outcomes are similar to younger patients [11–13]. Furthermore, some reports have gone further and showed that RC is safe and effective even in high-risk elderly patients with significant comorbidities [14,15]. The aim of this study was to characterize RC outcomes in elderly patients (over 80 years) with BC across Quebec during the years 2000– 2009, including post-operative complications, mortality rates at 30, 60 and 90 days and overall survival, and to assess potential related variables.
MATERIALS AND METHODS Our study cohort was created retrospectively using data of patients over 80 years who underwent RC for BC across Quebec between 2000
ß 2015 Wiley Periodicals, Inc.
and 2009. This was done by the linkage of two administrative databases: the Régie de l’assurance maladie du Québec (RAMQ), and the Fichier des événements démographiques de l’Institut de la statistique du Québec (ISQ). The RAMQ is the governmental organization responsible for the province’s universal health system. All healthcare services dispensed to Quebec residents are recorded in the RAMQ administrative databases, which are composed of a set of claims files that provides information on medical services. This database provides collected data on physician-based diagnoses (International Classification of Diseases, ninth revision, ICD-9), relevant therapeutic procedures and its calendar date, characteristics of the patient, health care providers, and the costs involved. The ISQ database provides information on all births and deaths in Quebec. After obtaining approval from the Commission de l’accès à l’information (CAI) of Quebec, the provincial agency that grants authorization for the use of linked administrative databases, we linked both databases using patient anonymous identifier (generated from the Numéro d’assurance maladie—NAM, which is a unique identifier for all legal residents of Quebec).\ We included patients who are 80 years or older, had RC for BC and also had medical services data available for the 2-year period preceding RC. We selected patients from January 1st, 2000 until September 30th, Conflicts of interest: The authors declare no conflict of interest. * Correspondence to: Armen G. Aprikian, MD, FRCS(C), Division of Urology, McGill University, Montreal General Hospital, 1650 Cedar Avenue, L8-309, Montreal, Quebec H3G1A4, Canada. Fax: 514-934-8297. E-mail: [email protected] Received 17 November 2014; revised manuscript received 27 December 2014; Accepted 29 December 2014 DOI 10.1002/jso.23887 Published online 8 February 2015 in Wiley Online Library (wileyonlinelibrary.com).
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2009. The calendar date of RC (index date) is the date which each patient entered the cohort. In order to not bias results, we excluded patients whose RC was preceded by neo-adjuvant treatments. Our studied post-operative outcomes included: (i) Presence of high grade post-operative (Clavien grade III–IV) complications (urinary tract complications, gastro-intestinal tract (GIT) complications and wound complications) which were identified using standardized provincial procedure act codes to treat such complications within the RAMQ database from admission to 90 days following RC, (ii) Postoperative mortality rates at 30, 60 and 90 days and (iii) Overall survival. We analyzed the effect of RCs performed in academic centers, defined by the presence of a urology training program, versus nonacademic (community) hospitals on post-operative outcomes. Descriptive statistics were used to summarize the characteristics of the study population, observed outcomes and variables. Statistical comparisons between groups and variable strata were performed by ttests and chi-squared tests, when applicable. Kaplan–Meyer curves were used for survival analysis and Cox-proportional hazard models were used to generate Hazard Ratio (HR) along with 95% Confidence Intervals (CI). All analyses were two-sided with P 0.05 being considered significant. SAS 9.3 (SAS Institute Inc., Cary, NC, USA) was used to conduct the calculations.
