Objective
We performed a population-based analysis to compare the clinical characteristics of women with mucinous tumors with women with other epithelial tumors.
Study Design
The Surveillance, Epidemiology, and End Results database was queried to identify all women with epithelial ovarian cancer diagnosed from 1988 to 2007. The natural history, clinical characteristics, and survival of women with serous tumors were compared with women with mucinous carcinomas.
Results
A total of 40,571 women including 4811 with mucinous carcinomas (11.9%) were identified. Among women with stage I neoplasms, the presence of mucinous histology had no effect on either cancer-specific survival (hazard ratio, 0.87; 95% confidence interval, 0.74–1.04). Survival was inferior in patients with advanced-stage mucinous compared with serous tumors. The hazard ratio for cancer-specific survival for women with stage III mucinous tumors was 1.55 (95% confidence interval, 1.43–1.96).
Conclusion
Although survival for early-stage mucinous and serous tumors is similar, survival for advanced-stage mucinous neoplasms is inferior to that of serous carcinomas.
In 2010, an estimated 21,880 cases of ovarian cancer were diagnosed in the United States, and 13,850 women died from their disease. More than 90% of women with ovarian cancer have epithelial tumors. Although serous tumors are the most common histologic variant, mucinous, endometrioid, clear cell, and transitional cell tumors are also classified as epithelial tumors. Despite the heterogeneity of this classification schema, the majority of therapeutic studies for ovarian cancer have included all of the epithelial histologic subtypes.
An increasing number of studies have now suggested that the various histologic subtypes of epithelial ovarian cancer are distinct entities. Both from a clinical and molecular standpoint, several of these tumor subtypes appear unique. Based on the growing body of evidence, many investigators have suggested that epithelial tumors should be reclassified. In several proposed classification schemas that are based on not only microscopic appearance but also expected clinical behavior and histogenesis, serous and mucinous ovarian tumors are considered distinct entities and are not merely classified as epithelial tumors.
Of the epithelial tumors, mucinous neoplasms in particular appear unique. It has long been recognized that these neoplasms occur in younger women and are often confined to the ovary at the time of diagnosis. In 2004, Hess et al noted that women with advanced-stage mucinous tumors had a worse prognosis than other histologic subtypes. The median overall survival in women with mucinous tumors was only 12 months compared with nearly 37 months in those with nonmucinous malignancies. These findings caused many to reevaluate the natural history of mucinous ovarian tumors.
Despite the growing body of evidence suggesting that mucinous tumors are unique, there are no large, population-based studies that have examined the natural history of mucinous tumors. We performed a population-based analysis of women with invasive mucinous tumors of the ovary. The goal of the study was to compare the clinical and pathologic characteristics of women with mucinous tumors with those of women with other epithelial tumors and to examine the influence of histology on stage-specific survival.
Materials and Methods
The Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute was utilized. SEER is a population-based cancer registry that includes approximately 26% of the US population. SEER is composed of several geographically distinct tumor registries. Data from SEER 17 registries were used.
Women with invasive epithelial tumors of the ovary diagnosed between 1988 and 2007 were included in our analysis. Patients were stratified based on histology into the following groups: serous, mucinous, endometrioid, clear cell, and transitional cell. Clinical and pathological data including age at diagnosis (<50 years of age, 50-65 years of age, >65 years of age), race (white, black, other), and marital status (single, married, other) were collected. Year of diagnosis was classified as 1988-1994, 1995-2000, or 2000-2007.
Subjects were categorized based on the geographic area of residence within the United States at the time of diagnosis: central (Detroit, MI, Iowa, Kentucky, Louisiana, and Utah), eastern (Connecticut; New Jersey; Atlanta, GA; and rural Georgia), and western (Alaska; California; Hawaii; Los Angeles, CA; New Mexico, San Francisco, CA; San Jose, CA; and Seattle, WA). Receipt of adjuvant radiation use (yes or no) and performance of a lymphadenectomy were documented for each patient. The staging information was derived from the American Joint Cancer Committee staging information and the recorded extent of disease codes.
