Colorectal cancer is one of the most common cancers worldwide. In about half of patients, the disease eventually spreads to other organs such as the liver, lungs, or the lining of the abdomen. When cancer has spread this far, treatment is usually not aimed at curing the disease, but at helping patients live longer while maintaining quality of life. This dissertation shows that aggressively treating as many visible metastases as possible — known as tumor debulking — does not extend overall survival compared to chemotherapy alone. Patients lived just as long in both treatment groups (around 30 versus 27.5 months on average), and the time before the disease started growing again was also nearly identical. Importantly, quality of life during the first year remained similar, even though serious treatment-related side effects occurred almost twice as often in patients who received debulking therapy. A previously promising microRNA profile failed to reliably predict who benefits most from treatment. However, patients with high levels of active immune cells (CD8+ T-cells) in the blood showed better survival, offering a hopeful direction for future research. The findings highlight that intensive local treatments for widespread metastases should not be used as standard care, and that better ways to identify the right patients for the right treatment are still urgently needed.
Lotte Bakkerus (1992) graduated with her medical degree from the University of Amsterdam in 2018. After a gap year as a research assistant in the Medical Oncology department at Amsterdam UMC, she conducted her PhD research within the ORCHESTRA study at Amsterdam UMC and Radboudumc. She is currently a junior doctor in Internal Medicine and has started her residency at UMC Utrecht.