12. Recurrent non-epithelial ovarian cancer

Most reports on ROC almost exclusively deal with epithelial ovarian cancer. Even with the EOC, the subgroup of mucinous cancers, which are less chemosensitive than their serous counterparts, arguably should more often be treated with surgery for first recurrence than with chemotherapy. The recent Gynecologic Cancer Intergroup (GCIG) report provided little guidance [87]. Two reports describe a very poor outcome when mucinous ovarian cancers relapse and caution about surgical intervention [88, 89]. It remains unclear whether recurrent mucinous cancer should be managed as recurrent pseudomyxoma peritoneii with extensive peritoneal resection and HIPEC.

There are fewer reports on the less common OC subtypes. Granulosa cell tumours, which have limited chemosensitivity compared to EOC typically have an indolent course. Whereas primary disease is often of low stage, recurrent disease is characterised by multi-site relapse which presents different surgical challenges if complete cytoreduction is the goal [90]. Given their more indolent behaviour there may be an argument for targeting symptomatic masses rather than CSC. For germ cell tumours, most of the information is extrapolated from data on male patients. Germ cell tumours are rare in females and the immature teratoma, defined by the presence of immature cancerous tissue, most often immature neural tissue, typically is managed by chemotherapy after initial surgery. Two conditions described in the literature on germ cell tumours are the "growing teratoma syndrome" and "chemotherapeutic retroconversion" are generally considered to be the same as histologically the tissue found is mature teratoma [91]. In the former, after successful chemotherapy, there is recurrent disease but of mature not immature teratoma; in the latter, chemotherapy given to immature teratoma resulted in subsequent mature elements only. This is important to recognise as otherwise disease-progression or recurrence (of original immature disease) is diagnosed. If further immature teratoma is diagnosed after primary treatment this is associated with a less favourable prognosis and pathological confirmation of recurrence as mature or immature is necessary to appropriately manage. Typically treatment of recurrent disease is conservative surgery and further chemotherapy [92]. The specific considerations are the young age of patients and fertility preservation, chemosensitivity and the growing

teratoma syndrome. The more usual indication for surgery is to remove a symptomatic mass or a growing mass that is causing pressure symptoms (the growing teratoma syndrome). In such cases, the focus of surgery in the typical young patient, with fertility preservation necessary, is not complete cytoreduction but resection of the symptomatic mass. A less common clinical problem is of peritoneal disease with mature glial tissue—gliomatosis peritoneii, which most often has a very indolent course. Typically the initial primary surgery has been fertility preserving. With relapsed disease, which may be in the pelvis or disseminated, including involvement of the retroperitoneal lymph nodes, it is important to determine whether the relapsed disease is mature or immature teratoma, and although both pathologies may be present the more common is mature teratoma [93]. For gliomatosis peritoneii, which is of different grades, surgery should be in symptomatic patients only, the goal is palliation and not complete cytoreduction, which is most often not feasible. When secondary surgery is undertaken for recurrent disease the reproductive organs should be preserved if possible (including the uterus). The surgical goal is cytoreduction with fertility preservation, and it is reasonable to leave small volume disease on the one remaining ovary.

### 13. Conclusion

subsequent relapse will be treated with chemotherapy or other drug therapy. The paucity of cases and reports on tertiary cytoreduction emphasises the uncommon clinical scenario of a patient with second relapse of EOC undergoing surgery. In a multi-centre retrospective review of 406 patients [84], based over a 16-year period, it was reported that residual tumour after secondary and tertiary surgery was an important prognostic factor and surgical outcome was compromised by ascites and upper abdominal disease. Avras et al. [85] reported that the surgical goal, as with first recurrence, should be complete cytoreduction as this improved overall survival. The usual factors to be considered for surgery in recurrent disease with the goal of complete cytoreduction, such as disease-free interval, were reported but they also found an association with increased size of recurrent disease and reduced benefit from surgery. Another report highlighted the importance of case selection and maximixing cytoreduction

Most reports on ROC almost exclusively deal with epithelial ovarian cancer. Even with the EOC, the subgroup of mucinous cancers, which are less chemosensitive than their serous counterparts, arguably should more often be treated with surgery for first recurrence than with chemotherapy. The recent Gynecologic Cancer Intergroup (GCIG) report provided little guidance [87]. Two reports describe a very poor outcome when mucinous ovarian cancers relapse and caution about surgical intervention [88, 89]. It remains unclear whether recurrent mucinous cancer should be managed as recurrent pseudomyxoma peritoneii with extensive

There are fewer reports on the less common OC subtypes. Granulosa cell tumours, which have limited chemosensitivity compared to EOC typically have an indolent course. Whereas primary disease is often of low stage, recurrent disease is characterised by multi-site relapse which presents different surgical challenges if complete cytoreduction is the goal [90]. Given their more indolent behaviour there may be an argument for targeting symptomatic masses rather than CSC. For germ cell tumours, most of the information is extrapolated from data on male patients. Germ cell tumours are rare in females and the immature teratoma, defined by the presence of immature cancerous tissue, most often immature neural tissue, typically is managed by chemotherapy after initial surgery. Two conditions described in the literature on germ cell tumours are the "growing teratoma syndrome" and "chemotherapeutic retroconversion" are generally considered to be the same as histologically the tissue found is mature teratoma [91]. In the former, after successful chemotherapy, there is recurrent disease but of mature not immature teratoma; in the latter, chemotherapy given to immature teratoma resulted in subsequent mature elements only. This is important to recognise as otherwise disease-progression or recurrence (of original immature disease) is diagnosed. If further immature teratoma is diagnosed after primary treatment this is associated with a less favourable prognosis and pathological confirmation of recurrence as mature or immature is necessary to appropriately manage. Typically treatment of recurrent disease is conservative surgery and further chemotherapy [92]. The specific considerations are the young age of patients and fertility preservation, chemosensitivity and the growing

[86]. No QoL data were presented in these papers.

286 Ovarian Cancer - From Pathogenesis to Treatment

12. Recurrent non-epithelial ovarian cancer

peritoneal resection and HIPEC.

Most patients with OC present with late stage disease and most are destined to develop recurrence and to die of disease. Consideration needs to be given as to how recurrence is diagnosed and whether the patient is asymptomatic or symptomatic. The majority of data on ROC is from studies on EOC, but the role of secondary surgery is influenced by the histologic subtypes of OC. Patients treated with second-line chemotherapy tend to have less favourable features than those treated initially with surgery. In non-randomised studies, where there is likely selection bias, usually showed a benefit in overall survival from secondary cytoreductive surgery compared to chemotherapy alone. Consistently non-randomised studies report that the benefit of surgery in terms of DFI and survival is seen only in patients with complete surgical cytoreduction. Only one of three current randomised trials has reported preliminary data which show a benefit from surgery and data on overall survival are awaited. As complete surgical cytoreduction at primary surgery is an important factor in improved outcome from primary treatment and from secondary treatment, patients with primary OC should be managed in specialist units where complete cytoreduction is achieved in the majority of patients. There may be a benefit from ip chemotherapy or HIPEC following cytoreductive surgery for ROC but level one evidence is needed.
