Thoracoscopic esophagectomy is a less invasive surgical procedure; however, evidence of its effect on long-term survival is limited. We evaluated long-term survival after the procedure in patients with esophageal carcinoma.

This retrospective multicenter study involved 1559 consecutive patients with esophageal carcinoma who underwent thoracoscopic esophagectomy or open esophagectomy between 2012 and 2019 at 2 Japanese high-volume cancer centers. Propensity score matching analysis was performed to compare short- and long-term outcomes. In addition, stage-specific survival rates were compared between the groups.

There were 313 patients who were matched and analyzed. The 1-, 3-, and 5-year overall survival rates were 84.5%, 60.5%, and 52.1%, respectively, in the matched open esophagectomy group; and 87.2%, 68.6%, and 61.8%, respectively, in the matched thoracoscopic esophagectomy group. The weighted Cox regression model showed significantly better survival in the thoracoscopic esophagectomy group than in the open esophagectomy group (hazard ratio, 0.74; 95% CI, 0.582-0.941). Deaths from other causes occurred more frequently in the open esophagectomy group than in the thoracoscopic esophagectomy group. Stratified analysis showed no significant survival differences between clinical stage I or II and pathologic stage 0 or I subgroups. However, the thoracoscopic esophagectomy groups with clinical stage III or IV and pathologic stage II, III, or IV had significantly better overall survival.

This study demonstrated the survival benefits of thoracoscopic esophagectomy, particularly for highly advanced esophageal carcinoma.

Although the efficacy of robot-assisted minimally invasive esophagectomy (RAMIE) in locally advanced esophageal cancer has been suggested, solid evidence is lacking. In this study, we examined the short- and middle-term outcomes of RAMIE in patients with highly locally advanced esophageal cancer who were initially diagnosed with cT3 borderline resectable or cT4b (cT3br/cT4b) disease and deemed resectable after preoperative treatment. Furthermore, we compared the short- and middle-term outcomes of RAMIE with conventional minimally invasive esophagectomy (cMIE).

Eighty-one patients with locally advanced initial T3br and T4 esophageal squamous cell carcinoma previously treated with chemotherapy or chemoradiation underwent minimally invasive esophagectomy with curative intent between 2018 and 2022. We then examined the short- and long-term outcomes of RAMIE compared with cMIE in patients initially diagnosed with stage cT3br/cT4b disease.

Among these 81 patients, 33 underwent RAMIE and 48 underwent cMIE. The average age of the 81 patients was 65.8 years, with tumors located primarily in the mid-esophagus (55.6%). Most patients initially had stage cT3br (56.8%) or cT4b (43.2%) disease, with 88.9% showing invasion near the trachea or bronchus. No significant differences were observed between the cMIE and RAMIE groups for operation time, blood loss, or common postoperative complications. However, the RAMIE group had a lower incomplete resection rate vs the cMIE group (9.0% vs 16.6%, respectively). The 3-year overall survival rate was 63.1%, with RAMIE showing slightly better survival rates compared with cMIE (p = 0.032). The prognostic factors in the RAMIE group indicated better outcomes for single-organ vs multiple-organ invasion (p = 0.036) and patients with a higher histological response (p = 0.048).

RAMIE may offer improved outcomes for highly locally advanced esophageal cancer, such as patients with stage T3br or T4b disease. Future studies that analyze data for high numbers of cases in multiple facilities are needed.

Esophageal cancer (EC) continues to be a significant global health concern, with two main subtypes: esophageal squamous cell carcinoma and esophageal adenocarcinoma. Prevention and changes in etiology, improvements in early detection, and refinements in the treatment have led to remarkable progress in the outcomes of EC patients in the past two decades. This seminar provides an in-depth analysis of advances in the epidemiology, disease biology, screening, diagnosis, and treatment landscape of esophageal cancer, focusing on the ongoing debate surrounding multimodality therapy. Despite significant advancements, EC remains a deadly disease, underscoring the need for continued research into early detection methods, understanding the molecular mechanisms, and developing effective treatments.

Docetaxel-cisplatin-5-fluorouracil (DCF) is a new standard neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) in Japan. However, some patients experience recurrence and require further systemic platinum-containing chemotherapy. It is unclear whether such regimens are appropriate after a poor histopathological response to neoadjuvant DCF.

Data were retrospectively collected on patients with recurrence of ESCC treated with palliative chemotherapy after neoadjuvant DCF at our institution between February 2014 and June 2022. We defined patients with a grade 0-1 histopathological response as insufficient responders (IRs) and those with grade 2-3 as good responders (GRs). The correlation between the histopathological response and the response to palliative chemotherapy was investigated.

Thirty-two patients (median age 63.5 years, range 46-76) were included. Performance status was 0 in 12 (37.5%), 1 in 16 (50.0%), and 2 in 4 (12.5%). Histopathological response grades 0/1/2/3 were 3.1%/68.7%/21.9%/6.3%, respectively. Platinum-containing chemotherapy was administered to 13 patients (56.5%) in the IR group and 9 (100%) in the GR group. The overall response rate was 34.8%, and median progression-free survival was 2.431 months in the IR group and 44.4% and 4.041 months, respectively, in the GR group. Multivariate analysis identified a chemotherapy-free interval of < 6 months as an independent prognostic factor (HR 4.096, 95% CI 1.116-15.037) but not the histopathological response (HR 1.137, 95% CI 0.309-4.177).

Histopathological response to neoadjuvant DCF therapy did not affect the efficacy of first-line chemotherapy for recurrent ESCC.

To evaluate the feasibility of and long-term survival with combined organ resection for esophageal cancer (EC). The optimal treatment strategy for EC that is invading adjacent organs is not established.

Ninety patients with EC invading adjacent organs who underwent combined organ resection after induction treatments during the time period 2003-2023 in our institute were eligible for the study. Short- and long-term outcomes were assessed, and survival analysis was performed to identify prognostic parameters in this cohort.

Most patients had primary tumors (78.9% vs 21.1% with recurrent disease). The resected organs were the trachea/bronchus in 75.6%, large vessels in 24.4%, and both in 5.6%. All but 1 patient underwent chemotherapy or chemoradiotherapy as prior induction treatment, and had R0 resection. The overall complication rate (Clavien-Dindo grade II or greater) was 54.4%, and in-hospital mortality was 2.2% (30- and 90-day mortality: 0% and 2.2%, respectively). Of the deaths, 47 (87.0%) were attributed to EC and 7 (13.0%) to other causes. Median disease-free survival was 6.5 months, and overall survival (OS) was 18.9 months. The 2-year OS values were 47.2% with trachea/bronchus resection, 38.4% with large-vessel involvement, and 37.5% if both were involved. Univariate analysis of OS demonstrated significant associations of operation time (hazard ratio [HR], 2.11; P = .0080), blood loss (HR, 2.85; P = .0003), all-layer tracheal resection (HR, 3.51; P = .0045), ypT (HR, 2.04; P = .022), and pathologic response (HR, 2.77; P = .0089).

If patient selection is highly selected, combined organ resection may be a feasible and promising option as a part of the multidisciplinary treatment for EC invading an adjacent organ.

Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable (T4) esophageal squamous cell carcinoma (ESCC), but the prognosis is poor. Borderline resectable (T3br) ESCC has been discussed, but its clinical features and appropriate treatment are unclear. The effects of docetaxel plus cisplatin and 5-fluorouracil (DCF) therapy and subsequent surgery for potentially unresectable ESCC remain controversial. This was a single-center retrospective cohort study. Patients with T3 or deeper ESCC lesions between January 2017 and June 2020 were examined. We identified T3br/T4 ESCC patients who initially received DCF therapy or dCRT, and analyzed the long-term outcomes of these patients. Seventy-four patients with T3br/T4 ESCC were identified. Forty-four patients initially received DCF therapy, while thirty initially received dCRT. The 3-year overall survival of T3br/T4 patients in the DCF group was better than that in the dCRT group (62.9% vs. 34.1%, P = 0.001). In the T3br cohort, 95.8% of patients underwent surgery after DCF therapy, with an R0 resection rate of 78.3%. In the T4 group, 40% of patients underwent surgery after DCF, with a 75.0% R0 resection rate. No cases of reoperation or in-hospital death occurred. For both subgroups, T3br and T4, the prognosis tended to be better in the DCF group than in the dCRT group. This study explored real-world data from T3br/T4 ESCC patients who initially received DCF and subsequent surgery and revealed that DCF is a promising treatment strategy.

This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC).

Chemotherapy-naïve patients with resectable ESCC (stage IB-III, Union for International Cancer Control, International Cancer Control seventh edition) were eligible for the study. All patients received 3 cycles of docetaxel, cisplatin, and 5-FU (DCF) therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every 3 weeks). Remarkable response was defined as a reduction in the tumor to T1, metastatic lymph nodes <1 cm on the short axis, and downstaging to stage IA after 3 cycles of DCF therapy. Remarkable responders then underwent dCRT, which included 2 courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1 to 4, repeated every 4 weeks, along with 50.4 Gy of concurrent radiation therapy. The primary endpoint was 1-year progression-free survival in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival.

Of the 92 patients registered, 90 were analyzed. A remarkable response to 3 courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range, 1-85 months), the 1-year progression-free survival was 89.8% (95% confidence interval [CI], 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and esophagectomy-free survival rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after 2 courses of DCF therapy was significantly associated with OS (P = .0049).

In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with 3 courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.

As a result of the recent advances in first-line treatment including chemotherapy, radiation therapy, targeted therapy, and immune checkpoint inhibitor immunotherapy (ICI) for locally advanced/metastatic initially unresectable esophageal and esophagogastric junction cancer, surgery aiming at cure after initial treatment, so-called "conversion surgery" has become more common in this field. Several studies have indicated encouraging survival outcomes for patients after conversion surgery with R0 resection. However, various issues, such the utility and the safety of conversion surgery remain unclear. In this review, we will focus on the surgical treatment for initially unresectable esophageal and esophagogastric junction cancer after first- or later- line treatment and review recent evidence regarding the safety and the efficacy of conversion surgery. Multidisciplinary treatment including surgery may serve as a novel treatment strategy for esophageal and esophagogastric junction cancer, thus provide a curative treatment option and potentially contribute to better prognosis for initially untreatable diseases.

Abdominal para-aortic lymph nodes (PANs) are sites of distant metastasis in esophageal squamous cell cancer (ESCC). The prognosis of patients with Stage IVB ESCC and abdominal PAN metastasis is extremely poor. However, chemotherapy for ESCC has recently been developed, and the effectiveness of combined induction therapy and conversion surgery remains unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of conversion surgery for ESCC and solitary abdominal PAN metastases after induction therapy.

