Patients with metastatic colorectal cancer (mCRC) should undergo targeted, personalized therapy based on their medical fitness and the most appropriate treatment goals. In nonsurgical cases, molecular tumor profiling should guide the choice of therapy, say European experts.
Using a consensus approach, the European Society for Medical Oncology (ESMO) has produced a series of recommendations that set out the role of specific biomarkers in profiling tumors, as well as a "toolbox" of local and locoregional treatment options.
The consensus guidelines were published online July 5 in theAnnals of Oncology.
The most important aspect of the guidelines, say the authors, is the treatment algorithm, which builds on recent breakthroughs in the understanding of factors affecting treatment choices. In the algorithm, the patient's condition is combined with therapeutic goals, such as tumor shrinkage or slowing disease progression, and the presence of molecular markers to determine the most appropriate treatment.
Lead author Eric Van Cutsem, MD, PhD, ESMO Guidelines Committee and professor of internal medicine at the University of Leuven, Belgium, said in a release: "Colon cancer management is making progress, leading...to prolonged survival ― up from 6 months to 30 months in many patients."
"With these long-awaited guidelines, the management of metastatic colorectal cancer officially enters the personalized era, addressing the role of existing and emerging biomarkers and their role in the clinic," commented Fotios Loupakis, MD, Istituto Toscano Tumori, Livorno, and the University of Pisa, in Italy. Dr Loupakis is also a member of the ESMO Faculty for Gastro-Intestinal Tumors. He was not one of the authors.
"The new guidelines move from the clinically defined historical categories, which were focused on the resectability of metastases, to a less sharp but more realistic assessment that gives more importance to additional elements, such as patient, tumor, and treatment characteristics," Dr Loupakis said in a statement.
Consensus Conference Approach
To take into account improvements in diagnosis, treatment, and patient management strategies that have emerged since the previous ESMO guidelines were issued in 2012, the guidelines committee used a consensus conference approach to update the clinical recommendations.
An international panel of experts was convened in Zurich in December 2014. It consisted of three working groups that focused on molecular pathways and biomarkers, local and ablative treatment, and the treatment of metastatic disease.
The working groups were assigned relevant questions, and they discussed recommendations relating to their questions. These recommendations were then presented to the entire panel and were modified until a consensus was reached
The resulting consensus guidelines emphasize that a diagnosis of mCRC should be confirmed by adequate radiologic imaging, as well as assessment of tissue and biopsy samples, before systemic therapy is initiated. The guidelines also emphasize the need to handle all tissue and biopsy samples appropriately to facilitate molecular testing for diagnostic, predictive, or prognostic biomarkers.
The guidelines recommend testing for the tumor's RASmutational status, as well as for the presence of BRAFmutations and microsatellite instability, which is strongly predictive of the effectiveness of immune checkpoint inhibitors.
Testing for other biomarkers of chemotherapy sensitivity and toxicity is not routinely recommended. There are a number of emerging biomarkers in mCRC, such as those relating to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2, the use of which is are not recommended at this stage outside of the clinical trial setting.
For local ablative treatment, the guidelines underscore the importance of the multidisciplinary team, which should ideally include a colorectal surgeon, a hepatobiliary and/or lung surgeon, a pathologist, a diagnostic radiologist, and radiation and medical/gastrointestinal oncologists.
In cases of oligometastatic disease that is localized to a few sites and lesions, the standard of care is systemic therapy. The best local treatment should be chosen from a "toolbox" of options, depending on disease localization, the treatment goal, treatment-related morbidity, and patient-related factors, such as comorbidities and age.
The toolbox is divided into local treatments, both thermal and nonthermal, and locoregional treatments. It comprises thermal ablation, stereotactic ablative body radiotherapy, chemo- and radioembolization, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases.
The central innovation of the guidelines is the treatment algorithm, which places assessment of the clinical condition of the patient as the first guiding step in choosing the most appropriate therapy.
As an example, patients deemed fit in terms of their medical condition may undergo surgery if they have clearly resectable metastases, or they may be directed toward either cytoreduction or disease control, whichever is more appropriate.
Patients in whom cytoreduction or disease control is appropriate should then undergo biomarker testing to determine the molecular profile of their tumor, which then guides targeted combination chemotherapy with or without an anti-EGFR drug, an antiangiogenic agent, such as bevacizumab, or a biological agent, depending on the result.
Patient and disease status should be assessed every 2 or 3 months, at which point treatment goals should be reevaluated. At this stage, progressive disease is treated with second-line therapies. Patients deemed unfit at initial assessment should be directed toward best supportive care.
Lead author and Chair of the ESMO Concensus Conference Eric Van Cutsem, MD, PhD, from the University Hospitals Gasthuisberg/Leuven, in Belgium, emphasized to Medscape Medical News that these new guidelines do not require the development of new services because they are "based on standard-of-care options."
He noted that complex decisions should be taken in multidisciplinary expert teams and more complex surgery, such as resection of metastases, should only be performed by experienced surgical teams. It cannot be performed in every hospital; therefore, a referral network should ensure that patients have access to the most appropriate care.
Dr Van Cutsem also pointed that for the resection of liver metastases, radioembolization "is, of course, not available in every hospital," and neither is HIPEC. Every hospital can give basic services, and when specific expertise is required, it can be provided from within the referral network.
"Management of metastatic colorectal cancer is becoming more complex, requiring a strategic approach and evidence-based patient selection for the best treatment options," Dr Van Cutsem said in a statement. He noted that progress in the management of colon cancer is attributed to the use of combination chemotherapy and the development of novel second-line agents, including angiogenesis inhibitors, EGFR antibodies, and new agents for chemorefractory disease, such as regorafenib and trifluridine/tipiracil.