Objective
The purpose of this study was to compare clinical characteristics and survival between patients with stage I epithelial ovarian cancer and fallopian tube cancer.
Study Design
We identified women with stage I epithelial ovarian cancer and fallopian tube cancer who underwent treatment from 2000-2010. Correlation between categoric variables was assessed with χ 2 test. The Kaplan-Meier survival analysis was used to generate overall survival data. Factors predictive of outcome were compared with the use of the log-rank test and Cox proportional hazards model.
Results
The study group consisted of 385 women with epithelial ovarian cancer and 43 women with fallopian tube cancer. Patients with fallopian tube cancer had a higher rate of stage IA disease (65% vs 48%; P = .02) and grade 3 tumors (60.4% vs 30.9%; P < .001). Patients with fallopian tube cancer had a significantly higher rate of breast cancer (25.6% vs 5.7%; P < .001) and BRCA 1 mutations (45.8% vs 9.1%; P < .001). There was no difference in the rates of platinum-based and paclitaxel chemotherapy between the groups. Women with fallopian tube cancer were more likely to have received ≥6 cycles of chemotherapy (58.1% vs 44.1%; P = .02). The 5-year disease-free survival rates were 100% in women with fallopian tube cancer and 93% in patients with epithelial ovarian cancer ( P = .04). The 5-year overall survival rates were 100% and 95% for fallopian tube cancer and epithelial ovarian cancer, respectively ( P = .7).
Conclusion
We found a higher rate of stage IA, grade 3, and serous carcinoma in fallopian tube cancer. Women with fallopian tube cancer had a higher rate of breast cancer. There was no difference in overall survival between the groups.
Epithelial ovarian cancer (EOC) is responsible for the largest number of deaths related to gynecologic cancer in the United States. Early-stage EOC, however, is associated with a good prognosis; the indicated 5-year survival for patients with surgically evaluated stage I disease is approximately 60-90%. Although the benefit of chemotherapy has been demonstrated in women with advanced staged EOC, this benefit has been more difficult to show in patients with early-stage disease, given the smaller number of patients and the better prognosis in this population. In general, women with well or moderately differentiated stage IA or IB ovarian cancers are treated with surgery alone; patients with stage IC, high-grade disease, or clear cell histologic condition receive adjuvant platinum-based chemotherapy.
When compared with EOC, primary fallopian tube cancer (FTC) is rare and poorly understood. FTC accounts for approximately 0.1-1.8% of all gynecologic cancers, but the difficulty of diagnosis suggests that there may be additional cases that are mistaken for ovarian malignancies. This low number of reported incidences prevents comprehensive prospective analysis of FTC. As a result, similarities between FTC and EOC have led physicians to apply data-driven therapies that have been recommended for early-stage EOC to treating FTC. There is limited evidence, however, that FTC and EOC behave identically in the clinical setting and therefore should be addressed with the use of the same treatment paradigm. The purpose of this study was to compare patient populations with early-stage FTC and EOC to identify potential differences in the presentation and behavior of these 2 malignancies. Evaluation of these differences will allow for better characterization of FTC and will indicate whether current treatments for early-stage FTC must be reassessed.
Materials and Methods
The institutional review board at the participating institutions approved the study. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I EOC and FTC who underwent surgical treatment at the 2 participating institutions between Jan. 1, 2000, and Dec. 31, 2010, were identified from the tumor registry database. All operations were performed by gynecologic oncology faculty. Patients were excluded from the study for the following reasons: histologic condition consistent with borderline cancer, surgical exploration at another institution, incomplete clinicopathologic data, or advanced-stage (FIGO stages II-IV) disease. Women who had a concurrent primary EOC and FTC were also excluded (n = 8).
Patients
Patient conditions were staged according to the FIGO (1987) criteria that used macroscopic findings and histologic analysis of specimens that were obtained during initial and restaging surgery. Histologic cell type and tumor differentiation were assessed according to the World Health Organization criteria. In each case, a dedicated gynecologic pathologist from the participating institutions confirmed the diagnosis. Once patients were selected, their clinical records were reviewed for demographics, treatment, and outcome parameters. The decision to offer adjuvant therapy (chemotherapy or radiation therapy) was based on the attending physician’s judgment. Tumor recurrence was diagnosed in 1 of 2 ways: computed tomographic findings of tumor recurrence or histopathologic confirmation.
