New Biomarkers Determine Bladder Cancer Lethality

Tumor markers can help guide future treatments for patients with bladder cancer.

New research published in Scientific Reports found that certain tumor markers can slow the aggressiveness of bladder cancer and help guide treatments.

In the United States, bladder cancer is the fourth most common cause of cancer-related death among men. It’s estimated that more than 75,000 new cases will be diagnosed this year alone, and more than 16,000 will die from this disease.

In a new study, researchers found several predictors for an increased risk of death with included the detection of poorly differentiated basal tumor cells in early stage cancers; the overexpression of cell division cycle 25C in the basal tumor cells; or the ability of tumor fragments to grow once they were transplanted into mice.

“If confirmed in larger studies, our findings could help physicians get a better handle on how a patient’s bladder cancer is likely to progress and allow them to personalize treatment based on that knowledge,” said study author Ralph Weichselbaum, MD.

For the study, researchers gathered tumor samples from 71 patients with bladder cancer, and used flow cytometry to isolate and count specific subtypes of tumor cells in each sample, according to the study. Researchers found that an excess of the basal tumor cell (BTC) was associate with a 3-fold increased risk of death.

The global expression of genes in BTCs was analyzed and allowed researchers to identify a potentially prognostic biomarker for bladder cancer called cell division cycle 25C (CDC25C), which drives cell division. In an expanded analysis that included 400 patients with bladder cancer, researchers found that the expression of CDC25C was associated with an increased risk of death, even when the cancerous bladder was removed.

This association was found to disappear, however, in patients who had undergone prior chemotherapy. These findings suggest that a test for CDC25C could help determine if a bladder cancer patient will most likely benefit from drug treatment or not, according to researchers.

When more invasive tumors were studied, researchers found that the presence of the number of BTCS had less prognostic value. They injected bladder cancer tissue fragments from 69 patients with more advanced cancers into the flanks of immune-deficient mice.

Approximately 60% of the tumor fragments were able to connect and grow in that setting, and was associated with a 6-fold increase in risk of death compared to tumor fragments that did not survive and grow after being transplanted.

“Prognostic knowledge can change a lot about how you choose to treat a cancer,” Weichselbaum said. “We may be able to avoid aggressive measures if we find a tumor has relatively few basal cells. We could treat an early-stage bladder cancer with less aggressive therapy, avoiding debilitating interventions like radical cystectomy. But if a bladder tumor has a lot of basal cells, we may need to take the entire bladder out and follow that with chemotherapy.”

The authors noted that further research is necessary, and their findings need to be confirmed in studies of larger size.