Overall trend of surgery in elderly patients
A total of 59698 patients with proximal gastric carcinoma identified from NCDB were initially screened into three age groups (<60 yrs: n=16766; 60-79 yrs: n=32931; and ≥ 80 yrs: n=10001). Among patients age ≥80 yrs, 2484 patients were recommended for surgery, with a significantly decreased proportion compared to the younger age groups (Figure 2a, ≥ 80 yrs: 30% vs. 60-79 yrs: 50% vs. <60 yrs: 50 %, P < 0.001). Among patients who were recommended for surgery, the proportion who ultimately underwent surgery decreased significantly in groups age ≥80 yrs (86% vs. 97% for 60-79 yrs vs. 98% <60 yrs groups, P < 0.001, Figure 2b).
A total of 2484 patients age ≥80 yrs with resectable proximal gastric carcinoma identified from NCDB were eligible for the final analysis. Patients' characteristics of the surgery group and no surgery group are summarized in Supplementary Table 1. Patients who underwent surgery were more likely to be younger, male gender, white race (P<0.001). However, CDCI, tumor size, differentiation grade, and TNM stage did not significantly differ between the two groups. Patients who underwent surgery were less likely to receive chemotherapy (P<0.001) or radiotherapy (P<0.001). Detailed therapeutic strategies of the patients were summarized in Supplementary Table 2.
Survival Comparison between Surgical and Non-surgical groups (All recommended for surgery)
For patients who were recommended for surgery, there was no significant difference in CDCI, and TNM stage between surgical and non-surgical groups. It showed that these two group patients were comparable, and the selection bias was well controlled. Our data showed that patients who underwent surgery had a significantly better survival than those who did not undergo surgery (1-year OS: 68% vs. 48%; 3-year OS: 39% vs. 15%; 5-year OS: 26% vs. 7% respectively, P<0.001, Figure 3a), especially in stage 0-I patients (5-year OS: 37% vs. 14%, P<0.001, Figure 3b). No significant difference was observed in stage II (5-year OS: 18% vs. 18%, P=0.11, Figure 3c) and III patients (5-year OS: 11% vs. 0%, P=0.08, Figure 3d). A significant survival benefit was observed in both healthy patients (CDCI score=0, 5-year OS: 29% vs. 7%, P<0.001, Figure 3e) and those with comorbidities (CDCI score=1, 5-year OS: 21% vs. 11%, P<0.001, Figure 3f; and CDCI score≥2, 5-year OS: 18% vs. 0%, P=0.001, Figure 3g). Interestingly, treatment with chemotherapy or radiotherapy did not significantly impact prognosis (HR: 0.90, 95% CI: 0.80-1.01, P=0.08 for chemotherapy, and HR: 1.00, 95% CI: 0.88-1.13, P=0.98 for radiotherapy). After adjustment for known factors including age, gender, CDCI , tumor size, differentiation grade, TNM stage using multivariable Cox proportional hazard model, surgery (HR: 0.66, 95% CI: 0.51-0.86, P=0.002) remained a significant independent prognostic factor for elderly surgical candidates with resectable proximal gastric carcinoma (Table 1).
Survival Analyses in Patients Who Underwent Surgery
Univariable Cox analyses in the subgroup who underwent surgery demonstrated that older age, male gender, higher CDCI, larger tumor size, lower differentiation grade, positive lymphovascular invasion, positive surgical margin, more number of lymph nodes (LNs) examined (continuous variable), and advanced TNM stage were associated with worse overall survival (Table 2). In addition, patients who underwent surgery with combined organ resection had a significantly worse survival (HR: 1.63, 95% CI: 1.33-2.00, P<0.001), while those who underwent local excisions had a significantly better survival (HR: 0.61, 95% CI: 0.52-0.70, P<0.001) when comparing with subtotal gastrectomy as reference. After adjustment using multivariable Cox regression, only age, CDCI, TNM stage, surgery type remained significant as independent factors for prognosis. Notably, neither chemotherapy (HR: 0.94, 95% CI: 0.82-1.08, P=0.36), radiotherapy (HR: 0.97, 95% CI: 0.84-1.13, P=0.72) nor the sequence of treatments (HR: 1.05, 95% CI: 0.77-1.43, P=0.76) had an impact on survival in patients undergoing surgery (Table 2).
Surgical Risk and Outcome Related to Facility
Nearly half of the elderly patients underwent surgery in academic/research program (AR-program, 992/2134, 46.5%). Compared to younger patients, 30-day and 90-day mortality rate was higher in patients age ≥80 yrs (Supplementary Figure 1a, and 1b), however, the mortality rate was much lower for elderly patients who underwent surgery at academic and research (AR) program than that in integrated network cancer program, comprehensive community cancer program or community cancer program (30-day mortality: 1.5% in AR-program vs. 4.7%, 3.6% and 6.6% in other three programs, P<0.001; 90-day mortality: 6.2% in AR-program vs. 14.6%, 13.6% and 16.4% in other three programs, P<0.001) (Supplementary Figure 1c, and 1d). Consistent with the result of surgical risk, the survival outcome was also significantly better in patients underwent surgery in AR-program than those treated in integrated network cancer program, comprehensive community cancer program or community cancer program (5-year OS: 30% vs. 27% vs. 22% vs. 18% respectively, P<0.001) (Table 2, and Supplementary Figure 2).