Important updates to guidelines for the diagnosis, treatment, and follow-up of newly diagnosed and relapsed epithelial ovarian cancer have been issued by the European Society for Medical Oncology (ESMO).

The updated guideline, which follows the previous iteration in 2013, provides “a comprehensive review of the evidence and treatment algorithms to help clinicians choose appropriate treatments for their patients”, co-author Professor Jonathan Ledermann, of the University College London Cancer Institute told the limbic.

It is now recommended that the standard workup for suspicion of epithelial ovarian cancer should include a detailed history, clinical examination, and relevant laboratory and imaging tests, including serum cancer antigen 125 (CA-125) measurement, pelvic ultrasound by an expert examiner, and a CT scan of the thorax, abdomen, and pelvis.

The authors have recommended that pathological examination of an adequate tumour sample should be undertaken, and that a gynaecological expert should make a diagnosis according to the 2020 WHO classification, which recognises at least five distinct subtypes of malignant EOC.

Also, all patients with diagnosed ovarian cancer should be surgically staged according to the revised 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system, they said.

Test for BRCA mutations and HRD at diagnosis

Patients with high-grade ovarian cancers should be tested for germline and somatic BRCA1/2 mutations and the presence of homologous recombination deficiency (HRD), as some treatments such as poly ADP-ribose polymerase (PARP) inhibitors are ineffective in these patients, highlighting an unmet need.

“It is important to test newly diagnosed patients for a BRCA mutation and test tumours for the presence of HRD [as] there are many patients for whom PARP inhibitors are ineffective,” said Prof Ledermann. “More research is needed in this identified group (HRD negative) for better treatments,” he added.

Adjuvant chemotherapy generally recommended for FIGO stage I-IIB

After surgery and surgical staging, early-stage ovarian cancer FIGO stage I-IIB should generally be managed with adjuvant chemotherapy consisting of a minimum three cycles of paclitaxel–carboplatin, six cycles of carboplatin, or six cycles of paclitaxel–carboplatin for high-grade or IC-II cancer.

Adjuvant chemotherapy may be considered optional in some circumstances, including for low-grade serous carcinoma (LGSC) stage IB-IC, clear-cell carcinomas (CCCs) stage iA-IC1, and low-grade endometrioid carcinomas (EC) stage IB-IC, and is not recommended in patients with LGSC stage IA, low-grade EC stage IA, or expansile mucinous carcinoma (MC). Observation is recommended for FIGO stage 1A cancers.

Surgery followed by systemic chemotherapy for newly diagnosed advanced ovarian cancer

For patients with newly diagnosed advanced epithelial ovarian cancer FIGO stage III-IV, primary cytoreductive surgery (PCS) followed by systemic chemotherapy is the gold standard, and feasibility of PCS should be evaluated by a specialised team.

Systemic therapy decisions should be informed by BRCA1/2-mut (germline and/or somatic) and HRD status testing carried out at primary diagnosis, as mentioned earlier by Prof Ledermann. Paclitaxel 175 mg/m 2 –carboplatin (AUC 5–6) every three weeks for six cycles is standard first-line systemic chemotherapy for advanced ovarian cancer; for frail patients, weekly chemotherapy at lower doses is an alternative.

The anti-angiogenic agent bevacizumab improves PFS in patients with stage III-IV ovarian cancer and should be considered in addition to paclitaxel–carboplatin.

First-line maintenance treatment with PARP inhibitors

“Incorporation of PARP inhibitors into the treatment of newly diagnosed ovarian cancer is the main new therapeutic area [in these guidelines],” Prof Ledermann said.

As such, for patients with BRCA1/2-mutated or BRCA1/2-wt/HRD-positive tumours with no evidence of disease at the end of chemotherapy, maintenance treatment with PARP inhibitors is recommended: olaparib for 2 years for BRCA1/2-mutated disease, and niraparib for 3 years for BRCA1/2-wt/HRD-positive disease.

For patients with HRD-negative tumours, maintenance treatment with either bevacizumab or niraparib for three years can be recommended. For LGSC, maintenance with anti-oestrogen therapy after first-line platinum-based chemotherapy can be considered.

Assess platinum versus non-platinum based systemic therapy for recurrent disease

More than two-thirds of patients with advanced (stage III-IV) high-grade ovarian cancer relapse within three years.

Systemic therapy for recurrent disease is based on platinum-containing or non-platinum-containing regimens, with treatment choices based on consideration of several factors including histotype, BRCA1/2 mutation status, response to previous treatment, and residual chemotherapy toxicity.

Relapsed patients who previously responded to platinum-based therapy without early relapse should be treated with either a platinum-based doublet with bevacizumab, or a platinum-based doublet followed by PARP inhibitor maintenance (for patients not previously exposed to PARP inhibitors).

Bevacizumab or PARP inhibitors should be continued until disease progression or the start of the next line of treatment.

“As PARP inhibitors move more to first line therapy, better treatments for recurrent disease are needed,” Prof Ledermann noted.

Relapsed patients for whom platinum therapy is not an option should receive integrated palliative care early in the treatment pathway. Single-agent non-platinum options that can be recommended include weekly paclitaxel, pegylated liposomal docorubicin, topotecan, and gemcitabine.

The updated guidelines additionally recommend surveillance of ovarian cancer patients for five years after their most recent remission; longer follow-up can be considered for BRCA1/2-mut carriers. Surveillance can include CA-125 assessment, physical examination, and CT scans.

Read the guidelines in full in the Annals of Oncology (link here).