Locally Advanced Rectal Cancer—Precision Therapy in a Time of Moving Targets and Competing Goals

In this issue of JAMA Oncology, Diefenhardt and colleagues¹ report a post hoc analysis of the previously published German CAO/ARO/AIO-04 trial² and found that the ability of patients with rectal cancer to complete planned neoadjuvant (but not adjuvant) therapy was associated with improved disease-free survival. The authors concluded “the findings emphasize the need for appropriate trial design with optimized nCRT [neoadjuvant chemoradiotherapy] dose and schedule and supportive strategies to facilitate good adherence and precision delivery, especially for intensified nCRT.”¹ Few would dispute this broad point, but the greater challenge lies in aligning their recommendations with current paradigms of rectal cancer treatment, which have evolved dynamically since the CAO/ARO/AIO-04 study.