Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO Guideline (2017; Amended 2020, 2024)

No AccessJournal of UrologyAUA Guideline Article25 Apr 2024Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024) Jeffrey Holzbeierlein, Brooke R. Bixler, David I. Buckley, Sam S. Chang, Rebecca S. Holmes, Andrew C. James, Erin Kirkby, James M. McKiernan, and Anne Schuckman Jeffrey HolzbeierleinJeffrey Holzbeierlein , Brooke R. BixlerBrooke R. Bixler , David I. BuckleyDavid I. Buckley , Sam S. ChangSam S. Chang , Rebecca S. HolmesRebecca S. Holmes , Andrew C. JamesAndrew C. James , Erin KirkbyErin Kirkby , James M. McKiernanJames M. McKiernan , and Anne SchuckmanAnne Schuckman View All Author Informationhttps://doi.org/10.1097/JU.0000000000003981AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail Abstract Purpose: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. Methodology/Methods: In 2024, the MIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. Results: Updates were made regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. Conclusions: This guideline seeks to improve clinicians' ability to evaluate and treat patients with MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care. REFERENCES 1. . Cancer statistics, 2024. CA Cancer J Clin.2024; 74(1):12-49. doi. 10.3322/caac.21820 Crossref, Medline, Google Scholar 2. . Muscle-invasive bladder cancer: evaluating treatment and survival in the national cancer data base. BJU Int.2014; 114(5):719-726. doi. 10.1111/bju.12601 Crossref, Medline, Google Scholar 3. . Epidemiology and risk factors of urothelial bladder cancer. Eur Urol.2013; 63(2):234-241. doi. 10.1016/j.eururo.2012.07.033 Crossref, Medline, Google Scholar 4. . Bladder cancer collaborative stage variables and their data quality, usage, and clinical implications: a review of seer data, 2004-2010. Cancer.2014; 120(suppl 23):3815-3825. doi. 10.1002/cncr.29047 Crossref, Medline, Google Scholar 5. . Cancer statistics, 2017. CA Cancer J Clin.2017; 67(1):7-30. doi: 10.3322/caac.21387 Crossref, Medline, Google Scholar 6. . Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder. J Urol.2006; 176(4 Pt 1):1354-1362. doi. 10.1016/j.juro.2006.06.025 Link, Google Scholar 7. International Bladder Cancer Nomogram Consortium, . Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol.2006; 24:3967-3972. doi. 10.1200/JCO.2005.05.3884 Crossref, Medline, Google Scholar 8. . Efficacy of high-intensity local treatment for metastatic urothelial carcinoma of the bladder: a propensity score-weighted analysis from the national cancer data base. J Clin Oncol.2016; 34(29):3529-3536. doi. 10.1200/JCO.2016.66.7352 Crossref, Medline, Google Scholar 9. . Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of radiation therapy oncology group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol.2014; 32(34):3801-3809. doi. 10.1200/JCO.2014.57.5548 Crossref, Medline, Google Scholar 10. . Gender and bladder cancer: a collaborative review of etiology, biology, and outcomes. Eur Urol.2016; 69(2):300-310. doi. 10.1016/j.eururo.2015.08.037 Crossref, Medline, Google Scholar 11. . Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol.2005; 23(27):6533-6539. doi. 10.1200/JCO.2005.05.516 Crossref, Medline, Google Scholar 12. . Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol.2014; 11(7):400-410. doi. 10.1038/nrurol.2014.129 Crossref, Medline, Google Scholar 13. . Predictors of survival in patients with soft tissue surgical margin involvement at radical cystectomy. Ann Surg Oncol.2013; 20(3):1027-1034. doi. 10.1245/s10434-012-2708-5 Crossref, Medline, Google Scholar 14. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature.2014; 507:315. Crossref, Medline, Google Scholar 15. . A molecular taxonomy for urothelial carcinoma. Clin Cancer Res.2012; 18(12):3377-3386. doi. 10.1158/1078-0432.CCR-12-0077-T Crossref, Medline, Google Scholar 16. . Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell.2014; 25(2):152-165. doi. 10.1016/j.ccr.2014.01.009 Crossref, Medline, Google Scholar 17. . Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A.2014; 111(8):3110-3115. doi. 10.1073/pnas.1318376111 Crossref, Medline, Google Scholar 18. International Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party now the National Cancer Research Institute Bladder Cancer Clinical Studies Group, European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, Australian Bladder Cancer Study Group, National Cancer Institute of Canada Clinical Trials Group, Finnbladder, Norwegian Bladder Cancer Study Group, Club Urologico Espanol de Tratamiento Oncologico Group, , , , , , , , . International phase iii trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol.2011; 29(16):2171-2177. doi. 10.1200/JCO.2010.32.3139 Crossref, Medline, Google Scholar 19. . Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med.2003; 349(9):859-866. doi. 10.1056/NEJMoa022148 Crossref, Medline, Google Scholar 20. ; VESPER Trial Investigators. Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (vesper): survival endpoints at 5 years in an open-label, randomised, phase 3 study. Lancet Oncol.2024; 25(2):255-264. doi. 10.1016/S1470-2045(23)00587-9 Crossref, Medline, Google Scholar 21. . Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med.2021; 384(22):2102-2114. doi. 10.1056/NEJMoa2034442 Crossref, Medline, Google Scholar 22. ; IMvigor010 Study Group. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (imvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol.2021; 22(4):525-537. doi. 10.1016/S1470-2045(21)00004-8 Crossref, Medline, Google Scholar 23. . Ambassador alliance a031501: phase III randomized adjuvant study of pembrolizumab in muscle-invasive and locally advanced urothelial carcinoma (MIUC) vs observation. J Clin Oncol.2024; 42(4_suppl l):LBA531. doi. 10.1200/jco.2024.42.4_suppl.lba531 Crossref, Google Scholar 24. . Prostatic urethral biopsy has limited usefulness in counseling patients regarding final urethral margin status during orthotopic neobladder reconstruction. J Urol.2008; 180(1):164-167. doi. 10.1016/j.juro.2008.03.037 Link, Google Scholar 25. . The role of preoperative prostatic urethral biopsy in clinical decision-making at the time of radical cystectomy. Can J Urol.2014; 21(2):7228-7233. Medline, Google Scholar 26. . Accuracy of urethral frozen section during radical cystectomy for bladder cancer. Urol Oncol.2016; 34(12):532.e1-532.e6. doi. 10.1016/j.urolonc.2016.06.014 Crossref, Medline, Google Scholar 27. . Prospectively packaged lymph node dissections with radical cystectomy: evaluation of node count variability and node mapping. J Urol.2004; 172(4 Pt 1):1286-1290. doi. 10.1097/01.ju.0000137817.56888.d1 Link, Google Scholar 28. . Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol.2002; 167(3):1295-1298. doi. 10.1016/s0022-5347(05)65284-6 Link, Google Scholar 29. . Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the surveillance, epidemiology and end results program data base. J Urol.2003; 169(3):946-950. doi. 10.1097/01.ju.0000052721.61645.a3 Link, Google Scholar 30. . Role of pelvic lymph node dissection in lymph node-negative patients with invasive bladder cancer. Jpn J Clin Oncol.2010; 40(3):247-251. doi. 10.1093/jjco/hyp147 Crossref, Medline, Google Scholar 31. . The number of nodes removed as well as the template of the dissection is independently correlated to cancer-specific survival after radical cystectomy for muscle-invasive bladder cancer. Int Urol Nephrol.2013; 45(3):711-719. doi. 10.1007/s11255-013-0461-8 Crossref, Medline, Google Scholar 32. . Outcome after radical cystectomy with limited or extended pelvic lymph node dissection. J Urol.2008; 179(3):873-878. doi. 10.1016/j.juro.2007.10.076 Link, Google Scholar 33. . Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. J Urol.2011; 186(4):1261-1268. doi. 10.1016/j.juro.2011.06.004 Link, Google Scholar 34. . Stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy. Int J Urol.2013; 20(4):390-397. doi. 10.1111/j.1442-2042.2012.03148.x Crossref, Medline, Google Scholar 35. . Lymph node counts are valid indicators of the quality of surgical care in bladder cancer: a population-based study. Urol Oncol.2015; 33(10):425.e15-425.e23. doi. 10.1016/j.urolonc.2015.06.005 Crossref, Medline, Google Scholar 36. . Relationship of the number of removed lymph nodes to bladder cancer and competing mortality after radical cystectomy. Eur Urol.2014; 66(6):987-990. doi. 10.1016/j.eururo.2014.07.046 Crossref, Medline, Google Scholar 37. . Extended versus limited lymph node dissection in bladder cancer patients undergoing radical cystectomy: survival results from a prospective, randomized trial. Eur Urol.2019; 75(4):604-611. doi. 10.1016/j.eururo.2018.09.047 Crossref, Medline, Google Scholar 38. . Adequate pelvic lymph node dissection in radical cystectomy in the era of neoadjuvant chemotherapy: a meta-analysis and systematic review. Cancers (Basel).2023; 15(16):4040. doi. 10.3390/cancers15164040 Crossref, Medline, Google Scholar 39. . Relationship between the number of lymph nodes dissected and prognosis in muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy. Int J Urol.2022; 29(11):1264-1270. doi. 10.1111/iju.14974 Crossref, Medline, Google Scholar 40. . The influence of lymph node count on oncological outcome of radical cystectomy in chemotherapy pre-treated and chemotherapy-naïve patients with muscle invasive bladder cancer. J Clin Med.2021; 10(21):4923. doi. 10.3390/jcm10214923 Crossref, Medline, Google Scholar 41. . Contemporary trends and efficacy of pelvic lymph node dissection at radical cystectomy for urothelial and variant histology carcinoma of the urinary bladder. Clin Genitourin Cancer.2022; 20(2):195.e1-195.e8. doi. 10.1016/j.clgc.2021.10.010 Crossref, Medline, Google Scholar 42. . Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish vesical cancer group. Scand J Urol Nephrol Supplementum.1991; 138:193-201. Crossref, Medline, Google Scholar 43. . Radical cystectomy versus bladder-preserving therapy for muscle-invasive urothelial carcinoma: examining confounding and misclassification Biasin cancer observational comparative effectiveness research. Value Health.2013; 16(4):610-618. doi. 10.1016/j.jval.2013.01.005 Crossref, Medline, Google Scholar 44. . Effects of age and comorbidity on treatment and survival of patients with muscle-invasive bladder cancer. Int J Cancer.2014; 135(4):905-912. doi. 10.1002/ijc.28716 Crossref, Medline, Google Scholar 45. . Similar treatment outcomes for radical cystectomy and radical radiotherapy in invasive bladder cancer treated at a United Kingdom specialist treatment center. Int J Radiat Oncol Biol Phys.2008; 70(2):456-463. doi. 10.1016/j.ijrobp.2007.06.030 Crossref, Medline, Google Scholar 46. . Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis. Lancet Oncol.2023; 24(6):669-681. doi. 10.1016/S1470-2045(23)00170-5 Crossref, Medline, Google Scholar 47. . Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the mgh experience. Eur Urol.2012; 61(4):705-711. doi. 10.1016/j.eururo.2011.11.010 Crossref, Medline, Google Scholar 48. . Phase 1 study of chemoradiotherapy combined with Nivolumab ± Ipilimumab for the curative treatment of muscle-invasive bladder cancer. Eur Urol.2022; 82(5):518-526. doi. 10.1016/j.eururo.2022.07.009 Crossref, Medline, Google Scholar 49. . Open vs robot-assisted radical cystectomy (BORARC): a double-blinded, randomised feasibility study. BJU Int.2022; 130(1):102-113. doi. 10.1111/bju.15619 Crossref, Medline, Google Scholar 50. . Quality of life and secondary outcomes for open versus robot-assisted radical cystectomy: a double-blinded, randomised feasibility trial. World J Urol.2022; 40(7):1669-1677. doi. 10.1007/s00345-022-04029-9 Crossref, Medline, Google Scholar 51. . SWOG S1011: a phase III surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at time of radical cystectomy for muscle invasive urothelial cancer. J Clin Oncol.2023; 41(16_suppl l):4508. doi. 10.1200/jco.2023.41.16_suppl.4508 Crossref, Google Scholar The complete unabridged version of the guideline is available at https://www.jurology.com. This document is being printed as submitted, independent of standard editorial or peer review by the editors of The Journal of Urology®. Amendment Panel Disclosures 2024: Consultant/Advisor: Jeffrey M. Holzbeierlein, Janssen Oncology; Sam S. Chang, GLG, Janssenn, BMS, Pfizer, Urogen, Virtuoso Surgical, mIR, Prokarium, KDx Diagnostics, Tu Therapeutics, Lantheus, Merck, Pacific Edge, Nonagen; James M. McKiernan, mIR Scientific; Anne K. Schuckman, vyriad Meeting Participant or Lecturer: Anne K. Schuckman, Photocure, Fergene Scientific Study or Trial: Jeffrey M. Holzbeierlein, MDx Health, Astellas Medivation; Sam S. Chang, NIH, NantBio; Anne K. Schuckman, Urogen Health Publishing: Sam S. Chang, Uro Today © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Supplementary Materials Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Keywordsurinary bladder neoplasmsradiotherapycystectomydrug therapyMetrics Author Information Jeffrey Holzbeierlein More articles by this author Brooke R. Bixler More articles by this author David I. Buckley More articles by this author Sam S. Chang More articles by this author Rebecca S. Holmes More articles by this author Andrew C. James More articles by this author Erin Kirkby More articles by this author James M. McKiernan More articles by this author Anne Schuckman More articles by this author Expand All The complete unabridged version of the guideline is available at https://www.jurology.com. This document is being printed as submitted, independent of standard editorial or peer review by the editors of The Journal of Urology®. Amendment Panel Disclosures 2024: Consultant/Advisor: Jeffrey M. Holzbeierlein, Janssen Oncology; Sam S. Chang, GLG, Janssenn, BMS, Pfizer, Urogen, Virtuoso Surgical, mIR, Prokarium, KDx Diagnostics, Tu Therapeutics, Lantheus, Merck, Pacific Edge, Nonagen; James M. McKiernan, mIR Scientific; Anne K. Schuckman, vyriad Meeting Participant or Lecturer: Anne K. Schuckman, Photocure, Fergene Scientific Study or Trial: Jeffrey M. Holzbeierlein, MDx Health, Astellas Medivation; Sam S. Chang, NIH, NantBio; Anne K. 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