• 1.
  

  a) F b) F c) T d) T e) T

The addition of a third agent to platinum-taxane combination therapy has not been shown to improve outcomes in the first line treatment of advanced EOC. A randomized phase III trial comparing carboplatin and paclitaxel with or without gemcitabine in this setting found that the addition of gemcitabine did not improve overall survival, and was associated with poorer PFS, excess treatment toxicity and poorer quality of life. Intraperitoneal chemotherapy has been found to improve survival outcomes compared to conventional chemotherapy, but at a cost of increased toxicity including neurotoxicity, abdominal discomfort and catheter related complications. This has been demonstrated in a meta-analysis of 60 trials in over 15500 women. The use of neo-adjuvant therapy is supported by the EORTC 55971 and CHORUS studies, which both found no difference in PFS or OS in the 2 arms but less morbidity associated with NACT. Although the benefits of platinum and taxane-based chemotherapy are well-established, the JGOG 3016, GOG 262 and MITO 7 studies have attempted to explore alternative schedules without consistent findings of superiority of one regimen over another. This remains an area under investigation, for example, the ICON 8 study.

• 2.
  

  a) T b) F c) T d) F e) F

Patients with early stage, high grade serous tumours benefited from 6 cycles of chemotherapy as opposed to a shorter duration of treatment. Clear cell carcinomas have poor response rates to platinum-taxane chemotherapy, but to date no alternative standard of care has been established. The combination of irinotecan and cisplatin was not superior to standard therapy in a randomised phase III trial. Mucinous tumours have histopathological similarities to gastrointestinal tumours, and a randomised phase II trial designed to compare a conventional ovarian cancer regimen of carboplatin and paclitaxel to a colorectal-style regimen of capecitabine and oxaliplatin as first line therapy was closed early due to poor recruitment. Notably, after central pathology review, the majority of cases enrolled were not found to be primary ovarian cancers, rather metastatic mucinous cancers from other sites. This underscores the need for a thorough work-up of apparent ‘ovarian’ mucinous tumours to exclude a gastrointestinal primary. Low grade serous cancers are a biologically distinct entity with negligible response rates to chemotherapy.

• 3.
  

  a) T b) F c) T d) T e) F

In the GCIG Symptom Benefit Study, 20% stopped treatment after 2 or fewer cycles largely due to rapid progression and early death. Baseline QOL was an independent predictor of stopping treatment within 8 weeks. Oral etoposide was associated with significant myelosuppression, including 3 deaths from treatment toxicity (2 from neutropenic sepsis; 1 bleeding). Each of the three named agents has been used, with response rates in the order of 10–20%. Response rates are typically poor and in the order of 10–15%. Median PFS is typically in the order of 3–4 months, with median OS one year or less

• 4.
  

  a) F b) F c) T d) F e) T

Persistent neurotoxicity limits the repeated use of taxanes for many women with platinum sensitive relapsed disease. Carboplatin and PLD is a preferable alternative, and was found to have superior PFS and equivalent OS to carboplatin and paclitaxel with significantly less neurotoxicity in the CALYPSO study. The MRC-05 study has established that there was no survival advantage associated with early initiation of chemotherapy in asymptomatic patients with recurrent disease based on GCIG CA125 progression alone. Early initiation of chemotherapy was also shown to have a negative impact on quality of life. Repeated courses of carboplatin are associated with a significant risk of hypersensitivity reaction, reported at up to 27% with 7 or more cycles of platinum-based therapy. This classically occurs with the second dose of the second course of platinum, but may occur at any time. After a carboplatin reaction, desensitisation may be attempted. Alternatively, some women will not demonstrate cross-reactivity with cisplatin and cautious rotation to this agent with appropriate monitoring may be a suitable option. Compared to carboplatin and paclitaxel, carboplatin and PLD demonstrated an improvement in median PFS (11.3 vs 9.4 months) and equivalent OS. The PLD regimen was associated with less neuropathy (5 vs 27%) and was administered every 4 weeks.

