Does histology really influence gastric cancer prognosis?

Gastric cancer (GC) is associated with poor survival despite curative-intent surgical resection and systemic therapy. Our objective is to examine the impact of histology on prognosis as well as the impact of linitis plastica (LP) on survival.

The GC database at a single institution was evaluated for patients who underwent resection from 2000 to 2015. Clinicopathologic characteristics were examined and descriptive statistics was used to analyze four groups of patients based on Lauren classification: intestinal (n=93), diffuse (n=20), diffuse with signet-ring cell features (n=57), and LP (n=40). LP patients had diffuse GC but also presented with circumferential infiltration of the gastric wall for at least a third of the stomach length on endoscopy or imaging. Fisher's exact test was used to compare groups; Cox regression was used for multivariate analysis and Kaplan-Meier method for survival.

Of 210 patients who underwent gastric resection, 112 (53%) were male with mean age 65.3 years (SD ±14.6 years). Intestinal GC patients were older at diagnosis but other patient demographics were similar between all groups. LP patients had a higher rate of R1 resection despite higher rates of total gastrectomy (P<0.01). Rates of perineural invasion (PNI) and nodal metastasis were higher in LP (P<0.001). The majority of intestinal GC patients (79%) had stage I/II disease compared to 70% of LP patients with stage III disease. Median overall survival (OS) was 13.7 months for LP, 79 months for intestinal, 97 months for signet-ring cell, and not reached for diffuse GC (P<0.001). When stratified by stage, there were no significant differences in survival by histology for stage II and stage III patients. However, by Cox regression analysis, factors associated with worse survival included lymphovascular invasion (LVI), nodal disease, and presence of LP. Neutrophil-lymphocyte ratio (NLR), neoadjuvant and adjuvant therapy, and tumor regression grade did not influence survival on multivariate analysis.

Intestinal GC is thought to have a better prognosis. Interestingly, this study demonstrates similar outcomes in patients with intestinal, diffuse, and signet-ring cell GC. However, a subset of diffuse GC-LP was associated with an infiltrative pattern of disease characterized by PNI and LVI. Despite controlling for poor prognostic markers, LP was independently associated with a worse prognosis. More research is needed to identify methods of earlier diagnosis and effective systemic therapy to treat this aggressive disease.