Urothelial cancer, also known as transitional cell cancer, is the most common type of bladder cancer; it’s also more complicated, and has more subtle differences from person to person, than scientists used to think. It encompasses several molecular subtypes, “each with its own distinct clinical and biological characteristics,” says urologist Trinity Bivalacqua, M.D., Ph.D., Director of Urologic Oncology.

These subtypes can be classified as either basal or luminal. “Basal tumors, while more aggressive, show the greatest improvements in survival outcome, with platinum-based neoadjuvant chemotherapy (NAC),” Bivalacqua continues. Luminal tumors, in contrast, “tend to be less aggressive, but may also receive less benefit from NAC” – and here is where understanding molecular subtypes may provide valuable insight.

“In the field of bladder cancer, we are desperately trying to find biomarkers for the selection of patients for NAC before surgery,” Bivalacqua says.

“If accurate, they could be used on tumor tissues obtained at transurethral resection of bladder tumor (TURBT) to identify high-risk patients who would benefit from chemotherapy, while low-risk patients might be spared the side effects of chemotherapy.”

Bivalacqua and Brady urologist Max Kates, M.D., have teamed up with other urologists worldwide “to determine whether we can use the molecular subtypes to help us select patients with high-risk, non-muscle-invasive bladder cancer who should be offered chemotherapy” at the time of radical cystectomy. “This is necessary,” Bivalacqua explains, “because some patients with T1 disease are actually understaged,” and more or higher-grade cancer is found after the removed bladder is examined by a pathologist. “This means these patients have more aggressive cancer, and thus may benefit from chemotherapy prior to radical cystectomy (bladder removal).”

In a study published in European Urology, Bivalacqua, Kates, and Hopkins colleagues looked at how various molecular subtypes fared when pathologists examined the removed bladder specimen – particularly, at the cancers that turned out to have spread beyond the bladder – in a multi-institutional cohort of patients with clinical T1-T2 bladder cancer who were treated with radical cystectomy. “This study provides valuable guidance,” says Bivalacqua.

“We found that luminal tumors were less likely to have spread outside the bladder compared with basal tumors.”