• 5.
  

  a) T b) F c) F d) T e) T

Multiple publications have indicated that fertility-sparing surgery may be prognostic. Patients who undergo fertility-sparing surgery have a 15–20% risk of developing a subsequent borderline tumour in the ipsilateral or contralateral ovary. Multiple reports have indicated that lymph node involvement with borderline tumour, which is equivalent to non-invasive peritoneal implants associated with serous borderline tumour, is not prognostic. Smoking has not been shown to affect prognosis of women with borderline ovarian tumours. Peritoneal implants influence prognosis. For women with a serous borderline tumour and non-invasive peritoneal implants, the lifetime risk of developing a low-grade serous carcinoma is approximately 20–50%. For women with invasive implants, the lifetime risk is greater than 50%. Multiple reports have indicated that the level of preoperative serum CA 125 is an indicator of outcome.

• 6.
  

  a) F b) F c) F d) T e) T

Approximately 90% of mucinous borderline tumours are stage I, not 60%. Based on the findings of multiple studies, routine lymphadenectomy is not recommended for either serous or mucinous borderline tumours. The main caveat is being aware that frozen section diagnosis is not very accurate for mucinous tumours, and the final diagnosis for either subtype may reveal invasive cancer in at least 10% of cases. The literature indicates that, following an ovarian cystectomy for borderline tumour, the relapse risk in the ipsilateral or contralateral ovary is approximately 15–20%. In considering surgical approach—open or minimally invasive—factors to be considered include size of the adnexal mass, body habitus, and number and type of previous operations. Frozen section examination is more accurate for serous compared to mucinous ovarian tumours according to multiple reports.

• 7.
  

  a) F b) T c) T d) F e) F

Sequencing technology is much better than 10 years ago and we have also identified several other genes that predispose individuals to breast and ovarian cancer.

• 8.
  

  a) T b) T c) T d) F e) F

Founder mutations are specific to an ethnic group and are the result of selection due to a population bottleneck and ongoing geographical or cultural isolation. The predominant example of founder mutations in hereditary cancer is the three BRCA1/2 founder mutations which are found in over 2% of the Jewish population. However most ethnic groups have specific associated founder mutations.

• 9.
  

  a) F b) T c) F d) F e) F

Almost all ovarian cancer associated with BRCA1 is high grade serous cancer. Clear cell and endometrial cancers do occur with BRCA mutations occasionally, but mucinous ovarian cancers and borderline tumours are not a feature of BRCA mutations.

• 10.
  

  a) F b) T c) F d) F e) F

BRCA1 mutation carriers are typically younger, having a median age of onset in the 40s rather than 50s. Furthermore, about out 40% of BRCA1 patients will develop ovarian cancer versus 18% for BRCA2 mutation carriers. Almost all of the cancers are serous in histology for both types of mutation carriers. Both mutations are transmitted in an autosomal dominant fashion.

• 11.
  

  a) F b) T c) F d) F e) F

Approximately 70% of SBTs are confined to one or both ovaries (stage I) at the time of diagnosis; the remaining tumours have spread within the pelvis (stage II) or upper abdomen (stage III). One-third of stage I tumours are bilateral. Benign non-invasive peritoneal implants are more frequently associated with exophytic than intracystic SBTs. In almost half of SBTs the papillary growth covers the outer surface of the ovary (exophytic growth). Most peritoneal implants are non-invasive and benign and require no adjuvant treatment as they regress spontaneously. Invasive peritoneal implants are rare (10% of peritoneal implants) and represent superficial and small foci of low-grade serous carcinoma; i.e., progression from SBT to low-grade serous carcinoma. For patients with stage I SBT, the risk of recurrence or the development of a second SBT in the contralateral ovary has been estimated to be 5–10%. Risk factors for recurrence include conservative treatment, particularly cystectomy with positive resection margins, resection of multiple cysts, bilaterality (stage IB), and incomplete staging. Transformation of SBT to low-grade serous carcinoma (LGSC) occurs in 6–7% of patients late in the course of the disease. MBTs of intestinal-type may exhibit areas of epithelial cell proliferation of four or more layers, scattered foci of cribriform or stroma-free papillary architecture, and moderate (grade 2) or severe atypical (grade 3) nuclei. Numerous studies have shown that these tumours, designated as MBT with “intraepithelial carcinoma” are almost always clinically benign.

