Global clinical trial ends 20-year debate over treatment of gastroesophageal cancer

Cancer patients could avoid unnecessary radiotherapy thanks to an international clinical trial led by Peter Mac University researcher Professor Trevor Leong. The TOPGEAR study showed that radiotherapy does not improve survival outcomes for patients with operable gastric and gastro-oesophageal junction cancer compared with chemotherapy alone.

The trial results were presented at the European Society for Medical Oncology (ESMO) 2024 congress, held in Barcelona from September 13 to 18. The study was published simultaneously in the journal New England Journal of Medicine.

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

All trial participants received chemotherapy before and after surgery – the “standard of care” in most countries – while some were randomised to also receive radiotherapy before surgery.

Professor Leong says there has been debate for 20 years about the role of radiotherapy in treating these cancers, after previous studies suggested a benefit from radiotherapy after surgery.

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

“The results of the TOPGEAR trial have the potential to change practice since some centers around the world, including the United States, currently use preoperative radiotherapy as standard treatment for gastric cancer.

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

TOPGEAR started at Peter Mac in 2009 and opened to international patients from 2014 with 70 sites in 15 participating countries.

Preoperative radiation therapy was found to improve the rate of complete pathologic response (meaning the cancer became undetectable) in trial participants, to 17% versus 8% for the chemotherapy plus surgery approach.

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

“Although the increase in complete pathological response is interesting and may warrant further investigation, in the longer term, radiotherapy did not significantly improve cancer control or prolong life,” says Professor Leong.

Professor Leong notes that because patients have to make multiple visits to their specialist cancer centre to complete their radiotherapy, removing this requirement would reduce the overall treatment burden for these patients.