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Flashcards in Ovarian cancer Deck (47)
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Life time risk of ovarian cancer?

1-1.5%, 3% if first degree relative.

Association with BRCA


3 main groups of ovarian ca? And what proportion of ovarian cancers do they account for?

Carcinomas (malignant epithelial cancers) - 90%
Malignant germ cell tumours - 2-5%
Potentially malignant sex cord-stromal tumours - 1-2%

(Borderline tumours)


Subtypes of carcinoma?

5 main subtypes (account for 98% carcinomas)
High grade serous (HGSC) - 70%
Endometroid - 10%
Clear cell - 10%
Mucinous - 3%
Low grade serous (LGSC) - <5%


Characteristics of HGSC

Includes primary peritoneal and primary fallopian tube cancers
Evidence that >60% HGSC in BRCA patients originate from the fallopian tube (most commonly fimbrial end)
Commonly present as advanced disease - <10% confined to ovary at diagnosis


What are the 3 main embryological cell lines of malignant germ cell?

embryo (teratoma)
yolk sac (yolk sac, endodermal sinus tumour)
trophoblast (choriocarcinoma)


Risk factors for ovarian cancer?

Personal hx of BRCA (especially BRCA1) or colon cancer
Use of perineal talc
HRT is also associated with a slightly raised risk.


FIGO stage 1 of ovarian cancer?

Stage 1 - tumour confined to ovaries
1a: Tumor confined to one ovary or
fallopian tube, intact capsule, no
tumor on surface, no tumor cells in
ascites or washings
1B: Tumor involves both ovaries or fallopian
tubes, otherwise like stage IA
1C: IC1: Intraoperative spill
IC2: Capsule rupture before surgery or
tumor on ovarian or fallopian tube
IC3: Positive peritoneal washings or


FIGO stage 2?

Stage 2: Tumor involves one or both ovaries or fallopian tubes with pelvic extension or primary peritoneal cancer

2a: Extension to or implant on uterus or
fallopian tubes, or some combination
2b: Extension to other pelvic
intraperitoneal tissues


FIGO stage 3?

Stage 3: tumor involves one or both ovaries or fallopian tubes with involvement of the peritoneum outside the pelvis, metastasis to the retroperitoneal lymph nodes, or both.

3a: IIIA1(i): Metastasis of ≤ 10 mm to the
retroperitoneal lymph nodes
IIIA1(ii): Metastasis of > 10 mm to the
retroperitoneal lymph nodes
IIIA2: Microscopic, extrapelvic
peritoneal involvement (above the
brim) with or without involvement of
retroperitoneal lymph nodes

3b: Macroscopic, extrapelvic, peritoneal
metastasis ≤ 2 cm with or without
involvement of retroperitoneal lymph
nodes (includes extension to capsule
of liver or spleen)

3c: Macroscopic, extrapelvic, peritoneal
metastasis > 2 cm with or without
involvement of retroperitoneal lymph
nodes (includes extension to capsule
of liver or spleen)


FIGO stage 4?

Distant metastasis excluding peritoneal

4a: Pleural effusion with positive cytology
4b: Distant metastasis including
parenchymal metastasis to liver,
spleen, or extraabdominal organs


Presenting symptoms?

70-75% present with stage III/IV disease
abdominal bloating
non-specific abdominal/pelvic pain
reduced appetite / indigestion / heart burn / nausea
weight loss
urinary frequency or obstruction
altered bowel habit
watery/bloody vaginal discharge
palpable mass


First line investigations?

Pelvic USS
CA125, CEA, CA19-9
CA125 raised in 90% malignant ovarian tumours, but also raised by many benign conditions
Women under 40yrs germ cell tumours are more likely - require BHCG, AFP, LDH


Hormones produced by germ cell tumours?

Dysgerminoma: HCG, LDH
Immature teratoma: a-FP, LDH
Yolk sac tumour: a-FP, LDH
Choriocarcinoma: HCG


How to calculate RMI and what figures constitute low, moderate and high risk?

RMI = USS x M x CA125
USS: multilocular, bilateral, solid areas, ascites, metastases (0,1, 3)
M: post menopausal = 3, premenopausal = 1
RMI <25 low risk (<3%), 25-250 moderate risk (20%), >250 high risk (75%)
All women with RMI >250 require MDM referral


Investigations for staging?

Histological diagnosis - necessary if considering neoadjuvant chemotherapy
Ascitic fluid for cytology
Needle biopsy
Surgical staging
Frozen section


What are the principles of management?

1. Cytoreductive surgery (aim to reduce to no visible disease)
2. 6 cycles platinum based chemotherapy
EITHER 3 cycles neoadjuvant chemo before surgery, then 3 cycles adjuvant chemo afterwards
OR cytoreductive surgery with 6 cycles adjuvant chemo afterwards


Summary of EORTC vs CHORUS trials

2 large RCTS comparing neoadjuvant chemo to initial debulking surgery
EORTC included biopsy proven stage IIIc/IV disease
CHORUS included stage IIIa,b,c/IV disease
No significant difference in progression free survival or overall survival between those getting NACT vs surgery
Better outcomes when NACT used for stage IV
NACT may improve outcomes for poor surgical candidates (e.g. high ECOG score, multiple comorbidities)


Aims of cytoreductive surgery

Women with optimally resected tumour have on average a 20-month increased survival compared to suboptimal resection
Reduce tumour burden to optimise response to chemo
Reduce disease related symptoms
Reduces cytokines produced by tumour cells to improve immune competence


Options of cytoreductive surgery

TAH-BSO and washings
Infracolic/gastrocolic omentectomy
Retroperitoneal lymph node dissection
Peritoneal disease resection
Resection of rectosigmoid
Resection of small bowel
diaphragmatic stripping
Splenectomy, hepatectomy, distal pancreatectomy, urological rescetion, abdominal wall


Which chemotherapy agents are used in platinum based therapy?

