A propensity-matched analysis comparing survival after primary minimally invasive esophagectomy followed by adjuvant therapy to neoadjuvant therapy for esophagogastric adenocarcinoma

Abstract

Objectives Prognosis for locally advanced esophagogastric adenocarcinoma (EAC) is poor with surgery alone and adjuvant therapy after open esophagectomy is frequently not tolerated. After minimally invasive esophagectomy (MIE), however, earlier return to normal function may render patients better able to receive adjuvant therapy. This study examined whether primary MIE followed by adjuvant chemotherapy impacted survival compared to propensity-matched patients treated with neoadjuvant therapy. Methods Patients with stage II or higher EAC treated with MIE (n=375) were identified. Using 30 pretreatment covariates, propensity for assignment to either neoadjuvant followed by MIE (n=183; 54%) or MIE as primary therapy (n=156; 46%) was calculated, generating 97 closely-matched pairs. Hazard ratios were adjusted for age, sex, BMI, smoking, comorbidity and final pathologic stage. Results In propensity-matched pairs, adjusted hazard ratio for death did not differ significantly for primary MIE compared to neoadjuvant (HR 0.83; 95% CI 0.60–1.16). Recurrence patterns were similar between groups and 65% of patients with IIb or greater pathologic stage received adjuvant therapy. Clinical staging was inaccurate in 37/105 (35%) patients who underwent primary MIE (n=18 upstaged and n=19 downstaged). Conclusions Primary MIE followed by adjuvant chemotherapy guided by pathologic findings did not negatively impact survival and allowed for accurate staging of the patient compared to clinical staging. Our data suggest that primary MIE in patients with resectable EAC may be a reasonable approach, improving stage-based prognostication and potentially minimizing overtreatment in patients with early-stage disease through accurate stage assignments. A randomized controlled trial testing this hypothesis is needed.

Does neoadjuvant/perioperative chemotherapy improve overall survival for T2N0 gastric adenocarcinoma?

“…While NAC has become a standard of care for patients with gastric and esophagogastric cancer, 12,13 some studies support omission of NAC, and it is unclear which specific stages, including T2N0, derive OS benefit. [14][15][16] In a recent analysis of the MAGIC trial, Smyth et al concluded that the presence of lymph node metastases and not cPR to chemotherapy was the only independent predictor of OS after chemotherapy plus resection, further raising question as to whether NAC provides OS benefit based on T stage. 17 In our study, NAC was not found to provide a significant OS benefit for patients with T2N0 gastric adenocarcinoma, a population with limited representation in gastric cancer trials.…”

The Combination Options and Predictive Biomarkers of PD-1/PD-L1 Inhibitors in Esophageal Cancer

“…The value of postoperative chemotherapy in resectable esophageal and EGJ cancers remains uncertain in the previous trials (22)(23)(24). After R0 resection, observation is advised for ESCC patients by National Comprehensive Cancer Network (NCCN) guidelines (25).…”

Upfront surgery and pathological stage-based adjuvant chemoradiation strategy in locally advanced esophageal squamous cell carcinoma

“…In this Taiwan Caner Registry database study, the neoadjuvant chemoradiation to upfront surgery ratio steadily increased from 0.66 in 2008 to 2.08 in 2014. Despite the advantages of early systemic micrometastasis control and tumor downstaging, neoadjuvant therapy has been criticized that the indication for chemoradiation is based on clinical staging rather than more accurate pathological staging and thus the risk of overtreatment 4 . On the other hand, upfront surgery plus adjuvant therapy is another approach of multidisciplinary treatments.…”

“…Guided by pathological stage, adjuvant treatment was administered to 49% of upfront esophagectomy patients. The authors reported that primary minimally invasive esophagectomy followed by adjuvant chemotherapy does not negatively influence survival compared with patients treated with neoadjuvant therapy 4 . In another study of the multimodal treatment combination of upfront surgery followed by adjuvant chemotherapy for esophageal squamous cell carcinoma, 45% of patients with positive lymph node involvement received adjuvant treatment, and the completion rate was as high as 91%.…”

“…For adenocarcinoma, Zahoor et al . reported that upfront minimally invasive esophagectomy may be a reasonable approach, improving stage-based prognostication and potentially minimizing overtreatment in patients with clinical stage II or higher tumors 4 . For squamous cell carcinoma, Matsuda et al .…”