Assessment And Management Of High-Risk Bladder Cancer

In a session moderated by Dr. Bernard Bochner, Memorial Sloan Kettering Cancer Centre, Dr. Victor Reuter spoke about "Morphologic High-Risk Tumour Characteristics". He discussed variable invasive pathologic properties of T1 tumours that may actually represent a varied spectrum for progression. The importance of tumour grade in bladder cancer is stage dependent, Dr. Reuter said. Regarding divergent differentiation of tumours, the incidence of squamous differentiation increases from 7% to 27% from TUR to cystectomy specimens. This does not translate into different clinical outcomes.

However, pure squamous differentiation does impart worse survival. A similar scenario exists for small cell carcinomas. This suggests that divergent differentiation has an effect that is less that a purely aberrant tumour histology. Also, he stated that micropapillary carcinoma typically presents as high-stage and the amount present pathologically in the specimen is prognostic for outcome. Dr. Reuter discussed that vascular invasion in cystectomy specimens correlates with nodal metastasis, and in node negative patients it correlates with progression and survival. Dr. Colin Dinney, M.D. Anderson Cancer Centre discussed "Clinical Importance of Aberrant Differentiation Patterns in Bladder Cancer". High-risk features such as micropapillary or small cell type have worse outcomes and at M.D. Anderson would prompt these patients to be enrolled in a clinical trial of peri-operative chemotherapy. However, whether treated by cystectomy alone or in combination with chemotherapy, patients with aberrant histology fare worse than patients with pure transitional cell carcinoma. In patients receiving neoadjuvant chemotherapy, downstaging occurs in 45% and 5-year disease-free survival is 50%. This patterns TCC patients, but 5-year survival in this group is 68%. Neoadjuvant chemotherapy followed by cystectomy for patients with small cell cancer resulted in a 2-year survival of 89%, compared to 45% for those who had cystectomy first. Micropapillary tumours treated with intravesical therapy did very poorly and more aggressive initial therapy should be considered.Dr. Dan Theodorescu, University of Virginia lectured on the "Changing Paradigm of Cancer Drug Discovery". Regarding bladder cancer, lack of new discoveries is in part due to limited funding, lower mortality than other tumours types and interest in bladder cancer research. Most important, however, is the cost of industry research and development and the cost of bringing a new drug to market is about $880 million. New chemical compounds are screened by high throughput systems in the laboratory, but this potentially misses many drugs that might work in cancer patients even if they didn't show high activity in vitro. The standard NCI 60 panel drug-screening panel does not include any bladder cancer cell lines, thus limiting the possibility of identifying new drugs active against TCC. Dr. Theodorescu stated that new approaches to gene chips and proteomics hold hope for identifying new agents active against TCC. He said that translating the NCI60 screening data against bladder cancer cell lines, then bladder cancer patients would provide an extrapolation method to enhance drug discovery for TCC. This is called COXEN Prediction Modelling. Using a computer model of this approach testing cisplatin and paclitaxel for translating effectiveness against TCC was 85% effective. He cited an example using breast cancer data from a trial and the COXEN predictive model was highly accurate for correlation with clinical outcomes in patients.(Source: The Society of Urologic Oncology Winter Meeting : Memorial Sloan Kettering Cancer Centre: January 2007.)