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ESMO Latest Clinical Practice Guidelines on ovarian cancer

ESMO Latest Clinical Practice Guidelines on ovarian cancer

European Society For Medical Oncology ,ESMO  Guidelines Committee has released latest Clinical Practice Guidelines on Non-epithelial ovarian cancer which has been Published in Annals of Oncology.These updated guidelines on non-epithelial ovarian cancer cover prevention, diagnosis, treatment and follow-up for early and advanced stages and recurrences of germ cell tumours, sex cord-stromal tumours and small cell carcinomas of the ovary hypercalcaemic type. The main recommendations are as follows-

Summary of recommendations

Diagnosis and pathology/molecular biology
  • Diagnostic work-up should include pelvic ultrasound, abdominopelvic CT scan and chest X-ray and PET scan in selected cases (GCTs) [III, B]
  • In young adult patients, hCG, α-FP, LDH and inhibin B levels, full blood count and liver and renal function tests should be carried out
  • In case of suspected gonadoblastomas, a preoperative karyotype should be obtained on all premenarche girls
  • Histological second opinion by an expert pathologist should always be considered. Diagnosis can be made on conventional histological material [V, B]
  • Neoplasms of pure ovarian stroma: in morphologically ambiguous cases, an immunopanel of inhibin alpha, calretinin and FOXL2, plus mutational analysis for FOXL2(402C-G), is useful to confirm AGCTs [V, B]
Staging and risk assessment
  • A surgical approach can be carried out through open route or, in selected cases, by laparoscopy and robotics approaches, thereby avoiding tumour rupture during surgery
  • A careful examination of the abdominal cavity is required
  • The staging procedure includes infracolic omentectomy, biopsy of the diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum and peritoneal washings (macroscopic stage I disease)
  • Unilateral salpingo-oophorectomy with preservation of the contralateral ovary and the uterus is considered an adequate surgical treatment for patients with GCTs. This should be considered even in advanced disease because of the sensitivity of the tumour to ChT [IV, B]. No systematic ovarian biopsy is necessary when the contralateral ovary is macroscopically normal [III, A]
  • Given the very high chemosensitivity of GCTs, potential nodal metastasis should be cured by adjuvant ChT in these patients [III, A]
  • Nodal dissection should be carried out only if evidence of nodal abnormality [III, A]
  • For SCSTs, retroperitoneal evaluation is not mandatory [III, A]
  • An endometrial curettage must be carried out to rule out concomitant uterine cancers in patients with granulosa cell tumours [IV, B]
  • Conservative surgery is also an acceptable approach in young patients with stage I SCSTs [IV, B]
  • In postmenopausal women and in patients with advanced-stage disease or with bilateral ovarian involvement, abdominal hysterectomy and bilateral salpingo-oophorectomy should be carried out with careful surgical staging for SCST [III, A]
Early-stage GCTs: management
  • Stage IA pure dysgerminoma should be treated with surgery only [III, A]
  • Patients with stage IA grade 1 immature teratoma do not require further adjuvant ChT after adequate surgical staging [III, A]
  • Adjuvant ChT in stage IA-IC G2-G3 immature teratoma, stage IA-IB YST with negative postoperative tumour markers and IB-IC dysgerminomas is recommended but active surveillance is an option [III, B]
  • 5-day BEP is the most used regimen [III, A]
  • The close surveillance schedule involves regular clinical review with clinical examination, radiological imaging including abdomen-pelvic intravaginal sonography at regular intervals and the monitoring of tumour markers to detect relapse over a period of 10 years, with a gradual increase of the interval between clinical appointments [III, C]
Advanced-stage and recurrent GCTs: management
  • Fertility-sparing surgery should be considered also in advanced stages [IV, B]. The aim of surgery is to remove as much gross tumour as possible; however, the procedure should be moderated to avoid delays in postoperative ChT and long-term morbidity
  • In postmenopausal women with advanced-stage disease or with bilateral ovarian involvement, abdominal hysterectomy and bilateral salpingo-oophorectomy could be carried out with careful surgical staging [III, A]
  • Platinum-based regimens are the treatment of choice with the BEP regimen being the most widely used, generally, three cycles of 5-day BEP regimen in completely resected disease and four cycles (bleomycin should be omitted to reduce the risk of lung toxicity after the third cycle) for patients with macroscopic residual disease [III, A]
