Outcomes Of Neoadjuvant Chemoradiation Vs Neoadjuvant Chemotherapy for Esophageal Junction Signet Ring Cell...

Gastroesophageal junction (GEJ) adenocarcinoma with signet ring cells (SRCs) is associated with resistance to therapy and poor outcomes. Standard neoadjuvant regimens for SRCs have been chemoradiation (nCRT) or chemotherapy (nCT), with little data specific to SRCs indicating which is optimal. We compared outcomes of resectable (stage I-III) GEJ SRC patients treated with nCRT or nCT followed by surgery.

Patients undergoing esophagectomy for GEJ SRCs after neoadjuvant therapy at 2 different institutions (2005-2022) were stratified by receipt of nCRT or nCT. Propensity scores, based on demographic and clinical characteristics, were used to match groups (2 nCRT:1 nCT). Outcomes were assessed using Kaplan-Meier and multivariable Cox regression models.

In sum, 104 (66.7%) nCRT and 52 (33.3%) nCT patients were included. Most patients were male (nCRT, n = 88 of 104, 84.6%; nCT, n = 43 of 52, 82.7%, P = .76) with clinical stage III (nCRT, n = 92 of 104, 88.5%; nCT, n = 48 of 52, 92.3%, P = .33). Patients treated with nCRT achieved pathologic complete response 11.5% vs 7.7% for nCT patients. At median follow-up of 27 months, median survival for nCRT patients was 34.3 months (95% CI, 24.9-72.1) compared with 34.5 months (95% CI, 29.0-58.8; P = 0.28) for nCT patients. Multivariate Cox regression indicated that lymphovascular invasion was an independent predictor of progression-free and overall survival, but choice of neoadjuvant therapy was not.

The treatment-resistant nature of SRCs pose consequential challenges that are not overcome either by nCRT or nCT. Novel therapeutic strategies are needed to improve outcomes for patients with GEJ adenocarcinoma with SRC.