Neoadjuvant strategies reviewed in curable gastro-oesophageal cancers

Australian clinicians have led an expert review of the management of early stage gastro-oesophageal cancer which emphasises the value of multidisciplinary approach to patient care.

The Review finds that adjunctive therapies in the form of pre-operative chemo-radiotherapy (CRT), or pre-operative chemotherapy alone, perioperative and post-operative chemotherapy, have improved survival in patients with operable cancer over surgery alone.

But there is more to be done, according to the Australasian Gastrointestinal Trials Group (AGITG) and international colleagues.

The Group highlights the following points:

  • Staging in oesophageal and gastric cancer form the basis of the initial treatment decisions and should be done accurately. A major focus of staging is to exclude patients from receiving futile curative-intent surgery when they have more advanced disease that is not curable.
  • Multimodal approach in the treatment of operable oesophagogastric cancer has improved survival compared to surgery alone.
  • Overall 5 year survival rates remain < 50% and further advances are needed to improve outcomes for these patients.
  • Neoadjuvant CRT followed by surgery is the favoured approach for patients with operable oesophageal SCC whereas either perioperative chemotherapy or neoadjuvant CRT could be considered as standard options for operable oesophageal adenocarcinoma.
  • Definitive CRT in esophageal SCC has similar survival outcomes however are associated with higher risk of loco-regional recurrence. There is a lack of randomised head to head comparison between definitive CRT versus neoadjuvant CRT and surgery and as such definitive CRT is the current standard of care for patients who are medically unsuitable for oesophagectomy or refuse surgery.
  • Perioperative chemotherapy remains the favoured approach with FLOT being the recommended chemotherapy regimen in operable locally advanced gastric cancer in the Western population.
  • Until recently adjuvant chemotherapy has been the preferred approach in East Asian patients although this may change towards a perioperative/neoadjuvant approach based on the recent PRODIGY/ RESOLVE studies presented in ESMO 2019.
  • Until the results of TOPGEAR, CRITICS II and ESOPEC trials are reported the role of neoadjuvant CRT in gastric cancer patients is not established.
  • Adjuvant (post-operative) CRT in select patients with gastric cancer is a reasonable option.
  • There is an unmet need to establish predictive biomarkers of treatment response in early
  • stage disease and the role of targeted agents and immunotherapy is evolving in this setting.
  • Enrolment to clinical trials with novel agents should be encouraged to enable identification of patient populations who may benefit from therapies that target specific molecular and immune pathways.

The AGITG findings are published in Expert Review of Anticancer Therapy.

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