DNA mutations linked to kidney cancer recurrence reveal way to optimize treatment

By Nick Paul Taylor, The Science Advisory Board contributing writer

February 23, 2023 -- Researchers have linked tumor DNA mutations to the likelihood of kidney cancer recurring, suggesting that treatment and follow-up can be optimized based on genetic factors.

At a time when molecularly defined treatment strategies are the norm in other tumor types, kidney cancer therapies continue to mostly treat all comers. Physicians still assess the likelihood of the cancer recurring based on characteristics such as the size of the tumor and how aggressively the cells behave under a microscope, rather than genetic factors.

The Clinical Cancer Research paper represents an attempt to change that. Naveen Vasudev, the co-lead investigator and associate professor at the Leeds Institute of Medical Research at St. James's, explained the need for new ways of determining the risk of recurrence in a statement.

"As well as helping us identify how often patients need to be seen by their doctors, it helps us to decide who to treat with immunotherapy. This treatment has recently been shown to reduce the chances of the cancer coming back but can cause side-effects. The danger currently is that some patients may be over-treated, so being able to better identify patients at low risk of recurrence is important since they could be spared more treatment," Vasudev said.

Vasudev and 43 collaborators at 23 institutions across Europe and Canada analyzed changes in the DNA of more than 900 kidney cancer samples. The analysis revealed four groups of patients based on the mutations in 12 specific genes. By looking at the rate of cancer recurrence in the groups, the researchers correlated the mutations to the likelihood of relapse.

In one group, 91% of patients were free from disease five years after surgery. In contrast, 51% of people in another group remained disease-free after five years. The finding suggests that people in the second group should potentially receive more-aggressive treatment and more-frequent follow-up because they are more likely to relapse in the years after the surgical resection of their tumors.

Up to 30% of localized kidney cancers return after surgery. Being able to identify those patients could benefit the groups most likely to relapse, as steps can be taken to improve their outcomes, as well as those that are least likely to relapse, because they can be spared aggressive treatments and the adverse events they cause.

Physicians already use DNA sequencing to determine the most appropriate treatment for other cancers. The new study suggests there may also be an opportunity to apply the technology to the management of kidney cancer.

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