Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers-Stage Challenges Categorical Assignments of Indolence & Aggressiveness

Abstract

Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed "histo-types", which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 200,658 EOC cases were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data. Kaplan-Meier survival analyses, one-factor ANOVA and Chi-square analyses were performed on 10-year DSS survivals. DSS strongly supported a 2-tiered classification (grade 1 vs. grade 2 & 3) for serous EOC. DSS of early stage serous EOC for grade 2 was significantly different from grade 3 indicating that a 2-tier classification for serous EOC applied only to late stage. DSS of Type I EOC was much better than Type II. However, DSS was 46-58% lower with late stage Type I than with early stage Type I indicating that Type I ovarian cancers should not be considered indolent. Early stage Type II EOC had much better DSS than late stage Type II stressing that stage has a large role in survival of both Type I and II EOC.

Keywords: Type I & Type II; epithelial ovarian cancer; grade; histo-types; stage; survival.

Figure 1

Kaplan–Meier ovarian cancer-specific survival showing number of women at risk according to grade of serous EOC (8441/3, 8460/3, 8461/3). Women with grade 1 well differentiated serous EOC (blue curve, n = 1,351; 50, 100 & 200-month survival is 80.0%, 66.2%, 55.0%), grade 2 moderately differentiated (red curve, n = 4,526; 50, 100 & 200-month survival is 55.8%, 36.5%, 25.7%), and grade 3 undifferentiated (green curve, n = 15,166; 50, 100 & 200-month survival is 48.3%, 27.7%, 19.0%). The number of women remaining at different survival points is shown for well differentiated screened (blue), moderately differentiated (red), undifferentiated (green) cases. Log-rank test p < 0.001.

Figure 2

Kaplan–Meier ovarian cancer-specific survival showing number of women at risk according to grade of endometrioid EOC, mucinous carcinoma and clear cell EOC. (A). Women with endometrioid EOC (8380/3) that was grade 1 well differentiated (blue curve, n = 1982; 50, 100 & 200-month survival is 94.8%, 91.4%, 86.5%), grade 2 moderately differentiated (red curve, n = 2761; 50, 100 & 200-month survival is 84.3%, 77.1%, 71.7%), and grade 3 undifferentiated (green curve, n = 2169; 50, 100 & 200-month survival is 66.4%, 52.9%, 44.4%). Log-rank test p < 0.001. (B). Women with mucinous EOC (8470/3, 8471/3, 8480/3, 8481/3, 8482/3) that was grade 1 well differentiated (blue curve, n = 1506; 50, 100 & 200-month survival is 84.5%, 80.7%, 76.4%, grade 2 moderately differentiated (red curve, n = 1431; 50, 100 & 200-month survival is 72.1%, 67.7%, 65.8%), and grade 3 undifferentiated (green curve, n = 699; 50, 100 & 200-month survival is 46.5%, 39.7%, 35.2%). Log-rank test p < 0.001. (C). Women with clear cell EOC (8310/3) that was grade 1 well differentiated (blue curve, n = 60; 50, 100 & 200-month survival is 77.4%, 74.7%, 74.7%), grade 2 moderately differentiated (red curve, n = 394; 50, 100 & 200-month survival is 76.2%, 69.0%, 63.3%), and grade 3 undifferentiated (green curve, n = 2151; 50, 100 & 200-month survival is 67.1%, 58.6%, 56.3%). The number of women remaining at different survival points is shown for well differentiated screened (blue), moderately differentiated (red), undifferentiated (green). Log-rank test p < 0.001.

Figure 3

Kaplan–Meier ovarian cancer-specific survival showing number of women at risk according to grade of ovarian carcinosarcoma and undifferentiated carcinoma. Women with ovarian carcinosarcoma (8950/3, 8951/3 & 8980/3) that was grade 1 well differentiated (blue curve, n = 29; 50, 100 & 200-month survival is 89.1.0%, 89.1%, 81.7%), grade 2 moderately differentiated (red curve, n = 40; 50, 100 & 200-month survival is 37.7%, 31.9%, 31.9%), and grade 3 undifferentiated (green curve, n = 1250; 50, 100 & 200-month survival is 31.8%, 21.8%, 18.9%). Log-rank test p < 0.001. Women with undifferentiated EOC (8020/3) that was grade 3 by definition (black curve, n = 304; 50, 100 & 200-month survival is 46.9%, 32.9%, 25.8%).

Figure 4

Kaplan–Meier survival of women with Type I & II EOC. (A). DSS of women with Type I EOC (blue curve, n= 12,417; 50, 100 & 200-month survival is 78.5%, 71.7%, 66.6%). DSS of women with Type II EOC (red curve, n= 23,484; 50, 100, & 200-month survival is 50.6%, 31.7%, 22.9%). p-value obtained by the log rank test. The number of women remaining at different survival points is shown for Type I (blue) and Type II (red) epithelial ovarian cancers. (Type I vs. Type II: p < 0.001). The number of women remaining at different survival points is color-coded for each of the four categories along the x-axis. Vertical lines identify censored data points. (B). DSS of women with Type I & II EOC according to stage. Early stage (I & II) Type I EOC (blue curve, n= 8,527; 50, 100 & 200-month survival is 91.9%, 87.7%, 84.9%). Early stage (I & II) Type II EOC (green curve, n= 4,261; 50, 100 & 200-month survival is 83.9%, 71.0%, 60.3%). Late stage (III & IV) Type I EOC (red curve, n= 3,069; 50, 100 & 200-month survival is 47.9%, 35.3%, 28.1%). Late stage (III & IV) Type II EOC (brown curve, n= 16,593; 50, 100 & 200-month survival is 44.2%, 23.4%, 15.2%) (Type I vs. Type II: p < 0.001). p-value obtained by the log rank test. The number of women remaining at different survival points is color-coded for each of the four categories along the x-axis. Vertical lines identify censored data points.