Australian real-world data suggest early-onset colorectal cancers that spread to the liver differ from those diagnosed after 50, with tumour biology potentially shaping treatment decisions.
Younger Australians with metastatic bowel cancer are presenting with a distinct mix of tumour characteristics and survival outcomes, adding weight to calls for treatment to be guided by biology rather than age alone.
An Australian study of 1691 patients with colorectal cancer that had spread only to the liver found those diagnosed at 50 years or younger were more likely to be female, have left-sided or rectal tumours, present with synchronous metastases, and carry BRAF mutations than patients diagnosed after 50.
The retrospective cohort study, published in the Medical Journal of Australia, drew on prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer registry between 2009 and 2024. Of the cohort, 276 patients (16.3%) had early-onset colorectal cancer.
The findings come amid mounting concern about bowel cancer in younger adults, with the researchers noting that Australia has the highest incidence of early-onset colorectal cancer globally.
Early-onset patients were almost as likely to be female as male, with women accounting for 48.2% of the younger group compared with 34.5% of patients aged over 50.
Three-quarters of younger patients had cancers in the left colon or rectum, compared with about two-thirds of older patients, while 53.3% had synchronous liver metastases compared with 42.1% of the older cohort.
BRAF mutations were also more common among younger patients who had testing, at 13.9% versus 8.1%. There were no significant differences between the age groups in KRAS or NRAS mutations or mismatch repair proficiency.
Lead author Professor Savio Barreto, a consultant with the HPB and Liver Transplant Unit at Flinders Medical Centre and researcher at Flinders University, said the findings helped build a clearer picture of a disease that remained poorly understood.
“We still have much to learn about why these cancers develop and how they differ from those diagnosed in older people,” he said.
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“Our study helps build a clearer picture of the disease and suggests that younger patients may have distinct tumour characteristics that should be considered when treatment decisions are being made.”
Survival also differed substantially. Median overall survival after diagnosis of liver-only metastatic disease was 3.20 years among patients aged 50 years or younger, compared with 2.38 years among older patients. The gap was particularly marked among patients whose liver metastases developed later, rather than being present at initial diagnosis.
But age was far from the whole story.
KRAS, NRAS, and BRAF V600E mutations were associated with poorer overall survival in the early-onset cohort, while KRAS and BRAF mutations were associated with poorer survival among older patients.
“Our findings reinforce the need to look beyond a patient’s age when planning treatment because every cancer is unique,” Professor Barreto said.
“The more we understand about the biology of a tumour, the better equipped we are to tailor treatment and identify the options most likely to benefit each patient.”
Treatment patterns differed too. Younger patients were more likely to receive active treatment, at 96.0% compared with 88.5% of older patients, and were almost twice as likely to receive chemotherapy or biological therapy followed by surgery, at 27.9% versus 14.1%.
Initial analyses found surgery followed by chemotherapy or biological therapy was associated with substantially better survival in both age groups, particularly among patients with synchronous metastases or a left-sided primary tumour.
However, the picture became less clear after researchers adjusted for treatment-selection differences. In patients aged 50 or younger, the apparent survival advantage associated with surgery-containing treatment sequences was attenuated and no longer statistically significant.
The researchers noted that the observational study could not establish that particular treatment sequences caused better survival.
Patients selected for surgery were more likely to have favourable disease or resectable metastases, and the registry data were susceptible to selection bias, residual confounding, and incomplete molecular data.
Professor Barreto said treatment decisions needed to account for overall health, disease burden, and the molecular characteristics of an individual tumour.
“Better understanding of these differences is an important step towards delivering more personalised care and improving outcomes for patients and their families,” he said.
The researchers concluded that differences in sex distribution, tumour location, BRAF mutations, and the impact of mutations on survival pointed to biological variation between early- and late-onset colorectal cancer that should be considered when planning treatment.
“The rising burden of EOCRC globally demands a better understanding of its biology and clinical behaviour,” they wrote.
“Differences in sex distribution, left sidedness, BRAF mutation expression and mutational impact on OS suggest biological variations between EOCRC and LOCRC that need to be considered when planning treatment strategies, including resectional surgery and liver transplantation.
“The treatment approach, particularly earlier timing of surgery, may provide improved survival outcomes, when feasible.”