Definitions
Complete surgical staging was defined as hysterectomy, bilateral salpingo-oophorectomy (BSO), pelvic and paraaortic lymphadenectomy, omentectomy, and peritoneal washings (multiple random peritoneal biopsies and appendectomy were optional). Some patients with grossly normal omentum underwent an omental biopsy, which was analyzed separately. Complete surgery involved a laparotomy or laparoscopy and included procedures that were completed at the time of primary surgery or at the time of surgical reassessment. High-risk histologic conditions included clear cell carcinoma and carcinosarcomas.
Statistical analysis
Continuous variables were evaluated by the Student t test or Wilcoxon-Mann-Whitney test, as appropriate. Categoric variables were evaluated by χ 2 test or Fisher exact test, as appropriate, for category size. Survival estimates were plotted with the Kaplan-Meier method. The log-rank test was used to quantify statistically these survival differences on univariate analysis. Disease-free survival (DFS) was defined as the time from the date of surgery to the date of first recurrence; overall survival (OS) was defined as the time from surgery to the date of death from EOC or FTC or the date of the last follow-up evaluation. Multivariate analyses were performed with a Cox proportional regression method to control for known prognostic factors in women with early-stage EOC. For continuous variables, the cutoff level that was chosen was their median value, unless otherwise specified. Variables known to influence recurrence or survival were included in the models. Length of survival was calculated from the date of initial surgery to the date of death; surviving patients were censored at the date of last contact. All statistical tests were 2-sided, and differences were considered statistically significant at a probability value of < .05.
Statistical analyses that included Kaplan-Meier curves were plotted with SPSS statistical software (version 16.0; SPSS Inc, Chicago, IL).
Results
Preliminary review identified 428 patients with histologically proven EOC and 54 patients with FTC who were treated from 2000-2010. Forty-three women with EOC and 11 women with FTC were excluded from the final analysis: 8 women had advanced-stage disease; 12 women were treated at outside hospitals, and follow-up data were incomplete; 6 women had a borderline tumor, and 20 women were lost to follow up. Eight women who had both a primary EOC and FTC were also excluded. The final study group consisted of 385 women with EOC and 43 women with FTC.
The demographic and histopathologic characteristics of the patients who were included in the final analysis are presented in Table 1 . The mean age at diagnosis was 58.3 ± 10 (standard deviation) years for women with FTC and 53.7 ± 13 (standard deviation) years for EOC ( P = .03). Patients with FTC had a higher rate of stage IA disease compared with EOC (65% vs 48%; P = .02). However, patients with FTC had a higher rate of grade 3 tumors (60.4% vs 30.9%; P < .001). There was a significant difference regarding histologic condition between the groups: women with FTC had a higher rate of serous carcinoma and a lower rate of endometrioid, mucinous, and clear cell carcinomas. There was no difference in the rate of concurrent endometrial cancer between women with FTC and EOC (11.6% vs 19.7%; P = .1). On the other hand, women with FTC had a significantly higher rate of breast cancer (25.6% vs 5.7%; P < .001) and more frequent BRCA1 mutations (45.8% vs 9.1%; P < .001). Twenty-four of the 43 women (55.8%) with FTC and 98 of the 385 women (25.4%) with EOC had genetic testing.