• 12.
  

  a) F b) F c) F d) T e) F

Women with germline mutations in BRCA1 or BRCA2 have a 30% to 70% risk of developing ovarian cancer by the age of 70. Carcinomas arising in patients with germline BRCA1 or BRCA2 mutations are almost invariably of high-grade serous type. Like TP53 mutations, BRCA inactivation seems to be a consistent genetic alteration of HGSC. Besides germline mutation, inactivation of the BRCA pathway may result from somatic mutation in either BRCA1 or BRCA2 , or promoter hypermethylation in BRCA1. p53 signatures are found in both, women with and without BRCA1 or BRCA2 mutations at the same frequency (10–38% versus 17–33%, respectively). TP53 mutation is an early event in the genesis of HGSC, occurring in p53 signature foci and leading to serous tubal intraepithelial carcinoma (STIC) in the distal fallopian tube. BRCA1 mutation also occurs early in the development of STIC but after TP53 mutation. Approximately 5% to 10% of BRCA -positive asymptomatic women have early HGSC, and 80% of them are associated with STIC. As a result, speculation that ‘‘all’’ HGSCs originated in the fallopian tube followed. However, the pathogenesis of HGSC appears to be more complex as indicated by the following: a) only 40% of advanced HGSCs show STIC; b) only 8% of HGSCs with SET (solid, pseudoendometrioid, transitional) morphology show STIC; and c) high-grade serous carcinomas with SET morphology tend to be BRCA -positive, the patients are younger, and their outcome is better. Thus, it seems that HGSC ( BRCA positive and BRCA negative) is not a homogeneous disease. Several variables, including age, histotype, STIC +/−, and patient outcome, allow segregation of two tumour groups: (a) younger BRCA -positive patients, without STIC and with favorable outcome; and (b) older BRCA -negative patients, with STIC, and with unfavorable prognosis. Therefore, recent studies suggest that HGSCs may have at least two different origins; i.e., ovarian surface epithelium (from stem cells) and tubal epithelium through STIC. The cells of HGSC are of intermediate size with scattered bizarre mononuclear giant cells. In contrast to LGSCs, these tumours show more than 3-fold variation in nuclear size. In cases with equivocal degrees of nuclear pleomorphism, mitotic activity greater than 12/10 high-power microscopic fields (HPF) favours a diagnosis of HGSC. Most patients with HGSC present with advanced stage disease (approximately 80%); tumours confined to the ovary at diagnosis are distinctly uncommon (<10%).

• 13.
  

  a) F b) T c) F d) T e) F

Smoking has consistently been associated with a decrease in risk of clear cell ovarian cancer. The reason for this is not clear but may relate to the fact that women who smoke may have lower oestrogen levels compared to those who do not smoke. Endometriosis has been consistently associated with an increase in risk of clear cell and endometrioid ovarian cancers and may be a pre-cursor lesion for these cancers. While use of menopausal hormone therapy increases the risk of serious and endometrioid cancers, two large pooled analyses have shown that MHT use is associated with a decrease in risk of clear cell cancers. Obesity appears to increase the risk of all the major ovarian cancer histotypes except for high-grade serous cancers (the most common histotype). Tubal ligation reduces the risk of ovarian cancer overall with the strongest inverse associations seen for clear cell cancers. This may relate to the reduction in retrograde menstruation and endometriosis.

• 14.
  

  a) T b) F c) F d) F e) F

Endometrioid tumours of the ovary closely mimic their uterine counterparts and are thought to arise from ovarian endometriosis. They are associated with ipsilateral ovarian or pelvic endometriosis in up to 42% of cases. Atypical endometriosis is now recognized to be the precursor lesion of endometrioid and clear cell carcinomas of the ovary and a direct transition from ovarian atypical endometriosis to endometrioid or clear cell carcinomas has been described in 15–32% of cases. Simultaneous endometrioid carcinomas of the uterine corpus and ovary, occur in 15–20% of ovarian tumours and in approximately 5% of uterine tumours. Usually, these tumours are associated with favorable prognosis and an independent origin has been proposed. Recently, however, whole-exome massively parallel sequencing done in 5 patients with synchronous endometrioid endometrial and ovarian carcinomas revealed that the tumours of each case displayed strikingly similar profiles of somatic mutations and gene copy number alterations. Although these results favour that the tumours are clonally related, and likely constitute dissemination from one site to the other, the “independent” origin of the ovarian EC arising from endometrial stem cells that have reached the ovary through menstrual reflux cannot be excluded. Most ovarian endometrioid carcinomas (EC) are low-grade adenocarcinomas that usually lack the TP53 mutations, BRCA abnormalities and chromosomal instability which are common in HGSC. However, high-grade ovarian EC is morphologically indistinguishable from HGSC and often expresses WT1. Gene expression profiling is also similar, suggesting that high-grade EC is not a distinct tumour type. CCC is typically found at early stage (stage 1 or 2 disease). Tumours are rarely bilateral. CCCs are associated with an unfavorable prognosis when they present at advanced stage. Both ovarian CCCs (46–57%) and ECs of the ovary (30%) carry ARID1A mutations and lack BAF250 protein. ARID1A mutations and loss of BAF250a expression have been found in the tumour and adjacent endometriosis, which suggests that ARID1A inactivation occurs early during the malignant transformation of endometriosis.

