Patient Population
A total of 129,864 NSCLC cases were identified based on demographics, tumor and treatment characteristics in our study, including 78,460 male and 51,404 female patients stratified by sex. Most patients in men or women were white race (81.8% versus 83.3%), regions of the population were distributed in the east (49.5% versus 46.6%). Their tumors were mainly located in the upper lung lobe (52.1% versus 50.7%), had a laterality to right (55.2% versus 56.0%), more likely to be poorly-differentiated grade (Grade III/IV: 34.0% versus 32.4%). Majority of the patients had 0-3 lymph nodes removed (73.5% versus 70.9%) and the most histological types was squamous cell carcinoma (78.7% versus 66.9%), followed by adenocarcinoma (13.3% versus 24.5%), and large cell carcinoma (8.0% versus 8.6%). More patients, both men and women, were stuck in the advanced stage (stage III/IV: 73.9% versus 71.0%), and nearly half of them receipt of chemotherapy (47.5% versus 44.7%). However, there was a lower proportion of patients with bone (7.3% versus 6.0%), brain (3.6% versus 3.8%), liver (3.9% versus 3.2%) and lung (6.8% versus 6.7%) metastasis. The majority of patients in the entire cohort were elderly (age ≥65 years: 68.5% versus 71.3%) and more often accompanied by a positive first malignant indicator (77.0% versus 77.2%). Socioeconomic factors for this population were divided into having a good insurance status (73.0% vs. 74.1%), a high level of schooling (80.2% vs. 79.0%), and a generally high level of household income (85.7% vs. 88.7%). Female patients were more likely to be divorced or separated compared to their male marital status (35.9% vs. 57.4%). The baseline characteristics of patients are presented in Table 1.
Kaplan-Meier OS and Median Survival for NSCLC Patients Stratified by Sex and Age at Stages IB through IV
Kaplan-Meier OS for the entire cohort was 21.8%, when further calculated in accordance with stage, was 42.6%, 34.2%, 20.8%, and 10.0% for stages IB, II, III, and IV respectively (Figure 2). Stage-specific OS was significantly better for female patients at each stage (log-rank test, P < 0.001 for all stages) (Figure 3). Kaplan-Meier analysis showed improved OS in the female group compared to the male group throughout all stages (P <0 .001). Further using age as a stratification factor, the survival curves were almost extremely similar at stages IB through IV(P<0.005), except for younger patients in stage IB and II (P=0.055, P=0.096), presenting a higher survival rate in female (Figure S1-S4).
The mean survival times for male patients at stages IB through IV were 52.82 (95%CI: 51.85-53.80), 44.19 (95%CI: 42.88-45.50), 25.09 (95%CI: 24.60-25.59), and 10.78 (95%CI: 10.51-11.04) months compared with 66.29 (95%CI: 65.06-67.52), 52.87 (95%CI: 51.09-54.66), 31.35 (95%CI: 30.62-32.09), and 15.14 (95%CI: 14.71-15.57) months respectively for female patients. Median OS for males were 33.00 (95%CI: 31.88-34.12), 23.00 (95%CI: 21.93-24.07), 11.00 (95%CI: 10.77-11.23), and 4.00 (95%CI: 3.90-4.10) months from stage IB to IV, respectively. For the female patients, the median OS were 52.00 (95%CI: 49.53-54.47), 30.00 (95%CI: 27.95-32.05), 13.00 (95%CI: 12.63-13.37), 5.00 (95%CI: 4.85-5.15) months respectively as counterparts. The survival difference values for the male and female cohorts were greater in stage IB/II (13.47 and 8.68 months) than in stage III/IV (6.26 and 4.36 months) (Summarized in Table2).
Chemotherapy for NSCLC Patients Stratified by Sex at Stages IB through IV
Kaplan-Meier OS for patients not receiving chemotherapy at stages IB through IV were 42.1%, 25.6%, 14.2%, and 6.8% respectively. In comparison, we calculated the improved OS were 44.4%, 42.7% 25.8%, and 13.4% (all P<0.001) in the corresponding stages when chemotherapy was administered (Figure 4). Similar Kaplan-Meier survival trends were observed in the gender subgroup analysis of all stages (P<0.05), indicating that chemotherapy could be a positive treatment for men or women at stages IB through IV (Figure 5-6).
Following the sequence of stages, the median OS for male cohorts who received chemotherapy compared to those without chemotherapy were listed as 35.00 (95%CI: 32.51-37.49) versus 32.00 (95%CI: 30.74-33.26), 30.00 (95%CI: 27.95-32.05) versus 16.00 (95%CI: 14.87-17.13), 15.00 (95%CI: 14.66-15.34) versus 5.00 (95%CI: 4.78-5.22), and 8.00 (95%CI: 7.84-8.16) versus 2.00 (95%CI: 1.96-2.05) months, respectively. A similar contrast in the female cohort was performed, the median OS for patients receiving chemotherapy compared to those without chemotherapy were enumerated as 52.00 (95%CI: 45.62-58.38) versus 52.00 (95%CI: 49.30-54.70), 46.00 (95%CI: 42.01-49.99) versus 19.00 (95%CI: 17.34-20.66), 19.00 (95%CI: 18.38-19.62) versus 7.00 (95%CI: 6.61-7.39), and 10.00 (95%CI: 9.73-10.28) versus 2.00 (95%CI: 1.90-2.10) months, respectively (summarized in Table 3). We get a conclusion from the data analysis described above that female patient who received chemotherapy or without seem to have a longer median OS in comparison with male patients at the same stage.
Establishment of A Multivariate Regression Model
A separate multivariable Cox proportional hazards model for mortality was constructed and the effect of all relevant variables on survival for each clinical stage are summarized in Table 4. Being in the male sex group was a statistically significant predictor for mortality at all stages, while a better survival effect was presented in the female groups (hazard ratios [HR] of 0.766, 0.797, 0.846, and 0.857 for stages I through IV, respectively [all P < 0.0001]). Another significant predictor for mortality that could not be ignored at all stages was the impact of increasing age on OS. An increasing HR for mortality was observed for the subgroup of patients with increasing age, such as for age≥75 were 2.812, 2.331, 1.474, and 1.303 at stages I through IV, respectively (all P < 0.001). We also predicted other clinically significant risk factors for mortality across all stages, including grade, histological type, lymph nodes removed, chemotherapy, first malignant indicator, and social impactors of insurance status, marital status, and median family income. Multivariable regression analysis also showed other statistically significant predictors for mortality only at specific stages. For example, among the subset of patients with bone/brain/lung metastasis for stage III/IV more often associated with worse OS.