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Gynae-Oncology > Ovarian, Fallopian Tube And Peritoneal Cancer > Flashcards

Ovarian, Fallopian Tube And Peritoneal Cancer Flashcards

1
Q

The lymphatic drainage of the ovaries and Fallopian tubes is via the…

A

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

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2
Q

What is the most common site for the dissemination of ovarian and Fallopian tube cancers?

A

The peritoneum, including the omentum and pelvic and abdominal viscera

This includes the diaphragmatic and liver surfaces
Pleural involvement is also seen

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3
Q

What are CA-125 levels useful for in the context of confirmed ovarian / Fallopian tube / peritoneal cancer?

A

Determining response to chemotherapy.

They do not contribute to staging.

They are also used to monitor recurrence during 5 years follow-up after remission.

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4
Q

Fallopian tube involvement can be divided into three categories:

A
  1. Intraluminal and grossly apparent Fallopian tube mass is seen with tubal intraepithelial carcinoma.
    - These cases should be staged surgically with histological confirmation of disease
  2. Widespread serous carcinoma is associated with a tubal intraepithelial carcinoma
  3. Risk reducing salpingo-oophorectomy with incidental finding of STIC
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5
Q

What are the eight types of epithelial ovarian cancer>

A
  1. High grade serous (70%)
  2. Endrometrioid (10%)
  3. Clear cell (10%)
  4. Mucinous (3%)
  5. Low grade serous (<5%)
  6. Brenner
  7. Undifferentiated carcinomas
  8. Mixed epithelial carcinomas
  9. Undesignated site
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6
Q

What is the most common type of cancer of the ovary and the Fallopian tube?

A

High grade serous - 70% epithelial ovarian cancer

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7
Q

What are the two types of serous carcinoma?

A

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
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8
Q

What are the most common type of ovarian cancers in women younger than 20?

A

Germ cell tumours

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9
Q

What are the most common types of ovarian cancers in women in their 30s and 40s?

A

Borderline tumours

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10
Q

What are the most common types of ovarian cancers in women after the age of 50?

A

Invasive epithelial ovarian cancers

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11
Q

What is the lifetime risk of developing ovarian cancer?
What if you have a FHx 1st degree relative with ovarian cancer?

A

1 in 70

1 - 1.5%
FHx - 3%

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12
Q

What percentage of women with high-grade non-mucinous ovarian cancers have germline mutations in BRCA1 or BRCA2?

A

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 age less than 70 should be offered genetic testing, even if they do not have a family history of breast / ovarian cancer

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13
Q

Women who carry germline mutations in BRCA1 have a _____% increased risk of ovarian, tubal and peritoneal cancer

A

20-50%

(FIGO, 2018)

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14
Q

Women who carry germline mutations in BRCA2 have a _____% increased risk of ovarian, tubal and peritoneal cancer

A

10-20%

(FIGO, 2018)

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15
Q

What are the ovarian cancers that typically occur in Lynch syndrome type II?
What is the % risk of ovarian cancer?

A

Endometrioid or clear cell
Usually Stage I

10% lifetime risk
40-60% risk endometrial cancer

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16
Q

What is the treatment of choice for women at high risk of ovarian / Fallopian tube cancer?

A

Risk reducing bilateral salpingoophorectomy

3 monthly CA125 and annual pelvic USS for screening in high risk women has been studied, but shows poor sensitivity and specificity, and a number of women still had advanced disease at first surgery.

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17
Q

What proportion of epithelial “ovarian” cancers are Stage III or IV at diagnosis?

A

70-75%

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18
Q

What are symptoms of ovarian cancer?

A

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

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19
Q

What are the possible primaries if the CEA is elevated?

How can CEA and CA125 be used to delineate likely ovarian from GI primary?

A

Gastric or colonic, with metastasis to the ovary (krukenberg tumour).

If the ratio CA125:CEA > 25:1 - supports ovarian primary.

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20
Q

What are the eight steps to a staging laparotomy for ovarian, Fallopian tube or peritoneal cancer?

A
  1. Careful evaluation of all peritoneal surfaces
  2. Retrieval of any peritoneal fluid or ascites. If there is none, washings of the peritoneal cavity should be performed
  3. Infracolic omentectomy
  4. Selective lymphadenectomy of the pelvic and para-aortic lymph nodes, at least ipsilateral if the malignancy is unilateral
  5. Biopsy or resection of any suspicious lesions, masses or adhesions
  6. 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
  7. TAH and BSO in most cases
  8. Appendectomy for mucinous tumours
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21
Q

The most important prognostic indicator in patients with advanced stage ovarian cancer is…

A

The volume of residual disease after surgical debulking.

