Department of Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, 1100 Walnut Street, Suite 500, Philadelphia, PA, 19107, USA.
Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College of Thomas Jefferson University, 1015 Chestnut Street, Suite 520, Philadelphia, PA, 19107, USA.
J Gastrointest Surg. 2020 Feb;24(2):288-298. doi: 10.1007/s11605-019-04161-9. Epub 2019 Feb 26.
Survival for patients with locally advanced esophageal cancer remains dismal. Non-response to neoadjuvant chemoradiation (nCRT) portends worse survival. We hypothesized that patients undergoing up-front esophagectomy may have better survival than those who do not respond to nCRT.
We identified all patients undergoing esophagectomy with a pathologic stage of II or greater at our institution between 1994 and 2015 and separated them into two groups: those who received nCRT and those undergoing up-front esophagectomy. The neoadjuvant group was further separated into patients downstaged to pathologic stage 0 or I (responders) and patients with either the same or higher pathologic stage after nCRT, or with pathologic stage II disease or greater (non-responders). Overall survival was compared between groups using Kaplan-Meier statistics. Covariate-adjusted Cox modeling was used to estimate hazard ratios (HR) for mortality associated with non-response.
Overall, 287 patients met inclusion criteria. Fifty-nine percent of the responders had pathologic complete response (pCR). The majority of non-responders and primary esophagectomy patients had stage II or III disease (94%). Median survival was 58.3 months in responders, 23.9 months in non-responders, and 29.1 months in primary esophagectomy patients (p < 0.01). The HR for mortality associated with non-response was 1.82 compared to response to nCRT (p < 0.01) and 1.09 compared to primary esophagectomy (p = 0.71).
In patients with esophageal cancer who do not respond to nCRT, neoadjuvant therapy may represent a toxic and costly treatment modality that does not improve survival and may delay potentially curative resection. Further research is needed to identify potential non-responders with advanced resectable disease and allow individual tailoring of pre-surgical decision-making.
局部晚期食管癌患者的生存率仍然很低。对新辅助放化疗（nCRT）无反应预示着生存率更差。我们假设直接行食管癌切除术的患者的生存率可能优于那些对 nCRT 无反应的患者。
我们在本机构 1994 年至 2015 年间，确定了所有接受食管癌切除术且病理分期为 II 期或更高级别的患者，并将其分为两组：接受 nCRT 的患者和直接行食管癌切除术的患者。新辅助组进一步分为病理分期降为 0 期或 I 期（有反应者）和 nCRT 后病理分期相同或更高，或有病理 II 期疾病或更高（无反应者）的患者。使用 Kaplan-Meier 统计比较两组之间的总生存率。使用协变量调整的 Cox 模型估计与无反应相关的死亡率的危险比（HR）。
总体而言，287 名患者符合纳入标准。有 59%的有反应者有病理完全缓解（pCR）。大多数无反应者和直接行食管癌切除术的患者患有 II 期或 III 期疾病（94%）。有反应者的中位生存时间为 58.3 个月，无反应者为 23.9 个月，直接行食管癌切除术的患者为 29.1 个月（p<0.01）。与 nCRT 有反应相比，无反应与死亡率相关的 HR 为 1.82（p<0.01），与直接行食管癌切除术相比为 1.09（p=0.71）。
对于对 nCRT 无反应的食管癌患者，新辅助治疗可能代表一种有毒且昂贵的治疗方式，不能提高生存率，并且可能延迟潜在的可治愈性切除。需要进一步研究以确定具有进展可切除疾病的潜在无反应者，并允许对术前决策进行个体化定制。
