Bladder-sparing treatment in MIBC: where do we stand?

INTRODUCTION The gold-standard treatment of muscle-invasive bladder cancer is radical cystectomy (RC), but this can be associated with morbidity and perioperative risks. Patients may not be fit for RC or choose to preserve their bladders. There are evolving bladder-sparing treatments that are often delivered in a multimodal approach. Here, we aim to review recent advances in bladder-sparing treatments. EVIDENCE ACQUISITION We undertook a narrative review informed by a Medline/PubMed literature search using a combination of terms for recent (5 years) articles in English. Relevant studies from authors' bibliographies were retrieved. EVIDENCE SYNTHESIS Bladder-sparing treatment consists of transurethral resection of bladder tumour (TURBT), radiotherapy and chemotherapy. Experimental approaches with immunotherapy and using gene signatures for radiation therapy and chemotherapy response are being explored. CONCLUSIONS Bladder-sparing treatment is an option for patients with bladder cancer. Those who may benefit most are those with solitary invasive cancers, those with good bladder capacity and compliance, those who choose to preserve their bladder and sexual function and who are not fit for RC. Multimodal bladder-sparing approaches may have comparable oncological outcomes to RC and so appear an attractive alternative in suitable patients.

[1]  K. Kihara,et al.  Impact of Immunohistochemistry-Based Subtypes in Muscle-Invasive Bladder Cancer on Response to Chemoradiation Therapy. , 2018, International journal of radiation oncology, biology, physics.

[2]  D. Tyler,et al.  Comparing Survival Outcomes and Costs Associated With Radical Cystectomy and Trimodal Therapy for Older Adults With Muscle-Invasive Bladder Cancer , 2018, JAMA surgery.

[3]  A. Feber,et al.  Robot-assisted radical cystectomy with intracorporeal urinary diversion versus open radical cystectomy (iROC): protocol for a randomised controlled trial with internal feasibility study , 2018, BMJ Open.

[4]  G. Guazzoni,et al.  Long-term outcomes of high-grade T1 bladder cancer treated with intravesical bacillus Calmette-Guérin: experience of a single center. , 2018, Minerva urologica e nefrologica = The Italian journal of urology and nephrology.

[5]  James B. Yu,et al.  Bladder Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer , 2018, Current Oncology Reports.

[6]  L. Reis,et al.  Muscle-invasive bladder cancer organ-preserving therapy: systematic review and meta-analysis , 2018, World Journal of Urology.

[7]  I. Thompson,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 , 2018, The Lancet.

[8]  A. Masson-Lecomte,et al.  Development of immunotherapy in bladder cancer: present and future on targeting PD(L)1 and CTLA-4 pathways , 2018, World Journal of Urology.

[9]  L. Eapen,et al.  Radiotherapy with radical cystectomy for bladder cancer: A systematic review and meta-analysis. , 2018, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[10]  A. Feber,et al.  Multidomain Quantitative Recovery Following Radical Cystectomy for Patients Within the Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion Versus Open Radical Cystectomy Randomised Controlled Trial: The First 30 Patients. , 2018, European urology.

[11]  Byron C. Jaeger,et al.  Impact of bladder cancer on health‐related quality of life , 2018, BJU international.

[12]  M. Amin,et al.  Updates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers. , 2018, European Urology.

[13]  W. Mackillop,et al.  Bladder-sparing Radiotherapy for Muscle-invasive Bladder Cancer: A Qualitative Study to Identify Barriers and Enablers. , 2017, Clinical oncology (Royal College of Radiologists (Great Britain)).

[14]  J. McKiernan,et al.  Systematic Review and Meta-Analysis on the Efficacy of Chemotherapy with Transurethral Resection of Bladder Tumors as Definitive Therapy for Muscle Invasive Bladder Cancer , 2017, Bladder cancer.

[15]  K. Hoadley,et al.  Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. , 2017, European urology.

[16]  K. Pang,et al.  Opportunities of next-generation sequencing in non-muscle invasive bladder cancer outcome prediction , 2017, Translational andrology and urology.

