Research is moving forward to adapt clinical practice to a new wave of early-onset cases of cancer in the digestive tract
Early-onset gastrointestinal (GI) cancers, occurring in people below the age of 50, are on the rise in high-income countries (JAMA Netw Open 2023 Aug 1;6(8):e2328171) - a trend that is especially worrisome because, taken together, GI cancers account for a quarter of all new cancer cases and a third of cancer deaths worldwide (Lancet Gastroenterol Hepatol 2024;9:229–37). Research is ongoing to understand the causes and inform prevention and management of these young patients, as a dedicated session at the ESMO Gastrointestinal Cancers Congress 2024 shows. Emerging data on the features and outcomes of early-onset disease lead us to a differentiated view of the phenomenon across different tumour types.
As presented in Munich, one study conducted at two institutions in Greece and Cyprus found that the clinical and molecular characteristics of colorectal cancer, the most common GI malignancy, are generally similar across patient age groups (Abstract 139P). Notable differences previously described pertain to the tumour location, which is more frequently the left colon in younger patients, and to an increased likelihood of early-onset disease being linked to a hereditary cancer risk such as Lynch syndrome (N Engl J Med 2022;386:1547-58). Early-onset colorectal cancer is also more likely to be diagnosed at an advanced stage, possibly because younger patients do not pay as close attention to the relevant symptoms. In the metastatic setting, patients younger than 50 years may additionally have a poorer prognosis than their older counterparts (Abstract 80P).
Early-onset cancer of the pancreas similarly appeared to be associated with more aggressive disease at several institutions in Tunisia, where patients under 45 years of age were reported to have lower rates of curative surgery and higher rates of relapse after surgery (Abstract 365P). Patients diagnosed with biliary tract cancer by the age of 50, by contrast, may have a somewhat better prognosis in the metastatic setting than their elders, with more opportunities to receive personalised therapies thanks to a higher frequency of targetable alterations such as FGFR2 fusions (Abstract 291P).
The optimal management of younger patients, for example through more aggressive treatment approaches, remains in many respects to be determined, and is further complicated by the specific psychosocial issues surrounding rehabilitation, returning to work after completing treatment and survivorship issues that this age group faces. However, the knowledge we do have provides a strong rationale for immediate changes in practice such as lowering the starting age of colorectal cancer screening programmes and offering germline genetic testing to all patients diagnosed before the age of 50, followed by genetic counselling for them and their relatives as appropriate. In the medium term, measures are also needed to strengthen citizens’ health literacy and improve overall participation in screening campaigns, which remain largely underutilised across Europe.
Future epidemiological research should aim to define more precisely the risk factors for early-onset GI cancers, as similar incidence trends across countries in the developed world suggest environmental and lifestyle causes that could become the target of future prevention strategies. The Western-style diet, low physical activity, obesity, alcoholism, tobacco consumption and use of antibiotics have all been proposed as contributors to changes in the gut microbiome and gut inflammation that can lead to carcinogenesis (Cancer Discov 2023;13:538–51), but their impact on cancer risk and its potential to be reversed still need to be confirmed. A society like ESMO will have its role to play in disseminating advances in our scientific understanding of this phenomenon and educating doctors and patients on health-promoting lifestyles that could help to break the trend.
