Tumor Downstaging After Neoadjuvant Chemotherapy Strongly Predicts Improved Outcome After Surgery in Esophageal and Esophagogastric Junction Cancer
In a European analysis reported in the Journal of Clinical Oncology, Davies et al found that pathologic tumor downstaging after neoadjuvant chemotherapy was the strongest independent predictor of overall survival in patients undergoing surgery for esophageal and esophagogastric junction adenocarcinoma. Compared with no response, downstaging was also associated with significantly lower rates of local and systemic recurrence.
Study Details
The study involved 584 consecutive patients undergoing resection for esophageal or esophagogastric junction adenocarcinomas at two high-volume cancer centers in London between 2000 and 2010. Of these, 400 (68%) received neoadjuvant chemotherapy, with 96% receiving epirubicin, cisplatin, and either fluorouracil (5-FU) or capecitabine or cisplatin plus 5-FU. The neoadjuvant regimen did not significantly affect the likelihood of tumor downstaging (P = .6665).
Lower Risk of Local and Systemic Recurrence
Tumors were downstaged after neoadjuvant therapy in 175 patients (44%). Compared with patients without downstaging, these responders had a significantly higher rate of R0 resection (74% vs 40%, P < .001), significantly lower rates of isolated local recurrence (6% vs 13%, P = .03) and systemic metastatic recurrence both alone (19% vs 29%, P = .027) and together with locoregional recurrence (30% vs 48%, P < .001), and significantly improved Mandard tumor regression scores (P < .001).
Improved Survival
On univariate analysis, downstaging was associated with significantly improved overall survival (hazard ratio [HR] = 0.37, P < .001). On multivariate analysis adjusting for age, initial tumor stage (cTNM), tumor grade, lymphovascular invasion, resection margin status, and surgical resection type, patients with downstaging had significantly improved overall survival (HR = 0.49, 95% confidence interval [CI] = 0.35–0.68) and recurrence-free survival (HR = 0.40, 95% CI = 0.29–0.54). Other significant predictors of overall survival and recurrence-free survival consisted of lymphovascular invasion (HR = 1.88, 95% CI = 1.39–2.55, for overall survival) and R1 resection margin (HR = 1.69, 95% CI = 1.27–2.25, for overall survival), but not clinical stage, age, tumor grade, or type of resection.
Patients with clinical stage cT3/4N+ who had downstaging had significantly improved 5-year overall survival (52.5% vs 12.6%, P < .001) compared with patients with no response. Significant improvement was seen in subgroups of patients downstaged from cT3/4N+ to ypT0N0, ypT1/2N–, ypT1/2N+, or ypT3/4N– (P < .001 for all).
The investigators concluded, “The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.”
Andrew R. Davies, MD, of St. Thomas’ Hospital, London, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Swedish Research Council, Swedish Cancer Society, and UK National Institute of Health Research. For full disclosures of the study authors, visit jco.ascopubs.org.
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