RESULTS A total of 2,988 patients underwent RC for BC in Quebec in the study period. Among them, 282 patients were more than 80 years old. After exclusion of seven patients who had neo-adjuvant treatment, our final cohort was formed of 275 patients. Baseline characteristics of the study population and the measured outcomes are shown in Table I. Males comprised 68.4% (n ¼ 188) of the cohort. Overall during the first 90 days following RC, 33.1% (n ¼ 91) of patients had at least one high grade post-operative complication while
TABLE I. Characteristics of the Study Population and the Measured Outcomes Cohort Number of patients Sex Males Females Type of hospital where radical cystectomy performed Academic hospitals (n ¼ 7) Community hospitals (n ¼ 31) Post-operative complications (first 90 days): At least one major complication More than one major complication Urinary tract complications GI tract complications Wound complications Post-operative mortality rates Mortality at 30 days Mortality at 60 days Mortality at 90 days
188 (68.4%) 87 (31.6%) 122 (44.4%) 153 (55.6%) 91 (33.1%) 44 (16%) 38 (13.8%) 12 (4.3%) 8 (2.9%) 16 (5.8%) 27 (9.8%) 36 (13%)
16% (n ¼ 44) had more than one high grade complication. Urinary tract complications ranked first, where 13.8% (n ¼ 38) of patients had at least one post-operative urinary tract complication mainly in the form of anastomotic site complications requiring per-cutaneous nephrostomy tube insertion, JJ stent insertion and per-cutaneous collection drainage for urinomas. Of all, 4.3% (n ¼ 12) of patients had GIT complications that needed surgical interventions in the form of exploratory laparotomies, bowel exteriorization surgeries (ileostomies and colostomies) or revision of bowel anastamoses. Wound complications such as dehiscence requiring intervention occurred in 2.9% of patients (n ¼ 8). The cohort post-operative mortality rates at 30, 60
Fig. 1. Number of radical cystectomies performed per hospital over the whole study period. Journal of Surgical Oncology
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Radical Cystectomy in Patients Over 80 Years Old and 90 days were 5.8%, 9.8% and 13%, respectively. Subgroup analysis showed that patients over 85 years old (n ¼ 59) had a 90 days postoperative mortality rate of 22%. All patients had their RCs performed in 38 hospital facilities across Quebec, of which 44.4% (n ¼ 122) were operated in seven academic hospitals, and the remaining 31 non-academic (community) hospitals performed 55.6% (n ¼ 153) of the cases. (Figure 1) Post-operative high grade complication rate in academic hospitals reached 27.8% (n ¼ 34) while community hospitals had a high grade complication rate of 37.2% (n ¼ 57) (P ¼ 0.1003). Post-operative mortality rates at 30, 60, and 90 days after RC performed in academic hospitals were 2.5%, 6.5% and 9%, respectively. On the other hand, community-based hospitals had post-operative mortality rates at 30, 60 and 90 days of 8.5%, 12.4% and 16.3%, respectively. (P < 0.001, for mortality rates comparison between the two groups). In addition, there was significant variation in the 90-day postoperative mortality rates across hospitals, as shown in Figure 2. The cohort had a median overall survival of 1.4 years (502 days), a mean overall survival of 3.2 years (1,180 days) and a 5-year overall survival rate of 27%. There was no difference in cohort survival according to gender (P ¼ 0.63) but the presence of post-operative complications as well as the number of these complications negatively affected cohort overall survival (P < 0.001) as shown in Figures 3 and 4. Multivariate survival analysis showed a non-significant trend towards a 9% decreased chance of mortality for patients who had RC performed in academic hospitals, compared to community hospitals (HR 0.91, 95% CI: 0.67–1.23, P ¼ 0.56)
DISCUSSION Radical cystectomy and urinary diversion, although can be curative, is a potentially morbid surgical procedure even in young patients. As elderly patients generally have more comorbid conditions, RC is often judged too risky by urologists [11]. However, several studies have
Fig. 2.
suggested that RC in octogenarians is underused and inappropriately denied [12]. Unlike radical prostatectomy for prostate cancer, with the generally accepted 10-year life-expectancy rule often used to justify curative treatment, for RC in BC there is no generally accepted limit [16]. Some authors have suggested a life expectancy of 2 years to consider RC for patients with muscle invasive bladder cancer [17,18]. However the usefulness of this limit is questionable due to the absence of equally effective radical alternative treatment options for controlling the disease. As seen with bladder-sparing protocols shown to have a worse prognosis when used in patients over 80 years old [19]. Our study aimed to add to the literature on the subject of morbidity and mortality after RC in patients with BC older than 80 years and presents results on a population basis. To our knowledge this is the first study reporting on post-operative complications, mortality and survival for this age group in Quebec and provides an opportunity to compare results with other geographic regions in the world. We reported an overall high grade complication rate of 33.1% which includes complications occurring early in the in-patient period until 90 days post-RC. However, one of the major limitations of our study is the reliance on administrative billing claims for measuring complications which usually are classified as Clavien grade III–IV. As such, our definition of complications was restricted to major complications that led to billable procedures. Thus, it is very likely that our study significantly underestimates the overall complications rates. The literature reported frequency of complications in the elderly after RC vary widely, due to changes in definition and non-standardized methods, resulting in difficulty to compare series [20]. Nevertheless, our high grade complication rates are comparable to those reported recently from individual or multicenter studies, which ranged from 26.6–35.9% for the same grade complications [6,21,22]. The reported post-operative mortality rates in patients over 80 years undergoing RC range between 0% and 11% [13,23–25]. Series that reported a zero mortality rate had small sample sizes, ranging from 12 to 50 patients. Furthermore, the authors of these series used definitions of
Number of radical cystectomies and mortality rates at 90 days sorted by hospitals.
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Fig. 3. Cohort overall survival according to presence of post-operative complications. Kaplan–Meier survival curves, P ¼ P-value using the log-rank test, blue (upper) curve is for patients without post-operative complications and red (lower) curve is for patients with at least one post-operative complication.
Fig. 4. Cohort overall survival according to number of post-operative complications. Kaplan–Meier survival curves, P ¼ P-value using the logrank test, blue (upper) curve is for patients without post-operative complications, red (middle) curve is for patients with only one post-operative complication, green (lower) curve is for patients with more than one post-operative complication. Journal of Surgical Oncology
Radical Cystectomy in Patients Over 80 Years Old mortality as in-patient mortality or 30-day mortality [16], which may not have included all surgery-related deaths. It is our opinion that measuring 90-day mortality is more relevant today since improvements in postoperative care may postpone surgery-related deaths beyond 30-days. Nevertheless, in Quebec, mortality rates at 30, 60 and 90 days were 5.8%, 9.8% and 13% respectively, which we believe are high when compared to the recent literature. More importantly, our 90-day mortality rates varied widely between hospitals across Quebec, with some hospitals reporting very high mortality rates (reaching 60%). Such observations support the recommendation of regionalization of surgical cancer care, at least for this age group, to centers with better outcomes. Results from our study can be used when obtaining informed consent from elderly patients who require RC. The relationship between health care provider volumes and outcome of RC in terms of complications, mortality and survival is well established [26–29], but there is a limited body of literature specifically concentrating on the elderly. Interestingly, our above mentioned results matched a recent report showing that within the Nationwide Inpatient Sample (NIS) study, most octogenarians undergoing RC were treated at low-/intermediate-volume hospitals (81.7%) and at nonacademic centers (60.6%). The inpatient hospital mortality was about twice as high in these patients (4.6 vs. 2.6%, P < 0.001), and adverse perioperative outcomes were more frequent, octogenarians were at increased risk of blood transfusions (odds ratio: 1.30) and postoperative complications (odds ratio: 1.22) [22]. In contrast, a study conducted in Germany by multiple community hospitals regarding RC on elderly patients showed that RC can be performed with acceptable morbidity and mortality rates [30]. However, our study showed significant difference in the 90 days post-operative mortality rates in favor of academic hospitals. Our cohort 5-year overall survival of 27% also matched the reported overall survival rates in elderly patients that ranged between 8% and 54% [13,31]. Our overall survival analysis showed a non-significant trend for a protective effect of RC performed in academic centers which was most apparent in the first 3.5 years after RC. Of course, due to our reliance on the RAMQ administrative database, our study contains several limitations including the lack of some important clinical information resulting in our inability to perform risk adjustment based on oncologic risk factors (e.g., tumor grade and stage) or patient functional status (e.g., patient’s comorbidity and Charlson comorbidity index), as well as the inability to measure disease-specific survival. Nevertheless, we believe that our results and those of others can be very useful and important for provincial health care ministries, hospital administrators, and departments of surgery, to inform hospitals, surgeons, and patients of the post-operative outcomes associated with RC, and to help reorganizing surgical oncologic care based on outcomes.
CONCLUSION Our study suggests that, although RC is a feasible procedure in patients older than 80 years of age, it is associated with significant adverse post-operative outcomes, especially high mortality at 90 days. Post-operative outcomes and mortality varied significantly across institutions, with statistically significant lower mortality rates after RC performed in academic hospitals as compared to community hospitals. Results from such studies can be used when obtaining informed consent from elderly patients who may require RC.
REFERENCES 1. Canadian Cancer Society’s Advisory Committee on Cancer Statistics: Canadian cancer statistics. Toronto, ON: Canadian Cancer Society 2013.ISSN 0835–2976. Journal of Surgical Oncology
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2. Mossanen M,Gore JL: The burden of bladder cancer care: Direct and indirect costs. Curr Opin Urol 2014;24:487–491. 3. Yeung C, Dinh T, Lee J: The health economics of bladder cancer: An updated review of the published literature. Pharmacoeconomics 2014;Nov;32:1093–1104. 4. Botteman MF, Pashos CL, Redaelli A, et al.: The health economics of bladder cancer. Pharmacoeconomics 2003;21:1315–1330. 5. Statistics Canada. Population projections: Canada, the provinces and territories. Ottawa; 2010. Available from: http://www.statcan. gc.ca/pub/91–520-x/2010001/aftertoc-aprestdm1-eng.htm (Accessed September 3, 2014). 6. Berger I, Martini T, Wehrberger C, et al.: Perioperative complications and 90-day mortality of radical cystectomy in the elderly (75þ): A retrospective, multicentre study. Urol Int 2014;93:296–302. 7. Pycha A, Comploj E: The dilemma of cystectomy in old-old and oldest-old patients. Expert Rev Anticancer Ther 2011;11:1863–1870. 8. Donat SM, Siegrist T, Cronin A, et al.: Radical cystectomy in octogenarians—does morbidity outweigh the potential survival benefits. J Urol 2010;183:2171–2177. 9. Tilki D, Zaak D, Trottmann M, et al.: Radical cystectomy in the elderly patient: A contemporary comparison of perioperative complications in a single institution series. World J Urol 2010;28:445–450. 10. Mendiola F, Zorn K, Gofrit O, et al.: Cystectomy in the ninth decade: Operative results and long-term survival outcomes. Can J Urol 2007;14:3628–3634. 11. Horovitz D, Turker P, Bostrom PJ, et al.: Does patient age affect survival after radical cystectomy. BJU Int 2012;110: E486–E493. 12. Tyritzis SI, Anastasiou I, Stravodimos KG, et al.: Radical cystectomy over the age of 75 is safe and increases survival. BMC Geriatr 2012;12:18. 13. Clark PE, Stein JP, Groshen SG, et al.: Radical cystectomy in the elderly: Comparison of clincal outcomes between younger and older patients. Cancer 2005;104:36–43. 14. Chang SS, Alberts G, Cookson MS, et al.: Radical cystectomy is safe in elderly patients at high risk. J Urol 2001;166:938–941. 15. Farnham SB, Cookson MS, Alberts G, et al.: Benefit of radical cystectomy in the elderly patient with significant co-morbidities. Urol Oncol 2004;22:178–181. 16. Froehner M, Brausi MA, Herr HW, et al.: Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol 2009;56:443–454. 17. Skinner EC, Stein JP, Skinner DG: Surgical benchmarks for the treatment of invasive bladder cancer. Urol Oncol 2007;25:66–71. 18. Peyromaure M, Guerin F, Debre B, et al.: Surgical management of infiltrating bladder cancer in elderly patients. Eur Urol 2004;45:147–154. 19. Wehrberger C, Berger I, Marszalek M, et al.: Bladder preservation in octogenarians with invasive bladder cancer. Urology 2010;75: 370–375. 20. Shabsigh A, Korets R, Vora KC, et al.: Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009;55: 164–176. 21. Berneking AD, Rosevear HM, Askeland EJ, et al.: Morbidity and mortality of octogenarians following open radical cystectomy using a standardized reporting system. Can J Urol 2013;20: 6826–6831. 22. Roghmann F, Sukumar S, Ravi P, et al.: Radical cystectomy in the elderly: National trends and disparities in perioperative outcomes and quality of care. Urol Int 2014;92:27–34. 23. Saika T, Suyama B, Murata T, et al.: Orthotopic neobladder reconstruction in elderly bladder cancer patients. Int J Urol 2001;8:533–538. 24. Chang SS, Smith JR, Wells JA, et al.: Estimated blood loss and transfusion requirements of radical cystectomy. J Urol 2001;166:2151–2154. 25. Lance RS, Dinney CP, Swanson D, et al.: Radical cystectomy for invasive bladder cancer in the octogenarian. Oncol Rep 2001;8:723–726.
