• 1.
  

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

Molecular markers are currently being used in staging classification of most cancers, including gynecologic cancers.

• 2.
  

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

p53 is a tumor suppressor gene that encodes nuclear phosphorylated p53, which is a transcription factor leading to inhibition of cell growth, cell-cycle arrest and apoptosis in response to DNA damage. Loss of function leads to chromosomal instability, aneuploidy and inhibition of apoptosis. All of the others are proto-oncogenes.

• 3.
  

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

MEK (MAPK pathway) inhibitors, receptor tyrosine kinase inhibitors and anti-VEGF antibodies are all under evaluation in ovarian/endometrial cancer. Two of the major potential roles for molecular markers are the potential to improve classification of histologic subtypes and to predict risk of clinical outcome including progression-free and overall survival.

• 4.
  

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

The definition of micro-invasive vulvar cancer (stage IA) has not changed. Patients with cancers up to 20 mm in diameter with no more than 1 mm of stromal invasion are the only patients with virtually no risk of lymph node metastases. About 30% of patients will be down-staged in the new staging system, because all patients with disease confined to the vulva and negative lymph nodes are now staged as IB instead of stage II. This is because it was shown that there was no significant difference in survival between patients with Stage IB and II in the old staging system. Because most of the patients with stage II disease in the old staging system had a very good prognosis and have been down-staged in the 2009 system, the number of patients with stage II disease in the 2009 system has decreased from about 20% to about 4%. Patients with stage III disease will now all have positive lymph nodes, so will be a homogeneous group. In addition, they have been sub-classified based on the morphological features of the positive nodes (diameter of metastatic deposit and presence or absence of extra-capsular spread) and the number of positive nodes. Patients with bilaterally positive nodes were previously classified as having stage IVA disease, but bilaterality has been shown not to be an independent risk factor if the number of positive nodes is taken into account, so there is no longer a separate stage for these patients.

• 5.
  

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

The morphology of positive lymph nodes has been shown to be important since the initial report by Origoni et al in 1992. They demonstrated that patients with nodal metastases greater than 15 mm diameter or any extracapsular spread had a poor prognosis.

The number of positive nodes has been shown to be the most important prognostic factor in many studies. This is well exemplified in the GOG study published by Homesley et al in 1991. The 5-year survival for 125 patients with 1–2 positive nodes was 75.2%, compared to 36.1% for 40 patients with 3–4 positive nodes, 24% for 19 patients with 5–6 positive nodes, and 0% for 16 patients with 7 or more positive nodes. The fact that bilaterality was not important if the number of positive nodes was taken into account was first demonstrated by Fons et al in 2009. They reported that papers reporting significance for bilaterality did not exclude from their analysis patients who only had one positive node. Use of separate incisions for the groin dissection has become routine practice since the first large series was reported by Hacker et al in 1981.

• 6.
  

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

Patients with one microscopically positive lymph node have an excellent prognosis and do not benefit from postoperative radiation therapy. Extracapsular spread confers a poor prognosis, and such patients should receive postoperative groin and pelvic radiation therapy. Faul et al in 1997 demonstrated that a small field of postoperative radiation therapy could significantly decrease local recurrence if the closest surgical margin on formalin fixed tissue was 5 mm or less. Patients with palpably enlarged groin nodes should have these nodes resected, and a frozen section obtained. If positive, full groin dissection is not necessary, so groin healing should be good. Postoperative bilateral groin and pelvic radiation therapy can usually be instigated within 3 weeks. It is unlikely that standard doses of radiation will sterilize bulky positive groin nodes. When the primary tumour involves the anus, surgical treatment will inevitably necessitate an ano-proctectomy and permanent colostomy. Pre-operative radiation will usually shrink or eliminate the primary cancer and avoid the need for a stoma.

• 7.
  

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

Only performance status is not an issue for stage 1 disease in terms of prognosis from the cancer itself.

• 8.
  

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

DES related cancers tend to be less aggressive tumours with a generally good prognosis. Most vaginal cancers tend to be in the upper vagina and due to it being midline with a complex network of lymphatics, bilateral involvement of inguino-femoral lymph nodes may well occur.

• 9.
  

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

After the treatment of VAIN, vaginal cancers can occur in up to 20% and these can occur long term, so follow-up needs to be long term. High risk HPV infections are the major risk factors in young women with squamous cell carcinoma of the vagina. DES related cancers tend to be less aggressive tumours with a generally good prognosis.

