Neoadjuvant Therapy Versus Upfront Surgery for Patients With Clinical Stage 2 or 3 Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

BACKGROUND: Although neoadjuvant therapy followed by surgery (NT) is the standard of care for esophageal cancer in Western countries, upfront surgery (US) followed by adjuvant therapy (when indicated) still is commonly used in Asia to minimize overtreatment. This study investigated the cost-effectiveness of NT versus US for patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients with a diagnosis of ESCC between 2010 and 2015 were divided into NT or US according to the intention to treat. Two propensity score-matched groups of patients with clinical stage 2 (135 pairs) or stage 3 (194 pairs) disease were identified and compared in terms of overall survival (OS) and direct costs incurred within 3 years after diagnosis. RESULTS: The esophagectomy rates after NT were 82% for stage 2 and 88% for stage 3 disease. Compared with US, surgery after NT was associated with higher R0 resection rates, a lower number of dissected lymph nodes, and similar postoperative mortality. On an intention-to-treat analysis, stage 3 patients who received NT had a significantly better 3-year OS rate (45%) than those treated with US (37%) (p = 0.029) without significant cost increases (p = 0.89). However, NT for clinical stage 2 disease neither increased costs nor improved 3-year OS rates (47% vs 47%; p = 0.88). At a willingness-to-pay level of US$50,000 per life-year, the probability of NT being cost-effective was 92% for stage 3 versus 59% for stage 2 ESCC. CONCLUSION: Because of its higher cost-effectiveness, NT is preferable to US for patients with clinical stage 3 ESCC, but US remains a viable option for stage 2 disease.

Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.

Endoscopic resection (ER) has become the first-line therapy for early esophageal cancer and offers a treatment alternative to surgery, owing to less morbidity and better quality of life. ER techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is faster, simpler, and cheaper than ESD, but limited by its ability to resect lesions larger than 1.5 centimeters. Piecemeal EMR has limitations, including a high local recurrence rate and a suboptimal specimen for an accurate pathologic assessment. ESD, on the other hand, allows en bloc resections with negative (R0) margins, irrespective of lesion size, providing an excellent pathologic specimen, however, is technically challenging with a higher risk of complications. The evaluation of ER specimens in pathology varies slightly from institution to institution. Our review summarizes the current practices and issues in the pathologic assessment of esophageal ER specimens, which highlights the necessity of a systematic approach and standardization of both macroscopic and microscopic evaluation. There is a need for a comprehensive and standardized pathology report that will allow for uniform terminology for endoscopists, surgeons, and pathologists, which, in turn, will result in better treatment guidance.

Macroscopic Assessment and Sampling of Endoscopic Resection Specimens for Squamous Epithelial Malignancies with Superficial Involvement of Esophagus.

Endoscopic resection is commonly used for superficial squamous cell carcinoma or high-grade dysplasia of esophageal squamous cell carcinoma. The depth of invasion, clearance from resection margins, and other pathological parameters are important parameters to be examined. The depth of invasion by carcinoma is associated with the risk of lymph node metastases. In endoscopic resection of superficial squamous malignancies of the esophagus, proper pathological examination of the resected specimen could guide the management of the patients in terms of the need for additional treatment, including lymph node dissection, chemotherapy, and radiation therapies.

Presentation, Treatment, and Outcomes of Vulnerable Populations With Esophageal Cancer Treated at a Safety-Net Hospital.

Social determinants of health have been associated with poor outcomes in esophageal cancer. Primary language and immigration status have not been examined in relation to esophageal cancer outcomes. This study aims to investigate the impact of these variables on stage of presentation, treatment, and outcomes of esophageal cancer patients at an urban safety-net hospital. Clinical data of patients with esophageal cancer at our institution between 2003 and 2018 were reviewed. Demographic, tumor, and treatment characteristics were obtained. Outcomes included median overall survival, stage-specific survival, and utilization of surgical and perioperative therapy. Statistical analysis was conducted using Chi-square test, Fisher's exact tests, Kaplan-Meier method, and logistic regression. There were 266 patients; 77% were male. Mean age was 63.9 years, 23.7% were immigrants, 33.5% were uninsured/Medicaid, and 16.2% were non-English speaking. Adenocarcinoma was diagnosed in 55.3% and squamous cell in 41.0%. More patients of non-Hispanic received esophagectomies when compared to those of Hispanic origin (64% vs 25%, P = 0.012). Immigrants were less likely to undergo esophagectomy compared to US-born patients (42% vs 76%, P = 0.001). Patients with adenocarcinoma were more likely than squamous cell carcinoma patients to undergo esophagectomy (odds ratio = 4.40, 95% confidence interval 1.61-12.01, P = 0.004). More commercially/privately insured patients (75%) received perioperative therapy compared to Medicaid/uninsured (54%) and Medicare (49%) patients (P = 0.030). There was no association between demographic factors and the utilization of perioperative chemoradiation for patients with operable disease. Approximately 23% of patients with operable disease were too frail or declined to undergo surgical intervention. In this small single-center study, race and primary language were not associated with median survival for patients treated for esophageal cancer. US-born patients experienced higher surgical utilization and privately insured patients were more likely to receive perioperative therapy. Many patients with operable cancer were too frail to undergo a curative surgery. Studies should expand on the relationships between social determinants of health and nonclinical services on delivery of care and survival of vulnerable populations with esophageal cancer.

Cost-effectiveness analysis of neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced esophageal squamous cell carcinoma based on the NEOCRTEC5010 trial.

BACKGROUND AND PURPOSE: The phase 3 NEOCRTEC5010 trial demonstrated that neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) had significantly greater efficacy than surgery alone did, but at the same time, the addition of NCRT places an economic burden on patients. This study assessed the cost-effectiveness of NCRT followed by surgery based on the NEOCRTEC5010 trial. MATERIALS AND METHODS: A three-state Markov model (disease-free survival, relapse and death) based on data from the NEOCRTEC5010 trial was used to estimate the incremental cost-effectiveness ratio (ICER) of NCRT plus surgery versus surgery alone for ESCC. The model evaluates the outcomes from the perspective of Chinese society. Costs, quality-adjusted life-years (QALYs), and the ICER in terms of 2019 US$ per QALY gained, were calculated. Model robustness was evaluated with one-way and probabilistic sensitivity analyses. RESULTS: Compared with surgery alone, NCRT plus surgery increased costs by $14933.57, while gaining 3.08 QALYs, resulting in an ICER of $4848.56 per QALY. The ICER was far below the commonly accepted willingness-to-pay threshold ($26,157 per QALY). The duration of disease-free survival (DFS) for the group that received NCRT was the crucial factor in determining the ICER. CONCLUSION: Compared with surgery alone, NCRT followed by surgery for locally advanced ESCC can be cost-effective because of significant clinical benefits.

Prediction of lymph node metastatic status in superficial esophageal squamous cell carcinoma using an assessment model combining clinical characteristics and pathologic results: A retrospective cohort study.

BACKGROUND: It is important to identify the risk of lymph node metastasis (LNM) in patients with superficial esophageal squamous carcinoma (SESC) who have received endoscopic resection (ER). We aimed to develop a risk-predicting model for metastasis of SESC to lymph nodes using clinicopathological features and pathological results. METHODS: Clinical data on 539 consecutive patients who underwent esophagectomy for SESC in our hospital were collected. Their post-surgical pathological results were assessed and analyzed. Multivariate logistic regression was used to identify all independent risk factors associated with LNM that then were incorporated into the prediction model. RESULTS: LNM was identified in 53 of 366 patients and 30 of 173 patients by positive histopathological results in the training and validation cohorts. The risk factors associated with LNM were large tumor size, poor tumor grade, deep invasion, and presence of angiolymphatic invasion. The model achieved good discriminatory ability of 0.80 (95%CI, 0.74-0.86) and 0.81 (95%CI, 0.75-0.86) in predicting LNM in the training and validation cohorts respectively. A LNM-predicting nomogram was formed with an area under curve of 0.80 (95% CI, 0.74-0.86), which had well-fitted calibration curves. CONCLUSIONS: A prediction model was constructed to generates 3 categories for estimated LNM risk in SESC patients. It provides a practical way of estimation of LNM risk in SESC patients who had received ER.

Outcomes of Endoscopic Submucosal Dissection vs Esophagectomy for T1 Esophageal Squamous Cell Carcinoma in a Real-World Cohort.