The vital status of each patient was recorded. Survival was calculated as the number of months from cancer diagnosis to the date of death. Patients who were alive at last follow-up were censored. Both overall and cancer-specific survivals were calculated.
Frequency distributions between categorical variables were compared using χ 2 tests. Cox proportional hazards models were developed to examine cancer-specific survival and overall survival and to account for other clinical and pathologic variables. Separate models were developed for women with stage I and stage III tumors.
Variables included in the models included histology, age, year of diagnosis, grade, race, SEER registry, marital status, performance of lymphadenectomy, and stage. Five year survival rates were calculated by stage and histology. Kaplan-Meier curves were developed to examine the stage-specific survival and compared using the log-rank test. All hypothesis tests were 2 sided. All analyses were conducted using SAS version 9.2 (SAS Institute Inc, Cary, NC).
Results
A total of 40,571 women with epithelial ovarian cancer were identified. The cohort included 25,228 with serous tumors (62.2%), 4811 with mucinous carcinomas (11.9%), 7230 with endometrioid tumors (17.8%), 3072 with clear cell carcinomas (7.6%), and 230 with transitional cell carcinomas (0.6%) ( Table 1 ). Patients with mucinous tumors were more often diagnosed in the early years of the study, were more frequently black, and were more commonly unmarried than subjects with serous tumors ( P < .05 for all). Women with mucinous tumors were younger at diagnosis, 1596 patients with mucinous neoplasms (33.2%) were younger than 50 years of age compared with 4522 with serous tumors (17.9%) ( P < .0001). Patients with mucinous tumors more commonly had low-grade tumors, 1360 of patients with mucinous neoplasms (28.3%) had grade 1 neoplasms compared with 1214 of those with serous tumors (4.8%) ( P < .0001). Mucinous tumors were often confined to the ovary at the time of diagnosis. Stage I tumors were found in 2640 of the subjects with mucinous tumors (54.9%) compared with 2774 of those with serous cancers (11.0%) ( P < .0001).
| Serous | Mucinous | Endometrioid | Clear cell | Transitional cell | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Characteristic | n | (%) | n | (%) | n | (%) | n | (%) | n | (%) | P value |
| 25,228 | (62.2) | 4811 | (11.9) | 7230 | (17.8) | 3072 | (7.6) | 230 | (0.6) | ||
| Age, y | < .0001 | ||||||||||
| <50 | 4522 | (17.9) | 1596 | (33.2) | 2391 | (33.1) | 916 | (29.8) | 59 | (25.7) | |
| 50-65 | 9964 | (39.5) | 1588 | (33.0) | 2852 | (39.5) | 1443 | (47.0) | 91 | (39.6) | |
| >65 | 10,742 | (42.6) | 1627 | (33.8) | 1987 | (27.5) | 713 | (23.2) | 80 | (34.8) | |
| Year of diagnosis | < .0001 | ||||||||||
| 1988-1994 | 4750 | (18.8) | 1379 | (28.7) | 1588 | (22.0) | 582 | (19.0) | 35 | (15.2) | |
