Neoadjuvant Chemotherapy versus Chemoradiation Prior to Esophagectomy: Impact on Rate of Complete Pathologic Response and Survival in Esophageal Cancer Patients

Abstract

Purpose To evaluate differences in pathologic complete response (pCR) rates and overall survival among patients receiving either neoadjuvant chemotherapy or chemoradiation prior to esophagectomy for locally advanced esophageal cancer. Patients and methods Esophageal cancer patients receiving either neoadjuvant chemotherapy or chemoradiation prior to esophagectomy were identified using the National Cancer Data Base (NCDB). Univariate analysis compared patient, tumor, and postoperative outcome characteristics. Logistic regression was performed to identify variables associated with achieving pCR. Kaplan-Meier analysis was performed to compare overall median survival by neoadjuvant therapy type and pCR status. Finally, a Cox proportional hazards model was fitted to identify variables associated with increased mortality hazard. Results From 2006 – 2012, 916/7,338 (12.5%) of patients received neoadjuvant chemotherapy while 6,422 (87.5%) received neoadjuvant chemoradiation. Neoadjuvant chemoradiation patients were more likely to achieve pCR (17.2% versus 6.4%, p<0.001) and less likely to have positive margins (5.6% versus 11.5%, p<0.001) than neoadjuvant chemotherapy patients, with no difference in 30- or 90-day mortality. Achieving pCR was associated with improved overall median survival (59.5 months ± 4.0 versus 30.1 months ± 0.76 for those with persistent disease, p<0.001). On logistic regression, neoadjuvant chemoradiation therapy was independently associated with achieving pCR (Odds Ratio 2.75, 2.01 – 3.77, p<0.001). Despite improvement in pCR rate with neoadjuvant chemoradiation, neoadjuvant therapy type was not independently associated with long-term survival (HR 1.12, 95% CI 0.97 – 1.30, p=0.12). Conclusion While neoadjuvant chemoradiation is more successful in downstaging esophageal cancer prior to esophagectomy, this therapy was not independently prognostic for improved long-term survival. Other factors affecting long-term survival among pathologic complete responders and among patients with persistent disease should be investigated to clarify this association.

Neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy: is it a superior approach for locally advanced resectable esophageal squamous cell carcinoma?

“…Most previous studies revealed nCRT was not associated with improved survival in spite of its apparent elevated pCR rate compared with nCT (3,20,21,25). It was worth mentioning that nCRT group carried an increased risk of postoperative mortality or had more deaths unrelated to disease progression in the first-year follow up period in these studies.…”

“…RM approach was a safe option for locally advanced ESCC, which was consistent with the conclusion from previous studies mainly focusing on esophageal adenocarcinoma. Previous studies have found that nCRT improved pathological complete response (pCR) rate and reduced lymph node metastases rate when compared to nCT (21,(23)(24)(25). The latest NeoRes trial (26) also confirmed the outcomes in ESCC subgroups.…”

“…In other trials, lymph node retrieval after nCRT also appeared to be lower (1,20,27). Besides, it was reported that chemoradiotherapy reduced lymph node harvest from within the radiotherapy field in rectal cancer (28,29).Most previous studies revealed nCRT was not associated with improved survival in spite of its apparent elevated pCR rate compared with nCT (3,20,21,25). It was worth mentioning that nCRT group carried an increased risk of postoperative mortality or had more deaths unrelated to disease progression in the first-year follow up period in these studies.…”

Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma

“…However, randomized trials did not result in consistent conclusions (2-7). Besides, studies reported that NCRT appeared to achieve better local control but did not significantly affect survival (12,13). It has been recognized that ESCC has different histological and clinical characteristics compared with esophageal adenocarcinoma carcinoma (EAC) (9,14,15).…”

Surveillance or resection after chemoradiation in esophageal cancer

“…In a prospective study, Lee et al showed that pCR was achieved in 43% [95% confidence interval (CI), 27-59%] of patients who underwent surgery after CRT (24). Samson et al reported that a pCR rate of 17.2% (30). There is a myriad of factors that likely influence the probability of achieving pCR.…”