Editorial Comment to Cancer death from non‐muscle invasive bladder cancer: Report of the Japanese Urological Association of data from the 1999–2001 registry in Japan

Abstract

The authors reported on 1919 clinical T1 (cT1) bladder cancer patients from the Japanese National Bladder Cancer Registry between 1999 and 2001, sponsored by the Japanese Urological Association. All survivors were followedup for at least 3 years (up to 5 years) and the 3-year cancer specific survival rate was 95.5%. The authors analyzed risk factors for bladder cancer death and concluded that large tumor size (>3 cm), positive urine cytology and nonpapillary tumor architecture were significant and independent risk factors. Histological grade is a well-known predictive factor for progression of non-muscle invasive bladder cancer. In the current study, however, the presence of a grade 3 lesion was not identified as an independent risk factor for bladder cancer death. This might be attributed to the lack of central pathology review and/or the relatively short-term follow up of the current study. Interestingly, urine cytology provided prognostic information on cT1 bladder cancer patients. Urine cytology reflects not only cellular atypia, but also the fragility of intercellular attachment of bladder cancer cells. Recent advances in translational research have shown that epithelial to mesenchymal transition (EMT) is critical for the progression of bladder cancer. During EMT of bladder cancer cells, expression of molecules determining epithelial features including E-cadherin and p63 is downregulated, leading to loosened intercellular attachment. At the same time, upregulation of mesenchyme-associated molecules, including Twist, Snail and N-cadherin, activates various oncogenic signaling pathways, increases cell motility and excretion of matrix metalloproteinases, and eventually promotes invasion and metastasis. Given these biological processes during progression of bladder cancer, it is conceivable that urine cytology provides prognostic value by reflecting EMT status. I look forward to further investigations to validate the prognostic value of urine cytology in non-muscle invasive bladder cancer patients.