[17]  Xiaozhi Zhao,et al.  Transperineal cryotherapy for unresectable muscle invasive bladder cancer: preliminary experience with 7 male patients , 2017, BMC Urology.

[18]  Yair Lotan,et al.  Treatment of Non‐Metastatic Muscle‐Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline , 2017, The Journal of urology.

[19]  J. Catto,et al.  Prospective Implementation of Enhanced Recovery After Surgery Protocols to Radical Cystectomy. , 2017, European urology.

[20]  T. H. van der Kwast,et al.  Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Muhammad S. Khan,et al.  Landmarks in the treatment of muscle-invasive bladder cancer , 2017, Nature Reviews Urology.

[22]  A. Niemierko,et al.  Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy. , 2017, European urology.

[23]  Ananya Choudhury,et al.  A Gene Signature for Selecting Benefit from Hypoxia Modification of Radiotherapy for High-Risk Bladder Cancer Patients , 2017, Clinical Cancer Research.

[24]  Young Seok Kim,et al.  Comparison of outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer: a propensity score matching analysis , 2017, Oncotarget.

[25]  E. Pietzak The Impact of Blue Light Cystoscopy on the Diagnosis and Treatment of Bladder Cancer , 2017, Current Urology Reports.

[26]  T. Powles,et al.  A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now. , 2017, Cancer treatment reviews.

[27]  S. Culine,et al.  Pembrolizumab as Second‐Line Therapy for Advanced Urothelial Carcinoma , 2017, The New England journal of medicine.

[28]  W. Sameh,et al.  Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients , 2016, Ecancermedicalscience.

[29]  E. Horwitz,et al.  Bladder Preservation Therapy: A Review of the Literature and Future Directions. , 2016, Urology.

[30]  A. Breda,et al.  Robot assisted retroperitoneal lymph-node dissection after adjuvant therapy: different indications. , 2016, Minerva urologica e nefrologica = The Italian journal of urology and nephrology.

[31]  I. Gill,et al.  Contemporary evidence for robot-assisted radical cystectomy for treating bladder cancer , 2016, Nature Reviews Urology.

[32]  J. Overgaard,et al.  The impact of hypoxia and its modification of the outcome of radiotherapy , 2016, Journal of radiation research.

[33]  G. Gakis,et al.  Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non-Muscle Invasive Bladder Cancer , 2016, Bladder cancer.

[34]  B. Bochner,et al.  Enhanced Recovery after Urological Surgery: A Contemporary Systematic Review of Outcomes, Key Elements, and Research Needs. , 2016, European urology.

[35]  M. Kaag,et al.  Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis. , 2016, The oncologist.

[36]  P. Dasgupta,et al.  A Single-centre Early Phase Randomised Controlled Three-arm Trial of Open, Robotic, and Laparoscopic Radical Cystectomy (CORAL). , 2016, European urology.

[37]  A. Goenka,et al.  Quality of Life Outcomes for Bladder Cancer Patients Undergoing Bladder Preservation with Radiotherapy , 2015, Current Urology Reports.

[38]  E. Carosella,et al.  A Systematic Review of Immunotherapy in Urologic Cancer: Evolving Roles for Targeting of CTLA-4, PD-1/PD-L1, and HLA-G. , 2015, European urology.

[39]  A. Kamat,et al.  Nonurothelial bladder cancer and rare variant histologies. , 2015, Hematology/oncology clinics of North America.

[40]  Ronald C. Chen,et al.  Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer. , 2015, International journal of radiation oncology, biology, physics.

[41]  R. Mak,et al.  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. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  Jianlin Yuan,et al.  Computed tomography imaging-guided percutaneous argon-helium cryoablation of muscle-invasive bladder cancer: initial experience in 32 patients. , 2014, Cryobiology.

[43]  J. Coebergh,et al.  Effects of age and comorbidity on treatment and survival of patients with muscle‐invasive bladder cancer , 2014, International journal of cancer.

[44]  Nicholas D James,et al.  Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. , 2014, European urology.

[45]  Katherine A. Hoadley,et al.  Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology , 2014, Proceedings of the National Academy of Sciences.

[46]  K. Baggerly,et al.  Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. , 2014, Cancer cell.

[47]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of urothelial bladder carcinoma , 2014, Nature.