Thirteen patients who underwent conversion esophagectomy for cStage IVB ESCC with solitary abdominal PAN metastasis after induction therapy between January 2017 and October 2022 at our institution were enrolled. The short- and long-term outcomes of conversion surgery were retrospectively evaluated.

Three patients (23.1%) had pathological abdominal PAN metastasis, and six patients (46.2%) without pathological abdominal PAN metastasis showed that chemotherapy eliminated the tumors in the abdominal PAN. Three patients (23.1%) had postoperative complications of Clavien-Dindo grade II or higher. The 3-year overall and recurrence-free survival rates were 83.1% and 51.3%, respectively.

Our findings showed that conversion surgery for ESCC and solitary abdominal PAN metastasis led to a good prognosis when induction therapy was successful.

This phase II trial investigated the safety and efficacy of chemoradiotherapy (CRT) followed by immunochemotherapy (iCT) and surgery in unresectable locally advanced esophageal squamous cell carcinoma (ESCC).

Patients with unresectable locally advanced ESCC received radiotherapy (50 Gy/25f, 5 days/week) and nab-paclitaxel (100 mg on day 1/week) plus cisplatin (25 mg/m2 on day 1/week) for 5 weeks, followed by tislelizumab (200 mg on day 1/cycle) plus chemotherapy (nab-paclitaxel 150 mg/m2 and cisplatin 75 mg/m2 on day 2/cycle) for two 21-day cycles. Patients who converted to resectable underwent surgery 2 to 4 weeks afterward. The primary endpoint was a 1-year progression-free survival (PFS) rate.

Thirty patients were enrolled and underwent CRT (median follow-up: 21 months), of whom 24 received iCT. Twenty (66.7%) patients achieved resectability (R0: 95.2%; pathologic complete response: 65.0%; major pathologic response: 90.0%). One-year PFS and overall survival (OS) rates were 79.4% and 89.6%, respectively. The R0 resection group exhibited longer PFS (median, not reached vs. 8.4 months; HR = 0.28; 95% confidence interval, 0.08-0.84; P = 0.02) and OS (median, not reached vs. 19.2 months; HR = 0.18; 95% confidence interval, 0.04-0.73; P < 0.01) than the nonsurgery group. Grade 3 to 4 adverse events were observed in 11 (11/30, 36.7%) patients, and immune-related pneumonitis was observed in 5 (5/24, 20.8%) patients. Post-CRT minimal residual disease before surgery was associated with unfavorable PFS and OS.

Our study met the primary endpoint. Conversion CRT and subsequent iCT followed by surgery was a promising treatment strategy for unresectable locally advanced ESCC.

The role of surgery in oligometastatic esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the oncological outcomes after esophagectomy in patients with ESCC with distant lymph node (LN) metastasis. Patients with ESCC and nodal metastasis treated with chemoradiotherapy or chemotherapy followed by esophagectomy between 2010 and 2020 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients with distant LN metastasis (dLN+) and exclusively regional LN metastasis (dLN-). The cohort comprised 69 dLN+ and 111 dLN- patients. Survival was significantly better in the dLN- group than in the dLN+ group (5-year OS, 51.9% vs. 25.5%, P < 0.001; RFS, 47.2% vs. 18.1%, P < 0.001). Stratified by the yp stage, 49 (44.1%) dLN- and 30 (43.5%) dLN+ patients achieved a pathological complete response (pCR). In the dLN- and dLN+ groups, the OS rates were significantly higher in the pCR group than in the non-pCR group (dLN-: 76.7% vs. 32.4%, P < 0.001; dLN+: 39.6% vs. 14.2%; P = 0.002). The dLN-/pCR group had the best OS, significantly outperforming the dLN-/non-pCR and dLN+/pCR groups. OS did not differ between the dLN-/non-pCR and dLN+/pCR groups. The dLN+/non-pCR group had the worst OS. The RFS analysis paralleled the OS findings. Patients with dLN+ disease had worse outcomes than their dLN- counterparts, irrespective of the pCR status. The survival rates were poor but comparable between the dLN+/pCR and dLN-/non-pCR groups. Adjuvant therapy may be required for dLN+ patients following systemic treatment and surgery, even after achieving pCR.

Patients with supraclavicular lymph node (SLN) metastasis from esophageal cancer encounter significant variations in treatment approaches due to differences in pathological subtypes and the lack of a unified regional staging system between East Asian and Western countries. The Tiger study aims to develop an internationally recognized staging system and to delineate the extent of regional lymph node dissection. In the context of esophageal squamous cell carcinoma (SCC) with SLN metastasis, the treatment paradigms from East Asia offer valuable insights. The Japan Esophageal Society (JES) 12th edition staging system guides a tailored comprehensive treatment strategy, emphasizing either radiotherapy and chemotherapy or surgical intervention. In contrast, esophageal adenocarcinoma (AC) predominates in Western countries, where the 8th edition of the American Joint Committee on Cancer (AJCC) staging system classifies SLN metastasis as a distant metastasis, advocating for systemic therapy as the primary treatment modality. Nonetheless, compelling evidence suggests that a multidisciplinary treatment approach, incorporating either radiotherapy and chemotherapy or surgery as the initial treatment, can yield superior outcomes for these patients compared to chemotherapy alone.

The objective was to evaluate the efficacy and safety of radiotherapy and the prognostic factors in patients with esophageal cancer who received definitive radiotherapy, using volumetric modulated arc therapy (VMAT).

Forty-seven patients who received definitive radiotherapy using VMAT between September 2017 and December 2020 were enrolled. Prescription doses were 60 Gy in 30 fractions to the planning target volume (PTV) primary and 48 Gy in 30 fractions to the PTV subclinical. Overall survival (OS), progression free survival (PFS), and toxicity were analyzed, and univariate and multivariate analyses were used to investigate the prognostic factors.

Median follow up time was 10 months. Most of the patients had an advanced disease stage (stage I, 12.8%; II, 8.5%; III, 27.7%; IV, 51.0%) patients (38.3%) had a T4 tumor. The median survival time was 14 months (range: 0-56 months). The 2-year OS and PFS were 31.3% and 20.4%, respectively. Acute adverse events (≥ Grade 3) were observed in 25 patients (53.2%), and the most frequent types were dysphagia, hematological toxicities including leukopenia, and febrile neutropenia in 14 (29.8%), 10 (21%), and 10 (21%) patients, respectively. Late adverse events (Grade 3 or higher) were observed in eight patients (17.0%), and the most frequent types were pneumonitis in four patients (8.5%), and Grade 5 in one patient (2.1%; esophageal fistula). In multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) > 3 (p = 0.026) was significantly associated with poor survival.

Definitive radiotherapy of 60Gy with VMAT is feasible and safe for patients with esophageal cancer. Pre-treatment NLR >3 was an independent prognostic factor for OS.

This study compared the surgical conversion rate and overall survival (OS) between induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with initially unresectable esophageal squamous cell carcinoma (iuESCC).

In this multicenter, retrospective cohort study, patients from four high-volume institutions with unresectable diseases were included. The primary endpoints were the conversion surgery rate and OS. A multivariate Cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting was applied to confirm the survival comparison between the iIC and iC cohorts.

A total of 309 patients (150 in the iIC cohort and 159 in the iC cohort) were included. A significantly higher conversion surgical rate was observed in the iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P < 0.001). The pathological complete response rates were 22.0% and 5.1% in the iIC and the iC cohorts, respectively (P = 0.001). A significant difference in the OS was observed between the iIC (not reached) and iC cohorts (median 95% CI 36.3 [range 27.2-45.5]). The stabilized inverse probability of treatment weighting yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI 0.102-0.454, P < 0.001) and operation (yes vs. no, HR 0.262, 95% CI 0.161-0.427, P < 0.001) were the significant prognostic factors for OS.

Immunochemotherapy plus conversion surgery in the induction setting may be a better treatment option to achieve high pathological responses and improve OS in iuESCC patients.

Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC).

Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate.

The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia.

Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.

Esophageal neuroendocrine carcinomas (NECs) are extremely rare. Published information on their clinical features, pathological findings, and prognosis is lacking. The optimal treatment for esophageal NECs has not yet been determined because they appear extremely malignant histologically and have a poor prognosis. We here report on a patient with an esophageal NEC who was successfully treated with multidisciplinary therapies.

The patient, a 47-year-old man, was admitted to our hospital with dysphagia and weight loss and an ECOG performance status of 3-4. Upper endoscopy showed a large circumferential neoplasm at the esophagogastric junction. Computed tomography showed lymph node metastases around the left gastric artery. Echocardiography raised a suspicion of invasion of the left atrium. Histopathological examination of biopsy tissue revealed diffuse proliferation of small atypical cells resembling naked nuclei with extensive necrosis and degeneration. The cells showed positive staining for CD56, chromogranin A, and synaptophysin on immunohistochemical analysis. Ki67 was positive in over 90% of cells. He was diagnosed with an esophageal NEC that had infiltrated the left atrium; his cancer was therefore inoperable. Because of his poor overall condition, palliative radiotherapy (30 Gy in 15 fractions) was administered, accompanied by nutritional management. This was followed by four courses of chemotherapy with carboplatin plus etoposide, after which the primary tumor and locoregional lymph node metastases were found to have shrunk. Thoracoscopic- and laparoscopic-assisted McKeown esophagectomy were performed. The postoperative pathological diagnosis was NEC pT3pN0M0 Stage II. The patient had a good postoperative course and received two courses of postoperative adjuvant chemotherapy (carboplatin plus etoposide). Currently, 3 years after commencing treatment, there is no evidence of recurrence.

As mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

Esophageal cancer in one of the most malignant and hard-to-treat cancers. Esophageal squamous carcinoma (ESCC) is most common in Asian countries, whereas adenocarcinoma at the esophago-gastric junction (EGJ AC) is more prevalent in the Western countries. Due to differences in both genetic background and response to chemotherapy and radiotherapy, both histologic subtypes need different paradigms of management. Since the landmark CROSS study has demonstrated the superior survival benefit of tri-modality including neoadjuvant chemoradiotherapy prior to esophagectomy, the tri-modality becomes the standard of care; however, it is suitable for a highly-selected patient. Tri-modality should be offered for every ESCC patient, if a patient is fit for surgery with adequate cardiopulmonary reserve, regardless of ages. Definitive chemoradiotherapy remains the best option for a patient who is not a surgical candidate or declines surgery. On the contrary, owing to doubtful benefits of radiotherapy with potentially more toxicities related to radiotherapy in EGJ AC, either neoadjuvant chemotherapy or peri-operative chemotherapy would be more preferable in an EGJ AC patient. In case of very locally advanced disease (cT4b), the proper management is more challenging. Even though, palliative care is the safe option, multi-modality therapy with curative intent like neoadjuvant chemotherapy with conversion surgery may be worthwhile; however, it should be suggested on case-by-case basis.

Oesophageal squamous cell carcinoma is a common malignancy worldwide. Definitive chemoradiotherapy is the standard treatment for patients with resectable stage oesophageal squamous cell carcinoma who cannot undergo surgery, as well as those with locally advanced unresectable oesophageal squamous cell carcinoma. However, it has several disadvantages such as poor survival, radiation-related toxicities and severe and lethal complications related to salvage treatment for residual or recurrent disease. Numerous clinical trials on chemoradiotherapy have been conducted to confirm the optimal combination of irradiation and chemotherapy. For advanced disease, multimodal treatment strategies including salvage surgery are essential. Palliative chemoradiotherapy is also crucial for dysphagia in locally advanced oesophageal squamous cell carcinoma with or without metastatic lesions. Recently, the synergistic mechanism of radiotherapy combined with immunotherapy has been reported. Early phase clinical trials suggest that a combination of immunotherapy and chemoradiotherapy can improve clinical outcomes with manageable side effects, but further investigations are needed. Here, we reviewed the existing clinical data and current development of chemoradiotherapy combined with immunotherapy in patients with oesophageal squamous cell carcinoma.

To evaluate the safety and efficacy of camrelizumab plus albumin paclitaxel and carboplatin in the neoadjuvant treatment of borderline resectable or unresectable locally advanced esophageal cancer.

A retrospective analysis was conducted on 27 patients with borderline resectable or unresectable locally advanced esophageal cancer who received neoadjuvant treatment with camrelizumab plus albumin paclitaxel and carboplatin at Shanxi Cancer Hospital from January 2020 to March 2022. Of these, 20 patients underwent thoracoscopic esophagectomy after neoadjuvant treatment.

Overall, 88.9% (24/27) of patients completed neoadjuvant treatment. The objective response rate was 79.2% (19/24) according to the RECIST criteria. Of the 20 patients who underwent surgery, the R0 resection rate was 95%, and 35% (7/20) achieved pathological complete response (pCR). During neoadjuvant treatment, 30% (6/20) of patients experienced grade ≥3 treatment-related adverse events (TRAEs), and 20% (4/20) had grade ≥3 postoperative complications. There were no cases of reoperation or perioperative mortality.

Camrelizumab plus albumin paclitaxel and carboplatin were found to be safe and effective in the neoadjuvant treatment of borderline resectable or unresectable locally advanced esophageal cancer. It was observed to improve the rate of curative resection without increasing perioperative complications.

M1 esophageal carcinoma goes beyond localized disease and requires treatment with systemic therapy. M1 status is primarily divided into two categories: M1 lymph node metastasis and distant organ metastasis. Oligometastasis is defined as a state of limited metastatic disease, and surgery for oligometastasis of distant organs is reported to be beneficial in limited conditions. The aim of this study was to investigate resected cases of M1 lymph node metastases as the only metastatic site in stage IVB esophageal carcinoma.

This study was a single-center retrospective cohort study. Patients with esophageal carcinoma who underwent esophagectomy with curative intent between April 2017 and December 2021 were examined. Neoadjuvant chemotherapy was our standard therapy and administered in almost all cases. We hypothesized that four sites of metastatic M1LN (supraclavicular (no. 104), pretracheal (no. 106pre), posterior thoracic para-aortic (no. 112aoP), and abdominal para-aortic (no. 16a2lat) LNs) were potentially resectable M1LN (rM1LN) metastases with curative intent and compared the prognosis of patients with and without rM1LN metastasis.

Six hundred eight-two patients were included in the study. Among these patients, 80 had rM1LN metastasis and received surgery for curative intent. Short-term safety outcomes were equivalent between patients with and without rM1LN metastases. After propensity score matching, there were no significant differences in overall survival between patients with and without rM1LN metastasis. Multivariate analyses revealed that the only independent prognostic factor was ypN status.

The present study suggests the feasibility and favorable OS in the patients with resection of rM1LN metastasis.

Oesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour regression observed in a proportion of patients after treatment, but prognostic improvement remains limited. Immunotherapy in combination with chemotherapy (CT) has been shown to be efficacious as the first-line treatment of advanced OC and neoadjuvant therapy. Therefore, we conducted a prospective, two-arm, randomised, unblinded phase II study to explore the efficacy of camrelizumab in combination with CT versus chemoradiotherapy for the conversion of unresectable advanced OSCC.

All participants meeting the inclusion criteria will be enrolled after signing an informed consent form. Patients with clinically cT4b or spread to at least one group of lymph nodes with possible invasion of surrounding organs and unresectable locally advanced squamous carcinoma of the thoracic segment of the oesophagus will be included in the study. Patients with suspected distant metastases on the preoperative examination will be excluded from this study. Patients eligible for enrolment will be grouped by centre randomisation according to the study plan. Patients will undergo radical surgery after completion of two cycles of chemotherapy (CT) combined with camrelizumab induction therapy or concurrent chemoradiotherapy if assessed to be operable. Patients evaluated as inoperable will be scheduled for a multidisciplinary consultation to determine the next treatment option. The primary endpoint is the R0 resection rate in patients undergoing surgery after treatment. Secondary endpoints are the rate of major pathological remission, pathological complete response rate, overall survival, progression-free survival and adverse events for all patients.