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26. Elting LS, Pettaway C, Bekele BN, et al.: Correlation between annual volume of cystectomy, professional staffing, and outcomes. Cancer 2005;104:975–984. 27. Konety BR, Dhawan V, Allareddy V, et al.: Impact of hospital and surgeon volume on in-hospital mortality from radical cystectomy: Data from the health care utilization project. J Urol 2005;173:1695–1700. 28. Barbieri CE, Lee B, Cookson MS, et al.: Association of procedure volume with radical cystectomy outcomes in a nationwide database. J Urol 2007;178:1418–1422.
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29. Zakaria AS, Santos F, Dragomir A, et al.: Postoperative mortality and complications after radical cystectomy for bladder cancer in Quebec: A population-based analysis during the years 2000–2009. Can Urol Assoc J 2014;8:259. 30. May M, Fuhrer S, Braun K-P, et al.: Results from three municipal hospitals regarding radical cystectomy on elderly patients. Int Braz J Urol 2007;33:764–776. 31. Zebic N, Weinknecht S, Kroepfl D: Radical cystectomy in patients aged 75 years: An updated review of patients treated with curative and palliative intent. BJU Int 2005;95:1211–1214.
Radical Cystectomy in Patients Over 80 Years Old in Quebec: A Population-Based Study of Outcomes AHMED S. ZAKARIA, MD, MSc,1 FABIANO SANTOS, PhD,2 SIMON TANGUAY, MD, FRCSC,1 WASSIM KASSOUF, MD, FRCSC,1 AND ARMEN G. APRIKIAN, MD, FRCSC1* 1 Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, Canada Department of Oncology, Division of Cancer Epidemiology, McGill University, Montreal, Canada
2
Objectives: To document radical cystectomy (RC) outcomes in patients over 80 years old across Quebec during the years 2000–2009 and to examine potentially related factors. Methods: Within Quebec health insurance medical services database, we identified patients over 80 years who underwent RC. The outcomes analyzed were post-operative complications, mortality rates at 30, 60 and 90 days and overall survival. Results: A total of 275 patients over 80 years old had RC performed in 38 hospitals across Quebec. Among them, 33% had major post-operative complications with 16% having more than one complication. Mortality rates at 30, 60 and 90 days were 5.8%, 9.8% and 13% respectively. 44.3% of RCs were performed in seven academic hospitals with mortality rates of 2.5%, 6.5% and 9% respectively. Community hospitals had mortality of 8.5%, 12.4% and 16.3% respectively (P < 0.001). The cohort 5-year overall survival rate was 27%. The presence of post-operative complications and the number of complications negatively affected overall survival (P < 0.001) Conclusion: Patients over 80 years of age have high post-RC mortality rates, especially at 90 days. In addition, it appears that they have lower postoperative mortality if their RCs were performed in academic centers. Mortality rates and complications can be used when obtaining informed consent.
J. Surg. Oncol. 2015;111:917–922. ß 2015 Wiley Periodicals, Inc.
KEY WORDS: radical cystectomy; elderly; complications; mortality; survival; Quebec
INTRODUCTION Urinary bladder cancer (BC) in Canada is the second most frequent genitourinary tract tumor in terms of incidence and mortality. In 2013, Quebec ranked first among all Canadian provinces regarding estimated new cases of BC in both males and females and ranked second in estimated deaths [1]. Worldwide BC in the elderly is expected to be a major health issue in the near future. It is estimated that BC has the highest per-patient lifetime costs (from diagnosis to death) of all cancers [2–4]. Canadian seniors (aged 65 years and over) represent the fastest-growing age group in the community and will continue to increase to represent 25% of the population by 2036 compared to 14% in 2009. The population aged 80 years and over would be 2.6 times higher in 2036 compared to 2009, possibly reaching 3.3 million persons [5]. Radical cystectomy (RC) in the elderly is a challenging surgical procedure associated with significant complications, including death. The reported rates vary widely with post-RC complication rates reaching 60% [6–9], and mortality rates sometimes exceeding 10% [10]. However, multiple reports have advocated RC in the elderly and demonstrated that in selected older patients the outcomes are similar to younger patients [11–13]. Furthermore, some reports have gone further and showed that RC is safe and effective even in high-risk elderly patients with significant comorbidities [14,15]. The aim of this study was to characterize RC outcomes in elderly patients (over 80 years) with BC across Quebec during the years 2000– 2009, including post-operative complications, mortality rates at 30, 60 and 90 days and overall survival, and to assess potential related variables.
MATERIALS AND METHODS Our study cohort was created retrospectively using data of patients over 80 years who underwent RC for BC across Quebec between 2000
ß 2015 Wiley Periodicals, Inc.
and 2009. This was done by the linkage of two administrative databases: the Régie de l’assurance maladie du Québec (RAMQ), and the Fichier des événements démographiques de l’Institut de la statistique du Québec (ISQ). The RAMQ is the governmental organization responsible for the province’s universal health system. All healthcare services dispensed to Quebec residents are recorded in the RAMQ administrative databases, which are composed of a set of claims files that provides information on medical services. This database provides collected data on physician-based diagnoses (International Classification of Diseases, ninth revision, ICD-9), relevant therapeutic procedures and its calendar date, characteristics of the patient, health care providers, and the costs involved. The ISQ database provides information on all births and deaths in Quebec. After obtaining approval from the Commission de l’accès à l’information (CAI) of Quebec, the provincial agency that grants authorization for the use of linked administrative databases, we linked both databases using patient anonymous identifier (generated from the Numéro d’assurance maladie—NAM, which is a unique identifier for all legal residents of Quebec).\ We included patients who are 80 years or older, had RC for BC and also had medical services data available for the 2-year period preceding RC. We selected patients from January 1st, 2000 until September 30th, Conflicts of interest: The authors declare no conflict of interest. * Correspondence to: Armen G. Aprikian, MD, FRCS(C), Division of Urology, McGill University, Montreal General Hospital, 1650 Cedar Avenue, L8-309, Montreal, Quebec H3G1A4, Canada. Fax: 514-934-8297. E-mail: [email protected] Received 17 November 2014; revised manuscript received 27 December 2014; Accepted 29 December 2014 DOI 10.1002/jso.23887 Published online 8 February 2015 in Wiley Online Library (wileyonlinelibrary.com).
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2009. The calendar date of RC (index date) is the date which each patient entered the cohort. In order to not bias results, we excluded patients whose RC was preceded by neo-adjuvant treatments. Our studied post-operative outcomes included: (i) Presence of high grade post-operative (Clavien grade III–IV) complications (urinary tract complications, gastro-intestinal tract (GIT) complications and wound complications) which were identified using standardized provincial procedure act codes to treat such complications within the RAMQ database from admission to 90 days following RC, (ii) Postoperative mortality rates at 30, 60 and 90 days and (iii) Overall survival. We analyzed the effect of RCs performed in academic centers, defined by the presence of a urology training program, versus nonacademic (community) hospitals on post-operative outcomes. Descriptive statistics were used to summarize the characteristics of the study population, observed outcomes and variables. Statistical comparisons between groups and variable strata were performed by ttests and chi-squared tests, when applicable. Kaplan–Meyer curves were used for survival analysis and Cox-proportional hazard models were used to generate Hazard Ratio (HR) along with 95% Confidence Intervals (CI). All analyses were two-sided with P 0.05 being considered significant. SAS 9.3 (SAS Institute Inc., Cary, NC, USA) was used to conduct the calculations.
