Patient demographics
Study entry criteria were met by 2,644 eligible patients (1,055 nonchemotherapy and 1,589 chemotherapy). In this population, only 16.4 percent were younger than 45 years, 56.1 percent aged 45 to 65 years, and 27.5 percent aged 65 years or older. A great majority of patients were the white race (n = 2243, 84.8%). Stage IA accounted for 44.2%, stage IB for 5.7%, stage IC for 38.4%, and stage IIA for 11.7%. Of the 2,644 patients, 59.1% were diagnosed with grade 1, and 40.9% with grade 2. Tumor laterality consisted of right (n = 1112, 42.1%), left (n = 1121, 42.4%) and other/unknown (n = 411, 15.5%). There were 44.3% of patients who had tumors smaller than 10 cm, 42.3% larger than 10 cm. In our study, endometrioid carcinoma accounted for 68.9%, and serous cystadenocarcinoma for 31.1%. Patients characteristics were presented in Table 1.
Table 1
Characteristics | No. | % |
Chemotherapy | | |
No/Unknown | 1055 | 39.9 |
Yes | 1589 | 60.1 |
Age | | |
≤ 45y | 434 | 16.4 |
45-65y | 1484 | 56.1 |
> 65y | 726 | 27.5 |
Race | | |
White | 2243 | 84.8 |
Nonwhite | 401 | 15.2 |
Stage | | |
IA | 1170 | 44.2 |
IB | 152 | 5.7 |
IC | 1014 | 38.4 |
IIA | 308 | 11.7 |
Grade | | |
1 | 1562 | 59.1 |
2 | 1082 | 40.9 |
Laterality | | |
Right | 1112 | 42.1 |
Left | 1121 | 42.4 |
Other/Unknown | 411 | 15.5 |
Tumor size | | |
≤ 10 cm | 1171 | 44.3 |
> 10 cm | 1119 | 42.3 |
Unknown | 354 | 13.4 |
Histology | | |
Serous | 821 | 31.1 |
Endometrioid | 1823 | 68.9 |
Note: No. number; % percent. |
Comparison Of Univariate Covariates
Before propensity score matching, chemotherapy groups tended to be younger than nonchemotherapy groups (≤ 45 years: 17.2% vs 15.3%; 45 to 65 years: 59.5% vs 51.0%, P < 0.001). They were less likely to be in stage IA (34.2% vs 59.3%, P < 0.001), more likely in stage IB (5.8% vs 5.7%, P < 0.001) and stage IC (46.0% vs 26.8%, P < 0.001). Compared with nonchemotherapy groups, grade 1 cases were less among chemotherapy groups (52.9% vs 68.3%, P < 0.001) and grade 2 cases were more (47.1% vs 31.7%, P < 0.001). More patients were serous cystadenocarcinoma in chemotherapy groups (33.5% vs 27.4%, P = 0.001). To eliminate the heterogeneity and imbalance between groups, we performed propensity score matching and logistic regression analysis. Results demonstrated that the two groups were equal number of patients and all clinical factors were well balanced without significant differences, indicating the potential covariates between groups were greatly decreased (Table 2).
Table 2
Comparison of univariate covariates
| | Before PSM | | | After PSM | |
Characteristics | Chemotherapy- (n = 1055) | Chemotherapy+ (n = 1589) | P | Chemotherapy- (n = 925) | Chemotherapy+ (n = 925) | P |
Age | | | < 0.001 | | | 0.254 |
≤ 45y | 161 (15.3) | 273 (17.2) | | 159 (17.2) | 183 (19.8) | |
45-65y | 538 (51.0) | 946 (59.5) | | 504 (54.5) | 503(54.4) | |
> 65y | 356 (33.7) | 370 (23.3) | | 262 (28.3) | 239 (25.8) | |
Race | | | 0.086 | | | 0.124 |
White | 911 (86.4) | 1332 (83.8) | | 793 (85.7) | 768 (83.0) | |
Nonwhite | 144 (13.6) | 257 (16.2) | | 132 (14.3) | 157 (17.0) | |
Stage | | | < 0.001 | | | 0.328 |
IA | 626 (59.3) | 544 (34.2) | | 499 (53.9) | 475 (51.4) | |
IB | 60 (5.7) | 92 (5.8) | | 57 (6.2) | 49 (5.3) | |
IC | 283 (26.8) | 731 (46.0) | | 283 (30.6) | 319 (34.5) | |
IIA | 86 (8.2) | 222 (14.0) | | 86 (9.3) | 82 (8.9) | |
Grade | | | < 0.001 | | | 0.530 |
1 | 721 (68.3) | 841 (52.9) | | 595 (64.3) | 581 (62.8) | |
2 | 334 (31.7) | 748 (47.1) | | 330 (35.7) | 344 (37.2) | |
Laterality | | | < 0.001 | | | 0.147 |
Right | 477 (45.2) | 635 (40.0) | | 407 (44.0) | 383 (41.4) | |
Left | 461 (43.7) | 660 (41.5) | | 405 (43.8) | 401 (43.4) | |
Other/Unknown | 117 (11.1) | 294 (18.5) | | 113 (12.2) | 141 (15.2) | |
Tumor size | | | 0.044 | | | 0.888 |
≤ 10 cm | 464 (44.0) | 707 (44.5) | | 414 (44.8) | 416 (45.0) | |
> 10 cm | 429 (40.7) | 690 (43.4) | | 386 (41.7) | 391 (42.3) | |
Unknown | 162 (15.4) | 192 (12.1) | | 125 (13.5) | 118 (12.8) | |
Histology | | | 0.001 | | | 0.226 |
Serous | 289 (27.4) | 532 (33.5) | | 257 (27.8) | 233 (25.2) | |
Endometrioid | 766 (72.6) | 1057 (66.5) | | 668 (72.2) | 692 (74.8) | |
Note: Data are expressed as n (%). P-value < 0.05 is regarded as statistically significant. PSM propensity score matching. |
Association Of Chemotherapy With Survival
We analyzed the association between chemotherapy and 5-year OS for stage IA-IIA. There were no statistically significant differences between chemotherapy and nonchemotherapy groups (stage IA: 46.5% vs 53.7%, P = 0.110; stage IB: 49.0% vs 49.1%, P = 0.059; stage IC: 46.1% vs 48.1%, P = 0.750; stage IIA: 39.0% vs 37.2%, P = 0.249). Early-stage patients could not benefit from chemotherapy to prolong their 5-year OS (Table 3 & Fig. 2).
