Higgins Luke M, Lester-Coll Nataniel H, Ades Steven, Barry Maura M, Borrazzo Edward C, Ganguly Eric K, Anker Christopher J
University of Vermont Larner College of Medicine, Burlington, VT, USA.
Division of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT, USA.
J Gastrointest Oncol. 2023 Apr 29;14(2):480-493. doi: 10.21037/jgo-22-633. Epub 2023 Apr 24.
A standard of care for nonmetastatic esophageal cancer is trimodality therapy consisting of neoadjuvant chemoradiation and esophagectomy, with evidence for improved overall survival versus surgery alone in the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial. Patients who receive treatment with curative intent but are poor candidates for or decline surgery receive definitive bimodality therapy. Literature characterizing patients who receive bimodality therapy compared to trimodality therapy, and their relative outcomes, is sparse, especially among patients who are too old or too frail to qualify for clinical trials. In this study, we assess a single-institution real-world dataset of patients receiving bimodality and trimodality management.
Patients treated for clinically resectable, nonmetastatic esophageal cancer between 2009 and 2019 who received bimodality or trimodality therapy were reviewed, generating a dataset of 95 patients. Clinical variables and patient characteristics were assessed for association with modality on multivariable logistic regression. Overall, relapse-free, and disease-free survival were assessed with Kaplan-Meier analyses and Cox proportional modeling. For patients nonadherent to planned esophagectomy, reasons for nonadherence were recorded.
Bimodality therapy was associated with greater age-adjusted comorbidity index, worse performance status, higher N-stage, presenting symptom other than dysphagia, and held chemotherapy cycles on multivariable analysis. Compared to bimodality therapy, trimodality therapy was associated with higher overall (3-year: 62% 18%, P<0.001), relapse-free (3-year: 71% 18%, P<0.001), and disease-free (3-year: 58% 12%, P<0.001) survival. Similar results were observed among patients who did not meet CROSS trial qualifying criteria. Only treatment modality was associated with overall survival after adjusting for covariates (HR 0.37, P<0.001, reference group: bimodality). Patient choice accounted for 40% of surgery nonadherence in our population.
Patients receiving trimodality therapy were observed to have superior overall survival compared to bimodality therapy. Patient preference for organ-preserving therapies appears to impact resection rate; further characterization of patient decision-making may be helpful. Our results suggest patients who wish to prioritize overall survival should be encouraged to pursue trimodality therapy and obtain early consultation with surgery. Development of evidence-based interventions to physiologically prepare patients before and during neoadjuvant therapy as well as efforts to optimize the tolerability of the chemoradiation plan are warranted.
非转移性食管癌的标准治疗方案是新辅助放化疗联合食管切除术的三联疗法，食管癌放化疗后手术研究（CROSS）试验表明，与单纯手术相比，三联疗法可提高总生存率。接受根治性治疗但不适合手术或拒绝手术的患者接受确定性双模态治疗。关于接受双模态治疗与三联疗法的患者特征及其相对预后的文献较少，尤其是在年龄太大或身体太虚弱而无法参加临床试验的患者中。在本研究中，我们评估了一个单机构接受双模态和三联疗法管理患者的真实世界数据集。
回顾2009年至2019年间接受双模态或三联疗法治疗的临床可切除、非转移性食管癌患者，生成一个包含95例患者的数据集。通过多变量逻辑回归评估临床变量和患者特征与治疗方式的相关性。采用Kaplan-Meier分析和Cox比例模型评估总生存率、无复发生存率和无病生存率。对于未按计划进行食管切除术的患者，记录未依从的原因。
多变量分析显示，双模态治疗与年龄调整后的合并症指数更高、体能状态更差、N分期更高、除吞咽困难外的其他症状以及化疗周期数更多有关。与双模态治疗相比，三联疗法的总生存率（3年：62%对18%，P<0.001）、无复发生存率（3年：71%对18%，P<0.001）和无病生存率（3年：58%对12%，P<0.001）更高。在不符合CROSS试验纳入标准的患者中也观察到了类似结果。调整协变量后，仅治疗方式与总生存率相关（HR 0.37，P<0.001，参照组：双模态治疗）。在我们的研究人群中，患者选择占手术未依从性的40%。
与双模态治疗相比，接受三联疗法的患者总生存率更高。患者对保留器官疗法的偏好似乎影响切除率；进一步了解患者的决策过程可能会有所帮助。我们的结果表明，应鼓励希望优先考虑总生存率的患者采用三联疗法并尽早咨询手术事宜。有必要制定基于证据的干预措施，在新辅助治疗前和治疗期间使患者在生理上做好准备，并努力优化放化疗方案的耐受性。