Ethical approval was obtained from the ethics committees of Fujian Medical University Union Hospital (No. 2022YF039-02). The findings will be disseminated in peer-reviewed publications.

NCT05821452.

Patients with oligometastases show distant relapse in only a limited number of regions. Local therapy such as surgical resection, radiotherapy, chemoradiotherapy, and radiofrequency ablation for the relapsed sites may thus improve patient survival. Oligometastases are divided into oligo-recurrence and sync-oligometastases. Oligo-recurrence indicates a primary lesion that is controlled, and sync-oligometastases indicate a primary lesion that is not controlled. The management of oligo-recurrence and sync-oligometastases in esophageal squamous cell carcinoma has not been clearly established, and treatment outcomes remain equivocal. We reviewed 14 articles, including three phase II trials, that were limited to squamous cell carcinoma. Multimodal treatment combining surgical resection and chemoradiotherapy for oligo-recurrence of esophageal squamous cell carcinoma appears to be a promising treatment. With the development of more effective chemotherapy and regimens that combine immune checkpoint inhibitors, it will become more likely that sync-oligometastases that were unresectable at the initial diagnosis can be brought to conversion surgery. Currently, a randomized, controlled phase III trial is being conducted in Japan to compare a strategy for performing definitive chemoradiotherapy and, if necessary, salvage surgery with a strategy for conversion surgery in patients who can be resected by induction chemotherapy.

This study updated 3-year analyses to further characterize the impact of docetaxel, cisplatin, and fluorouracil (TPF) chemotherapy followed by surgery.

This study was a single-center phase 2 clinical trial. Patients with a diagnosis of borderline resectable esophageal squamous cell carcinoma (BR-ESCC) because of the primary tumor or bulky lymph node that potentially invaded adjacent organs were eligible. The treatment started with TPF chemotherapy followed by surgery if the cancer was resectable, or by concurrent chemoradiation if it was unresectable. This updated report presents the 3-year overall survival (OS) and progression-free survival (PFS) rates.

Surgery was performed for 27 patients (57.4%), and R0 resection was confirmed in 25 patients (53.2%). Pathologic complete response was confirmed in four patients (8.5%). The median follow-up time for the surviving patients was 44.8 months (range, 3.4-74.6 months). The median OS for all the patients was 41.9 months (95% confidence interval [CI], 18.6-65.3 months), with a median PFS of 38.7 months (95% CI, 23.5-53.9 months). The 3-year survival rate for all the patients was 54.4%. The 3-year survival rate for the R0 patients was 65.4%.

Long-term follow-up evaluation confirmed that TPF followed by surgery is feasible and promising in terms of survival for BR-ESCC patients. Trial Registration ClinicalTrials.gov identifer: NCT02976909.

Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed.

All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN.

Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age.

Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.

Treatment for borderline resectable (cT3br) esophageal squamous cell carcinoma (SCC) is currently undefined. This study aimed to analyze the outcome of treatment strategies including induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) against T3br esophageal SCC.

A total of 32 patients with cT3br esophageal SCC enrolled in this study were treated with two cycles of DCF induction therapy.

The overall response rate to DCF induction therapy was 62.5%, while the disease control rate was 93.8% (complete response (CR), three; partial response (PR), 17; stable disease (SD), 10; progressive disease (PD), 2). After DCF induction chemotherapy, 27 patients underwent conversion surgery (CS) and five patients underwent definitive chemoradiotherapy (CRT). Out of 27 patients who underwent CS, 17 underwent transthoracic esophagectomy and 10 underwent thoracoscopic esophagectomy. Anastomotic leakage occurred in five patients (18.5%) and pneumonia in four (14.8%). Recurrent laryngeal nerve paralysis and arrhythmia were observed in two patients (7.4%). The R0 resection rate was 81.5%. Among the five patients who underwent definitive CRT, only one patient (20.0%) achieved CR. Two patients (40.0%) had PR and two (40.0%) had PD. Salvage esophagectomy was performed in one patient after definitive CRT. The 1-, 3-, and 5-year overall survival rates were 75.0, 50.6, and 46.4%, respectively, whereas the 1-, 3-, and 5-year disease-free survival rates were 54.9, 38.8, and 38.8%, respectively.

DCF induction therapy and subsequent CS or definitive CRT are promising treatment strategies for cT3br esophageal SCC.

The optimal treatment strategy for cT4b esophageal cancer has not been established yet. Although curative surgery is sometimes performed after induction treatments, the prognostic factor of cT4b esophageal cancer cases who underwent R0 resection remains unknown.

A total of 200 patients with cT4b esophageal cancer who underwent R0 resection after induction treatments between 2001 and 2020 in our institute were included in the present study. The relationship between clinicopathological factors and patient survival is evaluated to identify useful prognostic factors.

