title: External validation of a biomarker based pre-cystectomy algorithm to predict nonorgan confined urothelial cancers.
abstract: OBJECTIVE
  The role of neoadjuvant chemotherapy before surgery in patients with muscle invasive bladder cancer remains debated and the need for tools to identify patients who would benefit from chemotherapy is pertinent. We previously published a preoperative algorithm to predict nonorgan confined disease. This algorithm included tumor markers (CEA, CA 125 and CA 19-9) as well as clinical parameters. In this study we validated the accuracy of this algorithm in an independent, external cohort.
  
  
  METHODS
  We used the Toronto Biobank to measure preoperative serum levels of CEA, CA 125 and CA 19-9 in 76 consecutive patients with clinically organ confined bladder cancer (cT2 or less) who underwent radical cystectomy. Clinical parameters were retrieved from our prospective bladder information system database and incorporated into our marker based algorithm. A numerical score was generated for each patient and a previously published cutoff was used to predict the presence of nonorgan confined disease. The accuracy of the model was quantified with the area under the curve, and the positive and negative predictive values were calculated.
  
  
  RESULTS
  On pathological evaluation 38 patients (50%) had nonorgan confined tumors. The AUC of the algorithm was 0.79 (95% CI 0.69-0.89). The positive and negative predictive values were 79% (95% CI 71-87) and 74% (95% CI 66-82), respectively.
  
  
  CONCLUSIONS
  We externally validated a pre-cystectomy model to predict pathological stage. The algorithm may possibly aid in selecting patients who would benefit from neoadjuvant chemotherapy before cystectomy.
authors.affiliation: Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada. sdmargel@gmail.com
authors.forename: David
authors.initials: D
authors.lastname: Margel
authors.forename: Peter
authors.initials: P
authors.lastname: Bostrom
authors.forename: Jack
authors.initials: J
authors.lastname: Baniel
authors.forename: Ofer
authors.initials: O
authors.lastname: Yossepowitch
authors.forename: Alexandre
authors.initials: A
authors.lastname: Zlotta
authors.forename: Neil
authors.initials: N
authors.lastname: Fleshner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D003131:Combined Modality Therapy; D015653:Cystectomy; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen