For years, the treatment of esophageal carcinoma has been a subject of debate, with varying multimodal approaches tailored based on tumor location and staging. Traditionally, gastric cancer patients often underwent perioperative FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed by surgical resection. Meanwhile, esophageal carcinoma patients were typically treated with neoadjuvant chemoradiotherapy (CROSS regimen: carboplatin/paclitaxel with radiation) followed by surgery or upfront chemotherapy with reassessment for further treatment.
However, recent groundbreaking findings suggest a paradigm shift—highlighting the superiority of perioperative FLOT chemotherapy in improving overall survival (OS) and relapse-free survival (RFS) for esophageal cancer patients.
What’s New? A Closer Look at the Data
The ESOPEC trial, a phase 3, multicenter, randomized study published in The New England Journal of Medicine, directly compared perioperative FLOT therapy with the conventional preoperative chemoradiotherapy (CMT) plus surgery approach. The findings revealed compelling results:
- Overall survival (OS) at 3 years:
- 57.4% in the FLOT group vs. 50.7% in the chemoradiotherapy group.
- Hazard ratio (HR) for death: 0.70 (P = 0.01), indicating a significant survival benefit for perioperative FLOT.
- Progression-free survival (PFS):
- 51.6% with FLOT vs. 35.0% with chemoradiotherapy.
- HR for disease progression or death: 0.66 (P < 0.01).
- Postoperative Mortality:
- Lower in the FLOT group (3.1%) compared to the chemoradiotherapy group (5.6%).
While FLOT therapy led to slightly higher rates of grade 3 or higher adverse events (58%) compared to CMT (50%), the improved survival benefits outweigh the risks, reinforcing FLOT as the preferred perioperative strategy.
Why the Shift? Advantages of Perioperative FLOT
The advantages of adopting perioperative FLOT for esophageal carcinoma are clear:
- Improved Systemic Control:
FLOT delivers systemic chemotherapy both pre- and post-surgery, targeting micrometastatic disease early and reducing the risk of recurrence. - Superior Pathologic Responses:
The trial reported a higher rate of pathologic complete response (ypT0/ypN0) with FLOT compared to chemoradiotherapy, suggesting better tumor eradication potential. - Simplified Treatment Pathway:
The shift to FLOT reduces the complexity associated with radiation planning and potential long-term toxicities, making treatment planning more straightforward. - Improved Surgical Outcomes:
Resection rates with negative margins (R0) were comparable, with FLOT achieving 94.3% R0 resection, indicating effective tumor downstaging.
Practical Implications for Clinicians
With the compelling results favoring perioperative FLOT, oncologists should consider:
- Standardizing perioperative FLOT as the first-line approach for resectable esophageal carcinomas.
- Patient selection criteria, ensuring those with good performance status and adequate organ function receive FLOT therapy.
- Multidisciplinary collaboration, with surgical, medical, and radiation oncologists to optimize patient care.
What About Chemoradiotherapy?
Despite the shift towards FLOT, preoperative chemoradiotherapy remains an option in specific scenarios:
- Poor responders to chemotherapy: Those with contraindications to FLOT toxicity.
- Patients with squamous cell histology, where radiation offers locoregional control benefits.
- Tumors with significant esophageal involvement, where radiation may be necessary for downstaging.
However, for most patients with esophageal adenocarcinoma, it appears that “everyone gets FLOT” – echoing Oprah’s famous phrase – as it becomes the new standard of care.
Embracing the Future of Esophageal Cancer Treatment
The latest evidence underscores perioperative FLOT as the preferred approach for resectable esophageal adenocarcinoma, offering improved survival outcomes compared to traditional chemoradiotherapy. With new data driving clinical decisions, oncologists can confidently guide patients towards this evolving standard of care.
Key takeaway: If you or your loved one is facing a diagnosis of esophageal cancer, ask your healthcare provider about perioperative FLOT therapy and how it could improve outcomes.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.