RESULTS A total of 2,988 patients underwent RC for BC in Quebec in the study period. Among them, 282 patients were more than 80 years old. After exclusion of seven patients who had neo-adjuvant treatment, our final cohort was formed of 275 patients. Baseline characteristics of the study population and the measured outcomes are shown in Table I. Males comprised 68.4% (n ¼ 188) of the cohort. Overall during the first 90 days following RC, 33.1% (n ¼ 91) of patients had at least one high grade post-operative complication while
TABLE I. Characteristics of the Study Population and the Measured Outcomes Cohort Number of patients Sex Males Females Type of hospital where radical cystectomy performed Academic hospitals (n ¼ 7) Community hospitals (n ¼ 31) Post-operative complications (first 90 days): At least one major complication More than one major complication Urinary tract complications GI tract complications Wound complications Post-operative mortality rates Mortality at 30 days Mortality at 60 days Mortality at 90 days
188 (68.4%) 87 (31.6%) 122 (44.4%) 153 (55.6%) 91 (33.1%) 44 (16%) 38 (13.8%) 12 (4.3%) 8 (2.9%) 16 (5.8%) 27 (9.8%) 36 (13%)
16% (n ¼ 44) had more than one high grade complication. Urinary tract complications ranked first, where 13.8% (n ¼ 38) of patients had at least one post-operative urinary tract complication mainly in the form of anastomotic site complications requiring per-cutaneous nephrostomy tube insertion, JJ stent insertion and per-cutaneous collection drainage for urinomas. Of all, 4.3% (n ¼ 12) of patients had GIT complications that needed surgical interventions in the form of exploratory laparotomies, bowel exteriorization surgeries (ileostomies and colostomies) or revision of bowel anastamoses. Wound complications such as dehiscence requiring intervention occurred in 2.9% of patients (n ¼ 8). The cohort post-operative mortality rates at 30, 60
Fig. 1. Number of radical cystectomies performed per hospital over the whole study period. Journal of Surgical Oncology
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Radical Cystectomy in Patients Over 80 Years Old and 90 days were 5.8%, 9.8% and 13%, respectively. Subgroup analysis showed that patients over 85 years old (n ¼ 59) had a 90 days postoperative mortality rate of 22%. All patients had their RCs performed in 38 hospital facilities across Quebec, of which 44.4% (n ¼ 122) were operated in seven academic hospitals, and the remaining 31 non-academic (community) hospitals performed 55.6% (n ¼ 153) of the cases. (Figure 1) Post-operative high grade complication rate in academic hospitals reached 27.8% (n ¼ 34) while community hospitals had a high grade complication rate of 37.2% (n ¼ 57) (P ¼ 0.1003). Post-operative mortality rates at 30, 60, and 90 days after RC performed in academic hospitals were 2.5%, 6.5% and 9%, respectively. On the other hand, community-based hospitals had post-operative mortality rates at 30, 60 and 90 days of 8.5%, 12.4% and 16.3%, respectively. (P < 0.001, for mortality rates comparison between the two groups). In addition, there was significant variation in the 90-day postoperative mortality rates across hospitals, as shown in Figure 2. The cohort had a median overall survival of 1.4 years (502 days), a mean overall survival of 3.2 years (1,180 days) and a 5-year overall survival rate of 27%. There was no difference in cohort survival according to gender (P ¼ 0.63) but the presence of post-operative complications as well as the number of these complications negatively affected cohort overall survival (P < 0.001) as shown in Figures 3 and 4. Multivariate survival analysis showed a non-significant trend towards a 9% decreased chance of mortality for patients who had RC performed in academic hospitals, compared to community hospitals (HR 0.91, 95% CI: 0.67–1.23, P ¼ 0.56)
DISCUSSION Radical cystectomy and urinary diversion, although can be curative, is a potentially morbid surgical procedure even in young patients. As elderly patients generally have more comorbid conditions, RC is often judged too risky by urologists [11]. However, several studies have
Fig. 2.
suggested that RC in octogenarians is underused and inappropriately denied [12]. Unlike radical prostatectomy for prostate cancer, with the generally accepted 10-year life-expectancy rule often used to justify curative treatment, for RC in BC there is no generally accepted limit [16]. Some authors have suggested a life expectancy of 2 years to consider RC for patients with muscle invasive bladder cancer [17,18]. However the usefulness of this limit is questionable due to the absence of equally effective radical alternative treatment options for controlling the disease. As seen with bladder-sparing protocols shown to have a worse prognosis when used in patients over 80 years old [19]. Our study aimed to add to the literature on the subject of morbidity and mortality after RC in patients with BC older than 80 years and presents results on a population basis. To our knowledge this is the first study reporting on post-operative complications, mortality and survival for this age group in Quebec and provides an opportunity to compare results with other geographic regions in the world. We reported an overall high grade complication rate of 33.1% which includes complications occurring early in the in-patient period until 90 days post-RC. However, one of the major limitations of our study is the reliance on administrative billing claims for measuring complications which usually are classified as Clavien grade III–IV. As such, our definition of complications was restricted to major complications that led to billable procedures. Thus, it is very likely that our study significantly underestimates the overall complications rates. The literature reported frequency of complications in the elderly after RC vary widely, due to changes in definition and non-standardized methods, resulting in difficulty to compare series [20]. Nevertheless, our high grade complication rates are comparable to those reported recently from individual or multicenter studies, which ranged from 26.6–35.9% for the same grade complications [6,21,22]. The reported post-operative mortality rates in patients over 80 years undergoing RC range between 0% and 11% [13,23–25]. Series that reported a zero mortality rate had small sample sizes, ranging from 12 to 50 patients. Furthermore, the authors of these series used definitions of
Number of radical cystectomies and mortality rates at 90 days sorted by hospitals.