• 15.
  

  a) T b) T c) F d) F e) T

The main purpose of every staging is to establish the extent of tumour spread because that establishes the stage of disease. It has been known for a long time that apparent early stage disease can harbour subclinical or microscopic tumour seeding in the upper abdomen or retroperitoneal area. Staging can detect these lesions, thereby upstaging the disease. Without proper staging one can never be sure that early ovarian carcinoma is really ‘early’. Therefore, the definition of ovarian cancer as early ovarian carcinoma cannot be given without complete surgical staging. The average upstaging figure of proper staging is 31% with a range from 16% in grade I tumours to 42% in grade III tumours. There is convincing evidence from randomized and retrospective trials that proper surgical staging in early ovarian carcinoma is an independent prognostic factor for improved overall survival as well as disease-free survival.

• 16.
  

  a) T b) F c) F d) T e) T

Early ovarian carcinoma has a relatively good prognosis and long term survival is no exception. It has been demonstrated that 15–20 years following platinum based chemotherapy the risk of second primary tumours is significantly increased compared to the population’s standard risk during that period. That is particularly true for the incidence of leukaemia. After a complete and optimal surgical staging the presence of remaining disease after surgical treatment is minimized. Adjuvant chemotherapy in these circumstances has no substrate to work on. This has been shown in many studies. Combination chemotherapy has been shown to give a risk reduction in advanced ovarian cancer of maximally 25%. Early ovarian carcinoma is cured by surgery in about 80–90% of patients. A risk reduction of 25% in the remaining 10–20% adds up to 2–5 patients. There is at least circumstantial evidence that the effect of chemotherapy in patients with a recurrence of early ovarian carcinoma is better in chemo-naïve patients. This is an argument for postponing chemotherapy to the time of recurrence and not giving it in an adjuvant setting.

• 17.
  

  a) F b) T c) F d) T e) T

It is safe to leave the uterus and contralateral adnexum in situ in cases of a young early ovarian carcinoma patient with a wish to preserve her fertility. However, surgical staging should always be performed to rule out stage III disease. Stage I grade I, mucinous ovarian cancer has a very low risk of lymph node metastases. Therefore, it is reasonable to omit lymph node dissection during the staging procedure in these cases. There is no general agreement on the necessary extent of lymph node dissection at surgical staging of early ovarian carcinoma. However, the removal of at least 10 nodes from predefined retroperitoneal high-risk sites is regarded as a minimum staging requirement in most guidelines. These risk sites are: para-aortic and para-caval at the level between the inferior mesenteric artery and the left renal vein, common iliac, external iliac, internal iliac and obturator.

• 18.
  

  a) F b) T c) F d) T e) F

Data demonstrating that patients who started with large metastatic disease do not do as well as those who started with small metastatic disease, even when both groups were optimally cytoreduced, was first reported in 1983, and has been confirmed in all studies subsequently. This demonstrates the independent prognostic significance of tumour biology. Patients with mucinous carcinomas have been consistently shown to have a worse prognosis than patients with non-mucinous tumours. Although patients with no macroscopic residual disease have the best prognosis, patients with residual nodules up to 10mm have been shown to have a survival advantage of about 10 months, when compared to patients with larger residual tumour nodules. A report from the Mayo Clinic indicated that the only independent variables associated with optimal cytoreduction were the American Society of Anesthesiology (ASA) score, the presence of carcinomatosis, and the aggressiveness of the surgeon. Factors which were not significant included the age of the patient, the CA125 titre, the presence of ascites, and the presence of diaphragmatic or mesenteric involvement. There has been only one randomised trial investigating the role of systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancer, and it showed no benefit in overall survival, compared to patients having resection of bulky nodes only.

