Prognostic Factors of Early Stage Epithelial Ovarian Carcinoma

Abstract

We aimed to determine prognostic factors of early stage (I/II) epithelial ovarian carcinoma (EOC) including clinicopathologic and chemotherapeutic regimens. Four hundred and thirty-seven women who underwent primary staging surgery with adjuvant chemotherapy between January 1, 2000 and December 31, 2010 were retrospectively reviewed and analyzed from two medical centers. The prognostic factors were determined from multivariate survival analyses using Cox regression models. The majority of women were diagnosed with stage Ic (244/437, 55.8%). The histopathologic types were clear cell (37.5%), endometrioid (27.2%), serous (14.0%), and mucinous (13.3%). Fifty-seven percent (249/437) of the women received taxane-based (platinum plus paclitaxel) regimens and 43.0% received non-taxane (platinum plus cyclophosphamide) regimens as frontline adjuvant chemotherapy. Clear cell tumors (adjusted Hazard ratio (aHR) 0.37, 95% confidence interval (CI) 0.21⁻0.73, p = 0.001) showed better 5-year disease-free survival (DFS) than serous tumors. Women diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage II (aHR 5.97, 95% CI = 2.47⁻14.39, p < 0.001), grade 3 tumor without clear cell (aHR 2.28, 95% CI = 1.02⁻5.07, p = 0.004) and who received 3⁻5 cycles of non-taxane regimens (aHR 3.29, 95% CI = 1.47⁻7.34, p = 0.004) had worse 5-year overall survival (OS). Clear cell histology treated with taxane-based regimens showed significantly higher 5-year DFS (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21⁻0.93, p = 0.043) and 5-year OS (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13⁻0.70, p = 0.005) than those treated with non-taxane-based regimens. We conclude that stage, tumor grade, and chemotherapeutic regimens/cycles are independent prognostic factors for early stage ovarian cancer.

Keywords: disease-free survival; histologic type; ovarian cancer; overall survival; platinum; taxane.

Figure 1

Survival curves of 437 early stage epithelial ovarian carcinoma women with different histologic types or chemotherapeutic regimens by multivariate Cox regression models. (A) Estimated 5-year disease-free survival (DFS) curves. The clear cell type (88.3%) demonstrated the best 5-year DFS vs. the endometrioid (74.4%, aHR = 0.45, 95% CI = 0.21–0.98, p = 0.038), mucinous (72.3%, aHR 0.35, 95% CI = 0.16–0.79, p = 0.014), and serous (71.5%, aHR = 0.37, 95% CI = 0.21–0.73, p = 0.001) types by log-rank test. The 5-year DFS rates of patients with endometrioid, mucinous, and serous type did not differ (p = 0.177). (B) Estimated 5-year overall survival (OS) curves. The mucinous histology showed a trend towards a worse 5-year OS (81.1%) compared with the other histologic types, although it did not reach statistical significance (clear cell 89.2%, p = 0.143; endometrioid type 89.1%, p = 0.081; serous type 88.4%, p = 0.248). (C) Estimated 5-year disease-free survival (DFS) curves. There were no differences in the 5-year DFS rates between platinum and paclitaxel (PT) or platinum and cyclophosphamide (CP) regimens (79.8% vs. 78.2%, aHR = 0.92, 95% CI = 0.61–1.38, p = 0.678). (D) Estimated 5-year overall survival (OS) curves. Patients receiving the PT regimens had better 5-year OS than those receiving the CP regimens (89.3% vs. 82.7%, aHR = 0.59, 95% CI = 0.36–0.57, p = 0.038) (all by log-rank test).

Figure 2

Survival curves of 437 early stage epithelial ovarian carcinoma women stratified by chemotherapeutic regimens and histologic type with multivariate Cox regression models after adjusting for FIGO stage, tumor grade, and age at diagnosis. (A) Estimated 5-year disease-free survival (DFS) curves. A1: Serous type, A2: Endometrioid type, A3: Clear cell type, A4: Mucinous type. Patients with clear cell histology treated with platinum and paclitaxel (PT) regimens had significantly longer 5-year DFS than those treated with platinum and cyclophosphamide (CP) regimens (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21–0.93, p = 0.043, log-rank test). The 5-year DFS of the other histologic types did not differ with PT or CP regimens. (B) Estimated 5-year overall survival (OS) curves. B1: Serous type, B2: Endometrioid type, B3: Clear cell type, B4: Mucinous. The 5-year OS rate of patients with clear cell histology (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13–0.70, p = 0.005) treated with PT regimens was also higher than those treated with CP regimens. There was no difference in 5-year OS, regardless of treatment with PT or CP regimens, in patients with the serous (86.2% vs. 87.8%, p = 0.825), endometrioid (89.4% vs. 89.7%, p = 0.739), and mucinous (aHR = 0.63, 95% CI = 0.16–2.38, p = 0.520) types (all by log-rank test).

Figure 3

The survival curves of 437 early stage epithelial ovarian carcinoma women stratified by chemotherapeutic regimens and tumor grade or chemotherapeutic regimens and age at diagnosis by multivariate Cox regression models. (A) Estimated 5-year disease-free survival (DFS) curves. There was no difference in the 5-year DFS of different tumor grades between PT or CP regimens (grade 1/2 82.0% vs. 84.5%, aHR = 0.70, 95% CI = 0.18–2.63, p = 0.675; grade 3 78.4% vs. 72.3%, aHR = 0.73, 95% CI = 0.44–1.21, p = 0.224). (B) Estimated 5-year overall survival (OS) curves. The 5-year OS rate of patients with grade 3 tumors treated with PT regimens was higher than those treated with CP regimens (87.2% vs. 78.9%, aHR = 0.52, 95% CI = 0.28–0.95, p=0.034). However, the 5-year OS was not different between PT and CP regimens in grade 1/2 tumors (90.2% vs. 88.7%, p = 0.76). (C) Estimated 5-year disease-free survival (DFS) curves. There was no difference in the 5-year DFS between PT or CP regimens in the two age groups (≤50 years 82.3% vs. 74.9%, aHR 0.68, 95% CI = 0.38–1.22, p = 0.202; ≥50 years 78.2% vs. 79.5%, aHR 0.99, 95% CI = 0.55–1.78, p = 0.983). (D) Estimated 5-year overall survival (OS) curves. The 5-year OS rates of PT and CP were similar in both age groups (≤50 years, 89.8% vs. 82.9%, aHR 0.58, 95% CI = 0.29–1.18, p = 0.135; >50 years, 89.2% vs. 82.6%, aHR 0.60, 95% CI = 0.30–1.18, p = 0.141) (all by log-rank test).