Ex vivo chemosensitivity to mitomycin C in bladder cancer and its relationship with P-glycoprotein and apoptotic factors.

Background: Intravesical treatment with mitomycin C (MMC) leads to a complete response rate of around 40% in superficial bladder cancer (TCC). In order to determine in advance which patients will fail to respond, we describe a study assessing the feasibility of applying the ATP assay to test the chemosensitivity of samples from patients with this disease. Materials and Methods: TURBT or biopsy samples were received from 27 patients, 23 of which were suitable for the ATP assay (16 primary tumours and 7 recurrences). Results: The success rate of the assay was 91 %. There was a marked variation in the effect of MMC between patients with a >50-fold range in LC 50 values (drug concentration required to kill 50% of cells) from 2.99 - >150μM with a median value of 22.4μM. We were unable to determine any overall correlation between chemosensitivity and tumour stage or grade or the treatment status of the patient in this small data set. P-glycoprotein status and caspase-3 levels were assessed on these samples using immunohistochemistry but there did not appear to be any relationship between either of these parameters and MMC resistance. Apoptotic counts and mitotic counts were also measured but, whilst these appeared to correlate with grade (p<0.01), there was no overall significant relationship established with MMC chemosensitivity. Conclusion: This study suggests that it is possible to use the A TP assay for chemosensitivity testing in TCCs. Despite a lack of overall correlation between ex vivo MMC resistance and the conventional prognostic factors tested, further studies are warranted in a larger data set to test the ability of this technique to predict clinical outcome in this disease.