Locoregional Residual Esophageal Cancer after Neo-adjuvant Chemoradiotherapy and Surgery Regarding Anatomic Site and Radiation Target Fields

Abstract

Objective:Neoadjuvant chemoradiotherapy followed by surgery establishes a considerable pathologic complete response (pCR) in EC. The aim was to determine site of residual tumor and its prognostic impact.Summary Background Data:High rates of residual tumor in the adventitial region even inside the radiation fields will influence current decision-making.Methods:We evaluated resection specimens with marked target fields from 151 consecutive EC patients treated with carboplatin/paclitaxel and 41.4Gy between 2009 and 2018.Results:In radically resected (R0) specimens 19.8% (27/136) had a pCR (ypT0N0) and 14% nearly no response (tumor regression grade: tumor regression grade 4–5). Residual tumor commonly extended in or restricted to the adventitia (43.1%; 47/109), whereas 7.3% was in the mucosa (ypT1a), 16.5% in the submucosa (ypT1b) and 6.4% only in lymph nodes (ypT0N+). Macroscopic residues in R0-specimens of partial responders (tumor regression grade 2-3: N = 90) were found in- and outside the gross tumor volume (GTV) in 33.3% and 8.9%, and only microscopic in- and outside the clinical target volume in 58.9% and 1.1%, respectively. Residual nodal disease was observed proximally and distally to the clinical target volume in 2 and 5 patients, respectively. Disease Free Survival decreased significantly if macroscopic tumor was outside the GTV and in ypT2-4aN+.Conclusions:After neoadjuvant chemoradiotherapy, pCR and ypT1aN0 were seen in a limited number of R0 resected specimens (19.8% and 7.3%, respectively), whereas 6.4% had only nodal disease (yT0N+). Disease Free Survival decreased significantly if macroscopic residue was outside the GTV and in responders with only nodal disease. Therefore, we should be cautious in applying wait and see strategies.

Moderately differentiated esophageal squamous cell carcinoma has a poor prognosis after neoadjuvant chemoradiotherapy

“…Regarding the tumor residual pattern in the primary tumor, the dominant pattern in this study was diffuse remnant, followed by shallow remnant, central remnant, and deep remnant. Residual tumor cells were commonly present in adventitia, which is similar to the findings of recent studies on esophageal cancer treated with NCRT, which mostly comprised patients with esophageal adenocarcinoma (28). However, this finding is inconsistent with an observation made in a previous study, which reported that the mucosa and submucosa of the esophageal wall are commonly affected after chemoradiotherapy for esophageal cancer (29).…”

Longer interval between neoadjuvant chemoradiotherapy and surgery is associated with improved pathological response, but does not accurately estimate survival in patients with resectable esophageal cancer

“…However, >50% of patients with ESC are diagnosed at a locally advanced stage when the tumor has become inoperable, leaving them with limited management options and a poor prognosis (4,5). Recently, due to the application of multimodality approaches, neoadjuvant therapy has assumed a critical role in ESC management (6)(7)(8)(9)(10)(11). For example, neoadjuvant therapy has achieved a reduction in the tumor burden in patients with unresectable ESC, thereby providing them with the opportunity to undergo surgery (9).…”

“…For example, neoadjuvant therapy has achieved a reduction in the tumor burden in patients with unresectable ESC, thereby providing them with the opportunity to undergo surgery (9). Furthermore, neoadjuvant therapy has been shown to improve the R0 resection rate, leaving tumor residues in fewer cases and thereby causing a reduction in the postoperative recurrence of ESC in patients following surgery (10,11).…”

Potential Predictive Immune and Metabolic Biomarkers of Tumor Microenvironment Regarding Pathological and Clinical Response in Esophageal Cancer After Neoadjuvant Chemoradiotherapy: A Systematic Review

“… 1 Although 20–30% of patients achieved a pathologic complete response (pCR), more than half still have residual tumor after nCRT. 2 The tumor microenvironment (TME) is currently a focus in exploring additional treatment combinations. Several potential predictive markers have been evaluated to improve treatment outcome, including the expression of human epidermal growth factor receptor 2 (HER2) and programmed death-ligand 1 (PD-L1), as well as the prevalence of microsatellite instability (MSI).…”