Prediction of superficial bladder cancer chemoresponse

It is difficult to choose the most effective intravesical agent for managing each patient's superficial bladder cancer. To predict individual patient tumour response to chemotherapy we have used a single cell gel electrophoresis assay (SCGEA), which quantifies nuclear damage and repair in individual cells. Single cell suspensions were derived from forty superficial bladder transitional cell tumours within 4 hours of transurcthral resection. Each cell suspension was immediately exposed to a panel of standard intravesical chemotherapeutic agents (doxorubicin, epirubicin, mitomycin and thiotepa) The cells were then embedded in agarose, cell membranes were lysed and the nuclei subjected to alkaline electrophoresis. The nuclear DNA was stained with ethidium bromide and nuclear damage was measured using Fenestra image analysis equipment. For eight tumours, a dose-response curve was derived for each agent with respect to induced nuclear damage. The DNA repair kinetics were examined in twelve tumour suspensions. When DNA repair occurred, it was observed to be complete by 120 minutes. For each of twenty tumours, a differential, unique sensitivity to the panel of agents was demonstrated. Fourteen (70%) of these tumour suspensions demonstrated a response to at least one agent. Mitomycin caused the greatest nuclear damage in seven (50%) of these tumours, thiotepa caused the greatest damage in three (21.4%), doxorubicin in two (14.3%) and epirubicin in two (14.3%). These results were statistically significant (Mann-Whitney U test p=0.01). In vitro correlation with observed clinical chemoresponse was 85%. The results indicate that SCGEA is an accurate ex vivo method for quantifying the response of superficial bladder tumours to different chemotherapeutic agents. We have demonstrated that the highest in vitro and in vivo chemoresponse is with mitomycin. SCGEA exhibits great potential for indicating the most effective agent for the management of an individual patient's bladder tumour.