The median and 2-year overall survival were 40.1 months and 62.8%, respectively. Disease recurrence occurred in 98 (49%) patients after surgery. Compared to induction chemotherapy alone, chemoradiation-based induction treatments were associated with decreased locoregional recurrence (34.0% vs 60.8%, P = .0077) but increased pulmonary metastases (27.7% vs 9.8%, P = .0210) and dissemination (19.1% vs 3.9%, P = .0139) after surgery. Multivariate analysis of overall survival identified the preoperative C-reactive protein/albumin ratio (hazard ratio 1.7957, P = .0031), response to induction treatments (hazard ratio 2.9663, P = .0009), postoperative pneumonia (hazard ratio 2.3784, P = .0010), and pN (2-3) (hazard ratio 1.5693, P = .0355) as independent prognostic factors. Preoperative C-reactive protein/albumin ratio (hazard ratio 1.6760, P = .0068) and postoperative pneumonia (hazard ratio 1.8365, P = .0200) were also independent prognostic factors for recurrence-free survival.

Curative surgery after induction therapy for cT4b esophageal cancer achieved favorable survival. Preoperative C-reactive protein/albumin ratio, postoperative pneumonia, response to induction treatments, and pN were useful prognostic factors.

Malignant esophageal stenosis is a common and severe complication of advanced esophageal cancer that can be a serious problem in the continuation of chemotherapy and other anticancer treatments. The impact of chemotherapy regimens on the degree of improvement in esophageal stenosis is unknown. In this study, we focused on the impacts of chemotherapy on the direct anticancer effects, and in the improvement of malignant stenosis.

Patients who underwent radical esophagectomy after chemotherapy, either adjuvant 5-fluorouracil and cisplatin (FP) or docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen, were included. We assessed the length of the cancerous stenosis, the width of the narrowest segment, and the size of the intraluminal area in the stenotic segment by fluoroscopy, and compared the differences before and after chemotherapy. In addition, we evaluated the dysphagia score (Mellow-Pinkas scoring system) as the evaluation of patients' symptoms. The antitumor effects of chemotherapy were also investigated.

A total of 81 patients were enrolled: 50 were treated with FP, and 31 were treated with DCF. The expansion rate in the length of the narrowest part was significantly increased in the DCF group compared with the FP group. Furthermore, the stenosis index (intraluminal stenotic area/stenotic length) was significantly increased in the DCF group compared with the FP group (112% vs 96%, P = 0.038). Dysphagia score after chemotherapy significantly improved in the DCF group compared to the FP group (P = 0.007). The response rates were 60% in the FP group and 67.7% in the DCF group. Effective histopathological response (improvement to grade 2 or 3) was 24% in the FP group and 38.8% in the DCF group.

DCF therapy is more effective than FP treatment in the improvement of malignant esophageal stenosis.

We report the long-term results as primary endpoint in a multicentre randomized prospective Phase 2 trial which compared chemoradiotherapy (CRT) and triplet chemotherapy (CT) as the initial therapy for conversion surgery (CS) in T4b esophageal cancer (EC).

Patients with T4b EC were randomly assigned to the CRT group or CT group as initial treatment. CS was performed if resectable after initial or secondary treatment. The primary endpoint was 2-year overall survival, analysed by intention-to-treat.

The median follow-up period was 43.8 months. The 2-year survival rate was higher in the CRT group (55.1%; 95% CI: 41.1-68.3%) compared to the CT group (34.7%; 95% CI: 22.8-48.9%), although the difference was not significant (P = 0.11). Local and regional lymph node recurrence in patients undergoing R0 resection was significantly higher in the CT group compared to the CRT group (local: 30% versus 8%, respectively, P = 0.03; regional: 37% versus 8%, respectively, P = 0.002).

Upfront CT was not superior to upfront CRT as induction therapy for T4b EC in terms of 2-year survival and was significantly inferior to upfront CRT in terms of local and regional control.

The Japan Registry of Clinical Trials (s051180164).

Little is known about the survival impacts of pretreatment cancerous stenosis on patients with esophageal carcinoma (EC).

The clinicopathologic characteristics of patients who underwent surgery for EC between January 2010 and December 2018 were retrospectively reviewed. Esophageal stenosis was defined as present when a thin endoscope could not be passed through the tumor site. The impacts of stenosis on overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox hazards analysis.

Of the 496 EC patients in this study, 51 (10.3 %) had pretreatment esophageal stenosis. Stenosis was associated with lower body mass index (P < 0.001) and higher pStage (P < 0.001). The 3-year OS rate for the patients with stenosis was significantly poorer than for the patients without stenosis (40.2 % vs 69.6 %; hazard ratio [HR], 2.19; P < 0.001). The survival outcomes, especially CSS, for the patients with stenosis were significantly poorer than for the patients without stenosis for both pStage II-III (P = 0.009) and pStage IV (P = 0.006) disease. The OS and CSS curves were well stratified by the presence of stenosis even in early-stage (pStage II) patients (P = 0.04 and P < 0.01, respectively). Multivariable analysis showed esophageal stenosis, pStage III-IV disease, and non-curative resection to be independently associated with poor OS (HR, 1.61; P = 0.02) and poor CSS (HR,1.67; P = 0.02). Higher pStage was an independent predictor of poor CSS for patients without stenosis, but not for those with stenosis.

Esophageal carcinoma patients with pretreatment stenosis had significantly poorer survival outcomes, especially poorer CSS, than those without stenosis in both early- and advanced-stage diseases.