| Variable | Fallopian tube cancer (n = 43) | Epithelial ovarian cancer (n = 385) | P value |
|---|---|---|---|
| Age, y | 58.3 ± 10 | 53.7 ± 13 | .03 |
| Stage, n (%) | |||
| IA | 28 (65) | 184 (48) | .02 |
| IB | 2 (5) | 6 (1.5) | |
| IC | 13 (30) | 195 (50.5) | |
| Grade, n (%) | |||
| 1 | 4 (9.3) | 156 (47.8) | < .001 |
| 2 | 5 (11.6) | 96 (24.9) | |
| 3 | 26 (60.4) | 119 (30.9) | |
| Unknown | 8 (18.6) | 14 (3.6) | |
| Histologic condition, n (%) | |||
| Serous | 26 (60.5) | 62 (16.3) | < .001 |
| Endometrioid | 9 (20.9) | 136 (35.7) | |
| Transitional cell | 0 | 4 (1) | |
| Mucinous | 0 | 66 (17.3) | |
| Clear cell | 1 (2.3) | 52 (13.6) | |
| Carcinosarcoma | 0 | 6 (1.6) | |
| Mixed | 2 (4.7) | 45 (11.8) | |
| Other | 5 (11.6) | 10 (2.6) | |
| History of other malignancies, n (%) | |||
| Endometrial cancer | 5 (11.6) | 76 (19.7) | .1 |
| Breast cancer | 11 (25.6) | 22 (5.7) | < .001 |
| BRCA 1 mutation, n (%) a | 11/24 (45.8) | 9/98 (9.1) | < .001 |
| BRCA 2 mutation, n (%) a | 2/24 (8.3) | 6/98 (6.1) | .6 |
| Surgical procedures, n (%) | |||
| Hysterectomy | 41 (95.3) | 346 (89.8) | .7 |
| Bilateral salpingo-oophorectomy | 43 (100) | 350 (90.9) | .08 |
| Unilateral salpingo-oophorectomy | 0 | 35 (9.1) | .03 |
| Subsequent unilateral salpingo-oophorectomy | 0 | 10 (2.6) | .4 |
| Not subsequent unilateral salpingo-oophorectomy | 0 | 25 (6.4) | .4 |
| Pelvic lymph node dissection/sampling | 34 (79.1) | 299 (77.7) | .8 |
| Paraaortic lymph node dissection/sampling | 23 (53.5) | 120 (31.2) | .003 |
| Omentectomy | 32 (74.4) | 289 (75.1) | .9 |
| Omental biopsy | 5 (11.6) | 60 (15.6) | .4 |
| Restaging surgery | 18 (41.8) | 61 (15.8) | < .001 |
| Complete staging | 22 (51.2) | 114 (29.6) | .004 |
| Chemotherapy, n (%) | |||
| Platinum-based | 32 (74.4) | 261 (67.7) | .2 |
| Paclitaxel | 30 (69.7) | 245 (63.6) | .3 |
| Platinum-based and paclitaxel | 30 (69.7) | 245 (63.6) | .3 |
| Cycles of chemotherapy, n (%) | |||
| None | 11 (25.5) | 124 (32.2) | .02 |
| ≤3 | 3 (6.9) | 30 (7.8) | |
| 4 | 3 (6.9) | 49 (12.7) | |
| 5 | 1 (2.3) | 12 (3.1) | |
| 6 | 25 (58.1) | 168 (43.6) | |
| 8 | 0 | 2 (0.5) |
a Not all patients underwent BRCA status testing: complete staging: hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy, omentectomy, peritoneal washings (multiple random peritoneal biopsies and appendectomy were optional).
Table 1 shows the different treatments by disease site. There was no difference in the rate of hysterectomy between the groups (95.3% vs 89.8%; P = .7), but women with FTC less frequently underwent unilateral salpingo-oophorectomy instead of a complete BSO (0% vs 9.1%; P = .03). Of the 35 women with EOC who originally underwent unilateral salpingo-oophorectomy, 10 women (28.5%) subsequently underwent a salpingo-oophorectomy of the contralateral adnexa. There was no difference in the rate of pelvic lymph node dissection/sampling or omentectomy/omental biopsy between the groups. Women with FTC had a higher rate of paraaortic lymph node dissection (53.5% vs 31.2%; P = .003) and complete staging (51.2% vs 29.6%; P = .004), and they also underwent a restaging procedure more frequently (41.8% vs 15.8%; P < .001). There was no difference in the rates of platinum-based and paclitaxel chemotherapy between the groups, but patients with FTC were more likely to have received ≥6 cycles of chemotherapy (58.1% vs 44.1%; P = .02).
Women who underwent a complete staging were analyzed separately ( Table 2 ). Within this subset analysis, there was no difference in the mean age at diagnosis or stage between the groups. Women with FTC had a higher rate of grade 3 carcinomas (63.6% vs 33.3%; P = .002). As observed with the entire study population, there was also a difference regarding histologic condition between the groups. Women with FTC had a higher rate of serous carcinoma and a lower rate of endometrioid, mucinous, and clear cell carcinomas. There was no difference in the rate of concurrent endometrial cancer between FTC and EOC (13.6% vs 14%; P = 0.9), but women with FTC had a significantly higher rate of breast cancer (18.2% vs 6.1%; P = .05). There was no difference in the rate of chemotherapy, although women with FTC received ≥6 cycles more frequently (71.4% vs 38.6%; P = .06). Finally, patients with FTC underwent a restaging procedure after the original surgery more frequently (50% vs 21.9%; P < .001).
| Variable | Fallopian tube cancer (n = 22) | Epithelial ovarian cancer (n = 114) | P value |
|---|---|---|---|
| Age, y | 55.7 ± 8 | 52.8 ± 13 | .3 |
| Stage, n (%) | |||
| IA | 15 (68.2) | 60 (52.6) | .2 |
| IB | 1 (4.5) | 2 (1.8) | |
| IC | 6 (27.3) | 52 (45.6) | |
| Grade, n (%) | |||
| 1 | 1 (4.5) | 43 (37.7) | .002 |
| 2 | 3 (13.6) | 29 (25.4) | |
| 3 | 14 (63.6) | 38 (33.3) | |
| Unknown | 4 (18.1) | 4 (3.5) | |
| Histologic condition, n (%) | |||
| Serous | 13 (59.1) | 14 (12.4) | < .001 |
| Endometrioid | 5 (22.7) | 36 (31.9) | |
| Transitional cell | 0 | 4 (1) | |
| Mucinous | 0 | 22 (19.5) | |
| Clear cell | 1 (4.5) | 18 (15.9) | |
| Carcinosarcoma | 0 | 1 (0.9) | |
| Mixed | 2 (9.1) | 19 (16.8) | |
| Other | 1 (4.5) | 0 | |
| History of other malignancies, n (%) | |||
| Endometrial cancer | 3 (13.6) | 16 (14) | .9 |
| Breast cancer | 4 (18.2) | 7 (6.1) | .05 |
| BRCA 1 mutation, n (%) a | 5/13 (38.4) | 4/32 (12.5) | .04 |
| BRCA 2 mutation, n (%) a | 0 | 1/31 (3.2) | .5 |
| Surgical procedures, n (%) | |||
| Hysterectomy | 22 (100) | 114 (100) | .9 |
| Bilateral salpingo-oophorectomy | 22 (100) | 105 (92.1) | .3 |
| Unilateral salpingo-oophorectomy | 0 | 9 (7.9) | .3 |
| Subsequent unilateral salpingo-oophorectomy | 0 | 9 (7.9) | .3 |
| Pelvic lymph node dissection/sampling | 22 (100) | 114 (100) | .9 |
| Paraaortic lymph node dissection/sampling | 22 (100) | 114 (100) | .9 |
| Omentectomy | 21 (95.5) | 110 (96.5) | .8 |
| Omental biopsy | 1 (4.5) | 4 (3.5) | .6 |
| Restaging surgery | 11 (50) | 25 (21.9) | < .001 |
| Chemotherapy, n (%) | |||
| Platinum-based | 18 (81.8) | 74 (64.9) | .1 |
| Paclitaxel | 16 (72.7) | 71 (62.3) | .3 |
| Platinum-based and paclitaxel | 16 (72.7) | 71 (62.3) | .3 |
| Cycles of chemotherapy, n (%) | |||
| None | 4 (19) | 40 (35.1) | .06 |
| ≤3 | 0 | 9 (7.9) | |
| 4 | 1 (4.8) | 19 (16.7) | |
| 5 | 1 (4.8) | 2 (1.8) | |
| 6 | 15 (71.4) | 43 (37.7) | |
| 8 | 0 | 1 (0.9) |
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