Predictors of Major Complications and the Association with Oncological Outcomes After Radical Cystectomy for Bladder Cancer: A Nationwide Registry Study
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Abstract
Introduction Radical cystectomy improves survival of patients with muscle invasive and high-risk non-muscle invasive bladder cancer, but is a challenging surgical procedure as patients may experience major complications after surgery.
Objectives To assess the incidence of Clavien-Dindo ≥3 complications in patients who underwent radical cystectomy and to assess the association of these complications with pre-operative and peroperative parameters. The secondary aim was to study the association of complications with long-term oncological outcome.
Methods A nationwide registry was set up in 19 Dutch hospitals that studied patients with muscle invasive bladder cancer and high-risk non-muscle invasive bladder cancer treated by radical cystectomy. Major complications were classified as complications that were related to uretero-ileal anastomosis, intra-abdominal (e.g. urinoma, bowel leakage) infectious and cardiovascular complications. Multivariable logistic regression analyses were performed to assess the correlation between these groups and perioperative, clinical and pathological factors. Kaplan-Meier survival curves were constructed to analyze the correlation between complications and overall survival.
Results The study population consisted of 1,464 patients, of whom 420 (29%) developed severe complications. The most common complications were intra-abdominal (n=328, 60%) and uretero-ileal anastomosis related (n=92, 17%). Male gender (odds ratio 1.6, p=0.007), American Society of Anaesthesiologists score ≥3 (odds ratio 1.6, p=0.003), Charlson Comorbidity Index score ≥5 (odds ratio 2.1, p=0.002) and blood loss >700ml (odds ratio 1.4, p=0.044) were associated with severe complications. In addition, open radical cystectomy was associated with multiple complications (odds ratio 2.6, p=0.001). Furthermore, the overall survival of patients with major complications was worse than those who had no major complications. The median overall survival was 3.8 years versus 6.2 years for patients with and without severe complications (p<0.001).
Conclusions In a real-world setting, 29% of patients undergoing radical cystectomy developed severe complications. The risk of severe complications was higher in men, patients with impaired pre-operative condition, and in those who underwent open surgery. Severe complications had a negative impact on overall survival.
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References
2. Bochner BH, Dalbagni G, Sjoberg DD, et al. Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial. Eur Urol. Jun 2015;67(6):1042-1050. doi:10.1016/j.eururo.2014.11.043
3. Parekh DJ, Reis IM, Castle EP, et al. Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial. Lancet (London, England). Jun 23 2018;391(10139):2525-2536. doi:10.1016/S0140-6736(18)30996-6
4. Hubert J, Chammas M, Larre S, et al. Initial experience with successful totally robotic laparoscopic cystoprostatectomy and ileal conduit construction in tetraplegic patients: report of two cases. J Endourol. Feb 2006;20(2):139-43. doi:10.1089/end.2006.20.139
5. Vetterlein MW, Klemm J, Gild P, et al. Improving Estimates of Perioperative Morbidity After Radical Cystectomy Using the European Association of Urology Quality Criteria for Standardized Reporting and Introducing the Comprehensive Complication Index. Eur Urol. Jan 2020;77(1):55-65. doi:10.1016/j.eururo.2019.08.011
6. Fransen van de Putte EE, de Wall LL, van Werkhoven E, et al. Endo-Urological Techniques for Benign Uretero-Ileal Strictures Have Poor Efficacy and Affect Renal Function. Urol Int. 2018;100(1):18-24. doi:10.1159/000475508
7. Lawrentschuk N, Colombo R, Hakenberg OW, et al. Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol. Jun 2010;57(6):983-1001. doi:10.1016/j.eururo.2010.02.024
8. Bochner BH, Dalbagni G, Marzouk KH, et al. Randomized Trial Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: Oncologic Outcomes. Eur Urol. Oct 2018;74(4):465-471. doi:10.1016/j.eururo.2018.04.030
9. Nix J, Smith A, Kurpad R, Nielsen ME, Wallen EM, Pruthi RS. Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: perioperative and pathologic results. Eur Urol. Feb 2010;57(2):196-201. doi:10.1016/j.eururo.2009.10.024
10. Hinsenveld FJ, Boormans JL, van der Poel HG, et al. Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands. Urologic Oncology: Seminars and Original Investigations. 2022/02/01/ 2022;40(2):60.e1-60.e9. doi:https://doi.org/10.1016/j.urolonc.2021.06.018
11. Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB. Updates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers. Eur Urol. Apr 2018;73(4):560-569. doi:10.1016/j.eururo.2017.12.018
12. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. Aug 2004;240(2):205-13. doi:10.1097/01.sla.0000133083.54934.ae
13. Yuh BE, Nazmy M, Ruel NH, et al. Standardized analysis of frequency and severity of complications after robot-assisted radical cystectomy. Eur Urol. Nov 2012;62(5):806-13. doi:10.1016/j.eururo.2012.06.007
14. Johar RS, Hayn MH, Stegemann AP, et al. Complications after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. Eur Urol. Jul 2013;64(1):52-7. doi:10.1016/j.eururo.2013.01.010
15. Wijburg CJ, Michels CTJ, Oddens JR, Grutters JPC, Witjes JA, Rovers MM. Robot assisted radical cystectomy versus open radical cystectomy in bladder cancer (RACE): study protocol of a non-randomized comparative effectiveness study. BMC Cancer. Sep 3 2018;18(1):861. doi:10.1186/s12885-018-4779-6
16. Catto JWF, Khetrapal P, Ricciardi F, et al. Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial. JAMA. 2022;327(21):2092-2103. doi:10.1001/jama.2022.7393
17. Paolo DO, Elio M, Edward L, et al. The Effect of Surgical Experience on Perioperative and Oncological Outcomes After Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion: Evidence from a Referral Centre with Extensive Experience in Robotic Surgery. European Urology Focus. 2021;7(2):352-358. doi:https://doi.org/10.1016/j.euf.2020.01.016
18. Wijburg CJ, Hannink G, Michels CTJ, et al. Learning Curve Analysis for Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section Scientific Working Group. Eur Urol Open Sci. May 2022;39:55-61. doi:10.1016/j.euros.2022.03.004
19. Sung HH, Ahn JS, Seo SI, et al. A comparison of early complications between open and robot-assisted radical cystectomy. J Endourol. Jun 2012;26(6):670-5. doi:10.1089/end.2011.0372
20. Wijburg CJ, Michels CTJ, Hannink G, et al. Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy in Bladder Cancer Patients: A Multicentre Comparative Effectiveness Study. Eur Urol. Jan 11 2021;doi:10.1016/j.eururo.2020.12.023
21. Ornaghi PI, Afferi L, Antonelli A, et al. The impact of preoperative nutritional status on post-surgical complication and mortality rates in patients undergoing radical cystectomy for bladder cancer: a systematic review of the literature. World Journal of Urology. 2021/04/01 2021;39(4):1045-1081. doi:10.1007/s00345-020-03291-z
22. Cerantola Y, Valerio M, Hubner M, Iglesias K, Vaucher L, Jichlinski P. Are patients at nutritional risk more prone to complications after major urological surgery? J Urol. Dec 2013;190(6):2126-32. doi:10.1016/j.juro.2013.06.111
23. McPhee A, Ridgway A, Bird T, et al. The impact of cardiopulmonary exercise testing (CPET) and Charlson comorbidity index (CCI) in a large contemporary cohort of patients undergoing robot-assisted radical cystectomy and intracorporeal urinary diversion (RARC-ICUD). https://doi.org/10.1002/bco2.191. BJUI Compass. 2023/03/01 2023;4(2):187-194. doi:https://doi.org/10.1002/bco2.191
24. Schulz GB, Grimm T, Buchner A, et al. Surgical High-risk Patients With ASA ≥ 3 Undergoing Radical Cystectomy: Morbidity, Mortality, and Predictors for Major Complications in a High-volume Tertiary Center. Clin Genitourin Cancer. Dec 2018;16(6):e1141-e1149. doi:10.1016/j.clgc.2018.07.022
25. Adamczyk P, Pobłocki P, Kadlubowski M, et al. Complication Rate after Radical Cystectomy Depends on the Surgical Technique and Patient's Clinical Status. Urol Int. 2022;106(2):163-170. doi:10.1159/000517787
26. Chinapaw MJ, Buffart LM, van Mechelen W, et al. Alpe d'HuZes cancer rehabilitation (A-CaRe) research: four randomized controlled exercise trials and economic evaluations in cancer patients and survivors. Int J Behav Med. Jun 2012;19(2):143-56. doi:10.1007/s12529-011-9158-5
27. Oberle AD, West JM, Tobert CM, Conley GL, Nepple KG. Optimizing Nutrition Prior to Radical Cystectomy. Curr Urol Rep. Oct 18 2018;19(12):99. doi:10.1007/s11934-018-0854-4
28. Lakananurak N, Gramlich L. The Role of Preoperative Parenteral Nutrition. Nutrients. May 6 2020;12(5)doi:10.3390/nu12051320
29. Mossanen M, Krasnow RE, Zlatev DV, et al. Examining the relationship between complications and perioperative mortality following radical cystectomy: a population-based analysis. BJU Int. Jul 2019;124(1):40-46. doi:10.1111/bju.14636
30. Pavone C, Candela L, Fontana D, Simonato A. Postoperative complications and 90-day mortality in radical cystectomy in high-risk patients: A monocentric retrospective observational study. Urologia. Aug 2018;85(3):111-117. doi:10.1177/0391560317751600
31. Razdan S, Sljivich M, Pfail J, Wiklund PK, Sfakianos JP, Waingankar N. Predicting morbidity and mortality after radical cystectomy using risk calculators: A comprehensive review of the literature. Urol Oncol. Feb 2021;39(2):109-120. doi:10.1016/j.urolonc.2020.09.032