Biologic predictors of survival in node-negative gastric cancer

Abstract

Objective: To evaluate factors predictive of survival following curative resection for node-negative gastric adenocarcinoma.

Summary background data: Presence or absence of lymph node metastases is the most powerful predictor of survival following curative resection for gastric adenocarcinoma. Factors predictive of survival in node-negative gastric cancer have not been clarified.

Methods: Histopathology and clinical outcome for all patients undergoing R0 resections for gastric adenocarcinoma at a tertiary center between 1985 and 2001 were reviewed.

Results: Of 1,256 R0 resections performed, 507 (40%) were node-negative, 465 were T1-T3, and 317 of these were adequately staged, as defined by histologic evaluation of at least 15 lymph nodes. Median age was 67 years, and 62% were male. Forty percent had T1 tumors, 34% were T2, and 26% were T3. Median tumor size was 3 cm. Vascular invasion (VI) was present in 17% of tumors and neural invasion (NI) in 31%. Extended (D2) lymphadenectomy was performed in 75% of cases. Five- and 10-year disease-specific survival rates were 79% and 67% respectively. Factors associated with poorer disease-specific survival on univariate analysis were male gender, serosal invasion, presence of VI, presence of NI, and resection other than distal subtotal gastrectomy. On multivariate analysis, NI was not an independent predictor of survival, but correlated directly with advancing T stage and tumor size.

Conclusions: Serosal invasion and presence of VI are strong predictors of poor survival in this disease. NI correlates with T stage and tumor size and may serve as a marker of advanced disease.

Figure 1. Photomicrographs demonstrating histologic evidence of invasion. (A) Vascular invasion. Clump of tumor cells within a small vascular channel. (B) Neural invasion. Tumor cell rest lying within sheath of peripheral nerve.

Figure 2. Disease-specific survival for all 465 T1–T3 patients with node-negative gastric cancer (5-year survival, 79%; 10-year survival, 66%).

Figure 3. Relationship of T stage to disease-specific survival for all 465 patients with node-negative gastric cancer (T1–T3). The 188 patients with T1 tumors (heavy solid line) and the 158 patients with T2 tumors (thin solid line) had significantly better survival compared with the 119 patients with T3 tumors (broken line, P < .0001).

Figure 4. Relationship of presence of vascular or neural invasion to disease-specific survival for adequately staged patients. The 187 patients with neither vascular nor neural invasion (heavy solid line) had prolonged survival compared with the 77 patients with neural invasion (thin solid line) or the 28 patients with vascular invasion (broken line, P = .0002). The 25 patients with both vascular and neural invasion are not shown.

Figure 5. Relationship of tumor size to presence of vascular or neural invasion in adequately staged patients. White bars represent average tumor size for lesions lacking evidence of vascular (3.93 ± 0.16 cm, n = 264) or neural (3.53 ± 0.20 cm, n = 215) invasion. Black bars represent tumor size for the patients with vascular (3.99 ± 0.33 cm, n = 53) or neural (4.67 ± 0.27 cm, n = 102) invasion. *The difference in average tumor size in presence or absence of neural invasion is significant (P = .001, Student t test).

Figure 6. Relationship of percentage of lesions with vascular and neural invasion to T stage in adequately staged patients. Chart demonstrates the strong correlation between presence of neural invasion and advancing T stage (R = 1.0, Pearson coefficient). T4 lesions are included in this analysis.