Optimal surgical debulking is associated with 20 month increased survival compared to suboptimal debulking.

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22
Q

Which patients are suitable for Interval Debulking?

A

Selected patients with cytologically proven Stage IIIC and IV disease:

  • High ECOG
  • comorbidities
  • high tumour burden incompatible with complete resection
  • 3 cycles neoadjuvant chemotherapy
  • Interval debulking surgery
  • 3 cycles adjuvant chemotherapy

NB. If disease progression, OR still not fit for surgery due to ECOG/comorbidities/non-resectable after 3 cycles neoadjuvant therapy - surgery is not performed and continuation chemo considered.

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23
Q

How is chemotherapy used for the different stages of ovarian cancer?

A

IA/IB - chemo not indicated (Unless high grade)

IC - IV - adjuvant platinum based chemotherapy
(i.e. once positive ascites/peritnoenal washing/surgical spill/cancer on ovarian or tube surface - needs chemo)

IIIc and IV - consider neoadjuvant chemo and interval debulking surgery, followed by adjuvant chemo

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24
Q

What chemotherapy is used for ovarian cancer?

A

Platinum based +/- taxane
Carboplatin +/- paclitaxel (commonest)

Platinum: carboplatin / cisplatin
Taxane: paclitaxel or docetaxel

Usually adjuvant therapy of 6 cycles, 3 weeks apart

Stage IIIc/IV may have 3 cycles neoadjuvant, then IDS, then 3 cycles adjuvant.

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25
Q

What is the prognosis of borderline ovarian tumours?

A

10 year survival = 95%

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26
Q

What is the surgical management of a Stage I Borderline Ovarian Tumours?

A

Full surgical staging and TAH BSO if post-menopausal or not desiring fertility.

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.
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27
Q

What are germ cell tumours derived from?

A

Primitive germ cells of the embryonic gonad

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28
Q

How do germ cell tumours present?

A
  1. Acute abdominal pain
  2. Chronic abdominal pain
  3. Asymptomatic abdominal mass
  4. Abnormal vaginal bleeding
  5. Abdominal distension
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29
Q

What are the most common types of germ cell tumours?

A

Teratoma

Dysgerminoma

Yolk sac tumours

Mixed germ cell

Rare OGCTs:

Non-gestational choriocarcinoma, Embryonic carcinoma, Polyembryoma, Extraembryonal differentiation

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30
Q

What is the recommended surgical management for a germ cell tumour?

A

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

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31
Q

What chemotherapy options are suitable for women with advanced germ cell tumours?

A

3-4 cycles
Neoadjuvant chemotherapy
BEP: Bleomycin, etoposide, cisplatin

This provides preservation of fertility (unlike radiation)

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32
Q

What is the leading cause of death from gynaecological cancer in the UK?

A

Ovarian cancer

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33
Q

What is the overall survival rate of ovarian cancer?

A

Less than 35%

This is because most women present with advanced disease
Stage of disease is the most important factor affecting outcome

(NICE)

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34
Q

What is the average age of diagnosis of ovarian cancer in a woman with Lynch Syndrome?

A

4th decade (43-49 years old)

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35
Q

What is the average age of diagnosis of ovarian cancer in a woman with BRCA 1 or BRCA 2?

A

5th decade (54-59 years old)

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36
Q

List protective factors against ovarian cancer:

A
  • BSO most effective means for reducing risk.
  • Previous pregnancy (reduced by 8% for each additional pregnancy)
  • History of breastfeeding (reduced by 30%)
  • Combined oral contraceptives (>50% reduction with >=10 years use)
  • Tubal ligation (reduced by 20%)
  • Hysterectomy without BSO (reduced by 20%)
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37
Q

List risk factors for ovarian cancer:

A

• Increasing age
• Nulliparity
• Infertility and PCOS (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 type II (hereditary non-polyposis CC)

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38
Q

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.

A

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.
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39
Q

How much risk reduction of ovarian cancer is associated with parity 3 with breastfeeding?

A

50% risk reduction

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40
Q

How much risk reduction of ovarian cancer is associated with OCP use for more than 5 years?

A

50% risk reduction; effect lasts for 20 years after stopping.

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41
Q

How much risk reduction of ovarian cancer is associated with OCP use for >5 years PLUS parity 2?

A

70% risk reduction

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42
Q

What are the two types of sex cord stromal tumours that secrete hormones?

