ESMO E-Learning: Optimising Outcomes For Patients With Advanced Colorectal Cancer

In this E-Learning module, the authors emphasise that the survival of patients with metastatic colorectal cancer (CRC) can be optimised through the integration of systemic therapy, surgical resection and ablative modalities, where appropriate, preferably in a multidisciplinary team setting. Insights in the biology of the disease and biomarker-driven therapeutic strategies are expected to improve survival and rationalise therapeutic approaches. Furthermore, basic and translational cancer research leading to well defined hypotheses that are tested in appropriately stratified and molecularly-enriched clinical trials is the way forward.

The authors have divided the module into three parts. In the first part, the authors underline that the optimal sequencing of currently available therapies for non-resectable metastatic disease remains to be elucidated in terms of toxicity and patient’s tolerance, as well as biomarkers. The authors discuss tumour, patient’s and treatment characteristics as factors to decide about first-line treatment.

The authors elaborate current options for first-line therapy through answering the questions such as:

Does a combination strategy outperform sequential treatment?

What does bevacizumab add to the outcome?

What do EGFR inhibitors add to outcome in case of KRAS wt colorectal cancer? Should we add bevacizumab or an EGFR inhibitor in case of Ras wt colorectal cancer?

They provide the recommendations for RAS and BRAF mutations testing and elaborate atypical BRAF mutations. They also show evidence for continous versus intermitent first-line systemic therapy, the results from the clinical trials in second-line treatment, as well as standard and emerging options beyond second-line.  

Standardisation of the tissue processing for patients with metastatic CRC remains a challenge. In the second part of the module, beyond tissue handling, the authors elaborate actionable molecular aberrations, primary tumour sidedness, the importance of information in terms of microsatellite instability (MSI) status, the results from the studies with immune checkpoint inhibitors in MSI-high/MMR-deficient tumours, as well as findings from studies targeting HER2, NTRK fusions. They summarise the treatment options according to specific biomarkers and introduce a concept of liquid biopsy in CRC.

This part of the module is completed with information on the consensus molecular subtypes of CRC.

The last part of the module is dedicated to the management of oligometastatic disease: the treatment goal, principles of resection of colorectal, liver metastases, as well as induction chemotherapy for patients with borderline resectable metastases.