[48]  Dieter Jocham,et al.  Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. , 2013, European urology.

[49]  S. Porten,et al.  Should histologic variants alter definitive treatment of bladder cancer? , 2013, Current opinion in urology.

[50]  A. Zietman,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 2 trial. , 2013, The Lancet. Oncology.

[51]  J. Catto,et al.  Competing mortality in patients diagnosed with bladder cancer: evidence of undertreatment in the elderly and female patients , 2013, British Journal of Cancer.

[52]  S. Culine,et al.  Combined chemoradiation therapy with twice-weekly gemcitabine and cisplatin for organ preservation in muscle-invasive bladder cancer: long-term results of a phase 1 trial. , 2012, International journal of radiation oncology, biology, physics.

[53]  Mårten Fernö,et al.  A Molecular Taxonomy for Urothelial Carcinoma , 2012, Clinical Cancer Research.

[54]  Emma Hall,et al.  Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. , 2012, The New England journal of medicine.

[55]  A. Niemierko,et al.  Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. , 2012, European urology.

[56]  A. Qayyum,et al.  Clinical Investigation : Genitourinary Cancer Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node e Negative Invasive Bladder Cancer : Single-Institution Experience , 2012 .

[57]  J. Efstathiou,et al.  Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer. , 2012, The Journal of urology.

[58]  N. Vasdev,et al.  Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer , 2011, Current Urology.

[59]  G. Sonpavde,et al.  A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. , 2011, The Lancet. Oncology.

[60]  P. Hoskin,et al.  Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[61]  Ananya Choudhury,et al.  MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. , 2010, Cancer research.

[62]  E. Solsona,et al.  Feasibility of radical transurethral resection as monotherapy for selected patients with muscle invasive bladder cancer. , 2010, The Journal of urology.

[63]  J. Wolchok,et al.  Preoperative CTLA-4 Blockade: Tolerability and Immune Monitoring in the Setting of a Presurgical Clinical Trial , 2010, Clinical Cancer Research.

[64]  A. Zietman,et al.  Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. , 2009, Urology.

[65]  P. Hoskin,et al.  Carbogen and nicotinamide in locally advanced bladder cancer: early results of a phase-III randomized trial. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[66]  A. Vickers,et al.  Impact of renal impairment on eligibility for adjuvant cisplatin‐based chemotherapy in patients with urothelial carcinoma of the bladder , 2006, Cancer.

[67]  J Alfred Witjes,et al.  Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. , 2006, European urology.

[68]  R. Kuefer,et al.  Effect of a pT0 cystectomy specimen without neoadjuvant therapy on survival , 2005, Cancer.

[69]  K. Kurth,et al.  Role of urothelial cells in BCG immunotherapy for superficial bladder cancer , 2004, British Journal of Cancer.

[70]  J. Dunst,et al.  Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[71]  A. Zietman,et al.  Selective bladder preservation by combined modality protocol treatment: long-term outcomes of 190 patients with invasive bladder cancer. , 2002, Urology.

[72]  S. Groshen,et al.  Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  D. Grignon,et al.  Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival. , 2000, The American journal of surgical pathology.

[74]  B. Donnelly,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. , 1998, The Journal of urology.

[75]  I. Tannock,et al.  Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  A. Pollack,et al.  Muscle-invasive bladder cancer treated with external beam radiotherapy: prognostic factors. , 1994, International journal of radiation oncology, biology, physics.

[77]  A. Einstein,et al.  Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery. , 1987, JAMA.

[78]  V. F. Marshall,et al.  The prognosis with untreated bladder tumors , 1956, Cancer.

[79]  F. Soria,et al.  Salvage radical cystectomy after radiotherapy: A more complicated procedure? , 2017 .

[80]  Jacques Ferlay,et al.  Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. , 2017, European urology.

[81]  G. Hidas,et al.  Radical cystectomy vs. chemoradiation in T2-4aN0M0 bladder cancer: a case-control study. , 2015, Urologic oncology.

[82]  B. Bochner,et al.  Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. , 2009, European urology.

[83]  H. Herr,et al.  Transurethral resection of muscle-invasive bladder cancer: 10-year outcome. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.