Skip to main content

Advertisement

Log in

Current Landscape and Future Directions on Bladder Sparing Approaches to Muscle-Invasive Bladder Cancer

  • Genitourinary Cancers (S Gupta, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Although radical cystectomy is considered the gold standard approach for patients with muscle-invasive bladder cancer, tri-modal therapy (TMT) is a well-tolerated and efficacious alternative to radical cystectomy that is underutilized in inoperable patients and rarely offered to cystectomy candidates in the USA. Retrospective data suggest similar outcomes between radical cystectomy and TMT after adjusting for patient selection and other confounding factors. Nearly 70–80% of patients can keep their native bladder with favorable post-treatment quality of life metrics. Current trials are investigating novel combination strategies including immune checkpoint inhibition along with chemoradiation or radiation. Emerging techniques for improved patient selection and risk stratification include incorporating MP-MRI, and novel biomarkers such as inflammatory, stromal, and DNA damage response gene signatures may guide patient selection and expand the landscape of bladder preservation options available to patients in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.

    PubMed  Google Scholar 

  2. Liberman D, Lughezzani G, Sun M, Alasker A, Thuret R, Abdollah F, et al. Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder. 2011;77(3):660–6. https://doi.org/10.1016/j.urology.2010.07.537.

  3. Megwalu II, Vlahiotis A, Radwan M, Piccirillo JF, Kibel AS. Prognostic impact of comorbidity in patients with bladder cancer. Eur Urol. 2008;53(3):581–9. https://doi.org/10.1016/j.eururo.2007.10.069.

  4. Gray PJ, Fedewa SA, Shipley WU, Efstathiou JA, Lin CC, Zietman AL, et al. Use of potentially curative therapies for muscle-invasive bladder cancer in the United States: results from the National Cancer Data Base. Eur Urol. 2013;63(5):823–9.

    Article  PubMed  Google Scholar 

  5. National Comprehensive Cancer Network. Bladder Cancer (Version 2019). http://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed 20 Nov 2020.

  6. Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol. 2017;198(3):552–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. EAU Guidelines. Edn. presented at the EAU Annual Congress Copenhagen 2018. ISBN 978-94-92671-01-1.

  8. Ericson KJ, Murthy PB, Bryk DJ, Ramkumar RR, Broughman JR, Khanna A, et al. Bladder-sparing treatment of nonmetastatic muscle-invasive bladder cancer. Clin Adv Hematol Oncol. 2019;17(12):697–707.

    PubMed  Google Scholar 

  9. Rödel C, Grabenbauer GG, Kühn R, Papadopoulos T, Dunst J, Meyer M, et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol. 2002;20(14):3061–71. https://doi.org/10.1200/JCO.2002.11.027.

  10. Efstathiou JA, Spiegel DY, Shipley WU, Heney NM, Kaufman DS, Niemierko A, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol. 2012;61(4):705–11. https://doi.org/10.1016/j.eururo.2011.11.010.

  11. Panebianco V, Narumi Y, Altun E, Bochner BH, Efstathiou JA, Hafeez S, et al. Multiparametric magnetic resonance imaging for bladder cancer: development of VI-RADS (Vesical imaging-reporting and data system). Eur Urol. 2018;74(3):294–306.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Replacement of a surgical procedure called transurethral resection of bladder tumour with a painless imaging procedure called magnetic resonance imaging in patients with muscle invasive bladder cancer (ISRCTN35296862).

  13. Gospodarowicz MK, Hawkins NV, Rawlings GA, Connolly JG, Jewett MA, Thomas GM, et al. Radical radiotherapy for muscle invasive transitional cell carcinoma of the bladder: failure analysis. J Urol. 1989;142(6):1448–53 discussion 53-4.

  14. Kaufman DS, Shipley WU, Griffin PP, Heney NM, Althausen AF, Efird JT. Selective bladder preservation by combination treatment of invasive bladder cancer. N Engl J Med. 1993;329(19):1377–82. https://doi.org/10.1056/NEJM199311043291903.

  15. Stimson CJ, Cookson MS, Barocas DA, Clark PE, Humphrey JE, Patel SG, et al. Preoperative hydronephrosis predicts extravesical and node positive disease in patients undergoing cystectomy for bladder cancer. J Urol. 2010;183(5):1732–7.

    Article  CAS  PubMed  Google Scholar 

  16. Mak KS, Smith AB, Eidelman A, Clayman R, Niemierko A, Cheng JS, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. Int J Radiat Oncol Biol Phys. 2016;96(5):1028–36.

