• cT2 bladder cancer;
  • decision tree;
  • early cystectomy;
  • neoadjuvant chemotherapy;
  • pathological upstaging

What's known on the subject? and What does the study add?

  • Neoadjuvant chemotherapy is advocated for most patients with carcinoma invading bladder muscle. An improved risk-stratification of clinical stage T2 (cT2) patients can potentially identify candidates who may derive maximal benefit from this approach. cT2 patients who are pathologically upstaged at cystectomy have significantly worse prognosis than their counterparts who are not upstaged. The identification of such candidates who may be subsequently upstaged represents a strategy for selecting those patients who may benefit the most from neoadjuvant chemotherapy, whereas other patients can undergo early cystectomy.
  • The present study describes a unique cross-validated decision tree generated using precystectomy variables aiming to stratify patients with cT2 tumours based on the risk of pathological upstaging and adverse oncological outcomes. This model can be potentially employed as a tool for making clinical decisions with respect to neoadjuvant chemotherapy in these patients.


  • 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.

Patients and 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.


  • 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).


  • 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.