Tumor Response Assessment for Precision Cancer Therapy: Response Evaluation Criteria in Solid Tumors and Beyond

Abstract

Objective assessment of tumor responses and treatment results has been the basis for the advancement of cancer therapies, and imaging plays a key role to provide a “common language” to describe the results of cancer treatment. Although Response Evaluation Criteria in Solid Tumors (RECIST) has been the most widely accepted method for assessing tumor response in the past decades, the limitations of RECIST have increasingly becoming recognized, especially with the recent advances of precision-medicine approaches to cancer. This article reviews the current concept of tumor response evaluations based on RECIST, describes the limitations of RECIST, and proposes strategies to overcome the limitations. The article emphasizes specific limitations in the setting of precision cancer therapy and cancer immunotherapy and discusses the important insights provided by the cutting-edge investigations in the emerging fields.PRACTICAL APPLICATIONSRECIST1.1 is the current version of tumor response criteria that are widely accepted as a standardized method in most trials of solid tumors in general; it uses unidimensional diameters of target lesions and the sum of measurements of all target lesions as a quantitative measure of tumor burden. Major limitations of RECIST that universally affect the response assessment regardless of tumor types or agents include variability of tumor size measurements and tumoral heterogeneity both within a lesion and among different lesions in a patient. Among the specific limitations of RECIST in precision cancer therapy, in patients treated with molecular targeting agents with antiangiogenic activity, decrease of CT tumor density may reflect response to therapy even without tumor size decrease meeting the criteria for RECIST response; Choi criteria can contribute to address the pitfall. In patients with tumors harboring specific genomic abnormalities treated with effective molecular targeting therapy, tumors tend to show marked initial response and then slowly grow back while the patients are receiving therapy, where RECIST progression does not necessarily indicate treatment failure and the tumor growth rate may contribute to help therapeutic decisions. In patients treated with cancer immunotherapy using immune checkpoint blockade, atypical response patterns or pseudoprogression, although rare, can be noted, and several criteria have been proposed to address the unmet needs in the emerging field.