Perioperative chemotherapy for advanced gastric cancer - results from a tertiary-care hospital in Germany

ARTICLE HIGHLIGHTS

Research background

For ten years, European guidelines have recommended perioperative chemotherapy for advanced gastric cancer. The recommendation is based on a few randomized controlled trials (RCTs) of poor validity. Decisions regarding therapy often differ between selected patients included in an RCT and elderly patients with comorbidities in regular healthcare. Oftentimes, latter patients have to break up perioperative chemotherapy because of adverse effects. Considering the increasing incidence of proximal gastric cancer and the fact that gastric cancer is one of the most frequent reasons of tumour-associated deaths worldwide, it is particularly important to study this topic.

Research motivation

Guidelines should be applicable for daily patient treatment, but European guidelines do not mention tumour localization nor the age of the patient. In order to find out which patients will have a real benefit from perioperative chemotherapy, we wanted to analyse the effect of perioperative chemotherapy in patients from our clinic with respect to tumour localization and age. This is important to save resources and to protect patients who will not benefit from perioperative chemotherapy from experiencing adverse effects.

Research objectives

The aim of this study was to analyse the efficacy of perioperative chemotherapy in our total patient population as well as in subgroups with respect to tumour localization and age.

Research methods

Patient characteristics before and after therapy of every resected patient with advanced gastric adenocarcinoma between 2008 and 2016 were added to our database. Survival curves were obtained using the Kaplan-Meier method according to chemotherapy (yes or no), localisation of the gastric tumour (proximal or distal) as well as age (more or less than 75 years).

Research results

Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. Thus, our research could not confirm the data of RCTs, which are the basis of the European guidelines.

Research conclusions

Fifty-three patients of the above-mentioned 129 (41%) were 75 years of age or older when diagnosed. The lack of a significant survival benefit due to perioperative chemotherapy was independent of tumour localization and age. Gastric cancer is not very sensitive to chemotherapy. Therefore, all efforts have to be done to detect it earlier or to identify tumour characteristics whose treatment offers more personalized medicine. The treatment of advanced gastric cancer differs substantially in different parts of the world. Individual tumour stage depends on genetic diversity, prophylactic gastroscopy, quality of surgical treatment (e.g., D2 lymphadenectomy or not), and other differences in particular healthcare systems. The few RCTs that analysed perioperative chemotherapy in gastric cancer are known all over the world but led to different guideline recommendations on different continents. The study wanted to prove the hypothesis that perioperative chemotherapy is effective and that this efficacy is dependent on tumour localization or patient age. The retrospective analysis of our database does not provide any new methods. We found that patients treated due to advanced gastric cancer are on average much older than cohorts of RCTs on this topic. Elder patients (> 75 years) do not have worse prognoses compared to younger ones. The incidence of proximal gastric carcinomas decreases with increasing patient age. Elderly patients (≥ 75 years) receive perioperative chemotherapy far less often than younger. The 5-year survival time of patients with distal tumours did not significantly differ from that of patients with proximal tumours, regardless of whether they had received perioperative chemotherapy or not. The study could refute the hypotheses that perioperative chemotherapy is more effective in patients with proximal gastric cancer. The decision of whether or not to apply perioperative chemotherapy in future research is necessary. Until new insights arise, tumour conferences concerning the decision of perioperative chemotherapy should not be influenced by tumour localization but only by tumour stage.

Research perspectives

It is necessary to prove the applicability of guidelines to daily patient treatment, particularly if the guideline recommendations are based on few RCTs with poor validity. Stratification according to defined risk factors, such as tumour characteristics, should be introduced to identify possible responders to therapy and thereby reduce the number of unnecessary treatments, particularly because the clinical approach to oncological patients has switched from standardized to personalized medicine. For example, MSI status should be evaluated, as in recent studies it was shown that patients with mismatch repair deficiency should not be treated with perioperative chemotherapy because of severe adverse effects and missing survival benefits. Instead of new RCTs, which often fail due to the difficult recruitment of highly selected patients, we recommend analysing big cohorts of registered patients in order to better understand the real situation in a particular country.