A
  • Granulosa cell tumours (most common SCST): secrete oestrogen
  • Sertoli-Leydig cell tumours (extremely rare): secrete testosterone
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43
Q

Describe the ovarian cancer symptom index and the sensitivity of these symptoms in relation to ovarian cancer:

A
  • 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%
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44
Q

List the IOTA Group ultrasound B-rules (benign):

A
  • 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
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45
Q

List the IOTA Group ultrasound M-rules (malignant):

A
  • Irregular solid tumour
  • At least four papillary structures
  • Irregular multilocular solid tumour with largest diameter >=100 mm.
  • Ascites
  • Very strong blood flow
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46
Q

Describe how to calculate RMI

A

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

47
Q

When should genetic testing be offered?

A
  • 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 or BRCA 1 / 2
48
Q

Regarding women with Lynch syndrome type II (HNPCC):
What is their risk of ovarian cancer?
What is their risk of endometrial cancer?

A

Ovarian cancer risk 10-12%
Endometrial cancer risk 40-60%

49
Q

What is CA-125 primarily a marker for?

A

Epithelial ovarian carcinoma

(peritoneal involvement)

50
Q

What other conditions raise CA-125

A

Fibroids
Endometriosis
Adenomyosis
Pelvic infection

51
Q

When is MRI useful in evaluating ovarian cysts

A

Cysts/masses >7cm (hard to evaluate by USS

If USS findings equivocal

Increased BMI (which limits USS)

Younger women <40 years

52
Q

What is the sensitivity and specificity of an RMI 200 for gynaecological malignancy?

A 
Sensitivity = 78%
Specificity = 87%

Over 250:

Sensitivity = 70%
Specificity = 90%
53
Q

What is the sensitivity and specificity of the IOTA Rules for gynaecological malignancy?

A

Sensitivity = 95%

Specificity = 91%

54
Q

When should CT A/P be performed, in the context of an ovarian mass?

A
  • RMI > 200
  • Evaluate for metastasis when malignancy suspected
  • If non-ovarian primary suspected e.g. colon with ovarian mets
55
Q

What are three complications of advanced ovarian cancer?

A

Bowel obstruction

Ureteric obstruction
Ascites
Pleural effusions

VTE (particularly proximal /pelvic veins)

56
Q

What is the 5 year survival rate for Ovarian Cancer

Stage 1
Stage 2
Stage 3
Stage 4

A

Stage 1 = 80-90%
Stage 2 = 67-70%
Stage 3 = 29-59%
Stage 4 = 17%

57
Q

What was the finding of the Cochrane review looking at the risk of ovarian cancer in women treated with ovarian stimulating drugs for infertility?

A

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

58
Q

What was the finding of the Cochrane Review looking at chemotherapy vs surgery for initial treatment in advanced ovarian epithelial cancer>

A

For GIFO Stage III or IV
Little or no difference in primary survival outcomes between primary debulking surgery and neoadjuvant chemotherapy / IDS

59
Q

What was the finding of the Cochrane Reivew looking at HRT after surgery for epithelial ovarian cancer?

2020

A

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

60
Q

What is the ECOG Score?

A

It assesses performance status - i.e. ability to perform ADLs, mobilise, more strenuous activities. Can monitor deterioration due to disease burden or treatment.

0 - Normal activity
1 - Can perform light duties, incl. employment and house work
2 - Can manage self cares / hygiene but not light work
3 - Needs assistance with self care; bed/chair bound >50% time
4 - Significant disability - bed/chair bound
5 - Dead

61
Q

What are the side effects of carboplatin and paclitaxel?

If a patient does not tolerate this regime, what are the alternatives?

A

Carboplatin:

  • N&V
  • hypersensitivity
  • neutropenia
  • *- thrombocytopenia**
  • nephrotoxic

Paclitaxel:

  • *- Alopecia**
  • *- Myalgia and arthralgia**
  • *- Neurotoxicity**
  • N&V
  • hypersensitivity
  • neutropenia
  • thrombocytopenia
  • nephrotoxic

Options:

  • Platinum based single agent chemotherapy
  • If placlitaxel hypersensitivity - used doxetaxel or doxorubicin instead
62
Q

What are the 3 aims of cytoreductive surgery?

A
  • Reduce tumour burden to optimise response to chemo
  • Reduce disease related symptoms
  • Reduces cytokines produced by tumour cells to improve immune competence
63
Q

What is the procedure for cytoreductive surgery?

At what stage do you start doing cytoreductive as opposed to just primary staging surgery?

