Understanding the prognostic factors affecting survival of patients with primary gastric cancer treated with laparoscopic surgery

Abstract

The retrospective study by Gan et al evaluated the three-year survival rate and prognostic factors in 100 patients with primary gastric cancer who underwent laparoscopic surgery at a Chinese hospital between 2019 and 2021. The observed three-year survival rate was 73%. Multivariate analysis identified age, tumor-nodes-metastasis stage, tumor size, depth of invasion, lymph node metastasis, extent of lymph node dissection, postoperative adjuvant chemo-radiotherapy, postoperative carcinoembryonic antigen levels, surgical duration, extent of gastric resection, and postoperative complications as independent predictors of survival. Older age, advanced disease stage, larger tumors, deeper invasion, lymph node involvement, and elevated carcinoembryonic antigen were associated with poorer outcomes, while thorough lymph node dissection and adjuvant therapy improved survival. The study highlights the complex interplay of clinical and pathological factors affecting prognosis after laparoscopic surgery. Strengths include detailed perioperative data and robust analysis, though limitations are noted in its retrospective design and patient selection. The findings emphasize the need for multidisciplinary, individualized treatment planning, considering both disease and patient-related factors, to optimize outcomes in localized gastric cancer. Prospective studies are warranted to validate these results and refine treatment strategies.

Key Words: Gastric cancer; Prognostic factors; Multivariate analysis; Laparoscopic surgery; Survival

Core Tip: Laparoscopic surgery offers a promising three-year survival rate for patients with primary gastric cancer; outcomes are significantly influenced by a range of clinical and pathological factors. The findings underscore the importance of multidisciplinary collaboration to decide the optimal treatment plan for each patient. While making treatment decisions, nutritional status and quality of life should also be taken into consideration in addition to disease- and patient-related features. By identifying key risk factors, the study provides valuable insights for optimizing clinical interventions and improving survival among patients treated with laparoscopic surgery for primary gastric cancer.

INTRODUCTION

Gan et al’s study provides insights into the outcomes of primary localized gastric cancer treated with laparoscopic surgery[1]. The study included 100 patients, with a mean age of 60 years. All participants were followed for three years post-surgery to assess survival outcomes and to identify clinical parameters impacting prognosis. The researchers found that the three-year survival rate among these patients was 73%. Statistical analysis revealed no significant differences in survival based on sex, tumor location, alcohol consumption, smoking status, tumor differentiation, histological type, intraoperative blood loss, or surgical outcomes. Multivariate logistic regression analysis identified the following independent predictors of three-year survival: Age, tumor-nodes-metastasis (TNM) stage, tumor size, depth of invasion, lymph node metastasis, lymph node dissection, postoperative adjuvant radio-chemotherapy, postoperative carcinoembryonic antigen (CEA) levels, surgical duration, extent of gastric resection, and postoperative complications. Older age, advanced TNM stage, larger tumor size, deeper invasion, lymph node metastasis, and higher postoperative CEA levels were associated with poorer survival outcomes. Conversely, thorough lymph node dissection and the use of adjuvant radio-chemotherapy were linked to improved survival rates.

REVIEW OF THIS RESEARCH

The strengths of the study are robust recording of intraoperative and perioperative parameters and use of univariate and multivariate statistical analyses. The potential drawbacks include its retrospective design, and exclusion of patients with upfront nodal metastasis. The margin status was not definitively commented upon. While more than half of the patients were stage II or above, perioperative chemotherapy was not given as a standard treatment. The strict eligibility criteria of complete clinical data for all variables included in the study and no censored survival times before 3 years may have introduced unknown biases for making predictions for future patients. The inclusion of time-dependent variables, such as postoperative CEA levels and postoperative complications, that cannot be assessed at the time of surgery, is certainly appropriate for exploring relationships with subsequent survival. However, they cannot be included in multivariate models for predicting survival of future patients without using some type of time-dependent modeling procedures.

