Predicting the response to chemotherapy in gastric adenocarcinoma: who benefits from neoadjuvant chemotherapy?

Despite a decline in the overall incidence, gastric adenocarcinoma remains the second most common cause of cancer death worldwide and thus a significant global health problem. Even in early-stage locoregional confined disease the 5-year survival rarely exceeds 25-35 %. Randomized trials have demonstrated a benefit from neoadjuvant and perioperative chemotherapy. However the optimal approach in individual patients is not clear and remains controversial. A consistent finding is that patients who have a histopathological response to neoadjuvant therapy are more likely to receive a survival benefit. These clinical data provide a strong argument for the urgent development of methods to predict histopathological response to neoadjuvant therapies for gastric adenocarcinomas. Published data demonstrate that clinico-pathological features (tumour histology and location), imaging through metabolic response by FDG-PET and tissue/molecular biomarkers may all have a predictive value for neoadjuvant therapies. However it is still uncertain from published data whether or not they will be useful for clinical decision making in individual patients. Existing candidate biomarkers need to be properly qualified and validated and novel biomarkers are required and an optimal approach should involve the combination and integration of clinical, imaging, pathological and molecular biomarkers.