Book
Epithelial ovarian cancer
- Recommendations
➡️Diagnostic and Staging Work up
▪️ The standard work-up for patients suspected of having EOC (Epithelial Ovarian Carcinoma) should include detailed history and clinical examination, LFTs, KFTs, serum CA-125, serum CEA and CA 19-9 in case of mucinous carcinoma and endoscopy if either or both are elevated, as well as transabdominal and transvaginal US (should be done by an expert examiner), as well as CT of thorax, abdomen and pelvis.
➡️Strong recommendation, low grade evidence (4,5).
▪️ Pathological examination of adequate tumor sample from diagnostic biopsy
or surgical specimen should be done. In case of the presence of pleural effusion,
cytological assessment should be done.
➡️Strong recommendation, low grade evidence (4).
▪️ The revised 2017 FIGO staging system for EOC should be used.
➡️Strong recommendation, high grade evidence (6).[hk1]
➡️Management of early EOC (FIGO STAGE I-II)
▪️Surgical staging is recommended in presumed early-stage ovarian cancer for classification and recommendation of optimal systemic therapy.
➡️Strong recommendation, moderate grade evidence (6).[hk2]
▪️ The aim of surgery for early EOC is complete resection of the tumour and to undertake adequate staging, which should be performed by midline laparotomy and should include:
- Inspection and palpation of the whole abdominal cavity
- Peritoneal washing with cytological examination
- Biopsies from all visible lesions and all abdominal fields
- Bilateral salpingo-oophorectomy
- Hysterectomy
- Omentectomy
- Appendicectomy in MC
- Systematic pelvic and para-aortic lymphadenectomy
➡️Strong recommendation, low grade evidence (7).[hk3]
▪️ Fertility-sparing surgery should be considered in young patients, but always after full discussion with the patient about potential risks.
➡️Strong recommendation, low grade evidence (8).
▪️ Patients with any stage IA histotype or stage IC1-2 with unilateral ovarian involvement and favorable histology (i.e. low-grade tumors) would be amenable to contralateral ovary and uterus preservation, in combination with the other recommended surgical staging procedures.
➡️Strong recommendation, low grade evidence (8).
▪️ Adjuvant chemotherapy in early-stage ovarian cancer is generally recommended for FIGO stage I-IIB (see exceptions below), either paclitaxel-carboplatin or carboplatin alone (six cycles).
➡️Strong recommendation, high grade evidence (9-11).
▪️ The benefit of adjuvant chemotherapy is uncertain and can be considered as optional for:
- Low grade serous carcinoma (LGSC) stage IB-IC
- Clear cell carcinoma (CCC) stage IA-IC1
- Low-grade endometrioid carcinoma (EC) stage IB-IC
- Expansile mucinous carcinoma (MC) stage IC
- Infiltrative MC stage IA
➡️Conditional recommendation, low grade evidence (12-14).
▪️ For patients receiving paclitaxel-carboplatin, a minimum of three cycles are recommended except for high grade serous carcinoma (HGSC) /high-grade endometrioid carcinoma (EC) or any stage IC-II regardless of histotype, for which six cycles should be administered
➡️Strong recommendation, high grade evidence (15,16).
▪️ Adjuvant chemotherapy is not recommended in completely staged patients with LGSC stage IA, low-grade EC stage IA or expansile MC stage IA-IB.
Conditional recommendation, moderate grade evidence [hk4] (10,12-14).
➡️Management of advanced EOC (FIGO STAGE III-IV)
▪️ Patients with advanced EOC should be evaluated for primary cytoreductive surgery (PCS) by a specialized team, with the aim of achieving complete cytoreduction (absence of all visible residual disease).
➡️Strong recommendation moderate grade evidence (7,17,18).
▪️ When complete cytoreductive surgery is feasible, PCS is recommended; otherwise, obtaining adequate biopsy tissue for histology and molecular testing is recommended.
➡️Strong recommendation, low grade evidence (19).
▪️PCS should aim to maximal surgical effort and may require intestinal resection, diaphragmatic and peritoneal stripping, splenectomy and removal of bulky para-aortic lymph nodes and, in some cases, extra-abdominal disease.
➡️Strong recommendation, low grade evidence (17,18).
▪️ We recommend against systematic lymphadenectomy in patients with macroscopic complete resection and clinically negative nodes as this may lead to unnecessarily increases the rate of post-operative complications and mortality and should not be done.
➡️Strong recommendation, low grade evidence (20).
▪️ PCS is also recommended in patients with less chemo-sensitive subtypes (e.g. MC or LGSC), even if uncertainty about achieving complete resection exists and a small residual tumour (<1 cm) is likely to remain.
➡️Strong recommendation, low grade evidence (19).
▪️ When complete cytoreductive surgery is not feasible, neoadjuvant chemotherapy (NACT) for three cycles followed by interval cytoreductive surgery (ICS) and three cycles of paclitaxel-carboplatin are recommended, + staging laparoscopy.
➡️ Strong recommendation, high grade evidence (21,22).
▪️ Consider the use of bevacizumab in the neoadjuvant setting, before interval cytoreductive surgery (ICS).
➡️Conditional recommendation, moderate grade evidence (23-27).
▪️ When ICS is not possible, and in the absence of overt disease progression, three additional cycles of paclitaxel-carboplatin alone or with bevacizumab are
recommended.
➡️Strong recommendation, high grade evidence (21,22).
