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Prevention and early detection of gastrointestinal cancers take on new importance amidst a younger population

June 27, 2024 – Other – esmo, oncology

Emerging research on early-onset gastrointestinal cancers highlights need for better prevention, diagnosis and treatment

Less invasive, smart technologies could improve participation in and efficacy of GI cancer screening

Studies presented at the ESMO Gastrointestinal Cancers Congress 2024 could improve outcomes through better patient selection and optimised use of available therapies

27 June 2024, Munich, Germany – Treatment of gastrointestinal (GI) cancers is catching up with other areas of oncology and offering patients better prospects for survival and quality of life, but a significant uptick in early-onset cases is raising new questions about effective prevention, diagnosis and treatment. That was the subject of much discussion at the press conference – moderated by Angela Lamarca, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain, ESMO Press Officer – of the ESMO Gastrointestinal Cancers Congress 2024 taking place in Munich, Germany, 26-29 June.

Early-onset GI cancers: A growing concern
Gastrointestinal malignancies account for a quarter of cancer cases and for one in three cancer-related deaths globally, with colorectal cancer being among the three most common tumour types and causing over 900,000 fatalities each year. Annual new cases of early-onset disease, i.e., in individuals below the age of 50, have risen by 51% in high-income regions since the 1990s, and if this trend continues colorectal cancer could become the deadliest cancer in the 20-49 demographic by 2030.

Research presented in Munich tends to confirm that young GI cancer patients are more likely to be diagnosed at an advanced stage, a possible explanation for the poorer outcomes seen in this age group. Similarly, one study found that pancreatic cancer displays more aggressive behaviour in younger individuals, with lower rates of curative surgery and a higher risk of relapse. In the area of biliary tract cancers, by contrast, young patients appeared to have a better prognosis than their older counterparts in the advanced setting thanks to a higher prevalence of actionable molecular alterations such as FGFR2 fusions making them eligible for personalised therapies.

With almost 455,000 new cases of colorectal cancer diagnosed in Europe in 2022, including 20,000 patients aged between 18 and 49 years, ESMO President Andrés Cervantes highlighted the importance of better understanding the characteristics of this young patient demographic as well as the risk factors they are exposed to in order to help design effective strategies for prevention and early detection. Hereditary cancer risks such as Lynch syndrome make early-onset disease more likely, but these only account for a minority of the cases diagnosed. As the age shift is observed for different gastrointestinal cancers and across high-income countries globally, there is good reason to suspect lifestyle-related factors that affect the composition of the gut microbiome are playing a role, such as the Western diet, low physical activity or use of antibiotics, but these hypotheses still need to be scientifically confirmed.

From prevention to early diagnosis: New approaches to GI cancer screening
As a very heterogeneous group of diseases, gastrointestinal cancers remain overall an area with high unmet need and in which late diagnosis remains a common issue leading to poor outcomes. “We have a problem with prevention and screening in the GI field, where compliance with invitations to undergo stool testing or colonoscopies is lower than 30% across Europe, compared to adherence to breast cancer screening which is two to three times higher,” Cervantes emphasised, calling for educational efforts and collaboration with primary care physicians to improve awareness and acceptance.

Opening up new perspectives in this area are technologies that were previously used in the advanced disease setting, now being used to screen for cancers that are not yet clinically detectable.

“Multi-cancer early detection tests, mainly in the form of blood tests, are drawing a lot of interest to allow diagnosis of cancer patients at an earlier stage and increase their chances of being cured,” said Benedikt Westphalen, Comprehensive Cancer Centre Munich, Germany, chair of the ESMO Translational Research and Precision Medicine Working Group, who saw potential for these non-invasive methods to extend the reach of GI cancer screening both in the general population and particularly in younger age groups.

Research highlights from the ESMO GI Congress programme
Growing interest and scientific activity in the field of GI oncology are putting an end to the time when treatment of GI cancers was lagging behind other areas of oncology that saw successive waves of innovation with targeted agents and immunotherapy. “We had difficulties integrating these new therapies in gastrointestinal oncology in the past because we had to identify patient subgroups who could really benefit from them, but this is now changing,” Florian Lordick, University of Leipzig, Germany, editor-in-chief of the journal ESMO Gastrointestinal Oncology, explained, citing the example of GI tumours with microsatellite instability, the management of which has been transformed by immunotherapy, now allowing some patients to be spared major surgery.

Progress is increasingly coming from multidisciplinary approaches to managing gastrointestinal cancers, with research presented in Munich spanning the fields of medical oncology, surgery, radiotherapy, genetics and immunology. One such breakthrough is being achieved with liver transplants in patients with advanced colorectal cancer that has metastasised to the liver, with data to be presented for the first time in Europe during the ESMO Gastrointestinal Cancers Congress.

Another promising area of research is focusing on making better use of existing therapies to optimise outcomes for patients. “For example, final analysis of long-term data from the KEYNOTE-585 trial integrating immunotherapy in the treatment of advanced gastro-oesophageal cancer reveals that this works very well for some patients with high PD-L1 expression in the tumour tissue, but not for those with a negative biomarker,” Lordick explained. “It is interesting to look at these data in detail because we have to make decisions on a daily basis about who to give these drugs to.” Similarly, an update from the TOPAZ-1 study of durvalumab in biliary tract cancer shows the long-term survival achieved with this immunotherapy and offers insights into the specific results achieved within different patient subgroups.

A further study with potential practical implications showed that a subset of gastric cancer patients who are negative for all currently actionable biomarkers (HER2, PD-L1 and DNA mismatch repair deficiency) and thus have limited options could benefit from the integration of an old chemotherapy agent, paclitaxel, into their course of treatment. For a rare category of gastroenteropancreatic neuroendocrine tumours, data from a prospective randomised trial for the first time confirms the efficacy of a form of targeted treatment by intravenous radiotherapy across patient subgroups.

In colorectal cancer, too, new combinations of immunotherapy with chemotherapy or of immunotherapy with targeted agents in different settings are attempting to optimise the benefit for specific subgroups of patients. Existing diagnostic tools are also being used in complementary ways to further improve the identification of patients for treatments from which they are most likely to benefit.

“This is going to be a very rich congress with a lot of innovation being presented, but also a motivating one for attendees who will be able to go home to their practice with new tools and strategies to implement with their patients,” Cervantes concluded.

About the European Society for Medical Oncology (ESMO):
Representing more than 35,000 oncology professionals from 172 countries worldwide, ESMO is a reference for oncology education and information. Driven by a shared determination to secure the best possible outcomes for patients, ESMO is committed to standing by those who care about cancer through addressing the diverse needs of #ONEoncologycommunity, offering #educationforLIFE, and advocating for #accessiblecancerCARE. Visit: www.esmo.org