title: Refining patient selection for neoadjuvant chemotherapy before radical cystectomy.
abstract: OBJECTIVE
  We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy.
  
  
  METHODS
  We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings.
  
  
  RESULTS
  We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged.
  
  
  CONCLUSIONS
  The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity.
authors.affiliation: Department of Urology, University of Virginia, Charlottesville, Virginia, California.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Culp
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Rian J
authors.initials: RJ
authors.lastname: Dickstein
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Shanna M
authors.initials: SM
authors.lastname: Pretzsch
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Sima
authors.initials: S
authors.lastname: Porten
authors.affiliation: University of Southern California Institute of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Siamak
authors.initials: S
authors.lastname: Daneshmand
authors.affiliation: University of Southern California Institute of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: University of Southern California Institute of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Arlene
authors.initials: A
authors.lastname: Siefker-Radtke
authors.affiliation: Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Czerniak
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Neema
authors.initials: N
authors.lastname: Navai
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Wszolek
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.affiliation: Department of Urology, University of Texas M.D. Anderson Cancer Center, Los Angeles, California. Electronic address: cdinney@mdanderson.org.
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018579:Patient Selection; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents
keywords: 3-D; 3-dimensional; BC; CSM; DSS; EUA; HR; LR; LVI; MDACC; MIBC; NAC; OS; PFS; RC; TUR; USC; University of Southern California; University of Texas M.D. Anderson Cancer Center; VH; bladder cancer; cause specific mortality; cystectomy; disease specific survival; examination under anesthesia; high risk; low risk; lymphovascular invasion; muscle invasive bladder cancer; neoadjuvant chemotherapy; neoadjuvant therapy; outcomes assessment; overall survival; progression-free survival; radical cystectomy; risk; transurethral resection; urinary bladder neoplasms; variant histology
references.citation: J Urol. 2004 Feb;171(2 Pt 1):561-9
references.pmid: 14713760
references.citation: Urology. 2001 Jun;57(6):1063-6; discussion 1066-7
references.pmid: 11377305
references.citation: J Clin Oncol. 2001 Feb 1;19(3):666-75
references.pmid: 11157016
references.citation: Eur Urol. 2013 Aug;64(2):307-13
references.pmid: 22564397
references.citation: J Urol. 2006 Jun;175(6):2048-53; discussion 2053
references.pmid: 16697800
references.citation: J Clin Oncol. 2009 Jun 1;27(16):2592-7
references.pmid: 19414678
references.citation: Int Braz J Urol. 2007 Jan-Feb;33(1):25-31; discussion 31-2
references.pmid: 17335595
references.citation: BJU Int. 2005 Apr;95(6):786-90
references.pmid: 15794783
references.citation: Urol Oncol. 2003 Nov-Dec;21(6):464-7
references.pmid: 14693274
references.citation: Urology. 1992 Jan;39(1):12-6
references.pmid: 1728789
references.citation: BJU Int. 2011 Jan;107(1):58-62
references.pmid: 20560950
references.citation: Cancer. 2007 Jul 1;110(1):62-7
references.pmid: 17542024
references.citation: Urol Oncol. 2009 Sep-Oct;27(5):491-5
references.pmid: 18657452
references.citation: J Natl Cancer Inst. 2013 Apr 3;105(7):499-503
references.pmid: 23411591
references.citation: J Urol. 2006 Aug;176(2):486-92; discussion 491-2
references.pmid: 16813874
references.citation: J Urol. 2004 Aug;172(2):481-4
references.pmid: 15247709
references.citation: Lancet. 2003 Jun 7;361(9373):1927-34
references.pmid: 12801735
references.citation: J Clin Oncol. 1988 Oct;6(10):1590-6
references.pmid: 3171626
references.citation: BJU Int. 2008 Sep;102(8):952-7
references.pmid: 18485042
references.citation: J Clin Oncol. 2005 Sep 20;23(27):6533-9
references.pmid: 16116151
references.citation: J Clin Oncol. 2001 Oct 15;19(20):4005-13
references.pmid: 11600601
references.citation: BJU Int. 2009 Feb;103(4):475-9
references.pmid: 18990174
references.citation: Cancer. 2011 Jan 15;117(2):276-82
references.pmid: 20830767
references.citation: N Engl J Med. 2003 Aug 28;349(9):859-66
references.pmid: 12944571
references.citation: Eur Urol. 2007 Jan;51(1):137-49; discussion 149-51
references.pmid: 16793197
references.citation: Urol Oncol. 2005 Mar-Apr;23(2):77-81
references.pmid: 15869990
references.citation: J Urol. 2010 May;183(5):1732-7
references.pmid: 20299043