Schmeler, Kathleen M. MD; Tao, Xia MD; Frumovitz, Michael MD, MPH; Deavers, Michael T. MD; Sun, Charlotte C. DrPH; Sood, Anil K. MD; Brown, Jubilee MD; Gershenson, David M. MD; Ramirez, Pedro T. MD
From the Departments of Gynecologic Oncology, Pathology, and Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Corresponding author: Kathleen M. Schmeler, MD, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, P.O. Box 301439, Houston, TX 77230-1439; e-mail: firstname.lastname@example.org.
Financial Disclosure The authors did not report any potential conflicts of interest.
OBJECTIVE: To estimate the prevalence of lymph node involvement in women with primary mucinous ovarian carcinomas.
METHODS: A retrospective study was performed of patients with primary mucinous ovarian carcinomas evaluated at a single institution between 1985 and 2007. A gynecologic oncology pathologist evaluated all cases. Patients with tumors of low malignant potential and mucinous carcinomas metastatic to the ovary from other primary sites were excluded.
RESULTS: Patients with primary mucinous ovarian carcinomas were identified (n=107). All patients underwent primary surgery. At time of surgery, 93 patients (87%) had tumors that grossly appeared to be confined to the ovary, and 14 patients (13%) had evidence of extraovarian disease. Of the 93 patients with tumors that grossly appeared to be confined to the ovary at surgical exploration, 51 (55%) underwent lymphadenectomy (n=27 pelvic and paraaortic, n=19 pelvic only, n=5 paraaortic only). Of these 51 patients, none had metastatic disease to the pelvic or paraaortic lymph nodes. In addition, there were no significant differences in progression-free survival and overall survival rates between the patients who underwent lymphadenectomy and those who did not.
CONCLUSION: There were no cases of isolated lymph node metastases among women with primary mucinous carcinoma grossly confined to the ovary, suggesting that routine lymphadenectomy may be omitted in these patients.
LEVEL OF EVIDENCE: III
Primary mucinous carcinomas of the ovary account for less than 5% of all invasive epithelial ovarian cancers.1,2 When compared with serous carcinomas of the ovary, mucinous carcinomas have a distinct presentation, clinical course, and response to therapy.2–4 The majority of mucinous ovarian carcinomas are well or moderately differentiated and are confined to the ovary at the time of diagnosis. These early-stage mucinous ovarian carcinomas have significantly higher survival rates when compared with early-stage serous ovarian carcinomas.3 However, patients with advanced stage mucinous ovarian carcinomas have been shown to have a lower response rate to platinum-based chemotherapy and a poorer prognosis when compared with serous tumors.2,4–6
Although comprehensive surgical staging is recommended for all epithelial ovarian cancers, little is known about the patterns of metastasis of primary mucinous carcinomas of the ovary. In serous carcinomas of the ovary, approximately 10% to 20% of apparent stage I tumors will have occult nodal metastasis.7,8 However, recent data suggest that in patients with mucinous tumors that appear to be confined to the ovary on surgical exploration lymph node involvement is exceedingly low.7,9 It therefore remains unclear if complete staging with systematic lymphadenectomy and its associated morbidity is beneficial in this group of patients. To further explore this issue, we estimated the prevalence of lymph node involvement in patients with primary mucinous carcinoma of the ovary. In addition, we compared recurrence rates and survival between patients undergoing lymphadenectomy and those who did not.
MATERIALS AND METHODS
After receiving approval from the University of Texas M.D. Anderson Cancer Center Institutional Review Board, we searched the institutional databases of the departments of Gynecologic Oncology and Pathology at the University of Texas M.D. Anderson Cancer Center to identify patients with primary mucinous carcinoma of the ovary diagnosed between 1985 and 2007. The medical records were reviewed for age at diagnosis, ethnicity, surgical procedure performed, type and number of chemotherapy cycles administered, and vital status information. A gynecologic oncology pathologist evaluated all cases. Patients with tumors of low malignant potential without evidence of carcinoma and patients with mucinous carcinomas metastatic to the ovary from other primary sites were excluded.