▪️ Paclitaxel (175 mg/m2)-carboplatin (AUC 5-6) every 3 weeks for six cycles is the standard first-line chemotherapy in advanced ovarian cancer.
Strong recommendation, high grade evidence (28,29).
▪️ We recommend the schedule of weekly chemotherapy with paclitaxel (60 mg/m2)-carboplatin (AUC 2) as an alternative in frail patients.
Strong recommendation, high grade evidence (30).
▪️ Bevacizumab may be considered in addition to paclitaxel-carboplatin in high-risk patients, (defined as patients with stage III and macroscopic residual tumour >1 cm or stage IV).
➡️Conditional recommendation, high grade evidence (31).
▪️ Bevacizumab dose, if given, should be 7.5 mg/kg and the duration of treatment is 12 months.
➡️Strong recommendation, high grade evidence (31).
▪️ Intraperitoneal chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) are not considered a standard of care in first-line treatment.
➡️Conditional recommendation, high grade evidence (32,33).
▪️ Maintenance with anti-estrogen therapy after first-line platinum-based chemotherapy can be considered in ER positive low grade serous carcinoma (LGSC) or grade I endometrioid carcinoma.
Conditional recommendation, very low grade evidence (34).
▪️ Other recommended regimens (other than paclitaxel/carboplatin regime) such as docetaxel/carboplatin or 5FU/ calcium leucovorin/oxaliplatin or Capecitabin/Oxaliplatin specially in mucinous carcinoma may be used.
➡️Conditional recommendation, high grade evidence (35,36).
▪️ The following should be assessed when selecting treatment for patients with recurrent disease:
- Histotype
- Number of prior lines of treatment
- Exposure and response to prior treatment
- TFIp (treatment-free interval from last platinum)
- Possibility of achieving a complete secondary surgical
cytoreduction
- Residual chemotherapy toxicity
- The patient’s general condition and preferences
▪️ Patients with first relapse of ovarian cancer after >6 months of last platinum administration should be evaluated by a team experienced in surgery for ovarian cancer to identify potential candidates for surgical cytoreduction.
➡️ Strong recommendation, high grade evidence (37-40).
▪️ Patients who have previously responded to platinum without early symptomatic relapses (after >6 months) should be treated with either a platinum-based doublet (paclitaxel or gemcitabine with bevacizumab) or single agent (liposomal doxorubicin)
The selection should be based on safety and patient preference.
➡️Strong recommendation, high grade evidence (41,42).
▪️If combination therapy is contraindicated, carboplatin monotherapy should be used. Treatment is usually recommended for four to six cycles.
➡️Strong recommendation, high grade evidence (43).
▪️ Bevacizumab should be continued until disease progression (symptomatic) or the next line of treatment is started, as continuation of bevacizumab beyond progression has not been evaluated in the recurrent setting.
➡️Strong recommendation, high grade evidence (44).
▪️ Platinum rechallenge following treatment with a platinum regimen (monotherapy or combination) should be considered if the tumour is not refractory or resistant.
➡️ Strong recommendation, low grade evidence (45).
▪️ Patients with relapsed EOC for whom platinum is not an option should be defined by:
- Proven refractory (progression during platinum)
- Expected resistance (early symptomatic progression
post-platinum, response to rechallenge unlikely)[hk5]
- Platinum intolerance
- Patient choice
- QoL issues
➡️Good Practice Statement
▪️ For patients who are not candidates to receive platinum, integrating palliative care early in the treatment pathway is strongly recommended.
➡️Good Practice Statement
▪️ Single-agent non-platinum options that are recommended include weekly paclitaxel, a combination of gemcitabine and oral etoposide, navelbine, or metronomic cyclophosphamide.
➡️ Strong recommendation, high grade evidence (46-51).
▪️ Bevacizumab should be recommended in combination with weekly paclitaxel, or topotecan in patients without contraindications to bevacizumab (e.g. increased risk of intestinal fistulae, history of bowel obstruction or serosal invasion).
➡️Strong recommendation, high grade evidence (49).
▪️ Hormonal therapy ((e.g. aromatase inhibitors, tamoxifen or luteinising hormone-releasing
hormone agonists) is recommended for relapsed LGSC with ER and/or PgR expression.
➡️ Strong recommendation, high grade evidence (52).
Surveillance of ovarian cancer patients can include CA-125 determination, physical examination and CT scan evaluation, first year: every three months, second year: every six months, and annually thereafter.
➡️Good Practice Statement
➡️ Clinical Indicators
- Visits every 2–4 months for 2 years, then 3–6 months for 3 years, then annually after 5 years
- Physical exam including pelvic exam as clinically indicated
- C/A/P CT, MRI, PET/CT, or PET (skull base to mid-thigh) as clinically indicated
- CBC and chemistry profile as indicated
- CA-125 or other tumor markers if initially elevated
➡️Update of this guideline
This guideline will be updated whenever there is new evidence.
➡️ Research gaps
- Systematic inclusion of cost-benefit analyses in clinical trials with collection of health economic analysis such as incremental cost effectiveness ratio in order to facilitate clinical decision-making.
- Predictive biomarkers: response to specific systemic targeted therapies and immunotherapy.
- Improve models for pre-clinical testing of novel drugs.
- Search for tools to assess quality of life and in clinical trials.
- Dietary supplements, nutritional counselling, physical activity recommendations and psychological support as part of an integrative healthcare approach to care for people with ovarian cancer.
