Salvage esophagectomy for esophageal cancer after definitive chemoradiotherapy (dCRT) is a high-risk surgery, and radical lymph node dissection (RLND) can cause severe complications. However, the significance of RLND in salvage surgery remains unclear.

This study included 55 patients who underwent curative-intent salvage esophagectomy after dCRT for esophageal squamous cell carcinoma. We evaluated the prognostic impact of lymph node dissection of each station using efficacy indexes (EIs) and compared the outcomes between RLND and limited lymph node dissection (LLND).

Nine (16.4%) patients underwent RLND and 46 (83.6%) underwent LLND. Patients who underwent RLND had greater operative blood loss and a greater number of resected lymph nodes compared to patients who underwent LLND (P = 0.053 and 0.002, respectively). However, the incidence of postoperative complications was not significantly different between the groups. The EIs of the cervical and mediastinal lymph nodes were zero because no patients with involved nodes at these stations remained alive at 5 years. In contrast, perigastric lymph nodes had relatively high EIs. Overall and cancer-specific survival did not differ significantly between patients who underwent RLND and those who underwent LLND (P = 0.475 and 0.808, respectively).

The EIs of the cervical and mediastinal lymph nodes were zero, and RLND did not improve survival. Depending on tumor status, LLND may be sufficient for salvage esophagectomy.

Among patients with unresectable or metastatic esophageal cancer who receive definitive chemotherapy or chemoradiotherapy, the rates of treatment-related adverse events and incomplete treatment remain high. We conducted this study to investigate survival after definitive treatments and identify predicting factors for incomplete treatment. The data of patients who received definitive chemotherapy or chemoradiotherapy for esophageal cancer were retrospectively examined. The patients were assigned to Group 1: incomplete definitive treatment; Group 2: complete definitive treatment; or Group 3: complete definitive treatment with additional salvage surgery. The data of 273 patients (90, 166, and 17 in Groups 1, 2, and 3, respectively) were analyzed. In the survival analysis, the median overall survival of Groups 1, 2, and 3 were 2.6, 10.3, and 29.5 months, respectively. A significant difference in 3-year overall survival was observed among the groups (2.2%, 12.4%, and 48.5%, p < 0.001). In multivariable analysis, the independent risk factors for incomplete definitive treatment included poor performance score (hazard ratio (HR): 5.23, p = 0.001), bone metastasis (HR: 2.18, p = 0.024), airway invasion (HR: 2.90, p = 0.001), and liver cirrhosis (HR: 3.20, p = 0.026). Incomplete definitive treatment is associated with a far worse prognosis. Poor performance, bone metastasis, airway invasion, and liver cirrhosis are risk factors for incomplete treatment.

The clinical effectiveness of tumor markers for estimating prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. We assessed the clinical impact of changes in perioperative serum p53 antibodies (s-p53-Abs) titers in ESCC.

From January 2011 to March 2021, 249 patients were enrolled in this study. Titers of s-p53-Abs were measured before the initial treatment and 3 months after esophagectomy. Patients were divided into a s-p53-Abs decreased or unchanged group (Group D, n = 217) and an increased group (Group I, n = 32). Short- and long-term outcomes were compared between the groups.

There was no correlation between the changes in squamous cell carcinoma antigen and carcinoembryonic antigen titers and recurrence site, number of recurrent lesions, and prognosis. However, the recurrence rate was significantly higher in Group I than in Group D (53.1% vs. 28.6%, p = 0.008), especially for distant organ recurrence (37.5% vs. 18.4%, p = 0.019). Furthermore, the rate of polyrecurrence was higher in Group I than in Group D (34.4% vs. 14.3%, p = 0.009). Recurrence-free survival (RFS) was significantly worse in Group I than in Group D (median survival time, 21.2 months vs. 36.7 months, p = 0.015). Multivariate analysis revealed that lymphatic vessel infiltration (hazard ratio [HR], 1.721; 95% CI 1.069-2.772; p = 0.026), blood vessel infiltration (HR, 2.348; 95% CI 1.385-3.982; p = 0.002), advanced pathological stage (≥ III) (HR, 3.937; 95% CI 2.295-6.754; p < 0.001), and increased s-p53-Abs titers (HR, 2.635; 95% CI 1.488-4.667; p = 0.001) were independent predictors of poor RFS.

