Personalized adjuvant treatment in stage II colon cancer (WC2017-042)

Background

Starting date: 01/02/2017

Colon cancer (CC) is a major disease in The Netherlands (annual incidence 11.000, mortality 4000 (2015)) with a substantial burden for patients, care givers, health care and society. A large proportion of newly diagnosed colon cancer patients have stage II disease (~3000 per year) and it is foreseeable that this will increase under the recently initiated national screening program. Although CC care in The Netherlands has improved substantially during past decades, particularly the identification of patients that require adjuvant chemotherapy remains challenging.

In stage II CC, curative treatment can be realized by surgical resection. In addition, adjuvant chemotherapy is recommended for stage II patients with a high risk of recurrence. The correct identification of high-risk patients is thus essential to optimize survival probability, without inducing the harms of over-treatment in patients who will not benefit. Currently, high-risk patients are being identified based on clinical and pathological factors [1]. However, the value of these factors, which have been implemented in Dutch and international guidelines, is controversial.

Patient selection can be improved in several manners. Firstly, by accurate and systematic reporting of known risk factors as well as other relevant pathological data, the PALGA colon and rectal module for synoptic reporting, increasingly used since 2009, is expected to improve quality of care. For example, by in depth lymph node examination, micro-metastases may be identified in clinical stage II, which is related to increased risk of recurrence. Micro-metastases are reported in the PALGA module since start 2015. Secondly, molecular testing of tumours has provided insight in tumour heterogeneity. For a number of specific aberrations, like MMR, BRAF and possibly also (K)RAS mutations, an impact on prognosis and/or response to adjuvant chemotherapy has been reported. Thirdly, to cover the multi-factorial complex molecular nature of tumours, gene-expression signatures have been developed to identify distinct subtypes. The potential value of subtypes to inform adjuvant treatment decisions has been discussed and is focus of KWF/Alpe d’HuZes project CONNECTION (PI JPM).

Problem definition: Remaining issues to minimize under- and overtreatment in daily practice
• Incomplete assessment of nodal involvement, which is associated with disease recurrence.
• Although there is clinical evidence for the value of specific aberrations, like MMR status and BRAF mutations (possibly KRAS), the value of testing for these aberrations in general practice has not yet been evaluated and these aberrations are not routinely tested. This will lead to over- and under-treatment.
• Clinical data regarding gene expression based subtypes for the prediction of recurrences and/or adjuvant chemotherapy is very promising, but not yet validated and not ready for use for the individual patient.