BACKGROUND: Early recurrence after esophagectomy is often used as a surrogate for aggressive tumor biology and treatment failure. However, there is no standardized definition of early recurrence, and predictors for early recurrence are unknown. Therefore, we aimed to define an evidence-based cutoff to discriminate early and late recurrence and assess the influence of neoadjuvant treatment modalities for patients with esophageal or gastroesophageal-junction adenocarcinoma (EAC).

This dual-center retrospective cohort study included patients who underwent esophagectomy for stage II-III EAC after neoadjuvant treatment with chemotherapy using 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) or radiochemotherapy according to the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study (CROSS) protocol from 2012 to 2022. The optimal cutoff for early versus late recurrence was calculated by using the most significant difference in survival after recurrence (SAR). Multivariable logistic regression was used to identify variables associated with early recurrence.

Of 334 included patients, 160 (47.9%) were diagnosed with recurrence. Most patients had systemic (60.5%) or multiple sites of recurrence (21.1%), whereas local-only recurrence (9.2%) and carcinomatosis (9.2%) were rare. The optimal interval between surgery and recurrence for distinguishing early and late recurrence was 18 months (median SAR: 9.1 versus 17.8 months, p = 0.039) with only 24% of recurrences diagnosed after the calculated cutoff. Advanced pathologic tumor infiltration (ypT3-4, p = 0.006), nodal positivity (p = 0.013), poor treatment response (>10% residual tumor, p = 0.015), and no adjuvant treatment (p = 0.048) predicted early recurrence.

Early recurrence can be defined as recurrent disease within 18 months. Hallmarks for early recurrence are poor response to neoadjuvant therapy with persisting advanced disease. In those patients, adjuvant therapy and closer follow-up should be considered.

To compare the survival outcomes of patients with stage T2N0M0 esophageal cancer treated with surgery alone versus those treated with neoadjuvant chemoradiotherapy followed by surgery. Patients with stage T2N0M0 esophageal cancer, who either underwent surgery alone or received neoadjuvant chemoradiotherapy followed by surgery, were extracted from the Surveillance, Epidemiology, and End Results database covering the period from 2000 to 2020. Cancer-specific survival (CSS) and overall survival (OS) between the two treatment groups were compared. A total of 583 patients were included: 267 (45.8%) received surgery alone, while 316 (54.2%) underwent neoadjuvant chemoradiotherapy followed by surgery. Prior to propensity score matching, no significant differences were observed between the surgery alone and neoadjuvant chemoradiotherapy groups in terms of 5-year CSS (60.86% vs. 59.02%; hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 0.79-1.29; P = 0.916) and OS (50.64% vs. 49.81%; HR = 0.91, 95% CI: 0.75-1.12; P = 0.375). After propensity score matching, the 5-year CSS (66.43% vs. 56.67%; HR = 1.21, 95% CI: 0.89-1.64; P = 0.225) and OS (56.49% vs. 47.37%; HR = 1.09, 95% CI: 0.85-1.40; P = 0.481) remained statistically similar between the two groups. Subgroup analyses of patients with squamous cell carcinoma and adenocarcinoma revealed no significant differences in survival outcomes between the treatment modalities for either histological subtype. Neoadjuvant chemoradiotherapy followed by surgery does not confer a survival advantage over surgery alone in patients with stage T2N0M0 esophageal cancer, irrespective of histological subtype.

To evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ), a multinational high-volume center study was undertaken.

The optimal treatment approach with either NAT/S or PS for clinically staged cT2cN any or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials.

A retrospective analysis of prospectively maintained databases from 10 centers was performed. Between January 2012 and August 2023, 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II, or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. The primary endpoint was overall survival (OS).

In the cT2cN any cohort, 192 patients (29.8%) underwent PS and 453 (70.2%) underwent NAT/S. In all cT2cN0 patients (n = 333), NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older ( P < 0.001) and had a higher American Society of Anesthesiologists classification ( P < 0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts ( P > 0.4).Median OS was 51.0 months in the PS group (95% CI: 31.6-70.4) versus 114.0 months (95% CI: 53.9-174.1) in the NAT/S group ( P = 0.003) of cT2cN any patients. For cT2cN0 patients, NAT/S was associated with longer OS ( P = 0.002) and disease-free survival ( P = 0.001). After propensity score matching of the cT2N0 patients, survival benefit for NAT/S remained ( P = 0.004). Histopathology showed that 38.1% of cT2cN any and 34.2% of cT2cN0 patients were understaged.

Due to the unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach.

The objective was to provide evidence for age-dependent use of neoadjuvant treatment by clinical comparisons of young (lower quartile, <56.6 years) versus old (upper quartile, >71.3 years) patients with esophageal and esophagogastric-junction adenocarcinoma.

Neoadjuvant treatment is the standard of care for locally advanced and node-positive EAC. However, the effect of age on oncological outcomes is disputable as they are underrepresented in treatment defining randomized controlled trials.

Patients with EAC undergoing esophagectomy between 2001 and 2022 were retrospectively analyzed from three centers. Patients having distant metastases or clinical UICC-stage I were excluded. Cox proportional hazards regression was used to identify the variables associated with survival benefit.

Neoadjuvant treatment was administered to 185/248 (74.2%) young and 151 out of 248 (60.9%) elderly patients ( P =0.001). Young age was associated with a significant overall survival (OS) benefit (median OS: 85.6 vs. 29.9 months, hazard ratio 0.62, 95% CI: 0.42-0.92) after neoadjuvant treatment versus surgery alone. In contrast, elderly patients did only experience a survival benefit equaling the length of neoadjuvant treatment itself (median OS: neoadjuvant 32.8 vs. surgery alone 29.3 months, hazard ratio 0.89, 95% CI: 0.63-1.27). Despite the clear difference in median OS benefit, histopathological regression was similar ((Mandard-TRG-1/2: young 30.7 vs. old 36.4%, P= 0.286). More elderly patients had a dose reduction or termination of neoadjuvant treatment (12.4 vs. 40.4%, P <0.001).

Old patients benefit less from neoadjuvant treatment compared to younger patients in terms of gain in OS. Since they also experience more side effects requiring dose reduction, upfront surgery should be considered as the primary treatment option in elderly patients.