Ovarian, Fallopian Tube And Peritoneal Cancer Flashcards
The lymphatic drainage of the ovaries and Fallopian tubes is via the…
Utero-ovarian, Infudibulopelvic and Round Ligament Pathways
And an external iliac accessory route into the following regional lymph nodes:
External iliac, common iliac, hypogastric, lateral sacral, para-aortic lymph nodes and occasionally, to the inguinal nodes
The peritoneal surfaces can drain through the diaphragmatic lymphatic and hence to the major venous vessels above the diaphragm
What is the most common site for the dissemination of ovarian and Fallopian tube cancers?
The peritoneum, including the omentum and pelvic and abdominal viscera
This includes the diaphragmatic and liver surfaces
Pleural involvement is also seen
What are CA-125 levels useful for in the context of confirmed ovarian / Fallopian tube / peritoneal cancer?
Determining response to chemotherapy
They do not contribute to staging
Fallopian tube involvement can be divided into three categories:
- Intraluminal and grossly apparent Fallopian tube mass is seen with tubal intraepithelial carcinoma.
- These cases should be staged surgically with histological confirmation of disease - Widespread serous carcinoma is associated with a tubal intraepithelial carcinoma
- Risk reducing salpingo-oophorectomy with incidental finding of STIC
What are the eight types of epithelial ovarian cancer>
- Serous
- Mucinous
- Endrometrioid
- Clear cell
- Brenner
- Undifferentiated carcinomas
- Mixed epithelial carcinomas
- Undesignated site
What is the most common type of cancer of the ovary and the Fallopian tube?
Serous
What are the two types of serous carcinoma?
High grade
- including both classic appearing
- and those with SET features (Solid, Endrometrioid-like, and transitional)
- carry high frequency of mutations in TP53
Low grade
- often associated with borderline or atypical proliferative serous tumours
- often contain mutations in BRAF and KRAS and contain wild-type TP53
What are the most common type of ovarian cancers in women younger than 20?
Germ cell tumours
What are the most common types of ovarian cancers in women in their 30s and 40s?
Borderline tumours
What are the most common types of ovarian cancers in women after the age of 50?
Invasive epithelial ovarian cancers
What is the lifetime risk of developing ovarian cancer (in the USA)?
1 in 70
What percentage of women with high-grade non-mucinous ovarian cancers have germline mutations in BRCA1 or BRCA2?
15%
Importantly, almost 40% of these women do not have a family history of breast / ovarian cancer
Therefore, all women with high-grade nonmucinous invasive ovarian cancers should be offered genetic testing, even if they do not have a family history of breast / ovarian cancer
Women who carry germline mutations in BRCA1 have a _____% increased risk of ovarian, tubal and peritoneal cancer
20-50%
FIGO, 2018
Women who carry germline mutations in BRCA2 have a _____% increased risk of ovarian, tubal and peritoneal cancer
10-20%
FIGO, 2018
What are the ovarian cancers that typically occur in Lynch syndrome?
Endometrioid or clear cell
Usually Stage I
What is the treatment of choice for women at high risk of ovarian / Fallopian tube cancer?
Risk reducing bilateral salpingoophorectomy
What proportion of epithelial “ovarian” cancers are Stage III or IV at diagnosis?
Approximately 2/3
What are symptoms of ovarian cancer?
Vague abdominal/pelvic pain or discomfort
Early satiety, decreased appetite
Dyspepsia and other mild digestive disturbances
Abdominal distension and discomfort from ascites
Respiratory symptoms from increased intra-abdominal pressure or from the transudation of fluid into the pleural cavities
Urinary frequency / urgency
Menstrual irregularities
What are the possible primaries if the CEA is elevated?
Gastric or colonic, with metastasis to the ovary
What are the eight steps to a staging laparotomy for ovarian, Fallopian tube or peritoneal cancer?
- Careful evaluation of all peritoneal surfaces
- Retrieval of any peritoneal fluid or ascites. If there is none, washings of the peritoneal cavity should be performed
- Infracolic omentectomy
- Selective lymphadenectomy of the pelvic and para-aortic lymph nodes, at least ipsilateral if the malignancy is unilateral
- Biopsy or resection of any suspicious lesions, masses or adhesions
- Random peritoneal biopsies of normal surfaces, including from the undersurface of the right hemidiaphragm, bladder reflection, cul-de-sac, right and left parabolic recesses and both pelvic sidewalls
- TAH and BSO in most cases
- Appendectomy for mucinous tumours
The most important prognostic indicator in patients with advanced stage ovarian cancer is…
The volume of residual disease after surgical debunking
Which patients are suitable for Interval Debulking?
Selected patients with cytologically proven Stage IIIC and IV disease
3-4 cycles neoadjuvant chemotherapy
Interval debulking surgery
Additional chemotherapy
Equivalent survival with less morbidity compared with primary cytoreductive surgery
Who is interval debulking surgery most suitable for?
Poor performance status
Significant medical co-morbidities
Visceral metastasis
Large pleural effusions / gross ascites
What Chemotherapy is suitable for Stage I and II ovarian cancer?