Elevation of s-p53-Abs titers after esophagectomy can predict polyrecurrence in distant organs and poor prognosis.

In this review, we focused on four topics, namely, minimally invasive esophagectomy (MIE), robot-assisted minimally invasive esophagectomy (RAMIE), conversion and salvage surgery, and neoadjuvant and adjuvant therapy, based on notable reports published in the years 2020 and 2021. It seems that while the short-term outcomes of minimally invasive Ivor Lewis esophagectomy (MIE-IL) were better than those of open Ivor Lewis esophagectomy (OE-IL), there were no significant differences in the long-term outcomes between MIE-IL and OE-IL. Similarly, the short-term outcomes of minimally invasive McKeown esophagectomy (MIE-MK) were better than those of open McKeown esophagectomy (OE-MK), while there were no significant differences in the long-term outcomes between MIE-MK and OE-MK. Furthermore, the short-term outcomes of robot-assisted minimally invasive Ivor Lewis esophagectomy (RAMIE-IL) were superior to those of completely minimally invasive Ivor Lewis esophagectomy (CMIE-IL). On the other hand, there were advantages and disadvantages in relation to the short-term outcomes of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK) as compared with completely minimally invasive McKeown esophagectomy (CMIE-MK). However, there were no significant differences in the long-term outcomes between RAMIE-MK and CMIE-MK. Further research is needed to evaluate of short-term and long-term outcomes of transmediastinal esophagectomy with and without robotic assistance. Both induction chemotherapy and induction chemoradiotherapy appear to be promising to secure a higher rate of conversion surgery. Neoadjuvant chemoimmunotherapy and chemoimmunoradiotherapy have shown promising results and are expected as new powerful therapies.

Oesophageal cancer is the eighth most common cancer and sixth leading cause of cancer-related mortality worldwide. Salvage oesophagectomies are associated with an increased risk of mortality, although recent data suggests that long-term survival rates following salvage oesophagectomy are similar to planned oesophagectomy. The aim was therefore to meta-analyse outcomes for patients undergoing salvage versus planned oesophagectomies to assess the differences in short-term mortality and long-term survival.

A systematic review of Medline, Scopus, Web of Science and PubMed was performed to identify relevant studies. Data were extracted and compared by meta-analysis, using odds ratio and mean differences with 95% confidence intervals.

Nineteen studies meeting inclusion criteria were included in the meta-analysis, which compared patients in the planned oesophagectomy group (n = 23 555) to patients in the salvage oesophagectomy group (n = 2227). There were significant differences between the groups in terms of rates of postoperative mortality (5.7% salvage oesophagectomy versus 3.1% planned oesophagectomy, P = 0.0004), anastomotic leak (20.6% salvage oesophagectomy versus 14.5% planned oesophagectomy, P < 0.00001), pulmonary complications (37.1% salvage oesophagectomy versus 24.2% planned oesophagectomy, P < 0.0001) and R0 margin (87.6% salvage oesophagectomy versus 91.3% planned oesophagectomy, P < 0.0001). There was no statistical difference between long-term survival rates at 5 years with 39.2% for salvage and 42.6% for planned oesophagectomy (P = 0.28).

Salvage oesophagectomies do offer a meaningful chance of long-term survival (at 5 years) for select patients with oesophageal cancer, but the elevated risk of post-operative complications and mortality following salvage oesophagectomy should be recognized.

The optimal treatment approach for T4 esophageal cancer is not well established. We aimed to perform a systematic review and meta-analysis to determine the survival rates and safety of chemoradiotherapy followed by surgery (CRT-S) and chemoradiotherapy alone (CRT) in patients with T4 N_any M0 esophageal cancer.

We searched databases for eligible prospective or retrospective studies. The outcomes of interest were overall survival (OS) at 1, 3 and 5 years, treatment-related fistula formation and mortality rates. Meta-analyses were performed using the random effects models separately for studies evaluating CRT-S and CRT. Subgroup analyses were performed based on histology, radiation dose, chemotherapy regimen and duration of the interval between CRT and surgery.

We identified 23 studies including 1,119 patients with predominantly squamous cell carcinoma (93%) and adenocarcinoma (3%) histology. The OS rates of patients receiving CRT-S were 65%, 36% and 20% at 1, 3 and 5 years, respectively. The OS rates of patients receiving CRT were 30%, 11% and 10% at 1, 3 and 5 years, respectively. Treatment-related fistula formation rates were 4% for CRT-S and 9% for CRT. Treatment-related mortality rates were 3% for both groups. Subgroup analyses showed that the interval of >2 months between CRT and surgery was associated with significantly improved OS rates at 1, 3 and 5 years.

Chemoradiotherapy is an efficacious treatment approach for T4 esophageal cancer, with clinically acceptable rates of treatment-related fistula formation and mortality. Tri-modality approach with surgery can be considered in carefully selected patients. Our study findings should be interpreted with caution due to the lack of high-quality evidence. Randomized controlled trials are warranted to confirm these findings.

Extensive lymph node dissection increases the risk of postoperative complications, especially in salvage surgery, after definitive chemoradiotherapy (≥ 50 Gy) in patients with esophageal squamous cell carcinoma. The purpose of this retrospective study is to compare the outcomes of salvage esophagectomy with selective lymphadenectomy of only clinically positive lymph nodes.

Clinically positive lymph nodes, diagnosed as metastases using computed and positron emission tomography performed before chemoradiotherapy or salvage surgery, were targeted for dissection in selective lymphadenectomy. We compared postoperative complications between 52 patients who underwent salvage esophagectomy with selective lymphadenectomy and 207 controls who underwent nonsalvage esophagectomy with 3-field lymphadenectomy. We also analyzed postoperative recurrence pattern and survival in salvage group.

The mean number of dissected lymph nodes was 12.9 in the salvage esophagectomy group compared with 48.1 in the 3-field lymphadenectomy group (p < 0.001). Differences in the number of postoperative complications, comparing Clavien-Dindo all-grade and ≥ grade 3, were not significant between the groups. Both 30- and 90-day mortality were 0% (0/52) in the salvage group. Five cases had recurrence only in the locoregional area without distant metastasis. Of these five cases, only one had recurrence in the subcarinal lymph node without prophylactic mediastinal lymphadenectomy. A 3-year recurrence-free survival and 3-year overall survival from salvage esophagectomy were 43.3% and 46.3%, respectively.

It may contribute to obtaining good short- and long-term outcomes by dissecting only clinically positive lymph nodes in salvage esophagectomy.

Definitive chemoradiation (dCRT) is the mainstay treatment for cStage IVa esophageal squamous cell carcinoma (ESCC) with good performance status (PS), according to standard practice guidelines. Salvage surgery may incur operation complications and risk of mortality. According to the esophageal cancer practice guidelines outlined by the Japan Esophageal Society, when a tumor is residual and recurrent, chemotherapy and palliative symptomatic treatment is continued. However, salvage operation has been selected as a therapeutic option for recurrent or residual tumors after dCRT. There is weak evidence for not recommending surgery for cStage IVa ESCC exhibiting residual disease following dCRT. It has been reported that during salvage surgery the only prognostic factor that is thought to be performed is complete resection (R0), but at the same time, salvage esophagectomy increases the incidence of postoperative complications and mortality. The phase II chemoselection study by Yokota T et al. in Japan showed that multidisciplinary treatment initiated by induction therapy, in which docetaxel is added to cisplatin and 5-fluorouracil, resulted in a good prognosis in the short term. In this review, we discuss the surgical strategy and future of unresectable clinical T4 (cT4) ESCC.

Definitive chemoradiotherapy (dCRT) for the esophageal squamous cell carcinoma (ESCC) is performed for patients with cT4 disease without distant metastasis and also for those with cStage I-III who are unable to tolerate or who refuse surgery. The rates of clinical complete response (cCR) after dCRT differ depending on the cStage, and patients who once achieved cCR frequently experience tumor recurrence. For those with residual tumor or with recurrence, salvage treatment is performed to achieve a cure. Several procedures have been reported as salvage treatments. Salvage esophagectomy is associated with high rates of morbidity and mortality, but can offer long-term survival. With R0 resection, with cCR to dCRT, pulmonary complications appear to be important prognostic factors affecting overall survival (OS). Lymphadenectomy is performed for the patients with lymph node metastasis without recurrence of primary lesions or distant metastasis, but the contribution to long-term OS is unclear. Metastasectomy is performed when distant metastasis is limited to the lung and there are few lesions, possibly contributing to long-term OS. Endoscopic resection and photodynamic therapy are indicated for cT1a and cT1-2 residual or recurrent tumors, respectively, and can yield favorable outcomes. Re-CRT and re-radiotherapy are performed for the patients with contraindications for surgery, but neither appears to contribute to long-term OS despite high incidences of esophageal fistula and perforation.

Chemoradiotherapy is an alternative to surgery for esophageal cancer, with a putatively equivalent outcome. However, disease recurrence after a complete response is common and if follow-up surveillance detects recurrence, salvage treatments for potentially curable disease must follow.

We conducted a nation-wide questionnaire survey of institutions in Japan certified by the Japanese Esophageal Society to investigate outcomes of primary thoracic esophageal cancer patients initially treated by chemoradiotherapy with complete response diagnoses. The primary endpoint was overall survival, the secondary endpoint disease recurrence. Outcomes of patients who had undergone salvage treatments were also investigated. Cases were excluded from analysis if endoscopic study, endoscopic biopsy, or computed tomography data were lacking.

At 41 institutes 544 case records were collected; valid data on 392 patients were obtained; 5-year survival was 74.8%, 5-year disease-free survival, 66.8%. Clinical staging before treatment significantly affected both overall and disease-free survival rates, but differences between adjoining stages were unexpectedly small. The primary relapse site was classified as primary site (n = 58), regional lymph nodes (n = 36), or distant disease (n = 34). Salvage treatments with curative intent (surgery, endoscopic treatments, and additional radiation) were performed on 38, 23, and 4 cases; 5-year survival after esophagectomy (n = 22), endoscopic treatment (n = 23), and lymphadenectomy (n = 9) was 47.4%, 70.9%, and 33.3%, respectively.

A quarter of patients developed recurrent disease, mostly locoregional, after complete response. Complete response patients with originally advanced stage disease had fair clinical outcomes; salvage treatments after locoregional recurrence achieved modest long-term survival.

Salvage esophagectomy is an option for patients with recurrent or persistent esophageal cancer after definitive chemoradiation therapy or those who undergo active surveillance after induction chemoradiation therapy. Salvage resection is associated with higher rates of morbidity compared with planned esophagectomy but offers patients with locally advanced disease a chance at improved long-term survival. Salvage resection should be preferentially performed in a multidisciplinary setting by high-volume and experienced surgeons. Technical considerations, such as prior radiation dosage, radiation field, and choice of conduit, should be taken into account.

Definitive chemoradiotherapy (dCRT) using cisplatin plus 5fluorouracil (CF) with radiation is considered the standard treatment for unresectable locally advanced T4 esophageal squamous cell carcinoma (ESCC). Recently, induction chemotherapy has received attention as an effective treatment strategy.

We report a successful case of a 59-year-old female with unresectable locally advanced T4 ESCC treated by two additional courses of chemotherapy with CF after induction chemotherapy with docetaxel, cisplatin and fluorouracil (DCF) followed by dCRT. Initial esophagogastroduodenoscopy (EGD) detected a type 2 advanced lesion located on the middle part of the esophagus, with stenosis. Computed tomography detected the primary tumor with suspected invasion of the left bronchus and 90° of direct contact with the aorta, and upper mediastinal lymph node metastasis. Pathological findings from biopsy revealed squamous cell carcinoma. We initially performed induction chemotherapy using three courses of DCF, but the lesion was still evaluated unresectable after DCF chemotherapy. Therefore, we subsequently performed dCRT treatment (CF and radiation). After dCRT, prominent reduction of the primary tumor was recognized but a residual tumor with ulceration was detected by EGD. Since the patient had some surgical risk, we performed two additional courses of CF and achieved a clinically complete response. After 14 mo from last administration of CF chemotherapy, recurrence has not been detected by computed tomography and EGD, and biopsy from the scar formation has revealed no cancer cells.

We report successful case with tumor remnants even after DCF and subsequent dCRT, for whom a complete response was finally achieved with two additional courses of CF chemotherapy. Additional CF chemotherapy could be one radical treatment option for residual ESCC after treatment with induction DCF followed by dCRT to avoid salvage surgery, especially for high-risk patients.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.