Topic DiscussionTrimodality Versus Bimodality Therapy in Patients With Locally Advanced Esophageal Carcinoma: Commentary on the American Society of Clinical Oncology Practice Guidelines
Introduction
The treatment of locally advanced (LA) esophageal cancer has evolved over the past several decades in accordance with the shifting demographics of patients and improvements in diagnostic staging. When squamous cell carcinoma was the most prevalent subtype, patients often presented with unresectable disease either due to tumor extent or medical comorbidities, leading to definitive chemoradiation playing a major role in disease management. In recent decades, as the disease pattern shifted to lower esophageal and gastroesophageal adenocarcinomas in patients who were younger and had less of a smoking and alcohol history, treatment has been primarily surgery-based.1
Based on the CROSS trial, concurrent neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy has been a standard of care for patients with LA esophageal cancer.2 Whether all 3 treatment modalities are required in all patients, however, is an area of ongoing research and debate as data for chemotherapy alone either preoperatively or perioperatively has also shown benefit.3
In the recent American Society of Clinical Oncology (ASCO) guideline statement, a panel of experts systematically reviewed published literature and proposed treatment recommendations for patients with LA esophageal carcinoma and Siewert I or II gastroesophageal junction (GEJ) adenocarcinoma.4 The panel recommends a multimodality treatment approach for patients with locally advanced disease, defined as American Joint Committee on Cancer eighth edition stage ≥T2 or N+. These guidelines are notable for recommending either preoperative CRT or perioperative chemotherapy for patients with esophageal adenocarcinoma. The guidelines also present preoperative CRT followed by esophagectomy or definitive CRT without surgery as recommended treatment paradigms for patients with esophageal squamous cell carcinoma. Other expert guidelines, including NCCN, recommend a trimodality approach with preoperative chemoradiation followed by surgical resection for most patients with either adeno or squamous cell carcinoma, highlighting a growing controversy on the optimal treatment approach.3 Multiple randomized clinical trials are ongoing to inform future multimodality treatment (NCT01726452, NCT02509286, NCT04375605, NCT01404156, NTR4834, NCT02551458).
Section snippets
Preoperative CRT Versus Perioperative Chemotherapy for LA Adenocarcinoma
Recommendation 2 from the ASCO guideline states that preoperative CRT or perioperative chemotherapy (CT) should be offered to patients with LA esophageal adenocarcinoma, rating the quality of the evidence as “moderate” and the strength of the recommendation as “strong.” However, the panel noted that while both preoperative CRT and perioperative CT may improve overall survival (OS) over surgery alone, the certainty of evidence supporting this statement for preoperative CRT and perioperative CT
Preoperative Versus Definitive CRT for LA Squamous Cell Carcinoma
For LA esophageal squamous cell carcinoma, the ASCO guidelines recommend that preoperative CRT or definitive CRT is the standard of care.4 They also state that surveillance can be considered for patients with a complete clinical response to initial therapy at institutions that are comfortable with salvage esophagectomy.4 The recommendations are based on analysis of 2 European trials that showed an improved rate of local control with surgery without a benefit in OS and at the cost of increased
Conclusions
Although preoperative chemoradiation followed by surgical resection for locally advanced esophageal cancer remains the standard of care at many institutions, treatment paradigms are shifting. As described in recent ASCO treatment guidelines, trimodality or bimodality therapy (ie, perioperative CT and surgery) are accepted treatment strategies for patients with adenocarcinoma, although we believe preoperative CRT has important advantages, which are starting to be shown now in prospective
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Cited by (2)
CROSSing into New Therapies for Esophageal Cancer
2022, International Journal of Radiation Oncology Biology PhysicsCurrent landscape of radiation oncology in esophageal cancer: a narrative review
2022, Journal of Thoracic Disease
Sources of support: This work had no specific funding.
Disclosures: none.