Subsequent Development of Epithelial Ovarian Cancer After Ovarian Surgery for Benign Ovarian Tumor: A Population-Based Cohort Study

Figures & data

Figure 1 Flowchart of the current cohort study.

Figure 2 Accumulation number of patients developing EOC during this cohort period.

Table 1 Baseline Characteristics of the Study Subjects (Follow-Up Period Was 100 815 Person-Years)

Variables	Number (n=11,620)	%
Development of epithelial ovarian cancer
Yes	30	0.26
No	11,590	99.74
Socioeconomic status
≥40,000	1273	10.96
20,000–39,999	2874	24.73
<20,000	4649	40.01
Others	2824	24.30
Work
Yes	10,318	88.80
No	1302	11.20
Urbanization
Urban	3802	32.72
Suburban	5357	46.10
Rural	2461	21.18
Total/subtotal hysterectomy
Yes	4329	37.25
No	7291	62.75
Ovarian surgery
Partial oophorectomy	7596	65.37
UO/USO ± partial oophorectomy	979	8.43
BSO/BO	3045	26.20
Repeated ovary surgery
Yes	717	6.17
No	10,903	93.83
Tubal ligation
Yes	142	1.22
No	11,478	98.78
Pelvic inflammatory disease
Yes	8909	76.67
No	2711	23.33
Infertility
Yes	1168	10.05
No	10,452	89.95
Cardiovascular disease
Yes	1168	10.05
No	10,452	89.95
Diabetes mellitus
Yes	1365	11.75
No	10,255	88.25
Chronic liver disease
Yes	361	3.11
No	11,259	96.89
Surgery confirmed ovarian endometrioma
Yes	4408	37.93
No	7212	62.07
Rheumatic disease
Yes	531	4.57
No	11,089	95.43
Charlson comorbidity index
0	5749	49.48
1	2391	20.58
2	1488	12.81
≥3	1992	17.14

Abbreviations: BSO/BO, bilateral salpingo-oophorectomy/bilateral oophorectomy; USO/UO, unilateral salpingo-oophorectomy/unilateral oophorectomy.

Table 2 The Incidence Rate of Epithelial Ovarian Cancer in Women Treated with Ovarian Surgery for Benign Ovarian Diseases Based on the Different Age Status

	Age < 30 Years	Age 30–39 Years	Age 40–49 Years	Age ≥ 50 Years	P*
	n = 1883	n = 3484	n = 3565	n = 2688
Number of patients with EOC	3	14	11	2
Incidence per 10,000 person-years	1.57	4.71	3.59	0.94
Crude HR (95% CI)	1.00 (Reference)	2.986 (0.858–10.398)	2.277 (0.635–8.169)	0.593 (0.099–3.551)	0.0850
P**		0.0857	0.2066	0.5668
Adjusted HR^1 (95% CI)	1.00 (Reference)	2.998 (0.858–10.470)	2.415 (0.639–9.128)	0.610 (0.091–4.069)	0.0964
P**		0.0853	0.1938	0.6095
Adjusted HR^2 (95% CI)	1.00 (Reference)	1.347 (0.374–4.849)	0.468 (0.117–1.882)	0.052 (0.008–0.348)	0.0002***
P**		0.6489	0.2851	0.0023**
Adjusted HR^3 (95% CI)	1.00 (Reference)	3.312 (0.950–11.542)	4.029 (1.079–15.047)	1.298 (0.186–9.065)	0.1072
P**		0.0601	0.0382*	0.7924
Adjusted HR^4 (95% CI)	1.00 (Reference)	3.251 (0.931–11.352)	4.062 (1.051–15.707)	1.200 (0.157–9.160)	0.0990
P**		0.0646	0.0422*	0.8605
Adjusted HR^5 (95% CI)	1.00 (Reference)	1.540 (0.431–5.504)	1.076 (0.265–4.364)	0.142 (0.020–1.013)	0.0326*
P**		0.5064	0.9182	0.0515

