Outcomes of different treatment approaches after R0 endoscopic resection of high-risk T1 esophageal adenocarcinoma: An international multicentre retrospective cohort study

Aims Optimal management after R0 endoscopic resection (ER) of T1 esophageal adenocarcinoma (EAC) with≥1 high-risk histological feature (i.e. submucosal invasion, a/o poor differentiation, a/o lympho-vascular invasion) is subject to debate, given conflicting reports on risk of lymph node metastases (N+). This cohort study (NCT04818476) aimed to assess outcomes following R0 ER for high-risk T1 EAC.

Methods All patients who underwent R0 ER, i.e. radical deep margin, for high-risk T1 EAC (2008-2019) were retrospectively identified in 11 international centers specialized in Barrett’s neoplasia. Data were collected on treatment policies and outcomes, including rates of N+, distant metastasis (M+), and EAC-related mortality.

Results 131 patients (106 male) were identified: 46 high-risk T1a (HR-T1a), 27 T1sm1 without other risk factors (LR-T1b) and 58 T1b with other risk factor(s) (HR-T1b). Management after ER consisted of surgical resection n=34 (26%), with neo-adjuvant chemoradiotherapy (nCRT) in 2/34; endoscopic FU n=80 (61%); C/RT n=9 (7%); no further management n=8 (6%).

In the 34 patients (64±11 yrs) who underwent surgery, surgical morbidity was 56% (n=19, 95% CI 38-73) with anastomotic leakage in n=3. 30-day mortality was 0%. Among the 32 patients without nCRT, 11 (34%) had residual T1 disease and 3 (9%) N+in the surgical specimen. Review of clinical reports for all T1 cases identified 4 cases of endoscopic non-radical resection misclassified as R0. Another 3 cases were upstaged to R1 following pathological revision. After median 58 (IQR 40-85) months of FU after surgery, 1/32 (3%, 95% CI 0-10) developed N+; 2/32 (6%, 95% CI 0-15) developed M+and died. 1/32 (3%) died of unrelated cause. 5/32 (16%) were lost to FU.

80 patients (71±9 yrs) entered endoscopic FU. After median clinical FU of 46 (IQR 25-59) months, 5/80 (6%, 95% CI 1-12) were diagnosed with recurrent disease, of which 4 (5%, 95% CI 1-10) died. 15/80 (19%) died of unrelated causes. 9/80 (11%) were lost to FU.

In our cohort of N=112 (32 surgery without nCRT, 80 endoscopic FU), rates of N+and N+/M+were 7% (95% CI 2-12) and 9% (95% CI 4-14). EAC-related and overall mortalities were 5% (95% CI 1-10) and 20% (95% CI 12-27), resp.

Conclusions Despite limitations such as the retrospective setting, absence of standardized FU protocols and histological revision, and potential preselection of unfit surgical candidates for endoscopic FU, our results align with lower N+rates observed in endoscopic-oriented studies for high-risk T1 EAC. Our study demonstrates that majority of cases with surgical T1 had ER misclassified as R0, challenging previous studies that reported higher N+rates. It reflects that surgery is not a definitive curative approach and did not improve disease-specific mortality. Our results advocate for a larger cohort and prospective evaluation of outcomes in patients treated endoscopically for high-risk T1 EAC (PREFER, NCT03222635).

Publication History

Article published online:
15 April 2024