Bladder cancer and molecular testing

Molecular subtyping may not always be the best way to assess tumours.
Researchers at the Medical College of Georgia have just published a study comparing molecular subtyping of tumour tissue with standard microscopic pathology in determining tumour aggressiveness and patient survival. The researchers were surprised to find that in the case of muscle invasive bladder cancer, molecular subtyping of tissue from the tumour gave only a poor indication of the subsequent behaviour of the tumour. Standard descriptive characteristics of the tumour as determined by the pathologist looking through a microscope gave a better indication of how aggressive the tumour was and how long the patient was likely to survive.

Muscle invasive bladder cancer is a serious high-grade type of cancer associated with high mortality rates. Clinicians are always seeking better ways to assess diagnosis, treatment and survival. Molecular subtyping of tumours is widely used in cancer assessment and treatment today both to get an improved understanding of the type of tumour the patient has and to guide treatment. So-called “precision medicine” using special targeted therapies with new drugs relies on finding specific mutations in genes within the tumour.

Molecular subtyping of bladder tumours, which is currently being offered to patients, especially in the US, involves comparing DNA data from a sample of the patient’s tumour cells with databanks of gene expression and mutations present in a cancer type to find patterns of gene expression. These are then used to subtype tumours that "pathologically look similar under the microscope" but are molecularly different. The idea is that molecular subtypes are better equipped to indicate which cancer is more or less aggressive and to help steer treatment options like whether chemotherapy before surgery to remove a diseased bladder is better. However, in this case molecular subtyping was outperformed by standard tests long-used by pathologists to characterize cancer as low- or high-grade and to determine the extent of its invasion into the bladder wall, surrounding fat, lymph nodes, blood vessels and beyond, the researchers reported in a study featured on the cover of the Journal of Urology.

The authors suggest that part of the problem with subtyping may be the inherent heterogeneity of tumours. There is tremendous heterogeneity in the gene expression of tumours, even among the same tumour type, like bladder cancer, and within different parts of the same tumour as well. Furthermore, this pattern of heterogeneity can change both during tumour growth and treatment. This heterogeneity may cause problems when clinicians are trying to categorize a tumour into a single subtype.
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