title: A precystectomy decision model to predict pathological upstaging and oncological outcomes in clinical stage T2 bladder cancer.
abstract: OBJECTIVE
  To categorize patients with clinical stage T2 bladder cancer into risk groups based on their potential for pathological upstaging and eventual oncological outcomes at cystectomy. To pre-emptively identify such patients who will be upstaged and have poor outcomes after cystectomy, aiming to better determine the ideal candidates for neoadjuvant chemotherapy.
  
  
  METHODS
  A retrospective review was conducted of 1964 patients who underwent radical cystectomy for bladder cancer with intent to cure at the University of Southern California between 1971 and 2008. Neoadjuvant chemotherapy-naïve patients with clinically organ-confined urothelial carcinoma invading bladder muscle (cT2N0M0) were included. Univariate analysis and multivariable decision tree modelling with cross-validation were employed to identify precystectomy variables that could predict pathological upstaging and poor oncological outcomes.
  
  
  RESULTS
  A total of 948 patients met the inclusion criteria, of whom 512 (54%) patients were upstaged at cystectomy; upstaging was associated with a worse recurrence-free and overall survival (both P < 0.001). Age, presence of hydronephrosis, evidence of deep muscularis propria invasion and lymphovascular invasion on transurethral resection specimen, as well as tumour growth pattern and count, were significantly associated with upstaging. When these factors were included in a decision tree model, 70.6% of patients with hydronephrosis experienced upstaging and had the worst outcome (P < 0.001). In patients without hydronephrosis, tumour growth pattern was a second-tier discriminator (P < 0.001); in patients with non-papillary tumours, 71.7% of cases with evidence of deep muscularis propria involvement experienced upstaging compared to 53.8% of cases with no deep muscle involvement (P = 0.012), whereas, among patients with combined papillary and non-papillary features, 33% of cases aged ≤65 years were upstaged compared to 47% of cases aged >65 years (P = 0.036). The cross-validated decision tree resulted in three risk groups with significantly varying probabilities of recurrence-free and overall survival (both with overall P < 0.001).
  
  
  CONCLUSIONS
  Hydronephrosis, tumour growth pattern, deep muscle involvement and age can collectively identify patients with cT2N0M0 bladder cancer who have varying risks of pathological upstaging. Such categorization using a visually intuitive model can facilitate clinical decision-making with respect to neoadjuvant therapy in these patients.
authors.affiliation: Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: Anirban P
authors.initials: AP
authors.lastname: Mitra
authors.forename: Eila C
authors.initials: EC
authors.lastname: Skinner
authors.forename: Gus
authors.initials: G
authors.lastname: Miranda
authors.forename: Siamak
authors.initials: S
authors.lastname: Daneshmand
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy / Q000379:methods* / Q000401:mortality; D020000:Decision Support Systems, Clinical; D003663:Decision Trees; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D006869:Hydronephrosis / Q000150:complications / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents