Endoscopic Submucosal Dissection and Adjuvant Therapy for Higher Stage Esophageal Cancer: Ready for Prime Time?

Abstract Background Endoscopic submucosal dissection (ESD) is acceptable for pT1a esophageal cancers. Esophagectomy is standard-of-care for higher stages, even if negative margin is achieved with endoscopic resection. This is due to risks of occult nodal disease that would otherwise go undetected and untreated. Some patients are ineligible for esophagectomy (due to prohibitive medical comorbidities) or decline it. In these patients, multi-disciplinary tumor conferences struggle to understand the optimal treatment. We aimed to assess treatment patterns and outcomes for patients undergoing ESD for ≥pT1b cancers who were ineligible for or declined esophagectomy. Methods Retrospective cohort study was performed using prospectively-collected data. Patient population included all consecutive patients who underwent ESD at a tertiary hospital with pT1b or higher disease (declined or ineligible for esophagectomy). Complications and survival outcomes are reported. Univariable analysis was performed. For comparative analysis, patients who underwent esophagectomy were identified with no neoadjuvant therapy and who had pT1b or higher disease with proven pN0. Propensity-score matching (optimal matching, without replacement) was used to compare short and long-term outcomes of matched (2:1) patients undergoing ESD and esophagectomy. Perfect matching on pT-stage was mandated. Survival analysis was performed on the matched groups. Results Fifty-three ESD patients met inclusion criteria. Mean age was 74.8 (SD = 9.4) and 81.1% male. Majority were adenocarcinoma while 15.1% were squamous cell cancers. Chemoradiation was received by 24.5% (n = 13) of patients whereas 13.2% (n = 7) received adjuvant radiation alone. Most prevalent stages were pT1bSM2 (41.5%, n = 22) and pT1bSM3 (26.4%, n = 14). Incidence of positive margins (mostly focal deep positive margin) ranged from 0 in pT1bSM1 to 70–100% in pT2/pT3. Incidence of complications was 15.1% (n = 8); most requiring endoscopic dilatation. Twenty-five esophagectomy patients (no neoadjuvant) were compared to ESD population. Two-year and five-year progression-free/overall survival were not different in propensity-matched analyses (p 0.10). Conclusion Organ-preserving treatment with ESD and adjuvant chemoradiation/radiation is feasible and has minimal complications, with comparable survival to esophagectomy in patients with higher stage (pT1b) esophageal cancers. This was in patients who were ineligible for or declined esophagectomy; furthermore, there is higher likelihood of undiagnosed/occult nodal disease in the ESD group as the esophagectomy group was proven to be pN0. Thus, these analyses are highly biased towards worse outcomes for the ESD group. Larger comparative trials incorporating patient-reported outcomes and quality-of-life are required. Translational work to identify better biomarkers to select patients for adjuvant therapies is needed.