Classification of pathologic response to neoadjuvant therapy in esophageal and junctional cancer: assessment of existing measures and proposal of a novel 3-point standard.

Abstract

To assess existing measures of pathologic response to neoadjuvant therapy in esophageal and junctional cancer, and to recommend an optimum classification. Multimodal therapy is increasingly the standard of care for locally advanced esophageal cancer. Numerous measures of pathologic response have been studied; however, no international standardization exists and no measure is incorporated into the current American Joint Committee on Cancer staging system. A total of 393 consecutive patients completing multimodal therapy were studied, all with prospectively recorded Mandard tumor regression grades (TRG). Seven other published methods of response were compared, and a novel 3-point TRG [TRG 1 (complete); TRG 2/3 (partial); TRG 4/5 (none/minimal)] was tested. Clinical and pathologic evidence of nodal regression was assessed in a consecutive subset of 200 comprehensively staged patients. All models had similar discriminatory and stratification power, and they predicted survival (P < 0.0001) on univariate analysis. Conversely, only the 3-point TRG (P = 0.042) along with ypN (P < 0.001) and ypT stage (P < 0.001) independently predicted survival. The median survival for TRG 1 was 71 months compared with 30 and 17 months for TRG 2/3 and TRG 4/5, respectively (P < 0.0001). Apparent complete nodal response (cN1 to ypN0) was seen in 64% of the TRG 1 group, 30% of the TRG 2/3 group, and 5% of the TRG 4/5 group (P < 0.0001). No existing response measure independently predicts outcome. A complete response (TRG 1) defines a unique cohort after neoadjuvant therapy, associated closely with nodal response, and overall survival. This classification merits consideration for standardization of treatment response, and for inclusion in staging nomenclature.