Outcome and patterns of failure in pathologic stages I-IV clear-cell carcinoma of the endometrium: implications for adjuvant radiation therapy.

PURPOSE: To evaluate the outcome and patterns of failure in women with uterine clear-cell carcinoma and discuss implications for adjuvant radiation therapy (RT).
METHODS: Between 1980 and 2000, 686 endometrial carcinoma patients underwent primary surgery at our institution. Thirty-eight women (5.5%) had clear-cell tumors (18 clear-cell only, 8 clear-cell + adenocarcinoma, and 12 clear-cell + other unfavorable histologies [10 papillary serous, 1 uterine sarcoma, 1 both]). All underwent surgery and assessment of peritoneal cytology. None received preoperative RT. Pelvic and para-aortic node samplings were performed in 26 and 17 patients, respectively. FIGO stages were as follows: 3 IA, 4 IB, 5 IC, 4 IIA, 6 IIB, 8 IIIA, 2 IIIB, 3 IIIC, and 6 IV. Adjuvant therapies included the following: 5 none, 22 RT (13 pelvic RT, 2 vaginal brachytherapy, 7 both), 11 chemotherapy (8 alone, 3 after pelvic RT), and 3 hormones. No patient received whole-abdominal RT or para-aortic RT. Median follow-up was 36.5 months.
RESULTS: The 5-year actuarial disease-free survival of the entire group was 38.5%. No correlation was seen between relapse and stage, myometrial invasion, cytology, cervical extension, or involvement of extrauterine sites. Patients with clear +/- adenocarcinoma histology had a similar 5-year disease-free survival (38.8% vs. 38.7%, p = 0.95) compared with those with clear-cell + other unfavorable histologies. Sixteen patients relapsed (42%). Eight failed in the pelvis (5 vagina, 3 lateral pelvis). There were no pelvic failures in the group of 22 patients who received adjuvant RT, whereas in the group of 16 women who did not, 8 (50%) relapsed in the pelvis (p < 0.0001). Corresponding pelvic failure rates in the Stage IA-IIB patients with and without RT were 0/16 (0%) and 5/6 (83%) (p < 0.0001). Six patients (16%) failed in the para-aortic nodes and 2 (5%) in the abdomen. Only 1 (2%) patient developed an isolated abdominal failure (This patient had a mixed clear-cell/papillary serous tumor). Of the 26 women with clear-cell +/- adenocarcinoma histology, only 1 (3.8%) relapsed in the abdomen. Nine patients (24%) relapsed in distant sites, primarily the lungs and bone.
CONCLUSION: Clear-cell carcinoma comprises a small percentage of endometrial cancers, frequently presents as a mixed histology, and has a poor overall outcome. Unlike papillary serous tumors, clear-cell carcinoma does not seem to have a high propensity for abdominal failure. Our results thus do not support the routine use of whole-abdominal RT in these patients. Future protocols should focus instead on combinations of locoregional RT and chemotherapy to reduce the risk of local and systemic recurrence.