Patients and tumor characteristics
In all, 339 patients were successfully followed-up, whereas 315 patients were lost to follow-up after treatment. Overall, 147 patients with advanced-stage disease (II to IV) were excluded from this study. Finally, 192 patients were enrolled in the retrospective analysis. The women were then divided into five groups [A group (45.83%), non-adjuvant treatment; B group (5.73%), radiotherapy; C group (34.38%), chemotherapy; and D group (14.06%), MPA alone or combined with chemotherapy or radiotherapy]. Eleven patients and 66 patients received radiotherapy and chemotherapy, respectively. Twenty patients received adjuvant hormone therapy alone, and 7 patients received MPA combined with other adjuvant treatments (5 patients received chemotherapy and 2 patients received radiotherapy). The remaining 88 patients did not receive adjuvant treatment after surgery (Figure. 1).
The baseline characteristics of all patients are summarized in Table 1. The median follow-up for all patients was 51 months (range: 18-143). No significant difference was found among the four groups in terms of age, histologic subtype, ER expression or CA125 level in the serum. A few patients were diagnosed with rare pathological types, such as adenocarcinoma (endocervical type), adenocarcinoma/clear cell carcinoma, clear cell carcinoma, serous papillary carcinoma, mucinous papillary adenocarcinoma of the intestinal epithelium, and papillary adenocarcinoma (villous-tubular carcinoma subtype). The proportions of these rare subtypes did not differ among the groups. In addition, we found that histologic grade, FIGO stage and PR expression differed among the four groups (p = 0.0005, p = 0.0112 and p = 0.0064). Among 192 patients, 168 (87.5%) underwent pelvic lymphadenectomy, and 11.46% (22/192) underwent pelvic and para-aortic lymphadenectomy. No difference was found in the proportion of lymphadenectomy among the four groups (p = 0.9688 and p = 0.4211).
Table 1: Patient and tumor characteristics
Characteristic
|
A group
|
B group
|
C group
|
D group
|
p-value
|
N
|
88
|
11
|
66
|
27
|
|
Age (%)
|
|
|
|
|
0.2823
|
|
<60 y
|
69 (78.41)
|
7 (63.64)
|
55 (83.33)
|
24 (88.89)
|
|
|
≥60 y
|
19 (21.59)
|
4 (36.36)
|
11 (16.67)
|
3 (11.11)
|
|
Histologic type (%)
|
|
|
|
|
0.7971
|
|
Adenocarcinoma
|
81 (92.04)
|
11 (100)
|
62 (93.93)
|
27 (100)
|
|
|
Adenocarcinoma (endocervical type)
|
3 (3.41)
|
0 (0)
|
0 (0)
|
0 (0)
|
|
|
Adenocarcinoma/Clear cell carcinoma
|
1 (1.14)
|
0 (0)
|
2 (3.03)
|
0 (0)
|
|
|
Clear cell carcinoma
|
0 (0)
|
0 (0)
|
1 (1.52)
|
0 (0)
|
|
|
