Vol. 45 (6): 1090-1093, November - December, 2019 EDITORIAL doi: 10.1590/S1677-5538.IBJU.2019.06.03 High mortality rates after radical cystectomy: we must have acceptable protocols and consider the rationale of cutaneous ureterostomy for high-risk patients _______________________________________________ Fernando Korkes 1, Juan Palou 2 1 Disciplina de Urologia, Faculdade de Medicina do ABC, Santo André, SP, Brasil; 2 Fundacion Puigvert Universitat Autonoma de Barcelona, Espanha _______________________________________________________________________________________ Bladder cancer is a common disease, and In a SEER study that evaluated 6.737 patients in for T2-T4 stages, radical cystectomy is the first the USA with stage II disease (non-metastatic, treatment option (1). An interesting Swedish study muscle-invasive bladder cancer), only 8.3% un- has evaluated the natural history of urothelial bla- derwent radical cystectomy (8). The odds of an oc- dder cancer. After 6 months of diagnosis, 38% of togenarian to undergo radical cystectomy in the patients develop metastasis if untreated (2). Five- USA is five-times lower than a young patient (8). -year Cancer-specific survival is as low as 14% in Hispanic origin, Afro-American origin, and lower such scenery, and overall survival is only 5% (2). scholar level patients are also less treated properly On the other hand, if treated these patients have a when they have muscle-invasive bladder cancer 5-year CSS and OS of 60% and 48% respectively (8). According to a very interesting study that eva- (2). Radical cystectomy is, therefore, the first op- luated 27,578 patients from the SEER, only 6% tion, as it is also stated by the EAU, NCCN, AUA / of patients with muscle-invasive bladder cancer ASCO / ASTRO / SUO guidelines/consensus (3-5) is (pT2-pT4) in the USA underwent radical cystec- associated with a significant survival gain in com- tomy between 2007 and 2013 (8). Less than 19% parison to observation (2), to multiple resections, of patients with pT2 disease in the USA undergo chemotherapy or radiotherapy (6). In patients with radical cystectomy (9). stage II disease, cystectomy is associated with a And why does this happen? The answer is three-fold increase in survival, increasing mean because radical cystectomy is associated with high overall survival from 16 to 45 months (6). In a morbidity and mortality rates. When described in SEER study evaluating 328,560 patients, radi- the late 1940s, radical cystectomy was associa- cal cystectomy and chemotherapy were the only ted with a perioperative mortality of 33% (10). factors associated with improvements in survival In the 1970s perioperative mortality decreased to (7). Trimodal “bladder-sparing” approaches that 11% (and remained around 2.1% to 4.7% after the combine maximal transurethral resection, chemo- 1980s) (11). Analyzing mortality after radical cys- therapy, and radiotherapy or neoadjuvant chemo- tectomy is a slippery slope, as demonstrated in Ta- therapy with partial cystectomy are an option but ble-1. Studies report distinctive data. In-hospital only for a small percentage of patients (3). mortality is lower than 30-day mortality, which However, if we analyze data carefully, the is two to three-fold lower than 90-day mortality. guideline recommendations are rarely followed. And these numbers vary widely (1, 12, 13). 1090 IBJU | EDITORIAL Table 1 - Mortality after radical cystectomy in distinctive settings. Author N IHM 30-day 90-day Setting Barbieri, 2019, (14) 6,728 0.54% - - Large volume academic centers Udovicich, 2017. (15) 803 2.2% - - Victoria state, Australia Afshar, 2018, (12) 15,292 2.7% 7% English database Afshar, 2018, (19) 1.5% 4% English database (after centralization program) Waingankar, 2019, (1) 47,028 3.0% 8.2% SEER, USA Dell’Oglio, 2019, (16) 7,076 - - 10.7% SEER, USA Timoteo, 2019, (18) 5.097 7.38% - - DATASUS, Brasil DATASUS, 2019 1,377 8.5% - - DATASUS, state of SP DATASUS, 2019 161 8.1% - DATASUS, institution 1, São Paulo DATASUS, 2019 84 6.0% - DATASUS, institution 2, São Paulo DATASUS, 2019 71 11.3% - DATASUS, institution 3, São Paulo DATASUS, 2019 53 15.9% - DATASUS, institution 4, São Paulo DATASUS, 2019 81 14.8% - - DATASUS, suburban institutions of São Paulo IHM = in-hospital