• 10.
  

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

The incidence of metastases to the pelvic lymph nodes in patients with corpus-confined endometrial cancer who undergo lymphadenectomy varies between 5% and 18%. LN metastasis constitutes one of the most important prognostic factors of EC. Five year overall survival decreases from approximately 85% to 54% in patients with LN metastasis. LN ratio is suggested to improve the prognostic value associated with LN status but LN metastasis remains one of the most important prognostic factors of EC. Since 1988 this information is included in the International Federation of Gynecology and Obstetrics (FIGO) classification. In 2009, FIGO revised the classification of EC and LN invasion has been stratified into pelvic LN invasion (stage IIIC1) and para-aortic LN invasion (stage IIIC2). 29 to 67% of patients with pelvic LN metastasis have para-aortic involvement. On the contrary, only a few percent of patients with negative pelvic LN have para-aortic invasion. Various scores mainly based on primary tumoural characteristics are available to predict LN metastasis. Most of them have not been externally validated but can permit avoidance of lymphadenectomy in half of patients.

• 11.
  

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

Detection of metastatic LN is not mandatory before surgery for endometrial cancer since the decision to perform lymphadenectomy is mainly based on risk stratification for early stage cancer. Moreover, the accuracy of imaging (typically MRI) for detection of LN metastasis is limited by the size criteria used as thresholds for identifying metastatic LNs are based on enlargement (usually 10 mm). Even 18F-FDG is of limited interest for detection of LN involvement because of low sensitivity. One third of positive para aortic LN are above the inferior mesenteric artery without positive LN below the inferior mesenteric artery. Pooled detection rate for sentinel lymph node biopsy is 78% and pooled sensitivity 89%. Since the incidence of metastases to the pelvic lymph nodes is low (between 5% and 18%), sentinel lymph node biopsy cannot be recommended in routine practice yet. Larger studies are still needed to evaluate the false negative rate and the factors influencing the sensitivity before considering this method safe. The major limitation is using size criteria alone as thresholds for identifying metastatic LNs are based on enlargement (usually 10 mm). This size criterion was used in three out of the four studies that showed similar diagnostic accuracy for MRI and sentinel-node biopsy in women with EC in the meta-analysis published by Selman et al. This meta-analysis included 18 studies and 693 women. A limitation with this meta-analysis is that the included studies did not use diffusion-weighted imaging. LN specific magnetic resonance contrast agents which have been developed to improve LN staging of pelvic cancers. Sensitivity has been reported between 17 and 66%.

• 12.
  

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

In theory, not to miss any metastatic LN, complete pelvic and para aortic lymphadenectomy as well as resection of deep inguinal nodes is mandatory. However, the metastatic LN probability is particularly low in low risk groups (approximately 1%). Similarly, metastasis to the deep inguinal nodes is extremely rare (0.4 %) in EC. Various scores mainly based on primary tumoral characteristics are available to predict LN metastasis. Most of them permit avoidance of lymphadenectomy in half of patients by classifying patients into a low risk group. It is true that LN status improves survival prediction but since metastatic LN are particularly infrequent in low risk group patients, it should not be recommended in those patients. Retrospective studies have suggested that complete lymphadenectomy may be associated with improved survival outcomes, particularly for patients with LN metastases. On the contrary, two randomized clinical trials showed that lymphadenectomy did not provide an overall or recurrence free survival benefit in the early stages of disease. It is true that metastatic LN can justify administration of adjuvant chemotherapy. However, metastatic LN is particularly infrequent in low risk group patients and the benefit of chemotherapy in those patients has not been demonstrated.

• 13.
  

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

As per FIGO, the status of both the pelvic and para-aortic lymph nodes should be assessed intraoperatively in all patients as in some cases para-aortic lymph nodes may be positive in the absence of positive pelvic nodes. Lymph node dissection is considered an important aspect of the management of endometrial cancer. Complete pelvic and para-aortic node dissection should be performed compared to selective nodal sampling as the latter may miss positive nodes. Studies have reported that patients with high risk disease (stage IB, grade 3 or greater) who underwent extensive lymph node sampling had an increased 5-year survival as compared with those who had fewer lymph nodes removed (75.3% with one node removed versus 86.8% with ≥ 20 nodes removed). The incidence of lymph node metastasis also correlated with tumour size in endometrial cancer. Resection of bulky nodes along with chemo-radiation therapy is reported to be beneficial in endometrial cancer. As per earlier reports, a 10.6% increase in 5-year OS was reported for pelvic and para-aortic lymphadenectomy compared to pelvic lymphadenectomy alone in patients with endometrial cancer.