• 19.
  

  a) F b) T c) F d) F e) T

A recent German study reported 326 consecutive patients with stage IV ovarian cancer treated from 2000 to 2014. FIGO stage IV disease was due to a pleural effusion / pulmonary metastasis in 134 cases (41.1%), metastases to the abdominal wall in 133 (40.8%), extra-regional lymph nodes in 63 ((19.3%), liver in 45 (13.8%) and spleen in 22 (6.7%). Primary cytoreductive surgery was performed in 286 patients (87.7%). Median survivals for patients with no residual disease, 1–10 mm and >10 mm were 50, 25 and 16 months respectively (p = 0.001). A recent study from the Mayo Clinic reviewed 109 patients with stage IV ovarian cancer, of whom 58 had positive pleural cytology only. In the latter group, patients having optimal intra-abdominal cytoreduction (≤ 1 cm) had a median survival of 3.1 years, compared to 1.3 years for patients having suboptimal cytoreduction. Splenic metastases may also be due to direct infiltration from a large omental cake, but in either case, splenectomy is indicated as part of cytoreductive surgery. Parenchymal liver metastases have traditionally been considered an indication for neoadjuvant chemotherapy, and thorough investigation to exclude a non-ovarian primary tumour. Lim et al reported 16 patients who had parenchymal liver metastases at the time of diagnosis with advanced ovarian cancer. Two patients (12.5%) had haematogenous metastases which were un-resectable, while 14 (87.5%) had parenchymal invasion from peritoneal seeding, and were able to undergo complete resection. Patients such as this often require diaphragmatic stripping or resection at the time of liver resection. This approach remains experimental, but a German study evaluated the use of VATS to improve the accuracy of FIGO staging and to assess operability more reliably than using imaging alone. In this study, VATS altered the therapeutic management in 6 of 17 patients (35%).

• 20.
  

  a) T b) F c) T d) F e) F

Both the EORTC/NCIC and the CHORUS studies showed that there was no significant difference in progression-free or overall survival for patients with advanced ovarian cancer who had primary cytoreductive surgery followed by chemotherapy or NACT followed by interval debulking. It is easier to attain no residual disease status after NACT if the cancer is chemo-sensitive, because the chemotherapy will eliminate small metastatic nodules, which commonly occur on the diaphragm, bowel and its mesentery. Retrospective studies have shown significantly inferior survival for patients who attain no residual disease status after NACT, compared to patients who attain this status after primary cytoreduction. In addition, no residual status is much more likely after NACT, but the survival is no better than for patients having primary cytoreduction. Both the EORTC/NCIC and the CHORUS studies demonstrated better postoperative morbidity and mortality after NACT. The authors of the EORTC/NCIC study admitted that with the death of ovarian cancer in patients with chemo-sensitive disease, an inflammatory reaction occurred, with possible fibrosis, making surgical planes more difficult to develop, and rendering the surgery generally more difficult. The most important factor to consider is the “biological age” of the patient, not the “chronological age”. Data from the National Surgical Quality Improvement Program (NSQIP) revealed that the perioperative complication rate increased from 9.5% in women under 50 years to 14.6 % in women ≥70 years, but in a series of multivariate models, the number of extended cytoreductive procedures performed and the preoperative serum albumin level were the factors most consistently associated with morbidity. The authors concluded that women may benefit from NACT if they are likely to require extended cytoreduction, and have a poor performance status and low serum albumin levels.

• 21.
  

  a) T b) F c) T d) T e) F

A number of studies have demonstrated that age is an independent predictor of mortality from surgery for advanced epithelial ovarian cancer. Fagotti et al have prospectively studied and validated their “Predictive Index Value” (PIV) for the assessment of patients for primary debulking surgery or neoadjuvant chemotherapy. In patients with a score of ≥ 8, the probability of achieving an optimal cytoreduction was zero. A number of studies have demonstrated that patients undergoing a greater number of cytoreductive procedures have increased morbidity. In a study of 620 patients having primary surgery for advanced ovarian cancer at the Mayo Clinic between 2003 and 2011, 6.5% had a Body Mass Index (BMI) of ≥ 40 kg/m ² . This group had a significantly higher 30-day postoperative morbidity and 90-day mortality, although morbidity did not appear to increase the incidence of suboptimal debulking or long-term oncological outcomes. In a SEER study of patients undergoing primary cytoreductive surgery for epithelial ovarian cancer, the occurrence of more than two postoperative complications and initiation of chemotherapy longer than 12 weeks after surgery were associated with a significantly decreased survival.