IA - not indicated (? Unless high grade)
IB - not indicated (unless high grade)
IC - adjuvant platinum based chemotherapy is given to most patients
II - all patients should receive adjuvant chemotherapy
Between 3-6 cycles
What chemotherapy is suitable for advanced stage ovarian cancer?
All patients, following primary cytoreductive surgery
(Or before / after IDS)
6 cycles, FIGO says every 3 weeks
Platinum based combination therapy
Platinum: carboplatin / cisplatin
Taxane: paclitaxel or docetaxel
What is the prognosis of borderline ovarian tumours?
10 year survival = 95%
What is the surgical management of a Stage I Borderline Ovarian Tumours?
(Fertility sparing)
USO
After intraoperative inspection fo the contralateral ovary to exclude involvement.
Patients with only one ovary or bilateral cystic ovaries: partial oophorectomy or cystectomy. Recurrence however 15-50% same ovary but survival unchanged.
What is the surgical management of a Stage I Borderline Ovarian Tumours?
Full surgical staging and TAH BSO if post-menopausal or not desiring fertility.
What are germ cell tumours derived from?
Primitive germ cells of the embryonic gonad
How do germ cell tumours present?
- Acute abdominal pain
- Chronic abdominal pain
- Asymptomatic abdominal mass
- Abnormal vaginal bleeding
- Abdominal distension
What are the five classifications of germ cell tumours?
- Dysgerminoma
- Embryonic carcinoma
- Polyembryoma
- Teratoma
- Extraembryonal differentiation
What is the recommended surgical management for a germ cell tumour?
Conservative surgery is standard in all stages of all germ cell tumours
Laparotomy with careful examination and biopsy of all suspicious areas
Limited cytoreductive
Uterus and contra-lateral ovary should be left in tact
Wedge biopsy of a normal ovary is NOT recommended as it defeats the purpose of conservative therapy by potentially causing infertility
What chemotherapy options are suitable for women with advanced germ cell tumours?
3-4 cycles
Neoadjuvant chemotherapy
BEP: Bleomycin, etoposide, cisplatin
This provides preservation of fertility (unlike radiation)
What is the leading cause of death from gynaecological cancer in the UK?
Ovarian cancer
What is the overall survival rate of ovarian cancer?
Less than 35%
This is because most women present with advanced disease
Stage of disease is the most important factor affecting outcome
(NICE)
What is the lifetime risk of developing ovarian cancer in the general population?
Approx 1%
What is the average age of diagnosis of ovarian cancer in a woman with Lynch Syndrome?
4th decade (43-49 years old)
What is the average age of diagnosis of ovarian cancer in a woman with BRCA 1 or BRCA 2?
5th decade (54-59 years old)
List protective factors against ovarian cancer:
• BSO most effective means for reducing risk.
• Previous pregnancy (reduced by 8% for each additional pregnancy)
• History of breastfeeding (reduced by 30%)
• Oral contraceptives (>50% reduction with >=10 years use)
• Tubal ligation (reduced by 20%)
Hysterectomy without BSO (reduced by 20%)
List risk factors for ovarian cancer:
• Increasing age
• Nulliparity
• Infertility (not specifically fertility treatment). ?Fertility drugs: clomiphene citrate, gonadotrophins.
• Early menarche and late menopause: increased total number of ovulations in a woman’s lifetime
• Endometriosis: associated with EOC subtypes (endometrioid, clear cell) but overall risk appears to be low.
• Genetic syndromes:
§ BRCA1 and BRCA2
§ Lynch syndrome (hereditary non-polyposis CC)
What are some strategies to reduce the risk of ovarian cancer in BRCA 1 and 2 carriers?
Describe the magnitude of effect of these strategies.
Risk reduction salpingo-oophorectomy (rrBSO)
- Reduces risk of ovarian cancer by 80%.
- In BRCA 1 and 2 carriers, should be performed after childbearing is complete by 35-40 years of age.
- In BRCA carriers WITHOUT a history of breast cancer, also reduces risk of breast cancer if rrBSO is performed before age 50.
How much risk reduction of ovarian cancer is associated with parity 3 with breastfeeding?
50% risk reduction
How much risk reduction of ovarian cancer is associated with OCP use for more than 5 years?
50% risk reduction; effect lasts for 20 years after stopping.
How much risk reduction of ovarian cancer is associated with OCP use for >5 years PLUS parity 2?
70% risk reduction
What are the two types of sex cord stromal tumours and what does each type secrete?
- Granulosa thecal cell tumours: secrete oestrogen
- Sertoli-Leydig cell tumours: secrete testosterone
Describe the ovarian cancer symptom index and the sensitivity of these symptoms in relation to ovarian cancer:
- Pelvic or abdo mass
- Urinary frequency or urgency
- Increased abdo size or bloating
- Difficulty eating or early satiety
- Present for <1 year but for more than 12 days per month.
