Gastric Linitis Plastica: Clinical Characteristics and Outcomes from the National Cancer Database

Discussion

In this study, we reviewed a national database to evaluate the characteristics and outcomes of patients with gastric LP. Our results validate the findings of previous studies that these tumors are associated with a poor prognosis. In our analysis, we observed that surgical resection with systemic therapy (chemotherapy and/or radiation therapy) is associated with higher overall survival. We also observed that in a select group of patients, subtotal gastrectomy may be performed with acceptable perioperative mortality and good long-term outcomes, compared to a total gastrectomy.

Gastric LP is a rare gastric tumor with limited data, hence the optimum treatment strategy for this disease is not established yet. Historically, it was believed that these tumors represent a non-surgical entity as most patients present at an advanced stage disease with diffuse involvement of the stomach, nodal metastasis, peritoneal dissemination, and/or direct invasion into surrounding tissues (8, 10). In addition, the disease was associated with a high non-curative resection rate as well as high rates of locoregional and peritoneal recurrence following resection (11, 12). Therefore, it was proposed that patients with gastric LP should not be considered for surgery. However, on the contrary, few studies reported significant survival benefit of surgical resection in carefully selected patients.

Yoshikawa et al. performed a retrospective analysis of 233 patients with primary scirrhous gastric carcinoma out of which 182 (78.1%) underwent surgical resection. They observed a median survival of 380 days (12.5 months) in the resection group compared to 88 days (2.8 months) in the non-surgical group. They also reported that the median survival of patients whose tumors were curatively resected was 727.0±116.3 days, significantly longer than 272±34.9 days for those in whom resection ended non-curatively (13). Similarly, Schauer et al. reported their experience with 120 gastric LP patients who underwent total gastrectomy, out of which R0 resection was achieved in 37 (30.8%) patients. The overall median survival in their cohort was 8 months, whereas those who achieved R0 resection reached a median survival of up to 17 months (14). Pedrazzani et al. reviewed 102 patients with gastric LP out of which 92 underwent surgical exploration, with resection performed in 60 cases. Only 27.5% of patients in their study received R0 resection. The overall median survival was 5.7 months, and the median overall survival for patients receiving R0 resection was 15.8 months (15). Our review of NCDB validates the findings of these studies that surgical resection is associated with higher survival rates compared to non-surgical groups (OS, 24.6 vs. 10.9 months, p<0.001) and an R0 resection is associated with better outcomes (OS, 35.3 vs. 15.3 months, p<0.001).

In our results, we also noted a higher overall survival in patients receiving systemic therapy along with surgical resection. These findings are consistent with data reported previously demonstrating the best oncological outcomes associated with a multimodal strategy including both surgery and systemic therapy (chemotherapy and/or radiation). Thompson et al. in their review of 54 patients with gastric LP reported that a combination of surgery and chemotherapy resulted in a higher median survival (24.8 months) than surgery alone (9.9 months) (16). Another study by Chang et al. who reviewed the Surveillance, Epidemiology, and End Results (SEER) database, observed higher survival rates in patients who underwent surgical resection and/or radiation therapy compared with no surgery or no radiation (5). Unfortunately, the SEER database lacks information on the use of chemotherapy therefore, we utilized the NCDB which provides chemotherapy data in addition to surgery and radiotherapy. We observed a mean survival up to 28 months in patients receiving surgery + systemic therapy, compared to surgery alone (17 months) or systemic therapy alone (12 months). However, even in NCDB, important information on whether the systemic therapy was administered as a neoadjuvant, or adjuvant modality was lacking for most of the patients included in this cohort.

A review of previous literature also revealed limited data on neoadjuvant and adjuvant strategies in patients with gastric LP. Recently, Ikoma et al. in their institutional review of 150 patients with gastric LP observed that upfront systemic therapy, followed by gastrectomy provides the best long-term outcomes (6). The authors also proposed that preoperative chemotherapy could be a reliable strategy for testing the tumor’s biologic behavior and proposed the selective use of gastrectomy in patients who do not experience progression during preoperative systemic therapy. In addition, they proposed that preoperative systemic therapy may also shrink the tumor which can potentially help in achieving RO resection, which is an independent prognostic factor for better survival in gastric cancer. However, in contrast, JCOG0501, a randomized phase III trial, consisting of 316 patients (158 in the neoadjuvant arm and 158 in non-neoadjuvant arm) failed to demonstrate a survival benefit of neoadjuvant therapy in patients with Borrmann type 4 or large (≥8 cm) type 3 gastric cancer (17).

This study has limitations which include its retrospective nature and the inherent issues of using a national registry, therefore, all observations and outcomes should be interpreted with caution. These limitations include lack of data on tumor size, extent, anatomical location (central vs. peripheral, proximal vs. distal), extent of lymphadenectomy (D1 vs. D2), and neoadjuvant vs. adjuvant setting of systemic therapy. In addition, patient selection for any treatment modality is unknown and it is possible that patients who received these treatments had better functional status and favorable surgical or anatomical factors or maybe better responders to any neoadjuvant therapy than patients who did not receive either or any treatment. Finally, and perhaps, most importantly, a significant limitation is how LP was defined in the database. Heterogeneity in the definition amongst different regions and lack of consensus on the diagnostic criteria for gastric LP is a limitation acknowledged by previous studies as well. Although, to date, there is still lack of consensus on the diagnostic criteria and definition of gastric LP, Ikoma et al. recently proposed a diagnostic criterion that may help standardize the terminology and diagnosis (6). In their study, gastric LP was defined as thickening of the gastric wall, with a lack of distensibility and stiffening that involved more than 1/3 of the gastric surface of at least some part circumferentially. They recommended that these features must have been confirmed using at least two of three staging methods (endoscopic, radiological, and laparoscopic).