Purpose To review contemporary management of malignant ovarian germ cell tumors (MOGCT). Design The literature on the topic of MOGCT is reviewed, including pathology, prognostic factors, surgical strategies, postoperative therapy, late effects of therapy, and treatment of recurrence. Results Prognostic factors for MOGCT include the International Federation of Gynecology and Obstetrics staging system's stage, residual disease, histologic type, and elevation of serum tumor markers. Fertility-sparing surgery is possible in a large proportion of patients. The importance of comprehensive surgical staging is somewhat controversial. For patients with advanced-stage disease, maximum cytoreductive surgery appears to be beneficial. Although second-look surgery is not recommended routinely, selected patients may benefit from secondary cytoreduction. For those patients who require postoperative chemotherapy, standard therapy consists of the combination of bleomycin, etoposide, and cisplatin. However, there is a growing trend toward surveillance; this strategy continues to be studied. Although premature menopause may occur in a small proportion of patients, at least 80% of those who undergo fertility-sparing surgery and chemotherapy may expect to preserve reproductive function. For patients with early-stage disease, cure rates approach 100%. For those with advanced-stage disease, cure rates are reportedly at least 75%. Conclusion MOGCT is a rare malignancy that principally affects girls and young women. With optimal therapy, the prognosis is excellent, and most patients may retain reproductive function.

Purpose: The purpose of this study was to examine outcomes associated with hormonal maintenance therapy (HMT) compared with routine observation (OBS) after primary cytoreductive surgery and platinum-based chemotherapy in women with stage II to IV low-grade serous carcinoma of the ovary or peritoneum. Patients and Methods: Eligibility criteria for patients from our database were: treatment with primary surgery followed by platinum-based chemotherapy, stage II to IV disease, at least 2 years of follow-up for patients who had not experienced recurrence, and adequate clinical information. The two groups were compared for progression-free survival (PFS) and overall survival, and a multivariable Cox regression analysis was performed. Subset analyses for patients who were disease free or had persistent disease were also performed. Results: Between 1981 and 2013, 203 eligible patients—133 who underwent OBS and 70 who received HMT—were seen at our institution. Median PFS for patients who underwent OBS was 26.4 months, compared with 64.9 months for those who received HMT ( P < .001). No statistically significant difference in overall survival was observed between the two groups (102.7 v 115.7 months, respectively). For subgroups of women who were disease free or had persistent disease, median PFS was superior for those who received HMT (81.1 v 30.0 months; P < .001 and 38.1 v 15.2 months; P < .001, respectively). Women who received HMT had a significantly lower risk of disease progression compared with those who underwent OBS (hazard ratio, 0.44; 95% CI, 0.31 to 0.64; P < .001). Conclusion: Women with stage II to IV low-grade serous carcinoma who received HMT after primary treatment had significantly longer PFS compared with women who underwent OBS. These findings warrant further investigation using a prospective trial design.

OBJECTIVE: To analyze the clinical behavior of patients with stage II-IV low-grade serous carcinoma of the ovary seen at our institution who underwent primary surgery followed by platinum-based chemotherapy. METHODS: Patients with stage II-IV low-grade serous carcinoma of the ovary from 1978 to 2003 were identified using existing databases. Clinicopathologic information was obtained from medical records. Progression-free survival and overall survival were estimated by the method of Kaplan and Meier. The log-rank test was used to compare differences between survival curves. Univariable and multivariable analyses were performed using Cox proportional hazards regression. RESULTS: We identified 112 eligible patients. Median age was 43 years.; 90% had stage III disease. Preoperative serum CA 125 was elevated in 86% of patients. The most common sites of extraovarian disease were omentum, fallopian tubes, pelvic peritoneum, and uterus. Response rate to platinum-based chemotherapy in 10 evaluable patients (15% of patients with gross residual disease) was 80%, and 42 patients underwent second-look surgery: microscopically negative findings, 2 (5%); microscopically positive disease, 13 (33%); macroscopically positive disease, 24 (62%); and insufficient information, 3 (7%). Median progression-free survival and overall survival times were 19.5 and 81.8 months. Persistent disease after primary chemotherapy was the only factor associated with shorter overall survival time (hazard ratio 3.46, 95% confidence interval 2.00–5.97, P<.001). CONCLUSION: Metastatic low-grade serous carcinoma of the ovary is characterized by young age at diagnosis and prolonged overall survival. Segregating women with this diagnosis in future clinical trials is warranted. LEVEL OF EVIDENCE: II-3

Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m² by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40–50 mg/m² by body surface area once every 4 weeks; intravenous topotecan 4 mg/m² by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9–15·0) compared with 7·2 months (5·6–9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36–0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis.