title: Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review.
abstract: BACKGROUND
  Aims of bladder preservation in muscle-invasive bladder cancer (MIBC) are to offer a quality-of-life advantage and avoid potential morbidity or mortality of radical cystectomy (RC) without compromising oncologic outcomes. Because of the lack of a completed randomised controlled trial, oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown.
  
  
  OBJECTIVE
  This systematic review sought to assess the modern bladder-preservation treatment modalities, focusing on trimodal therapy (TMT) in MIBC.
  
  
  METHODS
  A systematic literature search in the PubMed and Cochrane databases was performed from 1980 to July 2013.
  
  
  RESULTS
  Optimal bladder-preservation treatment includes a safe transurethral resection of the bladder tumour as complete as possible followed by radiation therapy (RT) with concurrent radiosensitising chemotherapy. A standard radiation schedule includes external-beam RT to the bladder and limited pelvic lymph nodes to an initial dose of 40 Gy, with a boost to the whole bladder to 54 Gy and a further tumour boost to a total dose of 64-65 Gy. Radiosensitising chemotherapy with phase 3 trial evidence in support exists for cisplatin and mitomycin C plus 5-fluorouracil. A cystoscopic assessment with systematic rebiopsy should be performed at TMT completion or early after TMT induction. Thus, nonresponders are identified early to promptly offer salvage RC. The 5-yr cancer-specific survival and overall survival rates range from 50% to 82% and from 36% to 74%, respectively, with salvage cystectomy rates of 25-30%. There are no definitive data to support the benefit of using of neoadjuvant or adjuvant chemotherapy. Critical to good outcomes is proper patient selection. The best cancers eligible for bladder preservation are those with low-volume T2 disease without hydronephrosis or extensive carcinoma in situ.
  
  
  CONCLUSIONS
  A growing body of accumulated data suggests that bladder preservation with TMT leads to acceptable outcomes and therefore may be considered a reasonable treatment option in well-selected patients.
  
  
  RESULTS
  Treatment based on a combination of resection, chemotherapy, and radiotherapy as bladder-sparing strategies may be considered as a reasonable treatment option in properly selected patients.
authors.affiliation: Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, Canada; Department of Urology, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ploussard
authors.affiliation: University of Southern California Institute of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: Siamak
authors.initials: S
authors.lastname: Daneshmand
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
authors.affiliation: Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Harry W
authors.initials: HW
authors.lastname: Herr
authors.affiliation: University of Birmingham, School of Cancer Sciences, Edgbaston, Birmingham, UK.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
authors.affiliation: Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Claus M
authors.initials: CM
authors.lastname: Rödel
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.affiliation: Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.affiliation: Department of Urology, University of Berne, Berne, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, Canada. Electronic address: wassim.kassouf@muhc.mcgill.ca.
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D015653:Cystectomy; D006801:Humans; D009130:Muscle, Smooth / Q000473:pathology*; D009361:Neoplasm Invasiveness; D059351:Organ Sparing Treatments; D018579:Patient Selection; D011878:Radiotherapy; D016879:Salvage Therapy; D015996:Survival Rate; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000601:surgery / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents
keywords: Chemoradiotherapy; Chemotherapy; Cystectomy; Organ sparing treatments; Outcome assessment; Radiotherapy; Urinary bladder neoplasms