BACKGROUND & AIMS: Esophagectomy is the standard treatment for early-stage esophageal squamous cell carcinoma (EESCC), but patients who undergo this procedure have high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a less-invasive procedure for treatment of EESCC, but is considered risky because this tumor frequently metastasizes to the lymph nodes. We aimed to directly compare outcomes of patients with EESCC treated with ESD vs esophagectomy. METHODS: We performed a retrospective cohort study of patients with T1a-m2/m3, or T1b EESCCs who underwent ESD (n = 322) or esophagectomy (n = 274) from October 1, 2011 through September 31, 2016 at Zhongshan Hospital in Shanghai, China. The primary outcome was all-cause mortality at the end of follow up (minimum of 6 months). Secondary outcomes included operation time, hospital stay, cost, perioperative mortalities/severe non-fatal adverse events, requirement for adjuvant therapies, and disease-specific mortality and cancer recurrence or metastasis at the end of the follow up period. RESULTS: Patients who underwent ESD were older (mean 63.5 years vs 62.3 years for patients receiving esophagectomy; P = .006) and a greater proportion was male (80.1% vs 70.4%; P = .006) and had a T1a tumor (74.5% vs 27%; P = .001). A lower proportion of patients who underwent ESD had perioperative mortality (0.3% vs 1.5% of patients receiving esophagectomy; P = .186) and non-fatal severe adverse events (15.2% vs 27.7%; P = .001)-specifically lower proportions of esophageal fistula (0.3% of patients receiving ESD vs 16.4% for patients receiving esophagectomy; P = .001) and pulmonary complications (0.3% vs 3.6%; P = .004). After a median follow-up time of 21 months (range, 6-73 months), there were no significant differences between treatments in all-cause mortality (7.4% for ESD vs 10.9%; P = .209) or rate of cancer recurrence or metastasis (9.1% for ESD vs 8.9%; P = .948). Disease-specific mortality was lower among patients who received ESD (3.4%) vs patients who patients who received esophagectomy (7.4%) (P = .049). In Cox regression analysis, depth of tumor invasion was the only factor associated with all-cause mortality (T1a-m3 or deeper vs T1a-m2: hazard ration, 3.54; P = .04). CONCLUSION: In a retrospective study of patients with T1am2/m3 or T1b EESCCs treated with ESD (n = 322) or esophagectomy (n = 274), we found lower proportions of patients receiving ESD to have perioperative adverse events or disease specific mortality after a median follow up time of 21 months. We found no difference in overall survival or cancer recurrence or metastasis in patients with T1a or T1b ESCCs treated with ESD vs esophagectomy.

Retrospective Assessment of the Diagnostic Accuracy of the Depth of Invasion by Narrow Band Imaging Magnifying Endoscopy in Patients with Superficial Esophageal Squamous Cell Carcinoma.

PURPOSE: Treatment strategies for superficial esophageal squamous cell carcinoma (S-ESCC) are determined mainly on the basis of the depth of invasion. We retrospectively studied the accuracy of the depth of tumor invasion, comprehensively assessed using the Japan Esophageal Society (JES) classification. METHODS: The study group comprised 256 patients who underwent narrow band imaging (NBI) magnifying endoscopy, and endoscopic submucosal dissection for S-ESCC. The depth of invasion of S-ESCC was classified into three groups: EP/LPM, MM/SM1, and SM2. The following variables were studied retrospectively: (1) the diagnostic accuracy of non-magnifying white-light endoscopy, (2) the diagnostic accuracy of type B vessels, (3) the diagnostic accuracy of avascular area (AVA), (4) the diagnostic accuracy of the JES classification, and (5) the diagnostic accuracy of comprehensive diagnosis. The depth of invasion was assessed by white-light non-magnifying endoscopy, followed by NBI magnifying endoscopy. RESULTS: The positive predictive value (PPV) of white-light non-magnifying endoscopy was 86% for EP/LPM, 53% MM/SM1, and 74% for SM2. The PPV of the diagnosis of type B vessels was 93% for EP/LPM, 62% for MM/SM1, and 74% for SM2. The PPV of the AVA diagnosis was 73% for EP/LPM, 89% for MM/SM1, and 100% for SM2. The PPV of diagnosis according to the JES classification was 93% for EP/LPM, 65% for MM/SM1, and 77% for SM2. The PPV of the comprehensive diagnosis was 94% for EP/LPM, 63%, for MM/SM1, and 75% for SM2. CONCLUSIONS: The additional use of NBI magnifying endoscopy can enhance the diagnostic accuracy of the depth of invasion in patients with S-ESCC.