Abstract: Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility-sparing surgery and conventional surgery. Recurrence-free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low-quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single-arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options.

Plain-language summary: Five retrospective studies (including 535 women with a diagnosis of GCT) met our inclusion criteria. Two studies, which attempted to identify factors associated with better outcomes (in terms of overall survival), suggested that no apparent evidence could be found of differences in overall survival between surgical approaches (including whether the surgery was keyhole or open) whether a patient underwent lymphadenectomy (removal of lymph nodes) or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all women combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent only surgery. In three studies, no apparent evidence to suggest that disease recurrence was associated with type of adjuvant chemotherapy or type of surgery, although surgical staging may be important. In one study, disease recurrence was not noted to be different between patients who underwent fertility-sparing surgery, where only the affected fallopian tube and ovary were removed, and those treated with conventional surgery, in which both tubes and ovaries were removed. Given the high overall survival rate, fertility-sparing surgery may be an important treatment option for young patients wishing to have children in the future. Recurrence-free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life. All studies were at very high risk of bias (low quality). All five studies were retrospective (looked at past findings) and were at very high risk of bias (low quality); therefore future studies should look at current evidence in randomised studies on adult GCT of the ovary. Three randomised studies comparing chemotherapy are ongoing. The study that may be able to answer the question regarding best choice of chemotherapy in sex cord stromal tumours is an ongoing randomised study comparing the efficacy of two drugs (carboplatin and paclitaxel) versus standard chemotherapy (BEP - bleomycin, etoposide, cisplatin). Overall, the evidence in this review is of low quality, which may seriously weaken confidence in the results. Further research is very likely to have an important impact on evidence provided in the future. The effectiveness and safety of different ways of treating patients with adult-onset granulosa cell tumour of the ovary have not yet been assessed by high-quality studies. Such trials are required to assess toxicity and quality of life associated with different treatments and to assess the safety of the types of surgery used. Generally, current evidence is not robust enough to allow recommendations for changes in clinical practice.