A
  • Advanced disease - stage IIB - IV
    • (i.e. once extension to other peritoneal surfaces in pelvis beyond uterus/tubes/ovaries)

Procedure:

  • TAH-BSO
  • Ascites or peritoneal washings for cytology
  • Infracolic/gastrocolic omentectomy
  • Pelvic and para-aortic lymph node dissection
  • Optimal cytoreduction of any visible disease, may involve:
    • Peritoneal disease resection / diaphragmatic stripping
    • Resection of rectosigmoid / small bowel
    • Splenectomy, hepatectomy, distal pancreatectomy, urological resection, abdominal wall
64
Q

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

A

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

65
Q

Characteristics of HGSC

A

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

Associated mutations p53 tumour suppressor gene

66
Q

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

A

embryo (teratoma)

yolk sac (yolk sac, endodermal sinus tumour)

trophoblast (choriocarcinoma)

Mixed (dysgerminoma)

67
Q

FIGO stage 1 of ovarian cancer?

A

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 surface

IC3: Positive peritoneal washings or ascites

68
Q

FIGO stage 2?

A

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 thereof
2b: Extension to other pelvic intraperitoneal tissues

69
Q

FIGO stage 3?

A

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)
70
Q

FIGO stage 4?

A

Distant metastasis excluding peritoneal

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

71
Q

Hormones produced by germ cell tumours?

A

Dysgerminoma: HCG, LDH

Immature teratoma: a-FP, LDH

Yolk sac tumour: a-FP, LDH

Choriocarcinoma: HCG

72
Q

Investigations for staging?

A

Pre-op

  • CT AP
  • CXR
  • Histological diagnosis - necessary if considering neoadjuvant chemotherapy
    • Ascitic fluid for cytology
    • Pleural fluid for cytology
    • Core needle biopsy LNs/omentum (never usually primary tumour in case upstage)

Intra-op

  • Surgical staging
    • +/- Frozen section
73
Q

What are the principles of management?

A

Cytoreductive surgery (aim to reduce to no visible disease)

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

74
Q

Summary of EORTC vs CHORUS trials

A

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

Findings:

  • 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)
  • NACT associated with lower post operative morbidity
75
Q

Follow up and surveillance

A

3-4 monthly for first 2 years

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)

76
Q

What is a borderline ovarian tumour?

A

“A heterogeneous group of lesions defined histologically by atypical epithelial proliferation without stromal invasion.”

Can have peritoneal implants, and the implants can be invasive.

Make up 10-20% epithelial ovarian tumours

The behaviour of these tumors is distinct from low-grade ovarian carcinoma and they are considered a distinct clinical entity.

Exhibit behaviour that is intermediate between benign cystadenomas and invasive carcinomas.

Majority confined to ovary (70% stage I at diagnosis)

>30% diagnosed in women under 40 years - implications for fertility

77
Q

Histological types of borderline ovarian tumour?

A
  • serous (65-70%)
  • mucinous (11%)
  • rarely endometrioid, clear-cell, or transitional cell (Brenner) borderline tumours
78
Q

Prognostic factors for borderline ovarian tumours?

A
  • Older age at diagnosis
  • FIGO staging (which is the same as ovarian cancer)
  • Presence of micropapillary features
  • Serous histology has favourable outcomes
  • Residual disease at completion of primary surgery - cystectomy vs USO
79
Q

Management of malignant germ cell tumours

A

Surgery

  • 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

Adjuvant chemotherapy:

  • 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))

These cancers are VERY chemosensitive and even recurrences are highly treatable.

80
Q

Survival malignant germ cell tumours

A

Excellent.

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%

81
Q

Comment critically on the objectives or surgical Mx of epithelial ovarian cancer.

A

Staging laparotomy is crucially important:

  • as a prognostic index for the individual
  • to influence subsequent Rx (whether adjunctive chemoRx is required in early stage disease, whether additional surgery is required after conservative surgery
  • to provide data for use in clinical trials

Primary cytoreductive surgery is intended to:

  • improve tumour response to chemo- or radio-therapy
  • treat, prevent or delay complications caused by tumour masses eg. ascites, bowel obstruction
  • enhance immunological competence
  • provide psychological benefit

The value of such surgery in improving survival rates is unproven. Second-look procedures other than palliative surgery are controversial and their benefits uncertain eg. intervention cytoreductive surgery after chemotherapy, second-look laparotomy and secondary cytoreductive after recurrence of tumour.