Mucinous papillary adenocarcinoma of intestinal epithelium
|
1 (1.14)
|
0 (0)
|
0 (0)
|
0 (0)
|
|
|
Papillary adenocarcinoma (villous-tubular carcinoma subtype)
|
0 (0)
|
0 (0)
|
1 (1.52)
|
0 (0)
|
|
|
Serous papillary carcinoma
|
2 (2.27)
|
0 (0)
|
0 (0)
|
0 (0)
|
|
Histologic grade (%)
|
|
|
|
|
0.0005*
|
|
G1
|
64(72.73)
|
4(36.36)
|
26(39.40)
|
20(74.07)
|
|
|
G2
|
17(19.32)
|
5(45.45)
|
30(45.45)
|
5(18.52)
|
|
|
G3
|
3(3.41)
|
2(18.18)
|
8(12.12)
|
2(7.41)
|
|
|
Unknown
|
4(4.54)
|
0(0)
|
2(3.03)
|
0(0)
|
|
FIGO stage (%)
|
|
|
|
|
0.0112*
|
|
IA
|
80 (90.91)
|
7 (63.64)
|
49 (74.24)
|
23 (85.19)
|
|
|
IB
|
8 (9.09)
|
4 (36.36)
|
17 (25.76)
|
4 (14.81)
|
|
Lymphadenectomy
|
|
|
|
|
|
|
Pelvic lymph node
|
62 (70.45)
|
9(81.82)
|
54 (81.82)
|
21 (77.78)
|
0.9688
|
|
Pelviclymph + para-aortic node
|
12 ( 12.5)
|
1 (0.91)
|
8(12.12)
|
1 (3.7)
|
0.4211
|
CA125
|
|
|
|
|
0.395
|
|
<35 U/ml
|
40 (45.45)
|
6 (54.55)
|
35 (53.03)
|
10 (37.04)
|
|
|
≥35 U/ml
|
11 (12.50)
|
2 (18.18)
|
6 (9.09)
|
1 (3.70)
|
|
|
Unknown
|
37 (42.05)
|
3 (27.27)
|
25 (37.88)
|
16 (59.26)
|
|
ER (%)
|
|
|
|
|
0.0743
|
|
+
|
48 (54.55)
|
10 (90.91)
|
49 (74.24)
|
17 (62.97)
|
|
|
-
|
8 (9.09)
|
0 (0)
|
6 (9.09)
|
1 (3.70)
|
|
|
Unknown
|
32 (36.36)
|
1 (9.09)
|
11 (16.67)
|
9 (33.33)
|
|
PR (%)
|
|
|
|
|
0.0064*
|
|
+
|
41 (46.59)
|
7 (63.64)
|
45 (68.18)
|
18 (66.67)
|
|
|
-
|
15 (17.05)
|
3 (27.27)
|
9 (13.64)
|
0 (0)
|
|
|
±
|
0 (0)
|
0 (0)
|
1 (1.52)
|
0 (0)
|
|
|
Unknown
|
32 (36.36)
|
1 (9.09)
|
11 (16.66)
|
9 (33.33)
|
|
A group, no adjuvant treatment; B group: radiotherapy; C group, chemotherapy; D group, MPA+ chemotherapy (or) radiotherapy. Abbreviations: FIGO, International Federation of Gynecology and Obstetrics; ER, estrogen receptor; PR, progesterone receptor.
Survival outcomes
The total relapse and mortality rates of all 192 patients were 5.57% and 1.68%, respectively. During the follow-up period, 14 patients (7.29%) developed isolated local recurrence, and 2 patients (1.04%) died of recurrence. The 5-year OS and DFS rates of all patients were 93.75% and 95.83%, respectively. In this study, the log-rank test was used to test the significance of different treatments. No statistically significant differences were observed in the 5-year DFS, 5-year OS, OS, or DFS among the four groups of patients with stage I endometrial cancer (p=0.9849, 0.7430, 0.9754 and 0.4534) (Figure. 2). This result suggested that adjuvant chemotherapy, radiotherapy or hormone therapy + chemotherapy/radiotherapy after surgery did not improve the DFS and OS rates of patients with stage I endometrial cancer.
