Comparison of long-term outcomes for neoadjuvant chemoradiation (NA-CRT) followed by surgery versus (V) definitive chemoradiation (D-CRT) in localized gastroesophageal cancer (GEC): A single-center analysis.
Authors: McLaughlin Ronan Andrew , Sharma Divya , Bach Yvonne , Farooq Abdul Rehman , Ghazali Nadia , Harvey Harry , Coyne Zac , Aoyama Hiroko , Akhtar Sokaina , Jang Raymond Woo-Jun , Chen Eric Xueyu , Ma Lucy Xiaolu , Kalimuthu Sangeetha , Veit-Haibach Patrick , Wong Rebecca KS KS , Mesci Aruz , Yan Michael , Wakeam Elliot , Yeung Jonathan , Elimova Elena 
Published: January 2025

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Background:
The therapeutic approach in locally advanced GEC is evolving. NA-CRT followed by surgery has been recommended based on the
CROSS
trial. The
SANO
trial reports active surveillance may be an alternative in clinically complete response after D-CRT in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). SCC and AC in GEC are different diseases with differences in tumor location, etiology, and biology. Despite the evolving landscape, there still may be a role for both
CROSS
and
SANO
approaches. In our large observational cohort study, we sought to compare the long-term outcomes in localized GEC across all histological subtypes treated with NA-CRT+Surgery V D-CR+Surveillance.
Methods:
A retrospective analysis comparing NA-CRT + surgery V D-CRT in localized GEC between 2007-2023 treated at the Princess Margaret Cancer Centre was completed. Baseline characteristics including age, gender, race, performance status and Charlson Comorbidity index (CCI) were reviewed. The primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively and to compare these outcomes in both histologies. Cox proportional hazards analysis and Kaplan-Meier methods were employed. Outcomes were adjusted for baseline characteristics.
Results:
There were 529 patients (pts) included, 321 (61%) received NA-CRT+Surgery and 208 (39%) D-CR+Surveillance. Median age was 64yrs, 75% were male and 66% had N1+ disease. The proportion of pts with SCC treated with NA-CRT+Surgery and D-CR+Surveillance was 25% and 63%, respectively. There was a statistically significant difference in median OS and DFS between pts who received NA-CRT+surgery and D-CRT+surveillance (Table). Multivariate regression analysis shows a significant association between OS and age (adjusted HR 1.02, p=0.005), male sex (HR 1.55, p=0.003) but no significant association between OS and CCI (HR 1.1 p=0.36). In our subgroup analyses, there was no statistically significant difference in OS (p=0.33) and DFS (p=0.18) between SCC and AC. However, this was significant in D-CRT (OS p<0.0001, DFS p<0.001) favoring SCC.
Conclusions:
In contrast to the
SANO
trial, we found that NA-CRT+surgery was associated with a significantly better OS and DFS compared to D-CRT when subtypes were combined. However, in the D-CRT subgroup, SCC was associated with improved OS and DFS compared to AC. Thus, we continue to recommend current approaches in SCC. Awaited updates from
SANO
will inform whether active surveillance may also be appropriate in pts with AC subtype.

Median (95% CI)NA-CRT Surgery
Median (95% CI)D-CRT
Log-rank test p-value

OS (mo)
28.2 (15.1, 57.6)
15.6 (7.7, 33.7)
P=<0.0001

DFS (mo)
17.9 (9.6, 40.8)
9.4 (5.0, 20.7)
P=<0.0001

pathCR (%)
14
-

R0 resection (%)
89
-