A total of 207 patients diagnosed with epithelial ovarian cancer were included in this study. The highest number of cases were recorded in year 2013 and 2014 (n=24 cases, 11.6%) while the lowest was in year 2007 (n=9 cases, 4.3%), with an average of 18 cases per year. There were 77 deaths in total during the study period and a total of 73 cases had died within 5 years of diagnosis.
The crude incidence rate of epithelial ovarian cancer was 9.7 per 100,000 per year while crude mortality rate was 3.6 per 100,000 in the period 2007 to 2017 (Table 1). Crude incidence rate was 8.7 per 100,000 in the first period (2007-2011) and increased to 10.5 per 100,000 in the second period (2012-2017). However, crude mortality rate was more than double in the second period (4.9 per 100,000) as compared to the first period (1.8 per 100,000).
Age-specific incidence and mortality rates in the period 2007 to 2017 are shown in Figure 1. The lowest incidence rate was seen in patients below 40 years old (3.8 per 100,000) and the rates increased to 31.7 per 100,000 women in the 50-59 age group. A decrease was noted in those who were in the 60-69 age group (27.3 per 100,000) but the rate continued to increase to 34.4 per 100,000 for 70 years and above age group. The same trend can be seen for the age-specific mortality rates where patients below 40 years old recorded the lowest rate (0.3 per 100,000), followed by 40-49 age group (5.2 per 100,000), 60-69 years (13.1 per 100,000), 50-59 years (17.5 per 100,000) and 70 years and above (19.9 per 100,000). Age-specific incidence rates increased steadily with age for both time periods, with a drop in the 60-69 age group. However, incidence rates increased for the oldest age group ( years) in the first period (57.0 per 100,000) while incidence continued to decline in the second period (20.4 per 100,000). In the first period, age-specific mortality rates increased with age and peaked at 60-69 years (16.4 per 100,000) before beginning to decline in the oldest age group (14.2 per 100,000). Similar to the first group, mortality rates in the second period increased with age but dropped in the 60-69 age group (11.5 per 100,000) before continuing to increase in the oldest age group (23.4 per 100,000).
The ASIR by for epithelial ovarian cancer was 11.3 (95% CI: 9.7, 12.9) per 100,000 while the ASMR was 4.5 (95% CI: 3.4, 5.6) per 100,000 in the period 2007-2017 (Table 1). The ASIR was lower in the first period with 11.6 (95% CI: 8.9, 14.3) per 100,000 compared to the second period with 11.1 (95% CI: 9.1, 13.1) per 100,000. However, the ASMR increased in the second period with 5.6 (95% CI: 3.1, 8.1) per 100,000 from 3.0 (95% CI: 1.5, 4.5) per 100,000 in the first period.
Patients’ demographic and clinical characteristics are presented in Table 2. The overall mean age at diagnosis was 48.4 (standard deviation = 15.3) years, with the majority of the patients in the 50-59 age group (29.0%), followed by less than 40 years (27.5%), 40-49 years old (22.2%), 60-69 years old (12.1%) and 70 years old and above (9.2%). Majority of the patients were of Malay ethnicity (83.6%) while 10.6% and 5.8% were of Chinese and other ethnicities respectively. Most epithelial ovarian cancer patients resided in Brunei Muara district (68.2%), followed by Tutong (16.2%), Belait (13.6%) and Temburong (2.0%). Majority of the patients were diagnosed at localized stage (38.9%), followed by distant (33.7%), and regional stages (27.4%). The most common histological type was mucinous carcinoma (30.9%), followed by serous carcinoma (28.0%), undifferentiated or other epithelial (25.1%), endometrioid carcinoma (10.6%) and clear cell carcinoma (5.3%).
Table 3 reports the number of cases for epithelial ovarian cancer patients according to cancer stage. No significant differences in the proportion of districts (p=0.350) and ethnicities (p=0.443) were found between stages. More than half of the women aged 70 and above were diagnosed at distant stage (52.9%) while only 11.8% were diagnosed at localized stage. Approximately 62.5% of women aged 60-69 years were diagnosed at distant stage. However, most of the women aged 40 and below were diagnosed at localized stage (69.8%), followed by regional (17.0%) and distant stage (13.2%). Almost half of the total women with serous carcinoma histology were diagnosed at distant stage (49.0%), followed by regional (29.4%) and localized (21.6%). However, patients with mucinous carcinoma and clear cell carcinoma reported majority of them were diagnosed at localized stage.
The overall survival rates at 1, 3, and 5 years for epithelial ovarian cancer patients in Brunei Darussalam were 79.7% (95% C.I.: 73.6, 84.6), 69.7% (95% C.I.: 62.8, 75.6), and 61.4% (95% C.I.: 53.9, 68.1) respectively (Figure 2). However, the median survival time was not available as the estimated survival were above 0.5. Table 2 presents the 5-year survival rates and p-values of the log-rank test for each covariate. This study found significant differences in epithelial ovarian cancer patients’ survival age groups (p<0.001), cancer stage (p<0.001) and histology (p<0.001). The 5-year survival rate was highest for age group 40 years and below (92.6%), followed by 40-49 years (66.6%), 60-69 years (43.9%), 70 years and above (40.5%) and 50-59 years (40.4%), shown in Figure 3.
Epithelial ovarian cancer patients resided in Brunei Muara district (57.8%) had the lowest survival compared to the other districts. However, this study found no significant difference in survival between the four districts (p=0.229). There was also no significant difference in survival between ethnicities (p=0.241). The 5-year survival rates for cancer stages were 94.1%, 46.4% and 38.0% for localized, regional, and distant stages respectively (Figure 4). For histological subtypes, mucinous carcinoma had the highest 5-year survival rate (78.5%), followed by clear cell carcinoma (68.2%), serious carcinoma (62.3%), endometroid carcinoma (55.8%), and undifferentiated or other epithelial (39.6%) (Figure 5).
Multivariate Cox PH regression analyses found that age at diagnosis, district, cancer stage, and histology were the significant prognostic factors for epithelial ovarian cancer patients’ survival (p<0.05), shown in Table 4. No evidence of significant violations of proportional hazard assumptions were observed.
As compared to a patient below 40 years old, the expected hazard of death was highest for epithelial ovarian cancer patient in the oldest age group ( 70 years) [Adj. HR=7.21, 95% CI: 2.24, 23.23, p=0.001], followed by 50-59 years [Adj. HR=5.29, 95% CI: 1.99, 14.05, p=0.001] whereas the expected hazard of patients in the 40-49 and 60-69 age groups were found to be comparable to those below 40 years old (p>0.05). Patients residing in Belait district have significantly lower hazard of death [Adj. HR=0.31, 95% CI: 0.12, 0.80, p=0.015] compared to those residing in Brunei Muara.
Patients with distant stage have significantly higher hazard [Adj. HR=11.99, 95% CI: 4.46, 32.23, p<0.001] compared to patients with localized stage. This trend is also observed in patients with regional stage [Adj. HR=6.12, 95% CI: 2.26, 16.56, p<0.001]. Patients with undifferentiated or other epithelial have significantly higher hazard of death [Adj. HR=3.12, 95% CI: 1.63, 5.95, p=0.001] compared to patients with serous carcinoma. No significant differences were found in the hazards of death when comparing a patient with serous carcinoma with mucinous carcinoma (p=0.153), endometrioid carcinoma (p=0.132), and clear cell carcinoma (p=0.664).