Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial

BJU Int. 2012 Mar;109(5):685-90. doi: 10.1111/j.1464-410X.2011.010419.x. Epub 2011 Aug 18.


Objective: • To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial.

Patients and methods: • The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels. • We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. • Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy.

Results: • In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities.

Conclusions: • NMP22 is a strong, independent predictor of bladder cancer. • Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. • Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Carcinoma, Transitional Cell / diagnosis*
  • Carcinoma, Transitional Cell / urine*
  • Clinical Trials as Topic
  • Decision Support Techniques
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nuclear Proteins / urine*
  • Prospective Studies
  • Retrospective Studies
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / urine*


  • Nuclear Proteins
  • nuclear matrix protein 22