A total of 27 deaths were observed at 3 years of follow-up. A statistical “rule of thumb” is that at least 5 to 10 events (in this case, deaths) are required for each variable in a final multivariate model. Since there were 27 deaths, we would expect the final model to include about 3 to 6 variables. However, when all 12 variables with univariate P < 0.05 were included in a multiple logistic regression model, 11 variables apparently had P < 0.05 and the P value for the 12^th variable was 0.112. This is very unusual, especially since there are probably some strong correlations among these 12 variables. For example, the decision to administer postoperative adjuvant chemoradiation therapy was probably strongly correlated with American Society of Anesthesiologists, TNM status, tumor differentiation, tumor size, depth of invasion, etc. The result is probably a very unstable model that has been overfit to the study data so that conclusions about survival of future patients may not be very accurate. One possible solution would be to use a variable selection algorithm to sequentially build a final multivariate model that could be validated in future studies.

Gastric cancer is the fifth most commonly diagnosed cancer worldwide and ranks fifth in cancer-related mortality, with over a million new cases and approximately 660000 deaths annually. The incidence is highest in Eastern and Central Asia and parts of Latin America, South Korea, Mongolia, and Japan leading in both male and female cases[2]. Men are more affected than women, and developed countries generally see higher rates, though regional and cultural differences are significant. Major risk factors include chronic infection with Helicobacter pylori, which accounts for up to 90% of non-cardia gastric cancers, as well as dietary habits such as high salt intake, consumption of smoked or preserved foods, and low intake of fruits and vegetables. Smoking, obesity, and gastroesophageal reflux disease are also established contributors, particularly for cardia gastric cancer. Genetic predispositions, including mutations in the E-cadherin gene and certain hereditary cancer syndromes, further elevate the risk[3-6].

The European Society for Medical Oncology guidelines for localized primary gastric cancer suggest upfront surgery (open or endoscopic resection) only for stage IA gastric cancer (T1N0M0) disease. For T2 or higher disease, perioperative chemotherapy with the FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) regimen followed by assessment of surgery followed by adjuvant chemotherapy is the standard of care. Radical gastrectomy and D2 lymphadenectomy at a high-volume center is the recommended procedure. Various trials have now demonstrated improved survival, downstaging and increased proportion of R0 resections after perioperative chemotherapy rather than upfront surgery[7-9]. Data from the CRITICS and ARTIST group of trials did not show a definitive survival advantage with the addition of radiotherapy to adjuvant chemotherapy after surgery. However, adjuvant radiotherapy may be considered in patients with R1/R2 resection after a multidisciplinary tumor clinic discussion[10,11].

In this current retrospective review, only patients with localized gastric cancer who received laparoscopic surgical treatment were included for analysis. Patients with upfront nodal metastasis and endocrine diseases were excluded. While 41% of the cohort had stage I disease, 36% had stage II and 23% had stage III disease. The survival of patients with primary gastric cancer after laparoscopic surgery is influenced by a range of prognostic factors, as highlighted in the study. Key determinants include patient age, with older individuals experiencing lower survival rates due to declining physical and immune function and the presence of comorbidities such as diabetes and hypertension[12]. Tumor-related factors such as higher TNM stage, larger tumor diameter, and greater depth of invasion are associated with more advanced disease, making treatment more challenging and reducing the 3-year survival rate. Lymph node metastasis significantly worsens prognosis by facilitating cancer spread, while effective lymph node dissection during surgery can improve outcomes by reducing recurrence risk[13,14]. The extent of gastrectomy and longer operation times are linked to increased trauma and postoperative complications, which can further decrease survival. Postoperative complications, including bleeding, anastomotic fistula, and adhesive intestinal obstruction, directly impact patient prognosis if not managed promptly[15,16]. Additionally, elevated postoperative CEA levels could serve as markers for recurrence and poor prognosis[17,18]. Adjuvant chemo-radiotherapy was found to improve outcomes in the current study. The results of this study should be interpreted cautiously and considered as preliminary data for generating hypotheses that can be tested in future prospective studies.

CONCLUSION

While laparoscopic surgery offers a promising three-year survival rate for patients with primary gastric cancer, outcomes are significantly influenced by a range of clinical and pathological factors. The findings underscore the importance of multidisciplinary collaboration to decide the optimal treatment plan for each patient. While making treatment decisions, nutritional status and quality of life should also be taken into consideration in addition to disease- and patient-related features. By identifying key risk factors, the study provides valuable insights for optimizing clinical interventions and improving survival among patients treated with laparoscopic surgery for primary gastric cancer.