Neoadjuvant Rectal (NAR) Score: a New Surrogate Endpoint in Rectal Cancer Clinical Trials

Abstract

The conduct of clinical trials in colorectal cancer has historically relied upon endpoints such as disease-free (DFS) or overall survival (OS). While ideal, these endpoints require long-term follow-up, thus contributing to a slow pace of scientific progress in clinical research. Identification of short-term endpoints to serve as surrogates for DFS and OS would enable more rapid determination of success or failure of an experimental intervention and thus facilitate more scientific discovery and progress leading to clinical practice improvements. In rectal cancer clinical trials, there have been few validated alternatives to DFS and OS, including pathologic complete response (ypCR). The neoadjuvant rectal (NAR) score was developed as a composite short-term endpoint for clinical trials involving neoadjuvant therapy for rectal cancer. The NAR score is based upon variables routinely collected and available to clinical investigators during the conduct of prospective studies. Based upon two independent validation datasets, the NAR score predicts OS in rectal cancer clinical trials better than ypCR. While final dataset validation is ongoing, the NAR score offers an opportunity to incorporate a novel surrogate endpoint into early phase rectal cancer clinical trials.

Keywords: Clinical trial; Endpoint; NAR score; Neoadjuvant; Nomogram; Pathologic complete response; Rectal cancer; Surrogate; pCR.

Fig. 1

Calculation of the neoadjuvant rectal (NAR) score. cT is an element of the set {1, 2, 3, 4}, pT is in {0, 1, 2, 3, 4}, and pN is in {0, 1, 2}. cT clinical tumor stage, pT pathologic tumor stage, pN pathologic nodal stage

Fig. 2

Overall survival by neoadjuvant rectal (NAR) score by group in NSABP R-04 clinical trial