Urinary tyrosine-phosphorylated proteins: a non-invasive marker for diagnosis, prognosis and follow-up for bladder cancer

Introduction and objectives

A non-invasive, high sensitive and specific urine test is needed for bladder cancer (BC) diagnosis, prognosis and surveillance to substitute the invasive cystoscopy. We previously described the diagnostic effectiveness of urinary tyrosine-phosphorylated proteins (TPP) test. The aim of this study was to validate the diagnostic effectiveness of TPP and to evaluate the capacity of the TPP test to predict the recurrence and progression rate of the BC. We present the preliminary results of this ongoing study.

Materials and Methods

Urine samples (100 ml) were obtained from BC patients at the time of first diagnosis, during their follow-up and from control volunteers. The TPP urinary value  (standard unit – SU) was obtained through the TPP test. Wilcoxon and T-test were used to evaluate the correlation between the TPP SU and the BC grade. The BC recurrence rate and TPP SU correlation was evaluate using the Wilcoxon test. ROC curves were than created evaluating the capacity of histology, TPP-test or both to predict BC progression and recurrence rates.

Results

TPP cut of value was established in our previous trial in 261 SU.  120 patients were enrolled; of these for 45 patients we collect the first diagnosis and first follow-up urine samples, for 11 patients was collected also the second follow-up while for 3 patients also the third one.

The TPP value was higher in patients with recurrence at first follow-up, median 454 SU (IQR 370-545) versus 335 SU (IQR 284-447), p 0,03. The difference of TPP value between recurrent patients and controls or between negative follow-up cases and controls was higher in recurrent patients, p 0,04.

The ROC curve to evaluate the capacity to predict the recurrence was performed for histology, TPP test value at first diagnosis and both and we obtain an AUC of, respectively, 61%, 78% and 80% but with p>0,05.

Conclusion

The ongoing results of this prospective study are encouraging. The TPP tests correctly identify the BC and the BC recurrent patients from the non-recurrent one. The test, in this study, seems to be able to predict the recurrence rate of bladder cancer at first diagnosis even if the p value was > 0,05.

These preliminary results are encouraging and the TPP test could became a useful non-invasive urinary test for a better classify the BC patients and better define their follow-up schedule basing on the risk groups.