mortality In large volume academic referral centers the North of Brazil (18). Data from the public he- in the USA, in-hospital mortality after 6,728 cys- alth system (DATASUS) in the State of São Paulo, tectomies was as low as 0.54% (14). This results the most populated and wealthier state of Brazil, are impressive, and can be either effect of expe- between 2008-2018 demonstrated amid 1,377 ra- rience but also to a high selection bias. If we go to dical cystectomies reported, and 117 in-hospital other less selected settings, things start to change. deaths (8.5%). In the five largest academic institu- An Australian epidemiologic study has observed a tions in the city of São Paulo that treat exclusively 2.2% rate after 803 surgeries (15). A British stu- patients from the public health system, in-hospital dy evaluated 15,292 patients and have observed mortality varied from 6.0% to 15.9% (18). And it a mortality rate of 2.7% after 30 days and of 7% is important to state that these numbers represent after 90 months (12). In a large epidemiologic in-hospital mortality. Probably 90-day mortality study evaluating SEER data, the mortality rate of is even higher. 47,028 patients who underwent radical cystec- tomy in 1,162 centers was 3% after 30 days and Ureterostomy as a strategy to reduce mortality? 8.2% after 90 days (1). In another large SEER stu- Even though the AUA / ASCO / ASTRO / dy with 7,076 patients, 90-day mortality ranged SUO guidelines recommend as first-line treatment from 10.75% to 13.1% (16). In Spain a national for MIBC not only radical cystectomy but also uri- database study that has evaluated 7,999 patients nary diversion using intestinal segments (ileal con- found a 4.7% in-hospital mortality and 6.2% 90- duit, continent cutaneous diversion or orthotopic day mortality rate (17). neobladder) as standard treatments (4), this is not In developing countries, reality seems to what is currently done in more than 90% of pa- be much tougher in the public scenario. We have tients with MIBC in the USA, where only a fraction recently published a study demonstrating a 7.38% of patients with MIBC undergo radical cystectomy. in-hospital mortality rate, with a wide variation Data evaluating a series of patients undergoing ra- according to geographic regions, varying from dical cystectomy in developing countries are scarce 6.2% in the south to 28.6% in certain regions of in the literature, mainly because mortality rates are 1091 IBJU | EDITORIAL unacceptable in most public large volume centers. 3. Faba OR, Tyson MD, Artibani W, Bochner BH, Burkhard F, Gilbert Some key points that have been adopted by Eu- SM, et al. Update of the ICUD-SIU International Consultation ropean centers might urgently be adopted in the on Bladder Cancer 2018: urinary diversion. World J Urol. developing world (3). They include centralization 2019;37:85-93. 4. Statements G and Evaluation IP: American Society for of treatment and surgeries to referral centers (19, Radiation Oncology (ASTRO)/Society of Urologic Oncology 20), proper patient preparation and adequate choi- (SUO) BLADDER CANCER : AUA/ASCO/ASTRO/SUO American ce of diversion for each patient (12, 21). In high Urological Association (AUA)/American Society of Clinical risk patients, cutaneous ureterostomy might be also Muscle-Invasive Oncology (ASCO)/American Society. 2017: considered as a good alternative (3, 22). Several au- 1-42. thors have demonstrated a significant reduction in 5. Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis complications and mortality with cutaneous urete- M, Bruins HM, et al. Updated 2016 EAU Guidelines on Muscle- rostomy after radical cystectomy mainly in patients invasive and Metastatic Bladder Cancer. Eur Urol. 2017;71:462- with high risk for complications; it reduces the du- 75. ration of the surgery and all the complications rela- 6. Gild P, Nguyen DD, Fletcher SA, Cole AP, Lipsitz SR, Kibel AS, ted to bowel manipulation, thus decreasing the risk et al. Contemporary Survival Rates for Muscle-Invasive Bladder of mortality in patients with comorbidities (22-25). Cancer Treated With Definitive or Non-Definitive Therapy. Clin Genitourin Cancer. 