  • In patients previously treated with platinum, with platinum-sensitive relapse (progression > 4–6 weeks after completion of ChT), combinations with platinum should be considered [IV, C]
  • Patients resistant to a cisplatin-based combination may receive VAC or paclitaxel/gemcitabine or gemcitabine/oxaliplatin as salvage therapy [IV, C]
  • HDCT for recurrent ovarian GCTs may result in durable and prolonged remissions [IV, C]
  • Any resectable residual disease should be removed, particularly for patients with normal serum marker and for patients with immature teratoma in order to avoid the growing teratoma syndrome [III, A]
Early-stage SCSTs: management
  • Stage IA granulosa cell tumour disease has an excellent prognosis after surgery alone and does not require adjuvant therapy [III, A]
  • Adjuvant therapy should be considered for juvenile granulosa tumour stage IC patients [IV, B] or for AGCT stage IC2-IC3 patients [IV, C]. In these cases, platinum-based ChT is the treatment of choice [III, A]
  • For SLCTs, postoperative adjuvant ChT should be considered for patients with stage I poorly differentiated or heterologous elements (mesenchymal type) [IV, B]
  • BEP is the most commonly used regimen [III, A]. Alternative ChT options include paclitaxel and carboplatin [III, B], EP, CAP or platinum agent alone [III, A]
Advanced-stage and recurrent SCSTs: management
  • Debulking surgery remains the most effective treatment of advanced or recurrent granulosa cell tumour [III, A]
  • Platinum-based ChT is currently used for patients with advanced-stage SCSTs or recurrent disease [III, A]
  • BEP regimen for three cycles or six cycles of carboplatin/paclitaxel is recommended for postoperative ChT and patients with recurrent SCSTs [III, A]
  • Patients with steroid cell tumours that are pleomorphic, large, at an advanced stage or with an increased mitotic count should be treated with additional postoperative platinum-based ChT, either BEP (if not previously used) or a taxane–platinum combination [IV, C]
  • Response to GnRH agonists, tamoxifen, progestin and AIs has been reported and could be an interesting option specifically for adult GCT [IV, B]
  • For patients with persistent SLCTs, adjuvant ChT should be considered [III, B]
Early and advanced SCCOHT: management
  • All suspected cases should benefit from a review by an expert pathologist and be discussed in a specialised tumour board [V, A]
  • Optimal treatment: a multimodal approach including ChT [III, B], radical surgery [IV, A], HDCT [II, C] and RT [IV, C]
  • Debulking surgery (initial or interval) remains the most effective treatment [IV, A]
  • Combination of a cisplatin- and etoposide-based therapy is the most appropriate for all stages [III, B]
  • The use of pelvic RT, either concurrently or sequentially to HDCT and ASCT, may be considered for patients after surgery [IV, C]
  • Efforts should be made to treat patients in a more homogeneous way through national and international networks [V, A]
Response evaluation and follow-up after initial treatment
  • Serum tumour markers (hCG, α-FP, LDH, CA 125 and inhibin B) can correlate with tumour response during ChT [V, A]
  • A CT scan of the abdomen, pelvis and chest (in case of suspected lung metastases) and pelvic ultrasound are the most common and useful imaging techniques to evaluate the response to ChT [V, A]
  • For GCT, follow-up visits must include history, physical examination with pelvic examination and tumour markers every 3 months for the first 2 years, then every 6 months during the third year and then yearly until progression [V, A]
  • For SCSTs, follow-up visits including physical exam and tumour markers must be carried out every 6 months starting from the third year and this frequency should be maintained indefinitely [V, B]
  • A pelvic ultrasound should be carried out every 6 months in those patients who have undergone fertility-sparing surgery, whereas a CT scan of the abdomen and pelvis is carried out according to clinical indication
  • PET scan for tumour response evaluation or follow-up is not yet recommended [V, D]
Fertility and hormone replacement
  • Oocyte cryopreservation is an option for patients scheduled to receive ChT [V, C]
  • Hyperstimulation followed by oocyte cryopreservation 12 months after the end of ChT is another option [V, C]
  • Fertility preservation should not jeopardise the oncological management
  • HRT may be used safely for many GCTs [V, A]
  • An HRT approach should be avoided for SCST [V, D]

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