A translational sub-study for bladder cancer

The Below the Belt Research Fund has supported many members in the development of investigator-initiated studies. The fund has provided much needed seed funding to support four ANZUP members to progress new trial ideas to the point of becoming full scale studies. We congratulate Steve McCombie on his pilot study.

DR STEVE MCCOMBIE, UROLOGY SPECIALIST, FIONA STANLEY HOSPITAL, WA

Identifying tumour and immune stromal features that correlate with optimal benefit from BCG and mitomycin: a translational sub-study of patients in the BCGMM Trial

Optimal treatment of aggressive bladder cancer that has not yet invaded the muscle of the bladder wall involves removing all visible tumour using a fibreoptic telescope, followed by regular instillation of a bacterial protein called Bacillus Calmette–Guérin (BCG) into the bladder. BCG activates the body’s immune system to help kill cancer cells. Instillation of a chemotherapy agent called mitomycin into the bladder also has proven effective in the treatment of these tumours. Mitomycin works both by directly destroying cancer cells and may also cause release of cancer cell components that assist activation of the body’s immune system to help kill cancer cells. The BCGMM Trial is a currently recruiting ANZUP trial aiming to determine if the combination of BCG and mitomycin is more effective than BCG alone in the treatment of patients with aggressive bladder cancer that has not yet invaded the muscle of the bladder wall.

As part of this trial, tumour and biopsy tissue samples are telescopically removed from patient’s bladders at several timepoints during their treatment. We plan to perform extensive analyses on these samples to try and determine if it can be predicted which patients may do better with BCG treatment alone, combined BCG and mitomycin treatment, or those that may not be likely to respond to either BCG or the combination. These analyses include looking at how BCG sticks to cancer cells, studying ways in which cancer cells can defend themselves against mitomycin, testing whether the immune cells visible in the cancer tell us who will do best with which treatment, and identifying if different tumour sub-types do better with different treatments.

‘The core goal is to be able to predict the best treatment for patients with these bladder cancers through studying the cancer cells themselves, in order to better deliver personalised treatment that is most likely to improve outcomes without exposing the patient to unpleasant or dangerous side-effects from therapy that is unlikely to be effective.’ Dr Steve McCombie