Survival After Trimodality Therapy in Patients With Locally Advanced Esophagogastric Adenocarcinoma: Does Only a Complete Pathologic Response Matter?

Abstract

OBJECTIVE:

To evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival.

SUMMARY BACKGROUND DATA:

pCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint.

METHODS:

We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adeno-carcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis.

RESULTS:

Among 788 patients, median follow-up was 37.5 months (range, 0.4210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival ( P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR.

CONCLUSIONS:

ypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to >90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to > 90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.

• Authors: Smita Sihag, Tamar Nobel, Meier Hsu, Sergio De La Torre, Kay See Tan, Yelena Y Janjigian, Geoffrey Y Ku, Laura H Tang, Abraham J Wu, Steven B Maron, Manjit S Bains, David R Jones, Daniela Molena
• Journal: Annals of surgery (Ann Surg) Vol. 276 Issue 6 Pg. 1017-1022 (12 01 2022) ISSN: 1528-1140 [Electronic] United States
• PMID: 33214465 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Topics

• Humans
• Neoadjuvant Therapy
• Esophageal Neoplasms
• Adenocarcinoma (pathology)
• Neoplasm, Residual (pathology)
• Remission Induction
• Retrospective Studies
• Neoplasm Staging