| 1995-2000 | 6618 | (26.2) | 1342 | (27.9) | 2077 | (28.7) | 795 | (25.9) | 66 | (28.7) | |
| 2000-2007 | 13,860 | (54.9) | 2090 | (43.4) | 3565 | (49.3) | 1695 | (55.2) | 129 | (56.1) | |
| Grade | < .0001 | ||||||||||
| 1 | 1214 | (4.8) | 1360 | (28.3) | 1516 | (21.0) | 56 | (1.8) | 1 | (0.4) | |
| 2 | 4342 | (17.2) | 1279 | (26.6) | 2493 | (34.5) | 354 | (11.5) | 29 | (12.6) | |
| 3 | 14,698 | (58.3) | 739 | (15.4) | 2428 | (33.6) | 1167 | (38.0) | 157 | (68.3) | |
| Unknown | 4975 | (19.7) | 1433 | (30.0) | 793 | (11.0) | 1495 | (48.7) | 43 | (18.7) | |
| Race | < .0001 | ||||||||||
| White | 22,297 | (88.4) | 3990 | (82.9) | 6231 | (86.2) | 2509 | (81.7) | 193 | (83.9) | |
| Black | 1389 | (5.5) | 358 | (7.4) | 324 | (4.5) | 103 | (3.4) | 10 | (4.4) | |
| Other | 1500 | (6.0) | 446 | (9.3) | 657 | (9.1) | 455 | (14.8) | 27 | (11.7) | |
| Unknown | 42 | (0.2) | 17 | (0.4) | 18 | (0.3) | 5 | (0.2) | 0 | — | |
| SEER registry | < .0001 | ||||||||||
| West | 13,646 | (54.1) | 2501 | (52.0) | 3837 | (53.1) | 1759 | (57.3) | 156 | (67.8) | |
| Central | 6345 | (25.2) | 1340 | (27.9) | 1820 | (25.2) | 659 | (21.5) | 34 | (14.8) | |
| East | 5237 | (20.8) | 970 | (20.2) | 1573 | (21.8) | 654 | (21.3) | 40 | (17.4) | |
| Marital status | < .0001 | ||||||||||
| Married | 13,882 | (55.0) | 2387 | (49.6) | 3998 | (55.3) | 1684 | (54.8) | 114 | (49.6) | |
| Single | 10,695 | (42.4) | 2275 | (47.3) | 3022 | (41.8) | 1308 | (42.6) | 111 | (48.3) | |
| Unknown | 651 | (2.6) | 149 | (3.1) | 210 | (2.9) | 80 | (2.6) | 5 | (2.2) | |
| Radiation | < .0001 | ||||||||||
| Yes | 347 | (1.4) | 89 | (1.9) | 299 | (4.1) | 75 | (2.4) | 3 | (1.3) | |
| No | 24,749 | (98.1) | 4697 | (97.6) | 6875 | (95.1) | 2986 | (97.2) | 226 | (98.3) | |
| Unknown | 132 | (0.5) | 25 | (0.5) | 56 | (0.8) | 11 | (0.4) | 1 | (0.4) | |
| Lymphadenectomy | < .0001 | ||||||||||
| No | 10,484 | (41.6) | 2075 | (43.1) | 4212 | (58.3) | 1938 | (63.1) | 128 | (55.7) | |
| Yes | 14,744 | (58.4) | 2736 | (56.9) | 3018 | (41.7) | 1134 | (36.9) | 102 | (44.4) | |
| Stage | < .0001 | ||||||||||
| IA | 1318 | (5.2) | 1915 | (39.8) | 2157 | (29.8) | 1040 | (33.9) | 31 | (13.5) | |
| IB | 275 | (1.1) | 81 | (1.7) | 232 | (3.2) | 37 | (1.2) | 5 | (2.2) | |
| IC | 1075 | (4.3) | 546 | (11.4) | 1082 | (15.0) | 575 | (18.7) | 25 | (10.9) | |
| INOS | 106 | (0.4) | 98 | (2.0) | 134 | (1.9) | 55 | (1.8) | 3 | (1.3) | |
| II | 1850 | (7.3) | 323 | (6.7) | 1100 | (15.2) | 343 | (11.2) | 43 | (18.7) | |
| IIIA | 563 | (2.2) | 88 | (1.8) | 151 | (2.1) | 51 | (1.7) | 3 | (1.3) | |
| IIIB | 934 | (3.7) | 99 | (2.1) | 191 | (2.6) | 49 | (1.6) | 3 | (1.3) | |
| IIIC | 8773 | (34.8) | 471 | (9.8) | 1045 | (14.5) | 445 | (14.5) | 55 | (23.9) | |
| IIINOS | 2864 | (11.4) | 348 | (7.2) | 338 | (4.7) | 132 | (4.3) | 12 | (5.2) | |
| IV | 7470 | (29.6) | 842 | (17.5) | 800 | (11.1) | 345 | (11.2) | 43 | (18.7) | |
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