Society: SSAT

BACKGROUND: Despite the advances in the multidisciplinary treatment of gastric adenocarcinoma, the overall 5-year survival remains only 33.3% in North America. R0 resection with adequate lymphadenectomy remains the mainstay therapy. The National Comprehensive Cancer Network (NCCN) guidelines recommend harvesting 16 or more lymph nodes for adequate staging. This study examines the rate of adequate lymphadenectomy over recent years and its potential association with overall survival.

METHOD: The National Cancer Database (NCDB) was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression and the Kaplan-Meier survival methods were utilized.

RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Most patients were male (65.9%), Caucasian (73.8%), with a mean age of 67 years old (SD±11.3). Subtotal gastrectomy was the most common surgery type (48%), followed by total gastrectomy (42.4%). A total of 64.2% of patients underwent surgery in low-volume facilities (1-10 gastrectomies/year). Most patients were American Joint Commission on Cancer (AJCC) stage III (37.6%) and were treated in Academic Research Programs (44.6%). Only 50.6% of the patients had retrieval of ≥16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (Cochran-Armitage test: p<.0001). The independent predictors of adequate lymphadenectomy included surgery between 2015-2019 (OR: 1.68; 95%CI: 1.57-1.70), surgery in a high-volume facility with ≥ 31 gastrectomies/year (OR:1.68; 95%CI:1.54-1.84), AJCC stage III (OR: 1.55; 95%CI:1.48-1.62), and preoperative chemotherapy (OR:1.53; 95%CI:1.46-1.61). Compared to patients who received adequate lymphadenectomy, patients who underwent gastrectomy with the removal of < 16 lymph nodes had a worse overall survival: 43 months versus 59 months (Log-Rank: p<.0001). Adequate lymphadenectomy was independently associated with improved overall survival (HR:0.80; 95%CI:0.78-0.82). Other factors associated with improved survival included Asian race (HR:0.72; 95%CI:0.68-0.76), surgery in an Academic facility (HR: 0.91; 95%CI:0.88-0.95), high-volume facility (HR:0.87; 95%CI:0.81-0.90), surgery between 2015-2019 (HR:0.87; 95%CI:0.84-0.90), and receipt of perioperative chemotherapy (HR: 0.62;95%CI:0.59-0.66).

CONCLUSIONS: Although there was a significant improvement in the rate of adequate lymphadenectomy over the study period, as of 2019, 36.7% of patients lacked removal of 16 lymph nodes or more, which was independently associated with poorer overall survival. These findings identify areas for improving the quality of surgical treatment of gastric cancer in North America is warranted.

Figure 1. Mosaic plots showing the increased rate of adequate lymphadenectomy over the years. <br /> Footnote:<b> A:</b> Lymphadenectomy < 16 nodes; <b>B:</b> Lymphadenectomy ≥ 16 nodes. Cochran-Armitage trend test: P <.0001.

Figure 1. Mosaic plots showing the increased rate of adequate lymphadenectomy over the years.
Footnote: A: Lymphadenectomy < 16 nodes; B: Lymphadenectomy ≥ 16 nodes. Cochran-Armitage trend test: P <.0001.

Kaplan-Meier plot comparing the overall survival between patients who underwent gastrectomy for adenocarcinoma with and without adequate lymphadenectomy.<br /> Footnote:<b> Group 1:</b> Lymphadenectomy < 16 nodes; <b>Group 2: </b>Lymphadenectomy ≥ 16 nodes.

Kaplan-Meier plot comparing the overall survival between patients who underwent gastrectomy for adenocarcinoma with and without adequate lymphadenectomy.
Footnote: Group 1: Lymphadenectomy < 16 nodes; Group 2: Lymphadenectomy ≥ 16 nodes.

Background: Due to the aging population, the number of elderly patients (>80 years old) diagnosed with locally advanced gastric cancer (LAGC) in the US will continue to rise. According to NCCN guidelines, neoadjuvant treatment (NAT) is a recommended approach for locally advanced disease. However, most patients over the age of 80 have upfront surgery.

Methods: Patients 80 years and older who had a surgical resection for LAGC (stage IB-IIIC) were identified in the 2003-2017 National Cancer Database. Patients were grouped based on therapy sequence: those that received NAT prior to surgery, those that underwent surgery alone, and those that underwent up front surgery followed adjuvant therapy (UFS+AT). Multivariable logistic regressions were used to determine independent factors for R0 resection and receipt of AT and NAT. Overall survival (OS) from time of surgery was assessed using Kaplan-Meier analyses and Cox-proportional-hazards regression analyses examined for the impact of treatment pathway on the risk of death.

Results: Of 2731 patients, 68% received surgery alone, 18% had UFS+AT, and the remaining 15% NAT. During the latter half of the study period there was an increase in usage of NAT to 23% from 6%. Factors independently associated with receipt of NAT were diagnosis year 2011-2017, age <86, male gender, treatment at an academic facility, comorbidity score of 0, cT3 tumors, and cN1-2 disease (all p<0.001). Factors independently associated with receipt of adjuvant therapy were diagnosis year 2011-2017, age <86, Asian/Pacific Islander race, comorbidity score of 0, travel distance of 50-100mi, and node positive disease (all p<0.001). Factors independently associated with R0 resection include extent of surgery more than local excision, later date of diagnosis, treatment at an academic center, cT1 and cN0 disease, and grade I-II tumors (all p<0.001). Kaplan-Meier analyses showed a 29.5 month median OS for the NAT group (95% CI, 22.8-35.9) vs 29.5 months for surgery with AT (95% CI, 25.9-39.6) and 17.8 months for surgery alone (95% CI, 16.1-19.6) (P <0.0001). In a landmark analysis used to account for immortal time bias, NAT significantly improved overall survival compared to the UFS+AT group (p=0.018).

Conclusion: Of older patients with LAGC, less than 1/3 received some form of adjuvant or neoadjuvant therapy, which is the standard of care. NAT was associated with improved survival when compared to surgery followed by adjuvant therapy. Clinicians should advocate for receipt of NAT in older patients with LAGC.

Daniel Milgrom

Appearances