Global trial ends 20-year debate over gastro-esophageal cancer treatment

Cancer patients could avoid unnecessary radiation therapy as a result of an international clinical trial, led by Peter Mac researcher Prof Trevor Leong. The TOPGEAR study demonstrated that radiotherapy does not improve survival outcomes for patients with operable gastric and gastro-esophageal junction cancer when compared to chemotherapy alone.

The trial results were presented at the European Society for Medical Oncology Congress (ESMO 2024) 2024, held in Barcelona Sept. 13–18. The study has been published simultaneously in the New England Journal of Medicine.

More than 2,500 Australians are diagnosed with stomach cancer each year and the study investigated whether adding radiotherapy to the treatment approach of surgery plus chemotherapy would improve outcomes for patients.

All trial participants had chemotherapy before and after surgery—the “standard of care” in most countries—while some were randomized to also have radiotherapy before surgery.

Prof Leong says there has been a 20-year debate over the role of radiotherapy in treating these cancers, after earlier studies suggested a benefit of radiotherapy after surgery.

“Our results now demonstrate that even when delivered optimally as preoperative therapy, radiotherapy does not improve survival outcomes compared to chemotherapy alone,” says Professor Leong.

“The TOPGEAR trial results have the potential to be practice changing as some centers around the world, particularly in the U.S., currently employ preoperative radiotherapy as standard treatment for gastric cancer.

“Preoperative radiotherapy is also a standard of care treatment for patients with gastro-esophageal junction cancers, who comprised one third of the TOPGEAR patient cohort,” he said.

TOPGEAR started at Peter Mac in 2009 and opened to patients internationally from 2014 with 70 sites across 15 countries taking part.

Preoperative radiotherapy was seen to improve the rate of pathological complete response—meaning the cancer became undetectable—in trial participants, at 17% compared to 8% for the chemotherapy plus surgery approach.

However, at follow-up some five years later (median 67 months), there was no significant difference between these groups in progression-free and overall survival.

“While the increase in pathological complete response is interesting and may warrant further investigation, in the longer term radiotherapy did not meaningfully improve cancer control or extend lives,” Professor Leong says.

Professor Leong notes that as patients must attend their specialist cancer center multiple times to complete their radiotherapy, ceasing this requirement would reduce the overall burden of treatment for these patients.