Notes: IR: incidence rate (incidence per 10,000 person-years); EOC: invasive epithelial ovarian cancer; HR: hazard ratio; 95% CI: 95% confidence interval; P*: comparison among all groups. P**: comparison between study group and reference group (age <30 years). Adjusted HR¹: adjustment for pelvic inflammatory disease, infertility status, cardiovascular disease, diabetes mellitus, chronic liver disease, and rheumatic disease. Adjusted HR²: adjusted for pelvic inflammatory disease, infertility, and Charlson comorbidity index (CCI). Adjusted HR³: adjustment for total/subtotal hysterectomy, unilateral oophorectomy, unilateral salpingo-oophorectomy, bilateral oophorectomy, bilateral salpingo-oophorectomy, tubal ligation. Adjusted HR⁴: adjustment for conditions of HR¹ and HR³. Adjusted HR⁵: adjustment for conditions of HR² and HR³. * P < 0.05, ** P < 0.01, *** P < 0.001.

Table 3 Univariate Cox Regression Analysis

Characteristics	Number of Patients
	11,620	Hazard Ratio (95% Confidence Interval)	P
Endometrioma
No	7212	1 (Reference)
Yes	4408	1.714 (0.838–3.507)	0.1403
Age
≤39	5367	1 (Reference)
>39	6253	0.716 (0.348–1.475)	0.3654
Total /subtotal hysterectomy
No	7291	1 (Reference)
Yes	4329	0.252 (0.088–0.722)	0.0103*
Ovarian surgery			0.2753
BSO/BO	3045	1 (Reference)
UO/USO ± partial oophorectomy	979	3.047 (0.546–16.988)	0.2038
Partial oophorectomy	7596	2.253 (0.782–6.494)	0.1327
Tubal ligation
No	11,478	1 (Reference)
Yes	142	0	0.9847
Pelvic inflammatory disease
No	2711	1 (Reference)
Yes	8909	0.942 (0.404–2.195)	0.8892
Infertility
No	10,452	1 (Reference)
Yes	1168	1.805 (0.691–4.715)	0.2282
Cardiovascular disease
No	10,452	1 (Reference)
Yes	1168	0.584 (0.139–2.452)	0.4626
Diabetes mellitus
No	10,255	1 (Reference)
Yes	1365	1.086 (0.379–3.112)	0.8781
Chronic liver disease
No	11,259	1 (Reference)
Yes	361	0	0.9843
Rheumatic disease
No	11,089	1 (Reference)
Yes	531	1.423 (0.339–5.972)	0.6302
Charlson comorbidity index			0.0017**
0	5749	1 (Reference)
1	2391	0	0.9880
2	1488	37.531(4.804–293.193)	0.0005***
≥3	1992	53.484 (7.160–399.531)	0.0001***

Notes: *P < 0.05, **P < 0.01, ***P < 0.001.

Abbreviations: BSO/BO, bilateral salpingo-oophorectomy/bilateral oophorectomy; USO/UO, unilateral salpingo-oophorectomy/unilateral oophorectomy.

Table 4 Multivariate Cox Regression Analysis

Characteristics	Number of Patients
	11,620	Hazard Ratio (95% Confidence Interval)	P
Endometrioma
No	7212	1 (Reference)
Yes	4408	1.007 (0.445–2.278)	0.9866
Age
≤39	5367	1 (Reference)
>39	6253	0.880 (0.346–2.235)	0.7873
Total/subtotal hysterectomy
No	7291	1 (Reference)
Yes	4329	0.362 (0.081–1.614)	0.1826
Ovarian surgery
BSO/BO	3045	1 (Reference)
UO/USO ± partial oophorectomy	979	2.122 (0.304–14.824)	0.4482
Partial oophorectomy	7596	0.883 (0.195–3.998)	0.8722
Tubal ligation
No	11,478
Yes	142
Pelvic inflammatory disease
No	2711	1 (Reference)
Yes	8909	0.760 (0.301–1.920)	0.5622
Infertility
No	10,452	1 (Reference)
Yes	1168	1.387 (0.478–4.025)	0.5469
Charlson comorbidity index			0.0017**
0	5749	1 (Reference)
1	2391	0	0.9882
2	1488	59.165 (7.499–466.804)	0.0001***
≥3	1992	190.679 (24.333–1494.186)	<0.0001***

Notes: **P < 0.01, ***P < 0.001.

Abbreviations: BSO/BO, bilateral salpingo-oophorectomy/bilateral oophorectomy; USO/UO, unilateral salpingo-oophorectomy/unilateral oophorectomy.