Not all types of postoperative adjuvant treatment are conducive to survival. Therefore, we analyzed the influence of stage, age and tumor differentiation on the 5-year DFS, 5-year OS, DFS and OS of early endometrial cancer patients. The differences in log-rank tests of the estimates of 5-year DFS, 5-year OS, DFS and OS between stage IA and stage IB were all significant (hazard ratio, 0.1062, 95% CI, 0.0210–0.5366, p = 0.0046; hazard ratio, 0.0566, 95% CI, 0.078–0.4047, p = 0.0043; hazard ratio, 0.1062, 95% CI, 0.0273-0.6303, p = 0.0112; and hazard ratio, 0.0866, 95% CI, 0.0163–0.4584, p= 0.0040, respectively), which is similar to the pattern seen between different age groups in 5-year DFS, 5-year OS, DFS and OS (hazard ratio, 0.0838, 95% CI, 0.0181-0.3895, p = 0.0039; hazard ratio, 0.0372, 95% CI, 0.0058–0.2390, p = 0.0011; hazard ratio, 0.1203, 95% CI, 0.0279–0.5182, p = 0.0040; and hazard ratio, 0.0478, 95% CI, 0.0092–0.2478, p = 0.0004, respectively). It is worth mentioning that the 5-year DFS, 5-year OS, DFS and OS rates were not different between the different tumor differentiation groups (p = 0.5952, 0.6475, 0.5669 and 0.6200) (Figure. 3 and Figure. 4).
The clinical factors that affect survival status
To assess the risk factors that affect the survival status of women with stage I endometrial cancer, we performed a univariate analysis of different variables. The log-rank test (time series test) was used for the univariate analysis to analyze the impact of various factors on prognosis. Histologic grade, estrogen receptor status, progesterone receptor status and CA125 level were not associated with significant differences in DFS and OS (log-rank, p = 0.6946, 0.9199, 0.9347 and 0.3272), but patient age was associated with prognosis (log-rank, p = 0.0045 for DFS and 0.0003 for OS) (Table 2).
Table 2: Univariate analysis for risk factors affecting the survival status of women with stage I endometrial cancer
Parameter
|
Disease-Specific Survival
|
Overall survival
|
Chi-square
|
p-value
|
Chi-square
|
p-value
|
Age
|
8.0783
|
0.0045*
|
13.1273
|
0.0003*
|
Histologic grade
|
1.5171
|
0.6783
|
1.4468
|
0.6946
|
ER status
|
0.6729
|
0.7143
|
0.1670
|
0.9199
|
PR status
|
0.0054
|
0.9973
|
0.1350
|
0.9347
|
CA125
|
1.1792
|
0.2775
|
0.9601
|
0.3272
|
Adjuvant treatment
|
0.2145
|
0.9752
|
0.4775
|
0.9238
|
Furthermore, a Cox proportional hazard model was used for the multivariate regression analysis to determine the risk factors that affect the DFS or OS of stage I endometrial cancer patients. Six factors (age, histologic grade, ER status, PR status, CA125 level and adjuvant treatment) were introduced into the Cox model as independent variables. At a threshold of p < 0.05, no significant difference was found in prognosis among different histologic grades, ER and PR statuses, CA125 level and adjuvant treatment status (Table 3). However, age affected DFS and OS in early-stage endometrial cancer [HR (95% CI): 6.119 (1.502–24.924), p = 0.0115; and HR (95% CI): 9.088 (2.012–41.058), p = 0.0041].
Table 3: Multivariate analysis of risk factors affecting the DFS and OS status in women with stage I endometrial cancer
Parameter
|
Disease-specific survival
|
Overall survival
|
HR (95% CI)
|
p-value
|
HR (95% CI)
|
p-value
|
Age
|
6.119 (1.502-24.924)
|
0.0115*
|
9.088 (2.012-41.058)
|
0.0041*
|
Histologic grade
|
0.335 (0.079-1.412)
|
0.1361
|
0.49 (0.11-2.186)
|
0.3501
|
ER
|
0.133 (0.009-1.913)
|
0.138
|
0.227 (0.011-4.551)
|
0.3325
|
PR
|
0.974 (0.062-15.207)
|
0.9848
|
1.366 (0.063-29.5)
|
0.8424
|
CA125
|
-
|
0.9952
|
-
|
0.9961
|
Adjuvant treatment
|
1.513 (0.769-2.976)
|
0.2302
|
1.651 (0.828-3.294)
|
0.1547
|