Evidence-Based Care of Older Adults With Metastatic Colorectal Cancer: Insights From Landmark Clinical Trials

Abstract

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States with more than half of the patients diagnosed being older than 65 years, and an expected further increase in older adults (OA) diagnosed with this cancer in the coming years as the population ages. Prospective data guiding the management of older patients with metastatic CRC (mCRC) have been limited and treatment decisions for these patients are often guided by chronologic age, crude evaluation of performance status, and extrapolation from trials conducted in younger individuals. Recent evidence from randomized clinical trials specifically designed for OA supports treatment deintensification and dose modification to increase tolerability without compromising efficacy in older, frailer patients with mCRC. Additional studies support the incorporation of geriatric assessment (GA)-driven care to further improve the outcomes of OA with mCRC. Although the use of GA has not been validated in guiding specific treatment selection or modification for OA with mCRC, it provides a comprehensive and objective evaluation of a patient's functional status, comorbidities, risk of potential toxicities, effect on the quality of life, goals of care, and assists with personalizing therapy. With the increase in the number of OA we care for in our practices, it is time to stop extrapolating and define an evidence-based approach for this population that is based on data from prospective elderly specific clinical trials.

FIG 1.

Patient imaging. (A) Pretreatment, metastatic liver lesion measuring 4.8 × 4.7 cm. (B) Restaging imaging after 12 cycles of treatment, liver lesion measuring 6.8 × 6.6 cm.

FIG 2.

Suggested algorithm for treating older patients with metastatic colorectal cancer on the basis of geriatric assessment and molecular biomarkers. ^aAll patients who are being considered for treatment require molecular profiling of their tumor to determine RAS/BRAF status, as well as MMR testing. ^bComprehensive list of GA tools is available in published guidelines by the NCCN, ASCO.^{, c}Cancer and CARG Toxicity Tool, CRASH. 5-FU, fluorouracil; ADL, activities of daily living; ASCO, American Society of Clinical Oncology; CARG, Aging Research Group Chemotherapy; CRASH, Chemotherapy Risk Assessment Scale for High-Age Patients; ECOG PS, Eastern Cooperative Oncology Group performance status; GA, geriatric assessment; IADL, instrumental activities of daily living; MMR, mismatch repair; NCCN, National Comprehensive Cancer Network; WT, wild-type.