Surgical Oncology Resident Sri Shankara Cancer Hospital and Research Centre, Bangalore, India North Paravur, Kerala, India
Introduction: Non muscle invasive bladder cancer (NMIBC) constitutes the majority of all bladder cancers. Owing to its heterogeneity and its notoriety to cause recurrence and progression to muscle invasive type, optimal management of such patients is extremely difficult. Though EORTC is the best tool available for risk stratification, the positive predictive value is 70% across all studies. In our clinical practice, we see that majority of these patients are binned into the intermediate risk category and eventually are either over treated or under treated. The aim of our study is to assess the utility of molecular markers of NMIBC tumours in a clinical context and compare with the already established EORTC scoring system for prediction and prognostication.
Materials and
Methods: A total of 32 patients with non-muscle invasive bladder cancer were included in this prospective study and were followed up to a period of 18 months and their clinical and pathological parameters including the EORTC recurrence and prediction scores were noted. The gene expressions of the following 5 genes were studied in FFPE tumor blocks- namely FGFR3, E2F3, ERCC2, EGFR and TP53. The data was entered in MS Excel sheet and appropriate statistical analysis done.
Results: A total of 32 patients were included in the analysis. The mean age was 62 years and 84.3% of the cohort were males. Most of the patients were categorised into intermediate risk group according to the EORTC Recurrence score (75%) and EORTC Progression score (62.5%). Logistic regression was carried out considering recurrence as the outcome variable and genes expressions of the five analysed genes and EORTC score groups for each sample. This new risk assessment model with gene expression and EORTC score combined together has a higher predictive value with ROC curve showing AUC of 0.867. The recurrence free survival analysis with this combined score was statistically significant (p=0.013).
Conclusion: Our study highlights the role of gene expression signatures in predicting recurrence in non-muscle invasive bladder cancer. We formulated a combination model consisting of 5-gene-signature along with pre-existing EORTC risk assessment scoring system and found it to be superior to when they were used independently. For a small set of samples and markers in this explorative study, our results are promising. More large scale studies with longer follow up and more markers will make the predictive score robust and specific.