Sensitivity:
- Early disease: 56%
- Late disease: 80%
List the IOTA Group ultrasound B-rules (benign):
- Unilocular cysts
- Presence of solid component where largest component < 7mm.
- Presence of acoustic shadowing
- No blood flow
- Smooth multilocular tumour with largest diameter <100 mm
List the IOTA Group ultrasound M-rules (malignant):
- Irregular solid tumour
- At least four papillary structures
- Irregular multilocular solid tumour with largest diameter >=100 mm.
- Ascites
- Very strong blood flow
Describe how to calculate RMI
RMI = U x M x CA125
U = ultrasound scan score. 1 point for each of: multilocular cyst; solid areas; metastases; ascites; bilateral lesions.
Zero points U=0
1 point U=1
2-5 points U=3
M = menopausal status M = 1 if premenopause M = 3 if post-menopausal
CA 125 serum level
When should genetic testing be offered?
- Women < 70 years old with high grade, non-mucinous invasive ovarian carcinoma even if not family history of breast or ovarian cancer.
- Ashkenazi Jews
- FamHx suggestive of Lynch syndrome
Regarding women with Lynch syndrome type II (HNPCC):
What is their risk of ovarian cancer?
What is their risk of endometrial cancer?
Ovarian cancer risk 10-12%
Endometrial cancer risk 32-60%
What is CA-125 primarily a marker for?
Epithelial ovarian carcinoma
What other conditions raise CA-125
Fibroids
Endometriosis
Adenomyosis
Pelvic infection
When is MRI useful in evaluating ovarian cysts
Evaluation of more complex lesions
Increased BMI (which limits USS)
What % of women will have some form of surgery during their lifetime for the presence of an ovarian mass?
10%
RCOG GTG
What is the sensitivity and specificity of an RMI 200 for gynaecological malignancy?
Sensitivity = 78% Specificity = 87%
What is the sensitivity and specificity of an RMI 250 for gynaecological malignancy?
Sensitivity = 70%
Specificity = 90%
What is the sensitivity and specificity of the IOTA Rules for gynaecological malignancy?
Sensitivity = 95%
Specificity = 91%
What are the advantages to laparoscopic management of ovarian cysts, as per RCOG?
Lower post-operative morbidity
Shorter recovery time
Earlier discharge and return to work = cost effective
When should CT A/P be performed, in the context of an ovarian mass?
- RMI > 200
- Evaluate for metastasis when malignancy suspected
- If non-ovarian primary suspected e.g. colon with ovarian mets
What is the management for post-menopausal woman with an asymptomatic, simple, unilateral unilocular ovarian cyst <5cm diameter
If CA-125 normal, can be managed conservatively
Repeat USS in 4-6 months
Repeat at 1 year - if cyst remains unchanged or reduces in size, can be discharged
RCOG GTG
Why is aspiration of an ovarian cyst in a postmenopausal woman not recommended?
(C.f. Cystectomy)
- Diagnostic cytological examination of cyst fluid is poor
- 25% of cysts will recur within 1 year with aspiration
- Spillage and seeding of cancer cells into the peritoneal cavity
- leading to upstaging which affects prognosis
What are three complications of advanced ovarian cancer?
Bowel obstruction
Ascites
Pleural effusions
What is the 5 year survival rate for Ovarian Cancer
Stage 1
Stage 2
Stage 3
Stage 4
Stage 1 = 80-90%
Stage 2 = 67-70%
Stage 3 = 29-59%
Stage 4 = 17%
For simple premenopausal ovarian cysts, what is the management if
- <5cm
- 5-7cm
- > 7cm
<5cm: No follow up a required as very likely to be physiological and almost always resolve
5-7cm: Yearly USS follow up
> 7cm: Surgical intervention or MRI
RCOG GTG
What is the risk of chemical peritonitis with spillage of dermoid cyst contents?
0.2%
If there has been spillage of a dermoid,
Peritoneal lavage should be performed using large amounts of warmed fluids
RCOG GTG
With laparoscopic ovarian cyst removal (benign), which port should the ovarian cyst be removed from?
When possible, via the umbilical port
Less pain and quicker retrieval time
Allows for smaller lateral ports
Reduces incidence of incisional hernia, epigastric vessel injury
Improved cosmetics
RCOG GTG
What was the finding of the Cochrane review looking at the risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility?
Subfertile women treated with infertility drugs had increased rates of ovarian cancer compared to
- general population
- subfertile women not treated
The risk is slightly higher in nulliparous women, and for borderline ovarian tumours
What was the finding of the Cochrane Review looking at chemotherapy vs surgery for initial treatment in advanced ovarian epithelial cancer>
For GIFO Stage III or IV
Little or no difference in primary survival outcomes between primary debulking surgery and neoadjuvant chemotherapy / IDS
What was the finding of the Cochrane Reivew looking at HRT after surgery for epithelial ovarian cancer?
2020
HRT may slightly IMPROVE overall survival in women who have undergone surgical treatment for EOC
But the certainty of the evidence is low
Little or no effect on progression-free survival
Evidence is too limited to support/ refute that HRT is very harmful in this population