Table 3
Association of chemotherapy with 5-year OS
Stage | Chemotherapy- (n = 925) | Chemotherapy+ (n = 925) | P |
IA | 53.7% | 46.5% | 0.110 |
IB | 49.1% | 49.0% | 0.059 |
IC | 48.1% | 46.1% | 0.750 |
IIA | 37.2% | 39.0% | 0.249 |
Note: P-value < 0.05 is regarded as statistically significant. OS overall survival. |
Univariate Analysis Of Clinical Factors With Survival
We conducted univariate analysis of the matched population to explore prognostic effect of the clinical factors. No significant differences were found between chemotherapy and nonchemotherapy groups in 5-year OS (P = 0.245). Older age was a hazard factor for 5-year OS (P < 0.001). Tumors larger than 10 cm had lower 5-year OS (P = 0.014). Moreover, 5-year OS of endometrioid carcinoma was higher than serous cystadenocarcinoma (P < 0.001) (Table 4 & Fig. 3).
Table 4
Univariate analysis of clinical factors with 5-year OS
Characteristics | No. | 5-year OS (%) | P |
Chemotherapy | | | 0.245 |
No/Unknown | 925 | 50.2 | |
Yes | 925 | 45.8 | |
Age | | | < 0.001 |
≤ 45y | 342 | 51.5 | |
45-65y | 1007 | 49.3 | |
> 65y | 501 | 43.1 | |
Race | | | 0.833 |
White | 1561 | 48.9 | |
Nonwhite | 289 | 43.3 | |
Stage | | | 0.354 |
IA | 974 | 50.2 | |
IB | 106 | 49.1 | |
IC | 602 | 47.0 | |
IIA | 168 | 38.1 | |
Grade | | | 0.908 |
1 | 1176 | 51.2 | |
2 | 674 | 42.4 | |
Laterality | | | 0.163 |
Right | 790 | 46.7 | |
Left | 806 | 50.5 | |
Other/Unknown | 254 | 44.1 | |
Tumor size | | | 0.014 |
≤ 10 cm | 830 | 45.5 | |
> 10 cm | 777 | 44.8 | |
Unknown | 243 | 66.7 | |
Histology | | | < 0.001 |
Serous | 490 | 38.4% | |
Endometrioid | 1360 | 51.5% | |
Note: P-value < 0.05 is regarded as statistically significant. OS overall survival. |
Cox Proportional Hazards Model
The cox proportional hazards model is often used in medical research to investigate the association between survival time of patients and one or more predictive variables. The Kaplan-Meier method and log-rank tests describe survival according to one factor under investigation, but ignore the impact of any others. Additionally, they are available only when the predictive variables are categorical, and don’t work easily for quantitative predictors such as age. Given these problems, an alternative method is the cox proportional hazards regression analysis, which works for both quantitative predictive variables and categorical variables. Furthermore, the cox regression model extends survival analysis methods to assess simultaneously the effect of several risk factors on survival time.
To explore how clinical factors jointly impact on survival, we took all the factors associated with survival into a multivariate cox regression analysis. The results were shown in Table 5. Our analysis showed that elderly patients (≥ age 65) had higher risk and worse prognostic (HR = 1.486, CI = 1.208–1.827, P < 0.001). Endometrioid carcinoma was related to better 5-year OS (HR = 0.697, CI = 0.584–0.833, P < 0.001). Chemotherapy still had no statistically significant effect on the 5-year OS after excluding the influence of all the confounding factors (HR = 1.092, CI = 0.954–1.249, P = 0.201).
Table 5
Multivariate cox regression analysis for 5-year OS
Characteristics | HR (95% CI) | P |
Chemotherapy | | |
No/Unknown | Ref | |
Yes | 1.092(0.954–1.249) | 0.201 |
Age | | |
≤ 45y | Ref | |
45-65y | 1.044(0.877–1.244) | 0.627 |
> 65y | 1.486(1.208–1.827) | < 0.001 |
Race | | |
White | Ref | |
Nonwhite | 0.984(0.810–1.195) | 0.872 |
Stage | | |
IA | Ref | |
IB | 0.967(0.689–1.359) | 0.848 |
IC | 1.063(0.910–1.241) | 0.441 |
IIA | 1.128(0.862–1.475) | 0.381 |
Grade | | |
1 | Ref | |
2 | 0.865(0.743–1.008) | 0.063 |
Laterality | | |
Right | Ref | |
Left | 0.984(0.852–1.136) | 0.824 |
Other/Unknown | 1.115(0.862–1.443) | 0.407 |
Tumor size | | |
≤ 10 cm | Ref | |
> 10 cm | 0.984(0.848–1.141) | 0.830 |
Unknown | 0.760(0.630–0.918) | 0.004 |
Histology | | |
Serous | Ref | |
Endometrioid | 0.697(0.584–0.833) | < 0.001 |
Note: P-value < 0.05 is regarded as statistically significant. HR hazard ratios; CI confidence intervals; Ref reference. |