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We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. Back to Healio Key takeaways: Sex, left-sided cancers and mutational burden can significantly differ in early- and late-onset colorectal cancer with liver metastases. Patients with early-onset disease had significantly longer survival. Early-onset colorectal cancer with liver-only metastases can have significant differences in biology from late-onset malignancies. A study of nearly 1,700 individuals from Australia showed early-onset disease occurred more often in women, and patients had higher rates of BRAF mutations and left-sided cancers.
Data derived from Barreto SG, et al. Med J Aust. 2026;doi:10.5694\/mja2.70266.
Additionally, those with early-onset disease had better functional status, fewer comorbidities and significantly longer survival. Savio G. Barreto \u201cThese [biological differences] likely impact the behavior of the cancer and, hence, response to treatments,\u201d Savio G. Barreto, FRACS, PhD, professor of surgery at Flinders University in Australia, told Healio. \u201cUnderstanding these nuanced differences is key to the delivery of personalized therapy.\u201d \u2018Lack of clarity\u2019 Colorectal cancer incidence declined 0.9% annually in the U.S. between 2013 and 2022, but rose 3% per year for individuals aged 20 to 49 years, according to Colorectal Cancer Statistics 2026 report. Similar trends can be seen globally, and Australia has the highest prevalence of early-onset disease, according to study background. \u201cMetastases to the liver is a key determinant of poor long-term survival in such patients,\u201d Barreto said. \u201cThere is a lack of clarity on the ideal timing of the sequence of therapies [surgery vs. chemotherapy vs. immunotherapy], and given the low number of patients, it is difficult to carry out well powered prospective randomized controlled trials. \u201cTo empower clinical decision-making based on evidence, and to clarify if the \u2018one size fits all\u2019 policy for treating patients across all ages is justified, we decided to embark on this analysis comparing early- and late-onset colorectal cancer focusing on liver only metastases.\u201d Researchers used the Treatment of Recurrent and Advanced Colorectal Cancer registry in Australia to investigate. Their retrospective analysis included 1,691 consecutive adults (median age, 65 years; interquartile range, 55-75; 63.3% men; 83.7% with late-stage disease) enrolled in the registry between Jan. 14, 2009, and Sept. 2, 2024. Cancer biology, treatments and outcomes among patients with early-onset and late-onset colorectal cancer served as primary endpoints. \u2018Pleasantly surprised\u2019 The early-onset cohort consisted of significantly higher rates of women (48.2% vs. 34.5%), patients with a Charlson comorbidity index of 0 to 1 (97.1% vs. 80.4%), ECOG score of 0 to 1 (97.4% vs. 85%), left colon and rectal malignancies (76.1% vs. 65.7%) and synchronous metastases at presentation (53.3% vs. 42.1%; all P < .001). Patients with early-onset disease also had significantly higher rates of cancers with BRAF mutations (13.9% vs. 8.1%; P = .01), but not KRAS or NRAS mutations. Mismatch repair status did not differ between early- and late-stage disease, either. Clinicians offered active treatments to patients with early-onset malignancies at significantly higher rates (98.6% vs. 92.1%; P < .001). Those with early-onset disease also received active treatments with greater frequency (96% vs. 88.5%; P < .001). Researchers observed significantly longer median OS for patients with early-onset colorectal cancer (3.2 years vs. 2.38 years; P < .001). Among those with metachronous metastases, patients with early-onset disease also had significantly longer median OS (8.86 years vs. 3.83 years; P < .001). Among those undergoing liver resection, OS did not significantly differ. Among patients with early-onset colorectal cancer, researchers observed significantly worse survival among those with KRAS (HR = 2.38; 95% CI, 1.39-4.06), NRAS (HR = 3.57; 95% CI, 1.11-11.5) and BRAF V600E (HR = 2.83; 95% CI, 1.33-6.02) mutations. They found similar associations among patients with late-onset disease with KRAS (HR = 1.55; 95% CI, 1.22-1.98) and BRAF (HR = 2.61; 95% CI, 1.79-3.81) mutations. \u201cI was pleasantly surprised that the findings confirmed a long-held belief that early-onset cancers possess differences in biology and behavior compared to late-onset disease,\u201d Barreto said. \u201cWhile we have long since known about the importance of BRAF mutations negatively impacting survival in early-onset colorectal cancer, the impact of NRAS mutations is novel.\u201d Both cohorts had significantly improved survival if they had surgery then adjuvant chemotherapy and\/or biological treatments (early onset, HR = 0.19; 95% CI, 0.08-0.44; late-onset, HR = 0.34; 95% CI, 0.25-0.47). Barreto and colleagues observed greater benefit among patients with synchronous metastases (median survival, 6 years vs. 2.91 years) and left colon primary malignancies (median survival, 5.98 years vs. 4.67 years). Researchers acknowledged study limitations, including its observational nature and the population size. Barreto noted future research should investigate epigenetic biomarkers to better ascertain risk. Barreto and colleagues plan to continue analyzing the \u201ccardinal\u201d question, \u201cWhat is driving the rise in early-onset adult cancers?\u201d \u201cWe hypothesized that if the cumulative effect of exposures\/stressors overwhelms the body\u2019s own protective systems [nutritional, neurohormonal, immune, etc] at two critical time periods, namely, the perinatal period as well as adolescence and young adulthood, it could trigger epigenetic modifications,\u201d he said. \u201cWe now know that epigenetic modifications can influence every hallmark of cancer.\u201d Reference: For more information: Savio G. Barreto, FRACS, PhD, can be reached at savio.barreto@flinders.edu.au. Perspective Back to Top I see this as an important contribution to understanding early-onset colorectal cancer, particularly in patients with liver-only metastatic disease. Some findings were consistent with what I would expect: younger patients, defined here as age 50 years or younger, had fewer comorbidities, more left-sided tumors, and were more likely to receive active treatment. What stood out was the higher frequency of BRAF V600E mutations among younger patients with available testing despite longer overall survival in the younger group. That underscores the importance of considering tumor biology alongside overall health and<\/p>\n","protected":false},"author":1,"featured_media":3948,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-3947","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts\/3947","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3947"}],"version-history":[{"count":0,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/posts\/3947\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=\/wp\/v2\/media\/3948"}],"wp:attachment":[{"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3947"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3947"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/drsoniafawad.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3947"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
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