Adjuvant Chemotherapy May Improve Overall Survival Following Preoperative Chemoradiotherapy and Surgery in GastroEsophageal Cancer

SUMMARY: The American Cancer Society estimates that in the US, about 17,290 new Esophageal cancer cases will be diagnosed in 2018 and about 15,850 patients will die of the disease. Squamous Cell Carcinoma is the most common type of cancer of the Esophagus among African Americans, while Adenocarcinoma is more common in caucasians. Esophageal cancer is more common among men than among women. It is estimated that about 20% of patients survive at least 5 years after diagnosis.

Patients with resectable, locally advanced, Esophageal or GastricEsophageal junctional cancer are often treated with multimodality therapy. The CROSS trial (ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study) compared neoadjuvant chemoradiotherapy with weekly Carboplatin and Paclitaxel plus Radiotherapy followed by surgery, to surgery alone, in patients with Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus or GastricEsophageal junction. Neoadjuvant chemoradiotherapy when added to surgery in this study, conferred Overall Survival benefit, for both Squamous Cell Carcinoma and Adenocarcinoma histological subtypes and is now regarded as the standard of care, for this patient population. Nonetheless, it should be noted that the survival benefit was most pronounced in patients with squamous cell histology but was less definitive for those with adenocarcinoma histology, with approximately a third of patients developing distant failure. It has been postulated that the reduced dose and duration systemic chemotherapy given concurrently with radiation therapy, in preoperative setting, may have limited the efficacy of chemotherapy to prevent distant failure.

There is limited data on the role of adjuvant chemotherapy added to preoperative chemoradiotherapy and surgery, for patients with GastricEsophageal (GE) junctional adenocarcinoma. To address this question, the authors in this publication compared Overall Survival among patients with GE adenocarcinoma, receiving adjuvant chemotherapy versus postoperative observation, following preoperative chemoradiotherapy and surgical resection.

Using the National Cancer Database, the authors identified 10,086 patients, 9272 in the postoperative observation group and 814 who had received adjuvant chemotherapy. They then used propensity score matching to compare Overall Survival between the adjuvant chemotherapy and postoperative observation groups. Patients included in the study were diagnosed to have clinical stage T1,N1-3,M0 or T2-4,N0-3,M0 adenocarcinoma of the distal esophagus or gastric cardia, between 2006 and 2013, and were treated with preoperative chemoradiotherapy and surgical resection with a curative intent. Patients receiving adjuvant chemotherapy were younger and were more likely to have advanced disease and shorter postoperative hospitalization. A total of 732 patients in the adjuvant chemotherapy group were matched by propensity score to 3660 patients in the postoperative observation group.

It was noted that adjuvant chemotherapy was associated with improved Overall Survival compared with postoperative observation without adjuvant chemotherapy (median survival 40 months versus 34 months; HR=0.79, P <0.001). The Overall Survival at 1, 3, and 5 years was 94%, 54%, and 38% in the adjuvant chemotherapy group and 88%, 47%, and 34% in the observation group, respectively. The survival benefit with adjuvant chemotherapy was noted in most patient subgroups.

Based on this analysis it was concluded that for patients with locally advanced GastroEsophageal adenocarcinoma treated with preoperative chemoradiotherapy and surgical resection, adjuvant chemotherapy was associated with improved Overall Survival. Adjuvant Chemotherapy vs Postoperative Observation Following Preoperative Chemoradiotherapy and Resection in Gastroesophageal Cancer. A Propensity Score–Matched Analysis. Mokdad AA, Yopp AC, Polanco PM, et al. JAMA Oncol. 2018;4:31-38