The way we classify metastatic cancers may need to be revamped, scientists have said, proposing in its place a classification system that places the molecular characteristics of the cancer over the tissue of origin.
Traditional approaches to treating cancer – including surgery and radiation – target the organs in which the tumour is present. This practice formed the basis of classifying cancers after the organ in which they originate. But most deaths due to cancer are the result of the disease metastasising beyond the organ of origin; individuals with metastatic cancer are almost always treated systemically with drugs that enter the blood.
What motivates the need for change?
With technological improvements, doctors are also able to find which genetic mutations are responsible for a tumour in many cases, and target them with drugs. All cancers from the same organ don’t always share the same mutations, and these mutations aren’t limited to cancers of a single organ.
This development in precision oncology requires cancers to be classified based on their molecular and genetic characteristics rather than the organ in which they originate, a team of researchers from France has written in a paper. This way, according to them, cancer patients can also access life-saving drugs sooner.
Fabrice André, a medical oncologist at Gustave Roussy in France and lead author of the commentary, told this author that oncologists spend a lot of time testing new drugs in clinical trials in a sequential manner, leading to “delay in treatment access”.
Have any drug trials been delayed by sequential testing?
There is evidence to support this view. A 2012 clinical trial in the U.S. investigating the drug nivolumab included people with different types of cancers, including melanoma and kidney cancer. Nivolumab targets the receptor of a protein found in some tumours. It ameliorated symptoms in individuals with tumours with that particular protein.
The next logical step would have been to test nivolumab with people with tumours that expressed the protein irrespective of where the cancer originated. But since cancers are classified based on their organ of origin – breast, kidney, lung, etc. – researchers had to conduct trials one after the other for each type of cancer.
As a result, for many years, people with tumours expressing that particular protein couldn’t access nivolumab because the drug hadn’t been trialled for their specific type of cancer.
Most drugs tested in clinical trials in the past decade have a similar story.
How else can the new scheme help patients?
Naming cancers according to their biology rather than their anatomy “will reduce the time needed to run clinical trials,” said Dr. André, “because you only need a few randomised trials, instead of testing the drug in each disease defined by the organ of origin.”
Consultant medical oncologist and haemato-oncologist at Mumbai Oncocare Centre Kunal Jobanputra agreed. A trial for a drug targeting a particular genetic mutation will cover all cancer types with those mutations. “A positive effect could be that it will take less time for the trials to happen,” he said.
The revamped classification system could also help patients understand the rationale behind their treatment, according to Dr. André. For example, two people may have the same cancer but not the same therapy because the biological mechanisms underlying their tumours are different. This can confuse patients, he said.
“Naming cancers with biological mechanisms would decrease such heterogeneity, and will also help the patient to better understand the rationale for his/her therapy.”
Physicians often educate their patients about the molecular characteristics of their cancers, Dr. Jobanputra said. “When the connotation changes, the prognosis changes, the cost of treatment changes.
“We are moving towards a more personalised [treatment] approach,” he added.
What will take to reclassify cancer drugs?
Some change has also been evident over the last few years in regulatory agencies’ approval for certain drugs. In 2017, for example, the U.S. Food and Drug Administration (FDA) approved the use of the drug pembrolizumab to treat people carrying a certain mutation regardless of the organ in which the cancer originated. Following this, the FDA has also approved some other drugs to be used based on their biological targets.
For the various cancers to be reclassified in this way, regulatory agencies, scientific groups, and insurance companies will also need to clarify when a drug should be approved based on its molecular target. The FDA is working on a guideline to this effect.
A particularly important requirement is for institutions to establish teams that will focus on analysing patients’ molecular profiles irrespective of the cancer type, the researchers wrote in their paper. Medical students must be trained to understand the molecular basis of cancers instead of memorising the characteristics of primary tumours.
Are there hurdles to implementing the scheme?
Finally, this proposed change for classifying cancers can’t happen unless patients can access tests that reveal molecular alterations in their tumour.
This is particularly relevant in the Indian context, where we must take the proposed change with a pinch of salt, Dr. Jobanputra said, since most patients can’t afford genetic testing. These tests currently cost Rs 7,000-40,000 in Indian labs and up to Rs 3 lakh abroad. The availability and accessibility of genetic tests should be wider. “Only then can we jump to this diagnostic nomenclature.”
The proposed classification system is also not without faults, Dr. Jobanputra added. Unless trials conducted based on molecular signatures have a significant number of patients with each type of cancer, they could generalise the results for all cancers.
We can’t entirely do away with organ-level information either because disease location is an important factor in the outcome regardless of the genetic mutations, he continued. For example, lung and brain cancers with the same mutations will still behave differently.
But “if done properly,” the new nomenclature “can improve accessibility of drugs,” he said, even if this change will come only gradually.
Dr. André agreed. “It will probably take some decades. There is some important research to be done in terms of trial methodology before moving into that direction.”
Sneha Khedkar is a biologist-turned freelance science journalist based out of Bengaluru.
