Female genital organs and placenta

Rare cancer of the female genital organs and placenta

Domain 2

Rare gynaecological cancers encompasses a broad group of different tumor types that can be divided conveniently into three groups:

  • Gestational trophoblastic disease (GTD),
  • Rare ovarian tumours
  • All other rare gynaecological cancers arising in the uterus, cervix, vagina and vulva.

The G2 domain of EURACAN already includes the first two groups with the third now under development. Each year, about 21,000 EU women of childbearing age will develop GTD, a spectrum of disorders spanning the pre-malignant conditions of hydatidiform moles through to the malignant disorders of invasive mole, choriocarcinoma and the very rare placental site and epithelioid trophoblastic tumors. The massively improved survival of women with GTD has been achieved through the availability of an accurate biomarker, human chorionic gonadotrophin (hCG) together with centralized care in some EU countries enabling pathological and genetic review to improve diagnostic accuracy and develop expert clinical management. Cure rates achieved in expert centers justify a centralized management policy for these tumors in reference centers across Europe and the rest of the world.

Rare epithelial ovarian cancers include mucinous, clear cell and carcinosarcoma with a collective incidence of 1.2-7.3 per 100,000; all non epithelial ovarian cancers are rare and include sex cord stromal (SCST) and germ cell tumors (GCT) affecting 0.25 per 100,000. Amongst SCST, granulosa cell tumors comprise 90% of cases, Sertoli-Leydig cell 4%, the remainder being malignant thecoma, pure Sertoli cell or Leydig cell or malignant steroid cell tumors. SCST occur mainly in adulthood (median age was 56 years, range 6-93). GCTs, can differentiate into any cell type, the commonest histologies being immature teratomas (42%), dysgerminomas (33%), yolk sac tumors (15%) and mixed GCTs (4%). Embryonal carcinoma, polyembryoma, choriocarcinoma alone or combined with other germ cell elements are more rare (22). GCTs typically occur in children and young adults, but any age can be affected. The management of rare epithelial ovarian cancers is complex and varies with age, histological subtypes and initial stage and often involves surgery with or without chemotherapy with surgical removal of residual masses. For SCST hormonal therapies either before or after chemotherapy may be added. Like GTD, fertility conservation is very important in the younger women. Whilst most women with GCTs will be cured even when the disease is advanced, the outcomes are varied for rare epithelial ovarian and SCST and poor with advanced disease.

Harmonization of medical practice, guidelines and novel trials are needed to identify new treatments to improve outcomes for these rare gynaecological malignancies. Collaborations in research are needed within EURACAN, and with national and international cooperative groups such as ESGO, ESMO and GCIG to unify divergent management protocols and overcome regulatory barriers blocking international trials (23). This has enabled successful randomized clinical trials in some of these diseases (24). For even rarer tumors where trials are not yet possible, progress can still be made by robust collection of data through international registries, focusing of patients into expert centres and subsequent audits (23). The success of this approach in GTD serves as a paradigm that EURACAN can emulate across the EU. Indeed, the G2 gynaecology domain of EURACAN in conjunction with the European Organisation for the Treatment of Trophoblastic Disease (EOTTD) has fostered new expert GTD centres, international guidelines with patient pathways, cross-border multidisciplinary meetings and pathology expert reviews which need to be implemented across countries for all EU citizens, with a concerted effort by many different individuals including the European Patient Advocacy Groups (ePAGs).

Our network of reference centers across Europe promises improved quality of diagnosis, refined disease classification, clinical trials and translational research that will optimize chances of curative treatments for our patients.

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