Rise in early-onset CRC creates challenges in the clinic


By Mardi Chapman

7 Sep 2023

Associate Professor Kimmie Ng

The growing burden of early onset colorectal cancer (EOCRC) has not yet been explained but the younger age of patients, diagnostic delays and more aggressive disease have substantial implications for its management.

Associate Professor Kimmie Ng, director of the Young-Onset Colorectal Cancer Center at the Dana-Farber Cancer Institute in Boston told AGW 2023 that a survey of 1,000 patients with EOCRC found 41% waited more than six months before seeking attention for their symptoms.

Two thirds (67%) reported having to see two or more physicians before being correctly diagnosed with EOCRC and 71% were diagnosed with advanced stages of disease which were much less curable than earlier stages.

She said most younger patients had better performance status and fewer comorbidities than older patients and were at a stage in their life where “almost universally” they wanted to be aggressive in treating their disease.

“So younger patients do receive more treatment than older patients,” she told the meeting.

“More young patients receive postoperative chemotherapy even when it’s not indicated by national guidelines…and when they did they more often received multiagent regimens than older patients.”

“They also receive more surgery and radiation but there is no corresponding survival gain with all these additional treatments.”

She said a number of studies, including the Cancer and Leukemia Group B and SWOG 80405 trial [link here], had now shown the lack of survival benefit despite higher dose intensity and fewer adverse events in younger patients.

This supported the view that younger patients have more biologically aggressive tumours or tumours that are less responsive to treatment.

Associate Professor Ng, was a coauthor on the first international management guidelines for EOCRC which were published earlier this year [link here].

She said there were very few differences in the medical treatment of younger patients compared to older patients.

“Younger patients should all undergo multi-gene panel germline genetic testing and MSI testing but beyond that the treatment should be exactly the same,” she said.

She told the limbic it was very challenging to implement those guidelines in the real world.

“You can very easily state in international guidelines that there should be no difference in the treatment but when you have a young patient sitting in front of you, and they want to be around for as long as possible for their young children, it is extremely difficult.”

She said the evidence didn’t mean that any individual patient may not necessarily benefit from more intensive treatment.

“So I do think it has to be very individualised to the particular patient’s cancer and situation but then you do have to be honest and realistic about the data with them as well. It’s okay for them to hear ‘you could try this chemo, but it’s going to make you feel bad and it might not help’.”

“Oftentimes, patients are very motivated to want to get surgery even if their disease is already metastatic and not going to be curable. Sometimes you do need to refer them to the surgeon to have the surgeon say that. It’s very, very difficult.”

Professor Ng said other issues which should be managed better in EOCRC included fertility preservation and the high rates of anxiety and depression.

Risk factors

Professor Ng said people born in 1990 now have over four times the risk of developing rectal cancer and double the risk of colon cancer compared to those born in 1949.

“What this birth cohort effect suggests is that recent changes in environmental exposures or a combination of exposures is likely to account for the increased risk of disease, but what those are is still a topic of research.”

She said evidence from the Nurses Health Study II had shown obesity, sedentary behaviours and consumption of sugar sweetened beverages were risk factors.

“But we have all seen patients in our clinics with none of those risk factors so clearly something else is going on.”

Vitamin D appeared to be protective and the jury was still out on antibiotic use as a risk factor.

There were subtle differences in genomics and evidence of distinct microbiomes when comparing EOCRC with other CRC [link here].

She said earlier screening such as the USPSTF 2021 recommendations to start screening at 45 instead of 50 years was a step in the right direction towards reversing the trend to younger onset disease.

“But this is insufficient. We have all seen many 20-year olds and 30-year olds in our clinics and they would not be helped by this change in guidelines so it is of utmost important that we identify the underlying risk factors, know who is at high risk and identify those individuals for earlier screening.”

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