BGCS Flashcards
how common is EOC in the UK?
6th most common cancer in women
how common is death from EOC in the UK?
6% of cancer deaths in women
what is the peak age of EOC
60-64
what percentage of EOC is advanced at diagnosis?
70%
What percentage of EOC presents as an emergency admission?
26%
When do we worry about bowel origin when interpreting tumour markers
When CA125/CEA ratio is less than 25, especially if there is a raised CA19-9
Drawbacks of cytology-based diagnosis
No genetics
Serous borderline may be falsely diagnosed as carcinoma
Histological features of HGSOC
moderate to marked nuclear atypia
greater than 12 mitoses per 10 high power fields
Necrosis and multinucleate cells
IHC features of HGSOC
CK7, WT1, PAX8, oestrogen receptor and CA125 positive
They do not stain for CK20, CEA and CDX2
P53 shows aberrant expression, characterized by either diffuse strong positive staining in greater than 75% of cells or by complete lack of staining
What percentage of women with a high grade serous or G3 endometrioid ovarian cancer have an underlying germline BRCA mutation?
What proportion of these have no family history?
18%
44%
Advantages of BRCA testing
- Prognostics
- Genetic testing and risk reduction/screening for family members
- PARPi
what proportion of EOC is endometrioid ovarian cancer
10-15%
What is endometrioid ovary cancer associated with
Endometrioisis
or
10-15% chance of synchronous endometrial primary
How do you manage G3 endometrioid ovarian cancer
as per HGSOC
What ovary cancer is linked to endometriosis
Clear cell cancer
Endometrioid
What is clear cell carcinoma of the ovary linked to?
Endometriosis
Paraneoplastic hypercalcaemia
Venous thromboembolism
Clear cell histopathology
clear, or hobnail, cells arranged in papillary, glandular or solid patterns in a hyaline stroma
Clear cell IHC
typically WT1-/p53 wild type and show staining with napsin A. They mostly lack expression of oestrogen and progesterone receptors
What is unique in the management of clear cell cancer of the ovary
less chemoresponsive
What proportion of ovarian cancer is carcinosarcoma?
1-3%
What percentage of carcinosarcoma is advanced at presentation?
90%
what is the aim of surgery for early ovarian cancer?
complete macroscopic tumour resection and adequate surgical staging
Adequate surgical staging for ovarian cancer
peritoneal washings/ascitic sampling taken prior to manipulation of the tumour
bilateral salpingo-oophorectomy
total hysterectomy
multiple peritoneal biopsies from the para-colic spaces
and the sub-diaphragmatic spaces bilaterally
omentectomy
pelvic and bilateral para-aortic lymph node assessment up to the level of the insertion of the ovarian vessels in the absence of peritoneal dissemination
Staging difference in mucinous tumours
The rate of positive lymph nodes in mucinous tumours is very low and lymph node dissection is therefore not warranted. However, appendicetomy should be performed where a mucinous tumour is suspected.
What percentage of women with apparent early stage disease are upstaged by staging?
30%
What is the likelihood of high grade disease confined to the ovary having microscopic LN?
15%
Cass et al
Among these patients, 50% had positive pelvic nodes, 36% had positive para-aortic node and both were positive in 14% of the cases
What is fertility sparing surgery?
uterus/contra-lateral ovary preserving surgery, in combination with surgical staging of the remaining peritoneal surfaces +/- retroperitoneal lymph node chains
Who is appropriate for fertility sparing surgery?
Patients with grade 1 or 2 mucinous, serous, endometrioid, or mixed histology and FIGO stage IA or stage IC with unilateral ovarian involvement may be eligible
If unilateral disease, should we do unilateral or bilateral lymph node assessment?
Retrospective evidence reveals that 3.5%-11% of the women with unilateral disease will have contra-lateral pelvic lymph node metastases, despite negative ipsilateral nodes
When to or when not to operate twice in the primary treatment of advanced ovarian cancer
Attempt complete cytoreduction once.
ie: if small procedure or diagnostic first, worth cytoreductive surgery.
Not for “second-look” cytoreductive surgery after previous maximum effort cytoreductive surgery
Once a decision to operate has been made, when should it happen?
Within 2-4 weeks
If unable to achieve complete cytoreduction, what is the aim?
What is the evidence?
Du Bois 2009
Overall survival:
complete cytoreduction vs <1cm: HR 2.12
1mm to 1cm disease vs >1cm: HR 1.2
PFS:
complete cytoreduction vs <1cm: HR 2.03
1mm to 1cm disease vs >1cm: HR 1.25
ie: time to progression/death
0mm ; 15.5 months
1mm to 10mm: 10.1 months
>10mm: 7.8 months
Should we do systematic PLND or PALND in treatment of advanced ovarian cancer - what is the evidence?
