Patterns and risk of recurrence in patients with esophageal cancer with a pathologic complete response after chemoradiotherapy followed by surgery

Abstract

Objectives: A pathologic complete response in patients with locally advanced esophageal cancer after chemoradiotherapy and surgery is associated with improved overall and disease-free survival. Nevertheless, approximately one third of patients with a pathologic complete response still have a recurrence. The aim of this study was to evaluate risk factors and patterns of recurrence in patients with locally advanced esophageal cancer who achieved a pathologic complete response after chemoradiotherapy and surgery.Methods: We performed a retrospective review of a single-institution database of 233 patients with stage II and III esophageal cancer with a pathologic complete response after chemoradiotherapy and surgery between 1997 and 2017. A multivariable competing risk-regression model was used to identify predictors of recurrence.Results: A total of 61 patients exhibited recurrence in this cohort, 43 with adenocarcinoma and 18 with squamous cell carcinoma. Five-year cumulative incidence of recurrence did not vary by histology. Univariable analysis revealed that poor tumor differentiation (hazard ratio, 2.28; P ¼ .022) and advanced clinical stage (hazard ratio, 1.89; P ¼ .042) are predictors of recurrence in the esophageal adenocarcinoma subgroup, whereas poor tumor differentiation remained the only independent predictor on multivariable analysis in the entire cohort (hazard ratio, 2.28; P ¼ .009). Patients with esophageal adenocarcinoma had a higher incidence of distant recurrences, and patients with esophageal squamous cell carcinoma demonstrated a higher incidence of loco-regional recurrence (P ¼ .039).Conclusions: Poor tumor differentiation is an independent risk factor for recurrence in patients with esophageal cancer with a pathologic complete response. Although there is no difference in the cumulative incidence of recurrence between esophageal adenocarcinoma and esophageal squamous cell carcinoma, patterns of recurrence appear to differ. Thus, treatment and surveillance strategies may be tailored appropriately.

Higher lymph node harvest in patients with a pathologic complete response after neoadjuvant therapy for esophageal cancer is associated with improved survival

“…It has also been demonstrated that a pCR is associated with both increased disease‐free survival and overall survival (OS) 9–13 . This discovery is so valuable that the role of esophagectomy in patients with clinical complete response is still an active subject of research and debate 14,15 …”

“…[9][10][11][12][13] This discovery is so valuable that the role of esophagectomy in patients with clinical complete response is still an active subject of research and debate. 14,15 There is limited data regarding the benefit of lymph node harvest in patients who have a pCR. Retrospective studies with even modest-sized databases have shown that high lymph node counts in patients who have a pCR are no different than those with lower lymph node counts and that the number of lymph nodes sampled in patient who have a pCR was not an independent predictor of survival.…”

Hazard Curves for Tumor Recurrence and Tumor-Related Death Following Esophagectomy for Esophageal Cancer

“…In the meantime, there is growing evidence that 5-year survival following resection of esophageal cancer does not equal "cure". Even 5-year survivors of EC seem to have a decreasing but persistent residual risk of postoperative tumor recurrence and death from tumor recurrence up to 10 years from diagnosis [17].…”

Pathologic complete response after esophagectomy following neoadjuvant chemoradiation therapy for esophageal carcinoma: A cure sometimes?

“…Second, few studies have examined risk factors for recurrence after a pathologic complete response. Barbetta and colleagues 5 found that poor tumor differentiation is independently associated with an increased risk of recurrence. Similar to other studies, most (72%) of the recurrences were distant metastases, implicating a need for better systemic tumor control.…”

“…7 Indeed, despite numerous contemporaneous improvements in patient care, survival for patients with esophageal cancer has improved little during the past several decades. The knowledge that we gain from studies such as that of Barbetta and colleagues 5 should help us to evolve our patient care strategies and make strides against this disease.…”