• 14.
  

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

Systematic lymphadenectomy technique is usually used for the resection of enlarged and non- enlarged lymph nodes along with cyto-reductive surgery in these patients. Pelvic and para-aortic lymph node dissections have become an important part of the surgical treatment of gynaecological cancers as the presence of positive lymph nodes is a signal of advanced stage, high risk disease. Lymph nodes and lymph vessels (that carries lymph fluid) are the part of the body’s immune system that collects fluid, waste material, and other substances from body tissues. Cancer in the lymph nodes either start there itself or cancer cells can spread to lymph nodes through the normal circulation of body fluid. Lymphatic spread has been reported as a common feature of all stages of gynaecological cancers as per FIGO staging system. If cancer spreads to lymph nodes, there is a higher risk that the cancer might come back after surgery.

Radiotherapy, chemotherapy and/or surgery are the most common treatments to decrease tumour burden in cervical cancer. However, bulky pelvic and/or para-aortic nodes are resistant to radiotherapy and/or chemotherapy and pose a serious challenge. Hence, surgical debulking of enlarged lymph nodes would be effective in chemo-radiation resistant lymph nodes.

• 15.
  

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

De-bulking of negative and positive nodes including macroscopically enlarged nodes in endometrial carcinoma patients affords a survival benefit, however resection of bulky lymph nodes is reported to be beneficial if the patients had clear cell histology, myometrial invasion (>50%) and large tumor (>2 cm in diameter). For all types of gynaecological cancer, the finding of enlarged bulky lymph nodes poses a serious challenge and the success rates with de-bulking depend on compliance, morbidity and survival rates in cancer patients. The important prognostic factors for survival in women with cervical cancer are the status of lymph nodes, FIGO stage, or histological grade of disease. The incidence of nodal metastases increases with the FIGO stage, however the finding of positive lymph nodes does not alter FIGO stage.

There are four basic approaches for debulking retroperitoneal nodes in cervical cancer patients – extraperitoneal laparotomy, transperitoneal laparotomy, extraperitoneal laparoscopy and transperitoneal laparoscopy. Despite the prognostic involvement of lymph node metastasis, there is a great discussion about the role of pelvic and para-aortic lymph node dissection in the management of different gynaecological cancers. The role of enlarged positive bulky lymph node dissection on PFS and OS in these patients is not clear. There are some retrospective studies that have favoured the de-bulking of positive pelvic and para-aortic lymph nodes prior to radiation treatments for the management of gynaecological cancer.

• 16.
  

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

Retroperitoneal lymph node involvement is reported in 50–75% of patients with advanced stage disease. Routine pelvic and para-aortic lymphadenectomy is not indicated in early stage leiomyosarcoma of the uterus, as the incidence of lymph node metastases has been shown to be approximately 3%; however in advanced stage, lymph node involvement is common and de-bulking of enlarged positive lymph nodes is recommended as a part of optimal cyto-reduction. Distant metastatic disease has been correlated directly with primary tumour features and the site and volume of lymph node disease. Surgical de-bulking of enlarged nodes <2 cm may improve the control of pelvic disease by chemo-radiation, and pelvic disease control may reduce the risk of distant metastatic spread by 60–75%. The incidence of nodal metastases increases with the FIGO stage, however the finding of positive lymph nodes does not alter the FIGO stage. A randomized phase III trial reported that more than 90% of patients with clinically suspected lymph nodes had histologically positive lymph nodes. Hence, removal of positive bulky node along with cyto-reductive surgery could offer survival benefits in patients with gynaecological malignancies.

• 17.
  

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

Intraoperative rupture (“surgical spill”) is IC1; positive peritoneal cytology with or without rupture is IC3. Peritoneal washing (for cytological evaluation) is routinely done at the beginning of the operation as part of the staging on every patient. In case of intraoperative rupture, washing should be repeated after resection of the tumour. Positive peritoneal fluid is stage IC3 independent of rupture. Besides false negative peritoneal washings (sampling error), tumor rupture may occur on a benign irrelevant zone; i.e., benign fibrous tissue, haemorrhage etc. Cancers are not homogeneous but have different tissue components. Rupture through an irrelevant area would be prognostically better than rupture of a highly cellular and malignant component of the tumour.