LION trial 2019
If normal appearance of LN on imaging and at the time of surgery for advanced ovarian cancer and complete cytoreduction achieved..
No difference in PFS or OS with an increased risk of complications if undergoing systematic LNDs.
PDS vs NAC/IDS - evidence
Vergote 2010
CHORUS 2015
IDS is non-inferior to PDS with respect to outcomes
Chemotherapy response score - the evidence
Cohen 2019
CRS 3 is associated with improved PFS and OS and those with BRCA mutation more likely to achieve CRS 3
Intraperitoneal chemotherapy - evidence
Jaaback 2016 (cochrane)
Improves OS and PFS but greater toxicity:
Toxicity: gastrointestinal effects, pain, fever and infection
ICON 8
Carboplatin/Paclitaxel
No benefit to weekly chemotherapy vs 3 weekly
Third chemotherapy agent?
No benefit
Bookman et al 2009
More than six cycles of chemotherapy?
No benefit to more than 5 cycles of carboplatin
Lambert et al 1997
ICON 7
First line treatment - use of BEV
During and 12 months post
Prolongs PFS but no change in OS
CA 125 monitoring for follow up and evidence
Rustin 2010
No benefit for diagnosing relapse earlier and treating according to CA125
DESKTOP III
Secondary cytoreductive surgery appropriate for:
First relapse
Platinum-sensitive - 6+ months
Positive AGO-Score (good performance status (ECOG 0), complete resection at first surgery, and ascites ≤500 mL)
significant increase of OS, PFS and TFST with acceptable morbidity
SOC-1
Secondary cytoreduction followed by chemotherapy was associated with significantly longer progression-free survival than was chemotherapy alone in patients with platinum-sensitive relapsed ovarian cancer.
(iMODEL) score and PET-CT imaging to predict resectability
- FIGO stage
- residual disease after primary surgery
- platinum-free interval
- ECOG performance status
- CA-125 at recurrence
- presence of ascites at recurrence
Platinum Sensitive
Progress with an interval of > 12 months after completion of chemotherapy
Partially Plantinum Senstitive
Progress with an interval of between 6-12 months after completion of chemotherapy
Platinum Resistant
Progress with an interval of less than 6 months after completion of chemotherapy
Platinum Refractory
Progress during, or within 4 weeks after completion of chemotherapy
Treatment of LGSOC
Surgical management as low chemotherapy response
What is the chemotherapy response rate of LGSOC
25%
What proportion of serous OC is LGSOC
5%
Histological findings of LGSOC
Neither necrosis nor P53 mutation are features of LGSOC.
Treatment of LGSOC relapse
Surgical management can be reconsidered
What proportion of OC is mucinous
3-5%
What histological finding is associated with GI met
Infiltrative pattern
Infiltrative vs expansile mucinous carcinomas
Invasive mucinous carcinoma with an infiltrative pattern has a more aggressive course than mucinous carcinoma with an expansile pattern.
IHC of mucinous tumours
CK7+
CK20-
CDX2-
Origin of advanced stage mucinous tumours
Usually GI origin - appendiceal
Rarely - from teratoma
Investigations when mucinous tumour thought to arise from GI tract
bidirectional GI endoscopy and consideration of referral to GI MDT
What is a Wolffian tumour
Usually benign and composed of cysts of varying size with sieve like areas admixed with solid and spindled areas
Small cell carcinoma of the ovary - types
- hypercalcaemic (SCCOHT)
- pulmonary ( SCCOPT)
- large cell variant
- classical carcinoid
Small cell carcinoma of the ovary - advanced disease at presentation
75%
Site of origin of origin of ovarian metastasis
colorectal
gastric
pancreaticobiliary
appendicular adenocarcinomas
Characteristics of Krukenberg tumours
Bilateral solid ovarian masses, microscopically demonstrating replacement of the ovarian stroma by signet ring, mucinous cells.
Primary site of Krukenberg tumours
The primary site is most often gastric or breast, where similar signet ring mucinous cells are seen.
Treatment of borderline tumours
Complete surgical resection and adequate surgical staging
Pelvic and para-aortic lymph node sampling to stage cases of BOT is not recommended in the absence of bulky lymph nodes
Appendicectomy for mucinous BOT
No evidence for chemotherapy
Risk of malignancy in borderline ovarian tumours
who is at lower risk?
2% of those with BOT had malignant transformation
but
in those who did relapse - 30% had malignant transformation
lower risk if aged less than 40 at diagnosis