Induction chemotherapy followed by response evaluation and esophagectomy for advanced esophageal cancer

Patients with extensive locoregional and/or oligometastatic esophageal cancer have a poor prognosis and are often referred for palliative care. However, induction chemotherapy followed by response evaluation may be considered as an alternative treatment and some patients may qualify for surgery with curative intent. The aim of this study was to assess overall survival in patients receiving induction chemotherapy followed by surgery.

Patients with esophageal or junctional cancer who underwent induction chemotherapy between 2005-2022 in a Dutch tertiary referral center were identified. None of these patients were eligible for standard neoadjuvant therapy plus surgery due to locally advanced or limited metastatic disease. Response to induction chemotherapy was assessed by (FDG-PET) CT-scan and/or upper endoscopy or endoscopic ultrasound. Response to therapy and treatment options, including surgery or palliation, were discussed in the multidisciplinary tumor board. Overall survival was calculated using the Kaplan Meier method using date of diagnosis until date of death or last day of follow-up. Multivariate logistic regression analysis was used to investigate characteristics that predict which patients proceed to esophagectomy.

In total, 197 patients were identified. Most patients were male (77.2%) and had adenocarcinoma (68.5%). An irresectable primary tumor and/or widespread locoregional lymph node metastases (located outside the radiation field) was seen in 165 patients (83%), distant lymph node metastases in 24 patients (12%), organ metastases in 5 patients (3%) and data of 3 patients were missing (2%). The majority (88%) received taxane/platinum-based chemotherapy and 12% received anthracyclin-based triplets. After induction chemotherapy, 70 patients (36%) received palliative care because of progressive disease or no response. The median overall survival of this group was 13 months (95% CI 11.1-14.9). Esophagectomy was attempted in 127 patients (64%), but 22 patients (17%) had an irresectable tumor or distant metastases during surgery. Median overall survival of these 22 patients was 13 months (95% CI 10.0-15.9). Estimated 5-year overall survival of the 105 patients that underwent esophagectomy was 33%. Only clinical T-category (T2-3 versus T4) was associated with a higher chance for esophagectomy on multivariable analysis (p = 0.018). The presence of pathological lymph node metastases (HR 2.211, 95% CI 1.05-4.68, p = 0.038) and a positive resection margin (HR 2.316, 95% CI 1.32-4.07, p = 0.003) were associated with worse survival in multi-variable analysis.

Induction chemotherapy followed by response evaluation and surgery in highly selected patients who respond to induction chemotherapy is associated with a 5-year overall survival rate of 33%. The presence of pathological lymph node metastases and a positive resection margin were prognostic factors for overall survival.

The authors.

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All authors have declared no conflicts of interest.