Advanced esophageal cancer with tracheal invasion is fatal due to airway narrowing and the possibility of tracheoesophageal fistula (TEF) formation during the treatment process. If a TEF develops, palliative care is often chosen. It is very rare that curative treatment is performed including with chemoradiotherapy (CRT) or surgery in such cases. A 71-year-old man presented with dysphagia. He was diagnosed as having hypopharyngeal and cervical esophageal cancer with severe airway stenosis (cT4b [main bronchus, thyroid] N3 M0 cStage IIIC), and we initially created a tracheostomy. Second, we chose induction chemotherapy to avoid fistula formation by CRT, but after one course of chemotherapy, he developed a TEF due to remarkable tumor shrinkage. We strictly managed both his airway and nutrition by continuous suctioning over the cuff of the tracheal cannula and prohibiting swallowing of saliva and enteral nutrition via nasogastric tube. After three courses of chemotherapy were administered, we performed pharyngo-laryngo-esophagectomy followed by adjuvant chemotherapy. The patient remains alive and recurrence free at 9 years postoperatively. In cases of upper TEF caused by advanced hypopharyngeal and cervical esophageal cancer, radical treatment may be possible by effective induction chemotherapy combined with strict airway and nutritional management after prior tracheostomy.

Lymphovascular invasion (LVI) was previously reported to be an independent factor associated with survival in locally advanced esophageal squamous cell carcinoma (LAESCC) patients receiving neoadjuvant chemotherapy (NAC); however, the detailed clinicopathological significance of LVI remains unclear. This study evaluated the prognostic impact of LVI in patients with LAESCC after NAC with cisplatin and 5-fluorouracil (CF) or docetaxel, cisplatin and 5-fluorouracil (DCF) followed by surgery and in LAESCC patients with recurrence after NAC and surgery.

438 patients with thoracic LAESCC who had undergone NAC followed by an esophagectomy with three-field lymphadenectomy were assessed using a propensity score matched analysis, and their long-term outcomes were retrospectively reviewed.

In matched cohort, a multivariate analysis of relapse-free survival (RFS) in the NAC-CF group suggested that ypN (≥ 1, HR = 3.715, p = 0.004) and LVI (positive, HR = 3.366, p = 0.012) were independent factors associated with RFS; in the NAC-DCF group, ypN (≥ 1, HR = 4.829, p < 0.001) was the only independent factor associated with RFS. Comparisons of overall survival (OS) between the ypN + /LVI + group and other groups among patients with recurrence in each NAC regimen showed significant differences in both of NAC groups (p < 0.001, respectively). The ypN + /LVI + group had a significantly poor OS in both an oligometastatic recurrence (OMR) group (p < 0.001) and a non-OMR group (p < 0.001).

The present study suggested that the independent factor associated with prognosis of patients with LAESCC after NAC and surgery may differ according to the NAC regimen, and the presence of both ypN and LVI was a prognostic factor for patients with recurrence, including those with OMR. These results might be helpful when deciding on an additional treatment strategy for LAESCC patients.

Chemotherapy and chemoradiotherapy are common treatments for esophageal squamous cell carcinoma with distant metastasis; however, the prognosis remains poor, and complete remission is difficult to achieve. Here, we report a case of an older adult patient with esophageal squamous cell carcinoma who underwent surgery following combined treatment of immunotherapy and chemotherapy and achieved pathological complete response.

An 80-year-old woman presenting with difficulty swallowing was referred to our hospital. She was diagnosed with esophageal squamous cell carcinoma with distant metastasis of the lymph node at the dorsal side of the IVC and the left supraclavicular lymph node. She was treated with pembrolizumab, cisplatin, and 5-fluorouracil. After four pharmacotherapy courses, primary tumor and metastatic lymph node shrinkage was observed. The patient underwent thoracoscopic subtotal esophagectomy and regional lymph node dissection. The lymph node at the dorsal side of the IVC was not resected, and the left supraclavicular lymph node was removed. Histological examination revealed complete response with no residual tumor or lymph node metastasis. The patient had no recurrence 10 months postoperatively without adjuvant chemotherapy.

Conversion surgery following preoperative therapy, including immunotherapy, may be an effective treatment strategy for improving survival in patients with esophageal squamous cell carcinoma even among older adult patients.

We previously reported that endoscopic response evaluation can preoperatively predict the prognosis and distribution of residual tumors after neoadjuvant chemotherapy (NAC). In this study, we developed artificial intelligence (AI)-guided endoscopic response evaluation using a deep neural network to discriminate endoscopic responders (ERs) in patients with esophageal squamous cell carcinoma (ESCC) after NAC.

Surgically resectable ESCC patients who underwent esophagectomy following NAC were retrospectively analyzed in this study. Endoscopic images of the tumors were analyzed using a deep neural network. The model was validated with a test data set using 10 newly collected ERs and 10 newly collected non-ER images. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the endoscopic response evaluation by AI and endoscopists were calculated and compared.

Of 193 patients, 40 (21%) were diagnosed as ERs. The median sensitivity, specificity, PPV, and NPV values for ER detection in 10 models were 60%, 100%, 100%, and 71%, respectively. Similarly, the median values by the endoscopist were 80%, 80%, 81%, and 81%, respectively.

This proof-of-concept study using a deep learning algorithm demonstrated that the constructed AI-guided endoscopic response evaluation after NAC could identify ER with high specificity and PPV. It would appropriately guide an individualized treatment strategy that includes an organ preservation approach in ESCC patients.