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Fig. 3. Cohort overall survival according to presence of post-operative complications. Kaplan–Meier survival curves, P ¼ P-value using the log-rank test, blue (upper) curve is for patients without post-operative complications and red (lower) curve is for patients with at least one post-operative complication.
Fig. 4. Cohort overall survival according to number of post-operative complications. Kaplan–Meier survival curves, P ¼ P-value using the logrank test, blue (upper) curve is for patients without post-operative complications, red (middle) curve is for patients with only one post-operative complication, green (lower) curve is for patients with more than one post-operative complication. Journal of Surgical Oncology
Radical Cystectomy in Patients Over 80 Years Old mortality as in-patient mortality or 30-day mortality [16], which may not have included all surgery-related deaths. It is our opinion that measuring 90-day mortality is more relevant today since improvements in postoperative care may postpone surgery-related deaths beyond 30-days. Nevertheless, in Quebec, mortality rates at 30, 60 and 90 days were 5.8%, 9.8% and 13% respectively, which we believe are high when compared to the recent literature. More importantly, our 90-day mortality rates varied widely between hospitals across Quebec, with some hospitals reporting very high mortality rates (reaching 60%). Such observations support the recommendation of regionalization of surgical cancer care, at least for this age group, to centers with better outcomes. Results from our study can be used when obtaining informed consent from elderly patients who require RC. The relationship between health care provider volumes and outcome of RC in terms of complications, mortality and survival is well established [26–29], but there is a limited body of literature specifically concentrating on the elderly. Interestingly, our above mentioned results matched a recent report showing that within the Nationwide Inpatient Sample (NIS) study, most octogenarians undergoing RC were treated at low-/intermediate-volume hospitals (81.7%) and at nonacademic centers (60.6%). The inpatient hospital mortality was about twice as high in these patients (4.6 vs. 2.6%, P < 0.001), and adverse perioperative outcomes were more frequent, octogenarians were at increased risk of blood transfusions (odds ratio: 1.30) and postoperative complications (odds ratio: 1.22) [22]. In contrast, a study conducted in Germany by multiple community hospitals regarding RC on elderly patients showed that RC can be performed with acceptable morbidity and mortality rates [30]. However, our study showed significant difference in the 90 days post-operative mortality rates in favor of academic hospitals. Our cohort 5-year overall survival of 27% also matched the reported overall survival rates in elderly patients that ranged between 8% and 54% [13,31]. Our overall survival analysis showed a non-significant trend for a protective effect of RC performed in academic centers which was most apparent in the first 3.5 years after RC. Of course, due to our reliance on the RAMQ administrative database, our study contains several limitations including the lack of some important clinical information resulting in our inability to perform risk adjustment based on oncologic risk factors (e.g., tumor grade and stage) or patient functional status (e.g., patient’s comorbidity and Charlson comorbidity index), as well as the inability to measure disease-specific survival. Nevertheless, we believe that our results and those of others can be very useful and important for provincial health care ministries, hospital administrators, and departments of surgery, to inform hospitals, surgeons, and patients of the post-operative outcomes associated with RC, and to help reorganizing surgical oncologic care based on outcomes.
CONCLUSION Our study suggests that, although RC is a feasible procedure in patients older than 80 years of age, it is associated with significant adverse post-operative outcomes, especially high mortality at 90 days. Post-operative outcomes and mortality varied significantly across institutions, with statistically significant lower mortality rates after RC performed in academic hospitals as compared to community hospitals. Results from such studies can be used when obtaining informed consent from elderly patients who may require RC.
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