Side effects?

Carboplatin +/- paclitaxel (a taxane)

Carboplatin SE: N&V, hypersensitivity reaction, neutropenia, thrombocytopenia, nephrotoxity

Paclitaxel SE: Alopecia, N&V, arthralgia, myalgia, neurotoxicity, hypersensitivty, nephrotoxicity and neutropenia, neuropathy


Treatment pathway for stage 1 epithelial cell tumours

Stage 1-2a: TAH-BSO and comprehensive surgical treatment.

After surgery- if low grade stage 1A and 1B, chemotherapy may not be necessary. If high grade or >stage 1B then likely to require chemotherapy.

Conservative surgery aimed at maintaining fertility may be appropriate for very early disease (stage 1 grade 1 disease subsequently confirmed by histology and cytology)


Follow up and surveillance

Follow-up 3-4 monthly for first 2 years, then 6 monthly till 5 years
Pelvic exam and CA125 with each visit
CA125 good predictor of recurrence - rises 2-4 months before symptoms herald recurrence
BUT treatment started at initiation of rising CA125 vs awaiting symptoms does not increase overall survival (MRC/EORTC Trial 2010)


What is a borderline ovarian tumour?

Borderline tumour is a hyperplastic ovarian tumour without histological evidence of stromal invasion but with peritoneal implants. Although the implants can be invasive. Other histological criteria are nuclear atypia, stratification of the epithelium, formation of microscopic papillary projections.

Accounts for 10-15% of epithelial tumours.


Histological types of borderline ovarian tumour?

Histological types: serous (most common), mucinous, endometrioid, clear-cell and transitional-cell (or Brenner) tumours.


Prognostic factors for borderline ovarian tumours?

Age at diagnosis
FIGO staging (which is the same as ovarian cancer)
Residual disease at completion of primary surgery
Type of peritoneal implants
Presence of primary borderline tumour
Biomarker status (Ca 125)


What factors decrease the risk of ovarian cancer?

COCP > 5yrs (0.5)
2 SVD (0.6)
TL/hysterectomy (0.7)
Vit A derivatives


What are the components of surgical staging?

Who should have surgical staging?

Surgical staging for patients with early disease or borderline tumours

peritoneal washings for cytology
exploration of all peritoneal surfaces (incl. Diaphragm, bowel serosa, Pouch of Douglas)
biopsy of any suspicious lesions
infracolic colectomy and peritoneal biopsies
Adequate sampling of pelvic and para-aortic lymph nodes


Malignant germ cell tumours- subtypes?

yolk sac tumour: second most common germ cell malignancy (25% of all tumours)
histo finding – Schiller-Duval body (isolated papillary projection lined with tumour cells surrounding a single central blood vessel). Most secreta AFP, only 5% bilateral

50% dysgerminomas (15% bilateral) –secrete LCD or HCG. Most common ovarian tumour diagnosed in pregnancy- sometimes discovered in patients with primary amenorrhoea – often associated with gonadal dysgenesis and gonadoblastoma

20% immature teratomas – rarely bilateral < 5%

8% mixed germ cell tumours – include at least 2 different germ cells (dysgerminomas & endodermal sinus tumours)

Rare: embryonal carcinoma – aggressive if pure; secrete estrogen (ass with precocious puberty or irregular bleeding) plus hCG and AFP
choriocarcinoma – in children – signs of precocious puberty; adults signs of ectopic
polyembryomas – usually mixed, often metastased at diagnosis
gonadoblastomas – usually diagnosed in work-up of abnormal genitalia, virilisation or primary amenorrhoea. Karyotyping – single X (45 XO) or mosaic (45 XO/46XY) – 80% phenotypic women, rest phenotypic men with hypospadias, cryptorchidism & internal female organs. Of women – half normal & half virilized with primary amenorrhoea or abnormal genitalia


Management of malignant germ cell tumours

As most young, if no disease apparent outside affected ovary – unilateral salpingo-oophorectomy performed (leaving uterus & contralateral ovary)
Any suspicious lesions should be biopsied
Thorough staging procedure should be performed

Advanced disease – surgical cytoreduction performed

If stage 1A dysgerminoma or stage 1A grade 1 immature teratoma – surgery only
All other patients require adjuvant chemotherapy (currently = BEP (bleomycin, etoposide and cisplatin))


Survival malignant germ cell tumours

Most present early with disease limited to ovary
dysgerminomas have an excellent prognosis & most are cured
Stage 1A disease have > 95% 5yr survival
Even with advanced disease 5-yr survival rates of 85-90%
Patients with non-dysgerminomatous tumours in advanced stages have a 5 yr survival of 60-80%