One of Australia’s largest real world studies of younger adults with advanced bowel cancer has identified important differences between cancers diagnosed before and after 50, which could help doctors tailor treatments for younger adults more effectively, reports Newsweek.
Led by Flinders University and Flinders Medical Centre, the scientists analysed data from 1 691 people whose bowel cancer had spread only to the liver, comparing people diagnosed at 50 or younger with those diagnosed after 50.
Their findings suggest that early-onset bowel cancer has distinct features that could influence how doctors approach treatment.
The study, published in The Medical Journal of Australia, comes as increasing numbers of younger adults are being diagnosed with bowel cancer in Australia, which has one of the world’s highest rates of early-onset disease.
Study author Professor Savio George Barreto, from Flinders University, said scientists are still working to understand what is driving the increase in cases among younger adults. He pointed to a theory known as the PELICan hypothesis, which proposes that exposures during key stages of life may contribute to cancer risk.
“We hypothesise that if the cumulative effect of exposures/stressors overwhelms the body’s own protective systems (nutritional, neurohormonal, immune, etc.) at these two critical periods in an individual’s life, it could trigger epigenetic modifications,” he told Newsweek.
Barreto said factors like smoking, alcohol use, obesity and illicit drug use may play a role, although additional research is needed to prove the hypothesis and determine whether it can help guide prevention and early detection strategies.
Biological differences emerging before age 50
When the researchers compared younger and older patients, they found several notable differences. Patients diagnosed at 50 or younger were more likely to be women, more likely to have tumours on the left side of the bowel, and more likely to carry certain genetic mutations.
Those differences were accompanied by a survival advantage. Younger patients generally lived longer after their cancer had spread to the liver than patients diagnosed later in life.
The findings add to a growing body of evidence suggesting that bowel cancer in younger adults may have a different biological profile from cases diagnosed after 50, with Barreto saying they reinforced a theory researchers had suspected for some time.
“We were pleasantly surprised that the findings confirmed our long-held belief that early-onset cancers possess differences in biology and behaviour than late-onset disease.”
How genetics shape treatment decisions
Genetics also appeared to play an important role in outcomes. The researchers found that tumours carrying BRAF or KRAS mutations were linked to poorer outcomes regardless of a patient’s age.
That pattern was seen in both younger and older groups, highlighting the potential value of genetic testing in understanding how an individual’s disease is likely to behave.
The study also identified a potential role for another mutation. “Our new finding, too, is the value of NRAS mutations, too, to guide treatment strategies,” Barreto said.
Rather than relying on age alone when making treatment decisions, the researchers suggest doctors should pay close attention to the biology of a tumour, its genetic mutations and other disease characteristics. Such information could help identify patients who may benefit from more individualised treatment approaches.
Barreto said genetic information is already becoming increasingly important in clinical decision-making. “The use of BRAF mutations to inform decision making within existing treatment algorithms for our patients is increasing globally,” he noted, adding that the new findings could also help inform treatment decisions based on tumour location and whether liver metastases appeared at the same time as the primary cancer or developed later.
How treatment approaches differ for younger patients
The study also examined how treatment strategies were associated with outcomes. Patients who had surgery to remove liver tumours followed by drug treatment generally experienced better outcomes than those who received other treatment approaches.
Differences were also observed in treatment sequencing between younger and older patients. Upfront curative surgery, when feasible and associated with minimal morbidity, appeared to provide a greater survival benefit for patients with early-onset disease.
By comparison, certain patients in the older cohort, particularly those with right-sided cancers and liver metastases that developed later, appeared to benefit more from receiving chemotherapy first.
However, the researchers emphasised that the findings do not prove the treatment itself caused the improved survival. Because the study was based on real-world clinical data rather than a clinical trial, other factors may have contributed to the difference.
While more research is needed, the results could help inform future investigations into the rising rates of bowel cancer among younger adults.
Supporting younger patients beyond treatment
Barreto said one priority is understanding how best to support younger survivors, whose needs may differ substantially from those of older patients traditionally served by survivorship programmes. He highlighted the search for biomarkers that could eventually help identify people at higher risk before cancer develops.
“Can we identify epigenetic blood biomarkers of people at risk (if the PELICan hypothesis can be proven)? This will offer the ability to identify individuals at risk early on with the potential for targeted screening in the future,” he said.
The researchers say their findings support the idea that early-onset bowel cancer should not automatically be viewed as the same disease affecting older patients. Instead, younger people with the condition appear more likely to have distinct tumour characteristics and genetic patterns, as well as better overall survival in cases where the cancer has spread only to the liver.
Ultimately, understanding those differences could help guide more personalised treatment planning and improve care.
“The main message of the study is that bowel cancer diagnosed before age 50 is not simply the same disease occurring earlier in life,” they said.
Study details
Early-onset colorectal cancer with liver-only metastases: a retrospective cohort study integrating prospectively collected real-world clinical and molecular data from an Australian national database (2009–2024) to guide treatment planning
Savio Barreto, Christos Karapetis, Shahid Ullah et al.
Published in The Medical Journal of Australia on 18 August 2026
Abstract
Objective
To leverage the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (an Australian cancer database) to explore the ideal timing and sequence of therapies and the factors influencing these decisions in colorectal cancer (CRC) patients with liver-only metastases to inform contemporary decision-making and future trials.
Study Type
Retrospective registry-based cohort study using the TRACC registry.
Setting and Participants
Consecutive patients with liver-only metastatic CRC enrolled in the TRACC registry.
Main Outcome Measures
To explore cancer biology, intended treatment at presentation, actual treatment received and the resultant outcomes for early-onset CRC (EOCRC) (≤ 50 years) and late-onset CRC (LOCRC) (> 50 years) patients with liver-only metastases from a real-world perspective.
Results
Between 14 January 2009 and 2 September 2024, 1691 patients with liver-only metastatic CRC were enrolled in TRACC. These included 276 EOCRC patients (16.3%) and 1415 LOCRC patients (83.7%). In the EOCRC subset, there were more females (48.2% vs. 34.5%, p < 0.001), less comorbidity (Charlson comorbidity index score 0, 90% vs. 59%, p < 0.001), more left-sided primaries (76.1% vs. 65.7%, p < 0.001), more synchronous disease (53.3% vs. 42.1%, p < 0.001) and BRAF V600E mutations (13.9% vs. 8.1%; p = 0.010). Overall, EOCRC patients had a longer median survival compared with LOCRC patients (3.20 vs. 2.38 years, p < 0.001). For the 662 patients (39.1%) undergoing liver resection, median survival was 5.99 years in EOCRC patients and 5.88 years in LOCRC patients. For all patients and for those undergoing resection, respectively, B-Raf proto-oncogene, serine/threonine kinase (BRAF) (hazard ratio, 1.97 [p < 0.001] and hazard ratio, 2.25 [p < 0.001]) and Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations were associated with worse outcomes (hazard ratio, 1.29 [p < 0.001] and hazard ratio, 1.34 [p = 0.003]).
Conclusion
Differences in sex distribution, BRAF mutation rates, primary tumour site and overall survival suggest biological differences between EOCRC and LOCRC. Liver resection was associated with improved survival in LOCRC, with the benefits of all therapies varying depending on age, primary tumour site and whether patients presented with synchronous or metachronous liver-only metastases.
Newsweek article – Major study finds key difference in bowel cancer before 50 (Open access)
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