• 22.
  

  a) F b) T c) T d) F e) T

An analysis of a total of 267 patients revealed a group of women who mostly benefit from a secondary cytoreduction. Those women, who underwent complete tumour resection, have significantly better progression-free and overall survival (median OS 45.2 months vs. 19.7 months by patients with residuals >10mm, p<0.0001). Furthermore in a multivariate analysis ascites over 500ml in the recurrent situation and complete primary cytoreduction have been found independent prognostic factors. As a result, the combination of complete primary cytoreduction, minimal ascites (<500ml) at recurrence and good performance status constituted so called AGO-Score. Score positive patients are those who fulfill all three criteria. Meeting all of three criterion helps to identify women in whom complete resection of recurrent ovarian cancer is most likely. The subsequent prospective DESKTOP II trial validated AGO Score on a total 516 patients. 51% of those were classified as score-positive. The rate of complete macroscopic cytoreduction achieved 76% and the mortality rate of surgery was 0.8%.

• 23.
  

  a) T b) T c) F d) T e) T

All these indicators, except the rate of adjuvant chemotherapy, properly described in the EORTC guidelines, should be used by gynecological oncology surgeons and gynecological oncology units to audit and improve their practice in an easy and practical way.

• 24.
  

  a) T b) T c) F d) T e) F

Complete abdominal surgical resection is defined by the removal of all macroscopic disease in all abdominal areas. The optimal target is a complete surgical resection rate > 65%, with a minimum target of 50%. Furthermore, the proportion of primary debulking surgeries / patients referred with stage III/IV patients should be more than 50%. The optimal target is more than 100 surgeries with a minimum required target of 20 new cases per surgeon a year. There is also an intermediate target of more than 50 surgeries/year.

• 25.
  

  a) F b) T c) F d) T e) F

The diagnosis of ovarian cancer during pregnancy is challenging, because the majority of cysts are functional and only a small amount of them persist throughout the pregnancy. Also, the hormonal changes that take place during pregnancy can hamper the characterization of benign ovarian cysts (e.g. decidualization of endometriosis). However, the malignancy rate of ovarian cysts during pregnancy is reported to be 1 to 6%. During normal pregnancy, especially in the first and last trimester, decidua and granulosa cells produce CA 125, making its diagnostic value for ovarian cancer low. The use of these markers may however be useful in the evaluation of therapy. CT scan is not absolutely contraindicated during pregnancy, but should be considered only if maternal benefits from the scan are greater than the risk of fetal radiation exposure. MRI is a non-radiating alternative. The most common ovarian masses during pregnancy are functional cysts, like a follicular cyst or corpus luteum. These masses are hormonally influenced and resolve spontaneously within weeks or sometimes months in most cases. Due to their changing character, their morphology on ultrasound can vary widely especially when intracystic bleeding occurs. Physical examination and ultrasound investigation during pregnancy might enhance early diagnosis of ovarian tumours, likewise with incidentally detected tumours during Caesarean delivery. The published article about ovarian cancer in pregnancy report that a greater proportion of patients (60%) were diagnosed with early stage disease, in contrast to approximately 40% in the non- pregnant group.

• 26.
  

  a) F b) T c) F d) T e) T

The decision for performing surgery during pregnancy should be based on the appearance and the dimension of the mass and gestation. Surgery can be performed if malignancy is suspected, or if the ovarian mass carries the risk of ovarian torsion. However, simple cysts smaller than 5 centimetre, or with unequivocal benign features, are very likely to resolve and can be safely monitored during pregnancy. Surgery can be performed during all 3 trimesters of pregnancy. Surgery is considered safer after 16 weeks of gestation because, in cases of bilateral adnexectomy, the hormonal production necessary for maintaining the pregnancy will be provided by the placenta. Laparoscopy can be safely performed during pregnancy. Preferably a laparoscopic approach is scheduled between 16 and 20 weeks, to optimize visualization of the mass in contrast to the enlarged uterus, and to decrease the rate of preterm labour. The trocar placement can be different from non-pregnant women, in order to avoid injuries to the uterus. It is of utmost importance to avoid reduction of blood flow to the placenta and fetus during surgery. The position of the patient should be slowly changed to Trendelenburg allowing only mild inclination, and from 20 weeks onwards, the left lateral position should be used. Maintaining normal maternal oxygenation is important since fetal well-being is directly related to maternal condition. In cases of laparoscopic surgery the intra-abdominal pressure of the pneumoperitoneum should not exceed 10–13 mmHg. For advanced stage ovarian cancer (FIGO stage III or IV) cytoreduction to no residual disease is not possible. A biopsy or adnexectomy should be performed followed by neoadjuvant chemotherapy, with completion of surgery after delivery.

