A total of 80 patients with UCC were identified. Their mean age at diagnosis was 67 years (range 43 to 91 years) (). Most patients were Caucasian (86.3%, n = 69). Medical comorbidities at the time of diagnosis included hypertension (57.5%), diabetes (27.5%), and coronary artery disease (17.5%). Parity was known for 67 patients (83.8%), and of these patients, 95.5% were parous. Eighteen patients (22.5%) had a history of other malignancies. Seven patients (8.8%) had previously been diagnosed with breast cancer and 5 patients (6.3%) with colon cancer. A family history of malignancy in a first-degree relative was found in 34 patients (42.5%), with colon cancer being the most common diagnosis (12.5%, n = 10). Other malignancies in family histories included breast (10%, n = 8), uterus (7.5%, n = 6), ovary, prostate, lung, stomach, and brain tumor.
Twelve of the 80 patients (15%) had used hormone-replacement therapy for any duration of time. Eleven patients (13.8%) had a history of oral contraceptive use, and 5 (6.3%) had used tamoxifen. The majority of patients (62.5%, n = 50) had a BMI that classified them as overweight or obese. Twenty-five patients (31.3%) reported that they were past or current smokers.
Forty of the 80 patients (50%) had Stage I disease, 13 (16.3%) had Stage II, 12 (15%) had Stage III, and 15 (18.8%) had Stage IV disease (). The majority of patients (72.5%, n = 58) had clear cell histology in combination with serous and/or endometrioid histology. All patients with an endometrioid component had FIGO grade 2 or 3 disease.
Nineteen patients (23.8%) had positive peritoneal washings (). Eighteen patients (22.5%) had metastases documented at the time of diagnosis. Twenty-five patients (31.3%) had a focal (<10%) clear cell component within the endometrium. Twenty-two were pure clear cell tumors, and 33 were of mixed histology (). Thirty-three patients (41.3%) had lymphovascular space invasion. Forty-five patients (56.3%) had lower uterine segment involvement, 25 patients (31.3%) had endocervical involvement, and 10 patients (12.5%) had omental involvement. Thirteen patients (16.3%) had positive lymph nodes.
Radiation was part of the adjuvant treatment for 63 patients (78.8%) (). All but one of these patients received vaginal brachytherapy (remote after loading 192
Ir source to a total dose of 21 Gy in 3 fractions or 14 Gy in 2 fractions at 0.5
cm from the vaginal mucosa). One patient was treated only with external beam radiation therapy (EBRT). Five patients received EBRT along with vaginal brachytherapy. One patient received vaginal brachytherapy and whole abdomen radiation treatment with a pelvic boost. Two patients were treated with radiation therapy only at the time of recurrence. Fifty-three patients (66.3%) received chemotherapy (). Of these, 84.9% (n
= 45) were treated with a platinum-based regimen, 35 (66%) of whom received carboplatin (AUC = 6) and paclitaxel (175
) intravenously weekly for 6 cycles. Other regimens used were adriamycin/cyclophosphamide/cisplatin (CAP), topotecan, and weekly paclitaxel. Forty-one of the 53 patients who received chemotherapy also had vaginal brachytherapy.
Median followup for PFS and OS were 38 months (range: 0 to 175) and 54 months (range: 0 to 250), respectively. For patients with Stage I disease, median followup for PFS was 65.5 months (range: 0 to 160) and for OS was 69.5 months (range: 5 to 250). In Stage II disease, median followup for PFS was 30 months (range: 0 to 142) and for OS was 44 months (range: 10 to 142), and patients with Stage III cancers had median followup for PFS of 15 months (range: 1 to 95) and for OS of 20.5 months (range: 1 to 95). Patients with Stage IV disease had a median followup for PFS of 10 months (range: 0 to 175) and median followup for OS of 27 months (range: 0 to 175 months). At the end of this study, 48 patients (60%) were alive (5 [6.3%] with disease) and 32 patients (40%) had died (). A total of 17 patients (21.3%) recurred with 4 still alive and 13 succumbing to their disease. PFS was not significantly different between patients with early-stage (Stages I&II) disease and late-stage (Stages III&IV) disease (; P = 0.377). However, OS was significant between these two groups with early-stage disease having a median OS of 135 months (95% CI: 84–250) compared to those with late-stage disease of 65 months (; P = 0.008).
Figure 1 (a) Kaplan-Meier survival curve showing Progression-Free survival in early-stage versus late-stage disease in clear cell endometrial cancer, (b) Kaplan-Meier survival curve showing overall survival in early-stage versus late-stage disease in clear cell (more ...)
A patient's histology (pure clear cell, clear cell plus serous, or clear cell plus endometrioid) did not have a significant relationship with PFS or OS. In patients with pure clear cell histology (n = 22), median PFS was 30 months (range: 0 to 134), and median OS was 43.5 months (range: 1 to 134), while patients with any serous component (n = 36) had a median PFS of 32 months (range: 0 to 175) and OS of 47 months (range: 0 to 250). Patients with mixed endometrioid and clear cell histology (n = 22) had the best survival, with a median PFS of 61.5 months (range: 0 to 160) and OS of 65.5 months (range: 5 to 237), although this did not reach statistical significance when compared with other histologic subtypes (P = 0.21). Lymphovascular space invasion also did not correlate clinically with survival.
Operative notes were available for 72 patients. Of these patients, all but 4 were debulked to no residual disease (n
= 65) or residual disease of less than 1
= 3). All of the patients with residual disease had Stage IV disease. Their progression-free and overall survivals ranged from 1 to 70 months. When considering all patients, the presence of residual disease had a significant impact on OS (P
< 0.0001) but not on PFS (P
= 0.1). The median overall survival in patients with residual disease, even if optimally debulked to less than 1
cm of disease, was 17.5 months versus 135 months in those patients with no residual disease.
There was a significant relationship between age at diagnosis and OS (P < 0.001; hazard ratio 1.07; 95% CI 1.03–1.12), independent of FIGO stage. Increased age contributed to shorter overall survival. However, there was no significant relationship between age at diagnosis and PFS (P = 0.23; 95% CI 0.98–1.09).
In univariate analysis, vaginal brachytherapy, whether alone or in combination with other radiation therapy, had an impact on OS (median survival with radiation: 140 months versus without radiation: 50 months; P = 0.02), but not on PFS (P = 0.10). This association was not noted after testing in a multiple regression model. Adjuvant chemotherapy had no significant impact on OS (P = 0.26) or PFS (P = 0.27). When patients treated with vaginal brachytherapy plus carboplatin and paclitaxel (n = 28) were compared to patients who were not treated with this regimen, no significant difference was seen in OS or PFS (P = 0.82 and P = 0.39, resp.).