Radiation therapy has long been a cornerstone in the treatment of various cancers, including gastric cancer, particularly for locally advanced or high-risk cases. However, the evolving landscape of gastric cancer management has raised questions about the necessity of adding preoperative chemoradiotherapy to standard perioperative chemotherapy. The recently published TOPGEAR trial sheds new light on this topic, challenging the role of radiation in improving survival outcomes for patients with resectable gastric and gastroesophageal junction (GEJ) cancers.
Background: Why Radiation?
Historically, radiation therapy was incorporated into gastric cancer treatment to enhance tumor control and potentially downstage tumors before surgery. Studies such as the INT0116 trial established postoperative chemoradiotherapy as a standard in North America. However, the subsequent rise of perioperative chemotherapy as the standard of care, supported by trials like the MAGIC and FLOT4-AIO, questioned whether radiation still had a significant role in resectable gastric cancer.
In particular, for GE junction tumors or node-positive gastric cancer, preoperative chemoradiotherapy has been explored for its theoretical benefits of better tumor control and improved survival. The TOPGEAR trial, however, now provides clarity on this topic.
The TOPGEAR Trial: Design and Key Findings
The trial was a multicenter, randomized phase 3 study comparing two approaches for resectable gastric and GEJ adenocarcinoma:
- Perioperative Chemotherapy Alone: Using standard chemotherapy regimens like FLOT or ECF.
- Perioperative Chemotherapy Plus Preoperative Chemoradiotherapy: Adding 45 Gy of radiation with concurrent fluorouracil or capecitabine before surgery.
Key Results:
- Survival Outcomes: No significant difference in overall survival (OS) or progression-free survival (PFS) between the two groups. Median OS was 49 months for perioperative chemotherapy alone versus 46 months with added chemoradiotherapy.
- Pathological Response: While the addition of radiation improved pathological complete response (pCR) rates (17% vs. 8%) and tumor downstaging, these gains did not translate into better survival.
- Toxicity: Both groups had similar rates of grade 3 or higher toxicities, and surgical complications were comparable.
What Does This Mean for Clinical Practice?
- Radiation May Be Unnecessary in Many Cases
The trial underscores that perioperative chemotherapy alone is sufficient for most patients with resectable gastric or GEJ cancer. Adding radiation does not improve long-term survival outcomes but increases treatment complexity. - Focus on Systemic Therapies
The absence of survival benefit from radiation shifts the focus to improving systemic therapy. Novel regimens and targeted treatments tailored to gastric cancer’s unique biology could drive future improvements in outcomes. - Patient Selection Is Key
While radiation might not be necessary for most patients, select subgroups—such as those with more locally advanced tumors or incomplete surgical resections—might still benefit. Future trials should aim to identify biomarkers or clinical features that could predict who might benefit from radiation.
Implications for GE Junction Tumor
GEJ tumors have historically been treated similarly to lower esophageal cancers, where preoperative chemoradiotherapy (per the CROSS trial) showed survival benefits. The TOPGEAR trial suggests that for resectable GEJ adenocarcinomas, perioperative chemotherapy alone may suffice, aligning with findings from the ESOPEC trial that favor FLOT chemotherapy over chemoradiotherapy for such cases.
Looking Ahead: The Future of Gastric Cancer Treatment
The TOPGEAR trial’s findings encourage a paradigm shift:
- Deemphasizing Radiation: Reducing reliance on radiation in gastric cancer treatment may lower treatment burdens without compromising outcomes.
- Investing in Better Systemic Therapies: Research should prioritize next-generation chemotherapy regimens, immunotherapies, and molecularly targeted approaches to improve survival while reducing toxicity.
- Tailored Approaches: Ongoing studies should focus on tailoring treatment based on tumor biology, genetic profiling, and patient-specific factors.
The TOPGEAR trial provides critical insights, showing that adding preoperative radiation to perioperative chemotherapy does not improve survival for most patients with resectable gastric or GEJ cancer. This finding simplifies treatment decisions, reducing the need for radiation in standard practice while encouraging a shift toward optimizing systemic therapies. For patients and providers alike, this represents an opportunity to focus on more effective, less burdensome treatments in the fight against gastric cancer.
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. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
Leave a Reply