• 27.
  

  a) F b) F c) F d) F e) T

Platinum compounds can be safely administered during the second and third trimester. No increased risk of detrimental effects on the newborn have been observed, as only one out of 98 patients receiving cisplatin and none out of 17 patients receiving carboplatin had a major malformation possibly related to drug exposure. During the second and third trimester paclitaxel has been administered to 36 pregnant patients, in the majority of cases as a polytherapy. The only major malformation reported has been a pyloric stenosis in a fetus exposed to paclitaxel, doxorubicin and cytarabine. Therefore chemotherapy for epithelial ovarian cancer can be administered safely during the second and third trimester. Carboplatin is less nephrotoxic than cisplatin and should be preferentially used during pregnancy. In humans, no cases of systemic administration of bevacizumab during pregnancy have been reported to date. In order to avoid maternal hematopoietic nadir and neonatal myelosuppression, the last cycle of chemotherapy should be scheduled at least three weeks before delivery. If the diagnosis of advanced stage epithelial ovarian cancer is made preoperatively, neo-adjuvant chemotherapy could be proposed, before surgery. Cytoreduction including hysterectomy, is not achievable if the pregnancy needs to be preserved.

• 28.
  

  a) F b) T c) F d) T e) F

Bevacizumab is a recombinant monoclonal antibody that binds to circulating VEGF-A. Aflibercept is a fusion protein that binds to VEGF preventing it from binding to its receptors. ICON7 and GOG 218 are the two key first-line studies investigating the addition of bevacizumab to chemotherapy following surgery. High-risk disease is defined as incomplete cytoreductive surgery (>1cm residual disease) or FIGO stage IV disease. PFS for this population was 14.5 months in the chemotherapy alone arm vs 18.1 months in the chemotherapy plus bevacizumab arm. No OS benefit was seen in these trials. The AURELIA study adding bevacizumab to chemotherapy in ‘platinum-resistant’ relapse showed significant improvement in tumour response rate, progression free survival and patient-reported outcome. These are the main toxicities of all VEGF inhibitors. It is important to carefully select patients for treatment with bevacizumab as those with extensive serosal disease are at high risk of bowel perforation. There are no predictive markers to select which patients will benefit.

• 29.
  

  a) F b) F c) F d) T e) T

Double strand DNA breaks (DSB) are the most lethal insult to the genome and if left unrepaired, cell death will occur. Germline BRCA mutations are found in 10–15% of high-grade serous ovarian cancers. Approximately 50% of high-grade serous tumours have HRD and behave like BRCA mutated cancer (‘BRCAness’). Study 19 is the original trial evaluating the use of Olaparib as maintenance therapy in high-grade serous ovarian cancer after completion of platinum based therapy. BRCA status was unknown at the time of study entry, but was analysed retrospectively in a pre-specified analysis. In the BRCA mutated (germline or somatic) group of patients, the median PFS was significantly longer in the Olaparib group compared to the placebo group. However, there was also a benefit seen in the BRCA wild-type group. PARP inhibitors are oral tablets, which are generally well tolerated.

• 30.
  

  a) T b) F c) T d) F e) F

The risk of ovarian cancer decreases by approximately 20% for every five years of use. The risk reduction associated with combined OC use appears to have a very long-lasting effect with persistence to at least 30 years after last use. Large pooled analyses have shown no variation in the effect of OCs across time periods, suggesting the effect has not changed markedly with changes in oestrogen dose over time. The risk-reducing effect of combined OCs has also been observed for women who carry BRCA mutations. Few studies have assessed the association with oral POPs so at this point in time it is not clear whether or not they reduce ovarian cancer risk.