Ovarian low-grade serous carcinoma: a comprehensive update.

Ovarian low-grade serous ovarian carcinoma (OvLGSCa) comprises a minority within the heterogeneous group of ovarian carcinomas. Despite biological differences with their high-grade serous counterparts, current treatment guidelines do not distinguish between these two entities. OvLGSCas are characterized by an indolent clinical course. They usually develop from serous tumors of low malignant potential, although they can also arise de novo. When compared with patients with ovarian high grade serous carcinoma (OvHGSCa) patients with OvLGSCa are younger and have better survival outcomes. Current clinical and treatment data available for OvLGSCa come from retrospective studies, suggesting that optimal cytoreductive surgery remains the cornerstone in treatment, whereas chemotherapy has a limited role. Molecular studies have revealed the preponderance of the RAS-RAF-MAPK signaling pathway in the pathogenesis of OvLGSCa, thereby representing an attractive therapeutic target for patients affected by this disease. Improved clinical trial designs and international collaboration are required to optimally address the unmet medical treatment needs of patients affected by this disease.

Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum.

OBJECTIVE: To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. METHODS: We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients' medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients' responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as "patient-regimens." Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed. RESULTS: We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients' median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a progression-free survival duration of at least 6 months. Patient-regimens involving ER+/PR+ disease produced a longer median TTP (8.9 months) than patient-regimens involving ER+/PR- disease did (6.2 months; p=0.053). This difference approached but did not reach statistical significance. CONCLUSIONS: Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.

Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant.

PURPOSE: Previous studies have suggested that low-grade serous ovarian carcinoma is more chemoresistant to first-line or neoadjuvant chemotherapy than high-grade serous carcinoma. The purpose of this study was to further characterize this chemoresistance in recurrent low-grade serous ovarian carcinoma. METHODS: From a 1990-2007 search of the departmental databases at our institution, we identified recurrent low-grade serous ovarian carcinoma patients; abstracted chemotherapy response information from the medical records of those whose disease was: 1) histologically-confirmed, 2) measurable or evaluable, and 3) treated with chemotherapy; and retrospectively reviewed these data. Response was determined based on modified RECIST. Time to progression and overall survival were also calculated. RESULTS: We identified 58 evaluable patients with recurrent low-grade serous ovarian carcinoma who received 108 separate chemotherapy regimens ("patient-regimens"), which produced 4 responses-(1 complete and 3 partial; overall response rate, 3.7%). The overall response rate for the platinum-sensitive cohort was 4.9%, and for the platinum-resistant cohort, 2.1%. Stable disease was observed in 65 (60.2%) of 108 patient-regimens. Median overall survival was 87.1 months. The median time to progression was 29.0 weeks (34.7, platinum-sensitive cohort; 26.4, platinum-resistant cohort) (P=0.32). CONCLUSIONS: Compared with high-grade ovarian cancers, recurrent low-grade serous ovarian carcinoma appears relatively chemoresistant. Whether the latter's high rate of stable disease owes more to the tumor's biology or the influence of chemotherapy remains unclear. Based on these findings, phase II trials of novel targeted agents in recurrent low-grade serous ovarian carcinoma are warranted.