• 18.
  

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

Limited evidence suggests that dense adhesions of an apparent stage I tumor requiring sharp dissection (or when dissection results in tumor rupture) result in outcomes equivalent to those of tumors in stage II. Although it is not clear at this time whether upstaging based on dense adhesions is warranted, presence of malignant cells in the adherent fibrous tissue justifies upgrading. Stage II ovarian cancer is ill-defined and comprises a small and heterogeneous group making up less than 10% of ovarian cancers. Some investigators claim that the peritoneum is an anatomic unit and that pelvic involvement and extra-pelvic involvement are prognostically similar. Thus, they suggest classifying as stage III all cases with peritoneal involvement including uterine serosa (as it is done for stage IIIA endometrial carcinoma of the uterus). However, the Committee members felt that there was a clear division of stage II and III disease in terms of survival, and therefore the subdivision of IIA and IIB remains. All stage II carcinomas are currently treated with adjuvant chemotherapy, so sub-classification is not essential. Carried by the peritoneal fluid, cancer cells attach preferentially on the abdominal peritoneum or omentum (stage III). The 1988 sub-stage IIC (i.e. IIA or IIB but with tumour on surface, capsule ruptured, or ascites or positive peritoneal washing) was considered redundant and eliminated.

• 19.
  

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

Stage II tumour involves one or both ovaries or fallopian tubes with pelvic extension (below pelvic brim) or primary peritoneal cancer. In stage IIB, tumour has extended to extra-adnexal/extra-uterine pelvic intraperitoneal tissues. The new classification includes a revision of stage III and tumors that have spread to the retroperitoneal lymph nodes without intraperitoneal dissemination are assigned to stage IIIA1. Stage IIIA1 is further subdivided into IIIA1(i) (metastasis ≤10 mm in greatest dimension) and IIIA1(ii) (metastasis >10 mm in greatest dimension), even if there are no retrospective data supporting quantification of the size of metastasis in IIIA1. Measurement refers to the size of the metastatic tumor and not the size of the lymph node. Involvement of retroperitoneal lymph nodes must be proven cytologically or histologically; however, measurement of the largest metastatic nodule can only be done by the pathologist on surgically resected lymph nodes. Stage IIIA2 tumors show microscopic extra-pelvic peritoneal involvement with or without positive retroperitoneal lymph nodes; stage IIIB tumors are associated with macroscopic peritoneal metastasis beyond the pelvis up to 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes; and stage III tumors have macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes. In the 1988 FIGO staging system, patients who had ovarian tumours and retroperitoneal lymph node metastasis without extra-pelvic peritoneal involvement were upstaged from stage I to stage IIIC on the basis of the finding of positive lymph nodes alone. Subsequently, it was shown that these tumours, which represent less than 10% of ovarian cancers have a better prognosis than that of tumours with abdominal peritoneal involvement. They are currently classified as stage IIIA1.

• 20.
  

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

Inclusion criteria are:

• –
  

  Histologically proven primary squamous cell vulvar cancer with a depth of invasion > 1mm.

  
  
• –
  

  Tumors < 4cm, not involving anus/vagina/urethra

  
  
• –
  

  Uni-focal tumor

  
  
• –
  

  No clinically suspicious lymph nodes

  
  
• –
  

  Enlarged lymph nodes excluded by preoperative imaging (CT/ultrasound/MRI)

The sentinel node procedure has not been proven to be safe in local recurrent disease. Therefore, the procedure should only be performed in primary cancers. Until more data become available on this subject, patients with local recurrent disease should undergo uni- or bilateral inguino-femoral lymphadenectomy.

• 21.
  

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

The sentinel node procedure is only advised for patients with uni-focal tumours < 4cm. Therefore, in this case there is an indication for inguino-femoral lymphadenectomy. Because the tumor is within 1cm of the midline, bilateral groin treatment is advised.

• 22.
  

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

With ultra-staging, more and smaller metastases are diagnosed. The clinical implications of these micro-metastases are not clear, but there is evidence that smaller metastases have a better prognosis compared to larger metastases. This stage migration (patients with stage I become stage III when micro-mets are diagnosed) will therefore lead to better survival for the group of patients with stage III disease, because patients with smaller metastases that were previously not diagnosed are now classified as stage III. Probably this will also lead to better survival for patients with stage I disease, because more patients with previously occult metastases are no longer in this stage.

