Prevention and early detection are becoming increasingly important

The treatment of gastrointestinal cancer is catching up with other areas of oncology and offers patients better prospects of survival and quality of life. However, a significant increase in early-onset cases raises new questions about effective prevention, diagnosis and treatment.

(red) Malignant diseases of the gastrointestinal tract account for a quarter of all cancer cases worldwide and one in three cancer-related deaths, with colorectal cancer being one of the three most common tumor types and causing over 900,000 deaths annually. The annual number of new cases at an early stage, i.e. in people under the age of 50, has risen by 51% in high-income regions since the 1990s. If this trend continues, bowel cancer could become the deadliest cancer in the 20 to 49 age group by 2030. The research results now presented at the congress confirm that young patients with gastrointestinal cancer are more likely to be diagnosed at an advanced stage, which is a possible explanation for the poorer treatment results in this age group. Similarly, one study found that pancreatic cancer is more aggressive in younger people, with a lower rate of curative surgery and a higher risk of recurrence. In contrast, young patients with advanced-stage biliary tract cancer appear to have a better prognosis than their older counterparts, as they are more likely to have targetable molecular alterations such as FGFR2 fusions and are therefore eligible for personalized therapies.

With almost 455,000 new cases of colorectal cancer diagnosed in Europe in 2022, including 20,000 patients between the ages of 18 and 49, ESMO President Andrés Cervantes emphasized the importance of better understanding the characteristics of this young patient group and the risk factors they are exposed to in order to develop effective strategies for prevention and early detection. Hereditary cancer risks such as Lynch syndrome make early onset of the disease more likely, but they only account for a minority of diagnosed cases. As the age shift is observed in various gastrointestinal cancers and in high-income countries worldwide, there is a reasonable suspicion that lifestyle-related factors affecting the composition of the gut microbiome play a role, e.g. Western diet, low physical activity or antibiotic use, but these hypotheses have yet to be scientifically confirmed.

New approaches for the early detection of gastrointestinal cancer

As a very heterogeneous group of diseases, gastrointestinal cancers as a whole are an area of high unmet need where late diagnosis remains a common problem leading to poor outcomes. “We have a problem with prevention and screening in the area of gastrointestinal cancer, where compliance with requests for stool tests or colonoscopies is below 30% across Europe, compared to compliance with breast cancer screening, which is two to three times higher,” emphasized Cervantes, calling for educational measures and collaboration with GPs to improve awareness and acceptance.

New perspectives in this area are opening up technologies that were previously used for advanced diseases and are now being used to screen for cancers that are not yet clinically detectable. “Tests for the early detection of several types of cancer, especially in the form of blood tests, are attracting great interest as they allow cancer patients to be diagnosed at an earlier stage and increase their chances of recovery,” says Benedikt Westphalen, Comprehensive Cancer Center Munich, Germany, Chairman of the ESMO Working Group on Translational Research and Precision Medicine, who sees the potential of these non-invasive methods for expanding the early detection of gastrointestinal cancer, including in younger patients.

Research highlights at a glance

The growing interest and scientific activity in the field of GI oncology ends the period in which the treatment of GI cancers lagged behind other areas of oncology, which experienced successive waves of innovation with targeted agents and immunotherapy. “In the past, we had difficulties integrating these new therapies into gastrointestinal oncology because we had to identify patient subgroups that could really benefit from them, but this is now changing,” explained Florian Lordick, University of Leipzig, Germany, citing as an example GI tumors with microsatellite instability, whose treatment has been transformed by immunotherapy, allowing some patients to be spared major surgery.

One promising area of research focuses on making better use of existing therapies to optimize patient outcomes. “The final analysis of the long-term data from the KEYNOTE-585 study on the integration of immunotherapy in the treatment of advanced gastroesophageal carcinoma shows, for example, that it works very well in some patients with high PD-L1 expression in the tumor tissue, but not in those with a negative biomarker,” explained Lordick. An update of the TOPAZ-1 study of durvalumab in bile duct cancer shows the long-term survival achieved with this immunotherapy and provides insights into the specific outcomes achieved in different patient subgroups. Another study with potential practical implications has shown that a subset of gastric cancer patients who are negative for all currently applicable biomarkers (HER2, PD-L1 and DNA mismatch repair deficiency), and therefore have limited options, may benefit from the integration of an old chemotherapy agent, paclitaxel, into their treatment course. For a rare category of gastroenteropancreatic neuroendocrine tumors, data from a prospective randomized trial confirm for the first time the efficacy of a form of targeted treatment by intravenous radiotherapy in all patient subgroups.

Congress: ESMO Gastrointestinal Cancers Congress 2024