Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: The reverse of the Will Rogers phenomenon?

Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, downstage migration after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes. Cancer 2015;121:1724-1727. (c) 2015 American Cancer Society. Although downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials, the current study directly questions its value after preoperative treatment when assessing treatment efficacy.