• 23.
  

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

The standard treatment for positive SNs is lymphadenectomy. Because the tumor was well lateralized, left inguino-femoral lymphadenectomy in this case is sufficient. GROINSS-V-II investigated the use of radiotherapy as an alternative for inguino-femoral lymphadenectomy in cases of a positive SN. This study is still ongoing. Until further data become available, inguino-femoral lymphadenectomy is the standard therapy for all SN metastases, independent of their size.

• 24.
  

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

The risk of lymph node metastasis in stage 1a1 cervical cancer is <3% in general. The sensitivity of these imaging tools ranged from 50 – 82% only. There had been a randomized trial which had to be prematurely terminated because those patients assigned to have surgical staging had a significantly worse progression-free survival than those with clinical staging. A review article showed that the incidence of isolated para-aortic lymph node metastasis was only 1.1%. Cervical cancer is clinically staged and the stage will not be changed even in the presence of lymph node metastasis.

• 25.
  

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

It had been shown that about 22% with lymph node metastasis had poor prognostic factors, among which 51% involved both pelvic and para-aortic lymph nodes and 16% had isolated para-aortic node metastasis. A review article showed that laparoscopic surgery was associated with fewer postoperative complications (15.8 Vs 23.4%, odds ratio (OR) 0.62, 95% CI 0.52–0.73; p < 0.01), but higher intraoperative complication rate (9.4 Vs 7.0%, OR 1.35, 95% CI 1.05–1.74; p = 0.02) when compared with laparotomy. It has been shown that the 3-year disease free and overall survival, as well as the 3-year recurrence rate, were similar between both surgical approaches. The conversion rate was generally low for both methods and there was no difference in the estimated blood loss or transfusion rate. The lymphatic drainage system of endometrial cancer is mainly through the parametria, the broad and infundibulo-pelvic ligaments from the uterus.

• 26.
  

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

One review article showed that the spillage rates and upstaging rates were similar between the two groups. Commonly used parameters include omental cake, peritoneal and diaphragmatic carcinomatosis, mesenteric retraction, bowel and stomach infiltration, spleen and/or liver superficial metastasis. Zivanovic et al reported that the incidence of port-site metastasis was only 0.9% and one review article showed only one case of port-site metastasis among the eleven studies included in their meta-analysis. The incidence was higher in advanced ovarian cancer. FIGO stage IV (as compared to stage III) and the presence of ascites of >500ml had been implicated as independent risk factors for abdominal wall metastasis. The recent Cochrane review in 2013 failed to identify any randomized controlled or prospective case-control studies in this aspect.

• 27.
  

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

Meta-analyses in cervical and endometrial cancers showed that patients undergoing robot-assisted surgery had less blood loss, less blood transfusion and shorter hospital stay compared with those undergoing laparotomy. A recent retrospective study showed that the one-year survival and recurrence rates were similar between the robot-assisted and open approaches. The detection rates of sentinel lymph nodes in endometrial cancer varied between 40 and 100%, the false positive rate ranged 0 to 50% and the false negative rate was between 0 and 33%. The sensitivity is near 90% with 100% sensitivity and negative predictive value for cervical cancer less than 2cm. The numbers of lymph nodes sampled and the conversion rates are similar between single-port and conventional laparoscopic routes.

• 28.
  

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

This patient has stage III C disease. Options for treatment include: primary debulking surgery or neoadjuvant chemotherapy. Presence of diaphragmatic deposits would favour a decision towards neoadjuvant chemotherapy. Ideally such a patient should be discussed in a multidisciplinary team. Initial biopsy would not only help in histological diagnosis and immunohistochemistry but also provide tissue for molecular analysis as well as confirmation of a malignant process prior to any therapeutic or surgical intervention.

• 29.
  

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

Patients with massive pleural effusion (FIGO stage IVA) are at risk of operative and post –operative complications. Neo-adjuvant chemotherapy may be a better option for such patients with outcome similar to an approach of primary de-bulking surgery followed by chemotherapy.

• 30.
  

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

This patient has locally advanced disease. Concurrent chemotherapy (cisplatin 40 mg/m ² ) along with external radiation followed by intra-cavitary radiation is currently the standard treatment approach.