2019;17:e488-e93. Some key-points are that not every patient 7. Weiner AB, Keeter MK, Manjunath A, Meeks JJ. Discrepancies with MIBC is a candidate for radical cystectomy, in staging, treatment, and delays to treatment may explain but also not every patient suitable for radical cys- disparities in bladder cancer outcomes: An update from tectomy is a candidate for urinary diversion with the National Cancer Data Base (2004-2013). Urol Oncol. intestinal segments. Urinary diversion using in- 2018;36:237.e9-237.e17. testinal segments is responsible for a large num- 8. Williams SB, Huo J, Kosarek CD, Chamie K, Rogers SO Jr, ber of these deaths (23). Even though this insight Williams MA, et al. Population-based assessment of racial/ has been widely published before (22-25), mor- ethnic differences in utilization of radical cystectomy for tality rates at many Centers are still high. If in patients diagnosed with bladder cancer. Cancer Causes Control. one hand we discuss robotic use (21, 26-28) that is 2017;28:755-66. been used in the vast majority of patients treated 9. Williams SB, Huo J, Chamie K, Hu JC, Giordano SH, Hoffman with muscle-invasive bladder cancer, we have to KE, et al. Underutilization of Radical Cystectomy Among Patients Diagnosed with Clinical Stage T2 Muscle-invasive talk about this problem in our journals, meetings, Bladder Cancer. Eur Urol Focus. 2017;3:258-64. boards, and discussions and bring better solutions 10. Jewett HJ, Lewis EL. Infiltrating carcinoma of the bladder; to be sure that we are first of all not harming our curability by total cystectomy. J Urol. 1948;60:107-18. patients. We have to properly perform a correct 11. Hendry WF. Morbidity and mortality of radical cystectomy pre/intra/postop management of the patients and (1971-78 and 1978-85). J R Soc Med. 1986;79:395-400. therapeutic decisions might be in accordance to 12. Afshar M, Goodfellow H, Jackson-Spence F, Evison F, Parkin comorbidities and life expectancy. J, Bryan RT, et al. Centralisation of radical cystectomies for bladder cancer in England, a decade on from the ‘Improving Outcomes Guidance’: the case for super centralisation. BJU Int. 2018;121:217-24. REFERENCES 13. Corradi RB, Galvao GJ, Oliveira GM, Carneiro VF, Miconi WG, Salles PG, et al. Radical cystectomy with pelvic lymphadenectomy: pathologic, operative and morbidity 1. Waingankar N, Mallin K, Egleston BL, Winchester DP, Uzzo RG, outcomes in a Brazilian cohort. Int Braz J Urol. 2016;42:431-7. Kutikov A, et al. Trends in Regionalization of Care and Mortality 14. 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Timoteo F, Korkes F, Baccaglini W, et al: BLADDER elderly patients with several comorbidities undergoing CANCER TRENDS AND MORTALITY IN THE BRAZILIAN cutaneous ureterostomy with single stoma or ileal conduit PUBLIC HEALTH SYSTEM Title. Int Braz J Urol 2019; xxx: after radical cystectomy. BJU Int. 2016;118:521-6. xxx. 25. Burkhard FC, Wuethrich PY. Cutaneous ureterostomy: 19. Afshar M, Goodfellow H, Jackson-Spence F, Evison ‘back to the future’. BJU Int. 2016;118:493-4. F, Parkin J, Bryan RT, et al. Centralisation of radical 26. Dal Moro F, Haber GP, Wiklund P, Canda AE, Balbay MD, cystectomies for bladder cancer in England, a decade on Stenzl A, et al. Robotic intracorporeal urinary diversion: from the ‘Improving Outcomes Guidance’: the case for practical review of current surgical techniques. Minerva super centralisation. BJU Int. 2018;121:217-24. Urol Nefrol. 2017;69:14-25. 20. Seisen T. Examining the role of centralisation of radical 27. Tyritzis SI, Gaya JM, Wallestedt-Lantz A, Pini G, Everaerts cystectomy for bladder cancer. BJU Int. 2018;121:165-7. W, de Naeyer G, et al. Current role of robotic bladder 21. Hussein AA, Elsayed AS, Aldhaam NA, Jing Z, Osei J, cancer surgery. Minerva Urol Nefrol. 2019;71:301-308. Kaouk J, et al. Comparison of Long-Term Oncologic 28. Gaya JM, Vila-Reyes H, Gavrilov P, Territo A, Breda A, Outcomes among Historical Open and Minimally Invasive Palou J. Roboticvradical cystectomy. Arch Esp Urol. Retrospective Studies. J Urol. 2019: [Epub ahead of print] 2019;72:293-298. Fernando Korkes, MD ARTICLE INFO Departamento de Urologia Fernando Korkes Faculdade de Medicina do ABC http://orcid.org/0000-0003-4261-4345 Santo André, SP, Brasil, E-mail: fkorkes@gmail.com Int Braz J Urol. 2019; 45: 1090-3 1093