Ruolo dell'ADXBLADDER test per la rilevazione di recidive nel carcinoma vescicale non muscolo invasivo (NMIBC)

Bladder cancer is a type of tumour characterized by a great heterogeneity and a variety of factors involved in its development. A classification based on the invasiveness of cancer cells into muscle layers identifies two main categories of this tumour: the muscle invasive bladder cancer (MIBC) and the non-muscle invasive bladder cancer (NMIBC). NMIBC has a high rate of recurrence in the population, considering that bladder cancer is the sixth most commonly diagnosed cancer every year in Europe and the fifth in USA. Nowadays the cystoscopy is the gold standard method to determine the disease recurrence but it leads to high economic burden and, at the same time, due to its invasiveness, could cause some iatrogenic risks as bleeding, bladder perforation and psychological side effects also. Because of these limitations, some non invasive methods have been studied. Cytology of exfoliated tumour cells in urine is not able to reduce or replace the total amount of cystoscopies so many other diagnostic biomarkers have been evaluated. ADXBLADDER test is a method to detect Mini Chromosome Maintenance protein 5 (MCM5) in urine sample of patients during follow up. This protein is investigated for its role in cancer progression since it is a cell cycle trigger involved in DNA replication. Due to its function, it is actively expressed in proliferative cells, but absent or downregulated in quiescent, differentiated or senescence ones. When ADXBLADDER test detects in urine sample a significant amount of MCM5, patients could suffer from NMIBC recurrence. The aim of this trial was to verify the performances of ADXBLADDER test in comparison to urinary cytology results. All outcomes are confirmed with the cystoscopy: if ADXBLADDER will be able to give the same reliability as cystoscopy, the latter could be replaced with a less invasive but, at the same time, comprehensive methodology. In this study, a cohort of 186 patients was enrolled and for each patient anamnestic (smoke status, professional exposition and other risk factors) data were collected. For each subject, ADXBLADDER test were performed and all results were compared with cystoscopy in order to assess whether the new test could detect a tumour relapse and with urine cytology to evaluate if it has better performances. Comparing urinary cytology with cystoscopy, the sensitivity was 36%, specificity was 87%, with an accuracy of 77%, a Positive Predictive Value (PPV) of 37% and a Negative Predictive Value (NPV) of 86%. ADXBLADDER test showed a sensitivity of 85%, a specificity of 41%. The accuracy was 49% with a PPV of 25% and a NPV of 92%. Combining the results of the two non invasive methods we found a sensitivity of 36%, specificity was 93% and accuracy was 84%. In this approach, PPV was 50% but NPV (88%) was better than cytology alone while worse than ADXBLADDER test. ADXBLADDER test was confirmed to be a good assay for screening routine. Positive results could be influenced by different clinical conditions of patients so the test is not reliable to identify the presence of a relapse. Conversely, when test results are negative, it means that MCM5 is not detectable and a tumor relapse can be reasonably excluded. Introducing this test in follow-up routine would be a benefit for patients because it could be a less invasive diagnostic method and potentially replace cystoscopy in selected population.