Purpose: The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods: From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m² intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m² IV day 1, or 25 mg/m² IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results: The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion: This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.

Esophageal cancer is the ninth most frequent cancer and the sixth leading cause of cancer-associated death in the world.¹ More than 50% of patients with esophageal cancer reside in East Asia, and 90% of those patients have esophageal squamous cell carcinoma (ESCC).² For patients with locally advanced esophageal cancer, surgery remains the mainstay of current therapy. However, patients with locally advanced esophageal cancer who undergo surgery with no additional therapies have a low 5-year survival rate of only 25%.^3,4 Although recent evidence has suggested that neoadjuvant chemoradiotherapy (NCRT) plus surgery could prolong the overall survival (OS) of patients with locally advanced esophageal cancer,⁵ its role in the treatment of patients with ESCC remains controversial.^4,6-13 Therefore, identification of the efficacy of this multidisciplinary treatment for locally advanced ESCC is an important current research topic.

Background: Tertiary lymphoid structures (TLSs) play key roles in tumour adaptive immunity. However, the prognostic value and molecular properties of TLSs in oesophageal squamous cell carcinoma (ESCC) patients have not been studied.Methods: The prognostic values of the presence and maturation status of tumour‐associated TLSs were determined in 394 and 256 ESCC patients from Sun Yat‐sen University Cancer Center (Centre A) and the Cancer Hospital of Shantou University Medical College (Centre B), respectively. A deep‐learning (DL) TLS classifier was established with haematoxylin and eosin (H&E)‐stained slides using an inception‐resnet‐v2 neural network. Digital spatial profiling was performed to determine the cellular and molecular properties of TLSs in ESCC tissues.Results: TLSs were observed in 73.1% of ESCCs from Centre A via pathological examination of H&E‐stained primary tumour slides, among which 42.9% were TLS‐mature and 30.2% were TLS‐immature tumours. The established DL TLS classifier yielded favourable sensitivities and specificities for patient TLS identification and maturation evaluation, with which 55.1%, 39.5% and 5.5% of ESCCs from Centre B were identified as TLS‐mature, TLS‐immature and TLS‐negative tumours. Multivariate analyses proved that the presence of mature TLSs was an independent prognostic factor in both the Centre A and Centre B cohorts (p < .05). Increased proportions of proliferative B, plasma and CD4+ T helper (Th) cells and increased B memory and Th17 signatures were observed in mature TLSs compared to immature ones. Intratumoural CD8+ T infiltration was increased in TLS‐mature ESCC tissues compared to mature TLS‐absent tissues. The combination of mature TLS presence and high CD8+ T infiltration was associated with the best survival in ESCC patients.Conclusions: Mature TLSs improve the prognosis of ESCC patients who underwent complete resection. The use of the DL TLS classifier would facilitate precise and efficient evaluation of TLS maturation status and offer a novel probability of ESCC treatment individualization.

The demographic and clinicopathologic factors associated with 5-year survivors have not been well documented in oesophageal squamous cell carcinoma (OSCC). We evaluated factors predictive of actual 5-year survival in the present research. We analysed 1241 patients underwent oesophagectomy for invasive OSCC retrospectively. The demographic and clinicopathologic characteristics were compared between patients who were alive >5 years after oesophagectomy and patients who died within 5 years of oesophagectomy. Univariate analysis showed significant differences between the two groups regarding 11 different factors. Further analysis by logistic regression showed that eight factors were identified as independent predictors of actual 5-year survival. The independent positive predictors for actual 5-year survival are younger patients, female gender, absence of weight loss, R0 resection, lower pathological T stage, lower pathological N stage, higher histologic grade and more resected lymph nodes.