Group comparisons of patient characteristics were conducted. Continuous variables were evaluated using Mann-Whitney and independent t tests. Categorical variables were evaluated using χ2 tests. Progression-free survival and overall survival times were estimated using the method of Kaplan and Meier.10 Progression-free survival was defined as the date of diagnosis to disease progression or recurrence or to the date of death or last known contact, whichever occurred first. Overall survival was defined as the date of diagnosis to the date of the patient's death or last known contact. The log-rank test was used to compare differences between the survival curves. P<.05 was considered statistically significant. All P values were two-sided. Data were analyzed using SPSS 17.0 software (Chicago, IL).
Our database search and pathology review identified 107 eligible patients with primary mucinous carcinoma of the ovary. Patient characteristics are shown in Table 1. Median age at diagnosis was 41 years (mean 43 years, range 16–82 years). Median tumor size was 16 cm (mean 19 cm, range 6–40 cm). Preoperative CA 125 levels were available for 44 patients (median 35.4 units/mL, mean 75.1 units/mL, range 6.5–520.9 units/mL), and preoperative carcinoembryonic antigen levels were available for 18 patients (median 1.0 ng/mL, mean 24.3 ng/mL, range 1.0–178.4 ng/mL).
All 107 patients underwent primary surgery. None of the patients received neoadjuvant chemotherapy. At the time of surgery, 93 patients (87%) had tumors that grossly appeared to be confined to the ovary, and 14 patients (13%) had evidence of extraovarian disease (Fig. 1). The sites of macroscopic disease in patients with extraovarian disease included the peritoneum (n=7), omentum and peritoneum (n=3), omentum (n=2), liver (n=1), and supraclavicular lymph node (n=1). Of the 14 patients with evidence of extraovarian disease, 6 (43%) underwent lymphadenectomy (pelvic and paraaortic n=1, pelvic only n=4, paraaortic only n=1). Of these six patients with gross extraovarian disease who underwent lymphadenectomy, none had metastatic disease to the pelvic or paraaortic lymph nodes.
Of the 93 patients with tumors that grossly appeared to be confined to the ovary at surgical exploration, 51 (55%) underwent lymphadenectomy (pelvic and paraaortic n=27, pelvic only n=19, paraaortic only n=5) based on surgeon preference. Of these 51 patients, none had metastatic disease to the pelvic or paraaortic lymph nodes. However, eight patients (16%, 95% confidence interval [CI] 8–28%) had evidence of other microscopic disease (positive washings n=6, peritoneum n=1, diaphragm cytology n=1). Of the 42 patients who did not undergo lymphadenectomy, five (12%, 95% CI 5–25%) had evidence of microscopic disease (positive washings n=4, omentum n=1). Of all 93 patients with no gross extraovarian disease, 13 patients (14%, 95% CI 8–23%) had cases that were upstaged based on additional biopsies at the time of surgery; however, none of these cases were upstaged based on lymph node involvement. Appendectomy with normal findings was performed at the time of primary surgery in 46 patients (43%), and there was documentation of previous appendectomy for benign reasons in five patients (5%).
There were no significant differences in age at diagnosis, tumor size, and proportion of patients receiving chemotherapy between the group that underwent lymphadenectomy and the group that did not (Table 2). In addition, there were no significant differences in progression-free survival (P=.12) or overall survival (P=.23) between the two groups (Fig. 2). The 5-year progression-free survival in the lymphadenectomy group was 80% (95% CI 63–90%), compared with 63% in the group that did not undergo lymphadenectomy (95% CI 44–76%). Similarly, the 5-year overall survival rate was 83% (95% CI 67–91%) in the patients who underwent lymphadenectomy compared with 69% (95% CI 50–2%) in the patients who did not, and the 10-year overall survival rate was 75% (95% CI 52–88%) in the lymphadenectomy group and 69% (95% CI 50–82%) in the nonlymphadenectomy group.
Of the 93 patients with tumors that grossly appeared to be confined to the ovary at surgical exploration, 18 patients (19%) eventually had recurrent disease develop, including 7 of the 51 patients (14%) who underwent lymphadenectomy and 11 of the 42 patients (26%) who did not undergo lymphadenectomy (P=.13). Recurrent disease included metastasis to lymph nodes in two patients. The first patient initially underwent hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, omentectomy, and pelvic and paraaortic lymphadenectomy. The final pathology showed positive pelvic washings but no other evidence of extraovarian disease. She was subsequently treated with six cycles of paclitaxel and carboplatin. Six months after the completion of therapy, the patient was noted to have metastatic disease to the pelvic and paraaortic lymph nodes, as well as several peritoneal implants and lung nodules. The second patient initially underwent a hysterectomy, bilateral salpingo-oophorectomy, and omental and peritoneal biopsies. No lymphadenectomy was performed. The final pathology showed no evidence of extraovarian disease. The patient was subsequently treated with six cycles of paclitaxel and carboplatin. Five months after completing chemotherapy, recurrent disease consisting of lung nodules and mediastinal and paraaortic lymphadenopathy developed.
The key finding from our study is that isolated lymph node metastasis in mucinous carcinoma of the ovary is exceedingly rare. In our cohort, 51 patients with mucinous carcinoma that grossly appeared to be confined to the ovary at surgical exploration underwent lymphadenectomy. None of these patients were found to have lymph node metastases. In addition, there were no significant differences in recurrence rates, progression-free survival, or overall survival between the women who underwent lymphadenectomy and those who did not.
Our findings are similar to previous studies. Morice et al7 evaluated lymphatic spread in 276 women with epithelial ovarian carcinoma who underwent systematic pelvic and paraaortic lymphadenectomy. Of the 30 patients with mucinous carcinomas, 4 (11%) had positive lymph nodes. However, of the 20 patients with mucinous tumors apparently confined to the ovary at surgical exploration, none was found to have nodal involvement.7
A recent study by Cho et al9 reviewed the records of 264 patients with apparent early-stage ovarian mucinous tumors. Of these, 85 patients had invasive ovarian cancer, with 26 (31%) undergoing complete surgical staging and 59 (69%) undergoing incomplete surgical staging. Histopathologic results of extraovarian disease led to upstaging in five patients (6%) because of positive peritoneal cytology. However, there were no cases upstaged because of occult lymph node or omental metastasis. Similar to our findings, no significant differences in recurrence rates, tumor-related death, progression-free survival, or overall survival relative to the completeness of staging were noted. They concluded that complete surgical staging in patients with apparent stage I mucinous epithelial ovarian tumors would identify few patients requiring adjuvant therapy and could probably be omitted.9
In summary, we found that none of the patients in our study with apparent early-stage mucinous ovarian cancer had lymph node metastasis. This is consistent with previous reports that also found no cases of isolated lymph node metastasis in primary mucinous ovarian cancer. Our study is limited by retrospective data collection, a long study period, small sample size, and possible referral bias. In addition, there were varying surgical and chemotherapy treatment types used based on clinician preference. It also remains unclear if the lack of significant differences in recurrence rates and survival between patients undergoing lymphadenectomy compared with those who did not is attributable to our small sample size. Despite these limitations, our results suggest that routine lymphadenectomy may be omitted in women with clinically apparent early-stage primary mucinous carcinoma of the ovary. In addition, our findings provide hypothesis-generating information to help in the design of future studies for this group of patients. Given the distinct clinical and pathologic characteristics of mucinous carcinomas, these tumors should be considered separately from other epithelial ovarian cancers. Prospective, multiinstitutional clinical trials, focused specifically on mucinous ovarian carcinoma, are needed to make meaningful advances in the treatment of this disease.
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© 2010 by The American College of Obstetricians and Gynecologists.