“These findings have the potential to help identify patients with clinically hidden disease who may benefit from additional therapy, and to help avoid overtreating those with no evidence of residual disease.”
Bladder cancer desperately needs its own version of the PSA test – a test that could answer questions like, “How aggressive is my cancer?” and “Is my treatment working?” or “Which treatment is right for me?”
Urology resident Heather Chalfin, M.D., believes the answer may lie in smarter reading of circulating tumor cells (CTCs), cancer cells that have made their way to the bloodstream. She has made important discoveries about CTCs in prostate cancer, as well (see story) – insights that may be practicechanging. In both diseases, she has found that scientists could be looking at the wrong things.
“Bladder cancer circulating tumor cells (CTCs) have largely been studied with methods that rely on the epithelial marker, EpCAM, such as the CellSearch test,” she explains. Epithelial cells are in the membranous lining of tissue. “There have been many conflicting reports.”
But there are different CTCs, called EpCAM-negative, or epithelial-markernegative CTCs, and “they have not been studied,” Chalfin continues, and these might prove to be much more helpful to scientists hoping to understand the state of someone’s bladder cancer.
Looking at these EpCAM-negative CTCs in blood samples from Hopkins bladder cancer patients with a novel detection assay called RareCyte, “we were able to show that CTCs are present at all bladder cancer stage groups,” says Chalfin. Better yet, “they exhibit phenotypic diversity for cell size and epithelial marker expression.” Which means that these cells could provide a window – the long-sought “liquid biopsy” – into bladder cancer.
With the old CTC test, “no CTCs would have been detected in non-muscle invasive patients in our study. But with the novel method, we found EpCAMnegative CTCs. These findings have the potential to help identify patients with clinically hidden disease who may benefit from additional therapy, and to help avoid overtreating those with no evidence of residual disease.”
Even better: “We have the capability to pick out and isolate individual stained CTCs and will be performing copy number 22 variation analysis and single-cell sequencing on these CTCs,” which means that they can look for mutated genes that might be targets for precision drugs. “Also, in ongoing collaboration with the Greenberg Bladder Cancer Institute, we will be comparing CTC count with several other ‘liquid biopsy’ tests such as plasma-free tumor DNA as well as the MD Anderson molecular subtype, in an effort to identify the best options to personalize therapy for our patients.”