    Article  PubMed  Google Scholar 

  17. Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, et al. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of radiation therapy oncology group 89-03. J Clin Oncol Off J Am Soc Clin Oncol. 1998;16(11):3576–83.

    Article  CAS  Google Scholar 

  18. James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012;366(16):1477–88.

    Article  CAS  PubMed  Google Scholar 

  19. • Coen JJ, Zhang P, Saylor PJ, Lee CT, Wu CL, Parker W, et al. Bladder preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase II trial. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(1):44–51 A randomized, phase II trial investigating platinum-free chemotherapy regimens.

    Article  CAS  Google Scholar 

  20. Michaelson MD, Hu C, Pham HT, Dahl DM, Lee-Wu C, Swanson GP, et al. A phase 1/2 trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation after transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer (trial NRG oncology RTOG 0524). Int J Radiat Oncol Biol Phys. 2017;97(5):995–1001.

    Article  CAS  PubMed  Google Scholar 

  21. Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu C-L, et al. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase. Lancet Oncol. 2013;14(9):863–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dose dense gemcitabine and cisplatin without cystectomy for patients with muscle invasive bladder urothelial cancer and select genetic alterations (A031701).

  23. Cowan RA, McBain CA, Ryder WD, Wylie JP, Logue JP, Turner SL, et al. Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(1):197–207.

    Article  PubMed  Google Scholar 

  24. Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009;55(1):164–74.

    Article  PubMed  Google Scholar 

  25. Eswara JR, Efstathiou JA, Heney NM, Paly J, Kaufman DS, McDougal WS, et al. Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer. J Urol. 2012;187(2):463–8.

    Article  PubMed  Google Scholar 

  26. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41.

    Article  PubMed  Google Scholar 

  27. Kramer S, Gelber RD, Snow JB, Marcial VA, Lowry LD, Davis LW, et al. Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the radiation therapy oncology group. Head Neck Surg. 1987;10(1):19–30.

    Article  CAS  PubMed  Google Scholar 

  28. Landoni F, Colombo A, Milani R, Placa F, Zanagnolo V, Mangioni C. Randomized study between radical surgery and radiotherapy for the treatment of stage IB-IIA cervical cancer: 20-year update. J Gynecol Oncol. 2017;28(3):e34.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Leichman L, Nigro N, Vaitkevicius VK, Considine B, Buroker T, Bradley G, et al. Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med. 1985;78(2):211–5.

    Article  CAS  PubMed  Google Scholar 

  30. Büchser D, Zapatero A, Rogado J, Talaya M, Martín de Vidales C, Arellano R, et al. Long-term outcomes and patterns of failure following trimodality treatment with bladder preservation for invasive bladder cancer. Urology. 2019;124:183–90.

    Article  PubMed  Google Scholar 

  31. Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, et al. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009;27(25):4055–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zietman AL, Sacco D, Skowronski U, Gomery P, Kaufman DS, Clark JA, et al. Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. J Urol. 2003;170(5):1772–6.

    Article  PubMed  Google Scholar 

  33. Huddart RA, Hall E, Lewis R, Birtle A. Life and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int. 2010;106(6):753–5.

    Article  PubMed  Google Scholar 

  34. Bekelman JE, Handorf EA, Guzzo T, Evan Pollack C, Christodouleas J, Resnick MJ, et al. 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):610–8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Vashistha V, Wang H, Mazzone A, Liss MA, Svatek RS, Schleicher M, et al. Radical cystectomy compared to combined modality treatment for muscle-invasive bladder cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys. 2017;97(5):1002–20.

    Article  PubMed  Google Scholar 

  36. Zehnder P, Studer UE, Skinner EC, Dorin RP, Cai J, Roth B, et al. Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. J Urol. 2011;186(4):1261–8. https://doi.org/10.1016/j.juro.2011.06.004.

  37. Canter D, Long C, Kutikov A, Plimack E, Saad I, Oblaczynski M, et al. Clinicopathological outcomes after radical cystectomy for clinical T2 urothelial carcinoma: further evidence to support the use of neoadjuvant chemotherapy. BJU Int. 2011;107(1):58–62.

    Article  PubMed  Google Scholar 

  38. Giacalone NJ, Shipley WU, Clayman RH, Niemierko A, Drumm M, Heney NM, et al. Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the Massachusetts General Hospital experience. Eur Urol. 2017;71(6):952–60.

    Article  PubMed  Google Scholar 

  39. Chemoradiotherapy with or without atezolizumab in treating patients with localized muscle invasive bladder cancer (S1806).

  40. Efficacy and safety of pembrolizumab (MK-3475) in combination with chemoradiotherapy (CRT) versus CRT alone in muscle-invasive bladder cancer (MIBC) (MK-3475-992/KEYNOTE-992).

  41. Nivolumab plus chemoradiotherapy in patients with muscle-invasive bladder cancer (MIBC) not undergoing cystectomy (REQ-0000020479).

  42. Weickhardt AJ, Foroudi F, Lawrentschuk N, Galleta L, Seegum A, Herschtal A, et al. Pembrolizumab with chemoradiotherapy as treatment for muscle invasive bladder cancer: a planned interim analysis of safety and efficacy of the PCR-MIB phase II clinical trial (ANZUP 1502). J Clin Oncol. 2020;38:485.

    Article  Google Scholar 

  43. Atezolizumab after chemo-radiotherapy for MIBC patients not eligible for radical cystectomy (UC-0160/1715).

  44. Cuellar MA, Medina A, Girones R, Valderrama BP, Font A, Juan-fita MJ, et al. Phase II trial of durvalumab plus tremelimumab with concurrent radiotherapy as bladder-sparing therapy in patients with localized muscle invasive bladder cancer: a SOGUG study. J Clin Oncol. 2020;38:TPS5097-TPS.

  45. Vázquez-Estévez S, Fernandez Calvo O, Alvarez-Fernandez C, Bonfill T, Domenech M, GarcIa SAnchez J, et al. Efficacy of atezolizumab concurrent with radiotherapy in patients with muscle-invasive bladder cancer (MIBC) (SOGUG-2017-A-IEC(VEJ)-4). J Clin Oncol. 2020;38:TPS601-TPS.

  46. Kiss B, Volkmer AK, Feng D, McKenna KM, Mihardja S, Chao M, et al. Magrolimab and gemcitabine-cisplatin combination enhance phagocytic elimination of bladder cancer. J Clin Oncol. 2020;38:e17035-e.

  47. Matsuo T, Miyata Y, Mitsunari K, Ohba K, Sakai H. Long-term outcomes of patients with locally advanced bladder cancer that underwent intra-arterial chemotherapy with/without radiotherapy for organ preservation. J Clin Oncol. 2020;38:574.

    Article  Google Scholar 

  48. Choudhury A, Nelson LD, Teo MTW, Chilka S, Bhattarai S, Johnston CF, et al. MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res. 2010;70(18):7017–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kawashima A, Nakayama M, Kakuta Y, Abe T, Hatano K, Mukai M, et al. Excision repair cross-complementing group 1 may predict the efficacy of chemoradiation therapy for muscle-invasive bladder cancer. Clin Cancer Res. 2011;17(8):2561–9.

    Article  CAS  PubMed  Google Scholar 

  50. Efstathiou JA, Mouw KW, Gibb EA, Liu Y, Wu C-L, Drumm MR, et al. Impact of immune and stromal infiltration on outcomes following bladder-sparing trimodality therapy for muscle-invasive bladder cancer. Eur Urol. 2019;76:59–68.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Batista da Costa J, Gibb EA, Bivalacqua TJ, Liu Y, Oo HZ, Miyamoto DT, et al. Molecular characterization of neuroendocrine-like bladder cancer. Clin Cancer Res. 2019:clincanres.3558.2018.

  52. Grivas P, Bismar TA, Alva AS, Huang H-C, Liu Y, Seiler R, et al. Validation of a neuroendocrine-like classifier confirms poor outcomes in patients with bladder cancer treated with cisplatin-based neoadjuvant chemotherapy. Urol Oncol. 2020;38:262–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Omar Y. Mian MD, PhD.

Ethics declarations

Conflict of Interest

James R. Broughman declares that he has no conflict of interest. Winston Vuong declares that he has no conflict of interest. Omar Y. Mian declares that he has no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Genitourinary Cancers

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Broughman, J.R., Vuong, W. & Mian, O.Y. Current Landscape and Future Directions on Bladder Sparing Approaches to Muscle-Invasive Bladder Cancer. Curr. Treat. Options in Oncol. 22, 3 (2021). https://doi.org/10.1007/s11864-020-00800-5

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11864-020-00800-5

Keywords

Navigation