Palliative surgery aims to improve quality of life but survival is often limited (eg. resection bypass or colostomy)

82
Q

Critically appraise the morbidity of chemotherapeutic regimens for ovarian epithelial cancers and the measures which might be taken to minimise the side-effects of therapy.

A

SE:

  • hypersensitivity
  • nausea and vomiting
  • bone marrow suppression (particularly thrombocytopaenia),
  • neutropenia and infection,
  • Leukaemia,
  • neuropathy
  • alopecia,
  • arthralgia/myalgia

Minimise side-effects:

  • sedation,
  • effective anti-emetics prior to and during Rx,
  • steroids and H2 antagonists
  • fluid loading prior to treatment,
  • overnight administration of cytotoxics agents
  • limitation of Rx if no response after three pulses of therapy - limitation of Rx to one year beyond which it is not helpful and the risk of leukaemia is incr.
  • alopecia is prevented by selection of appropriate chemotherapy; cold caps
  • specilaised support and treatment in a cancer centre
83
Q

Types of sex cord-stromal tumours

A

Arise from gonadal stroma surrounding oocytes including granulosa cells, thecal cells, sertoli cells, leydig cells and fibroblasts

Either from sex cord (sertoli or granulosa cell tumour)

Or stromal cells (fibroma, thecoma, leydig cell)

Or both (Sertoli-leydig)

84
Q

Treatment of stage 2 and 3 epithelial cancers

A

Stage 2b-3b: start with cytoreductive and staging surgery, aiming at complete resection.

After this then chemotherapy (typically 6 cycles) is required.

If advanced disease or the woman is too unwell for surgery then may need to start with 3 cycles of chemotherapy and then reassess and consider debulking at this stage. Normally then requires another 3 cycles of chemo after debulking/staging surgery.

85
Q

Treatment of stage 4 epithelial cancers

A

Stage 3c-4:

Start with neoadjuvant chemotherapy.

Then decide if patient is fit for radical surgery and there is evidence that disease is not progressing. If so then aim for debulking.

If not then for another 3 cycles of neoadjuvant chemotherapy. (Although may start with surgery)

86
Q

Typical presentation of malignant germ cell tumours

A

Most germ cell tumours are diagnosed in young women in their teens or twenties

Often present with acute pain or palpable rapidly enlarging abdominal mass.

May also have abnormal vaginal bleeding

87
Q

Screening if BRCA +ve

A
  • Monthly breast self-examination (BSE) beginning at age 18
  • Clinical breast examination 6 monthly beginning at age 25
  • Annual mammography or breast MRI beginning at age 25
  • Until prophylactic mastectomy
  • No evidence for routine pelvic USS and CA125 screening - unless declining rrBSO

PLCO trial

  • screening has not been associated with a statistically significant reduction in mortality from ovarian cancer
  • causes harm by surgery for false positive results
  • Its use cannot be routinely recommended even in women deemed at high risk
  • Interval cancers can develop between screening visits and are often advanced at presentation.
  • Serum CA125 levels are only elevated in 50–60% of stage I ovarian cancers
  • 6 monthly USS and CA125 screening should only be offered in women declining risk-reducing surgery, in the absence of a better alternative. It should be started from 35 years.
88
Q

Prophylactic surgery in BRCA carriers

A
  • Risk reducing BSO recommended for women once childbearing completed
  • BRCA1 at age >35 and <40
  • BRCA2 age <45
  • Reduces risk breast ca by 30-75% (also recommend bilateral mastectomy)
  • Improves survival by 60-76%
  • Still carries a risk of primary peritoneal disease (2%)
  • If no personal hx of cancer can offer HRT until around 50 - although small increased risk in breast Ca, no increased risk of breast cancer related mortality.
89
Q

Lynch syndrome cause

A

germline mutations in the DNA mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2)

90
Q

Risk of malignancy with Lynch syndrome

A

Increased risk of early-onset cancer of multiple types, including colorectal, endometrial, ovarian, gastric, small bowel, hepatobiliary, brain, ureteric and renal pelvic cancers. The lifetime risk for endometrial cancer is 40–60% compared with a risk of 3% in the general population. For ovarian carcinoma, the lifetime risk is 10–12% compared with the general population risk of 1.4%.

91
Q

How to assess families for potential Lynch syndrome

A

Families with Lynch syndrome are identified clinically using the Amsterdam criteria and the Bethesda Guidelines

92
Q

Risk reducing surgery for women with Lynch syndrome

A

Evidence lacking for endometrial surveilance

Offer TLH-BSO

93
Q

Peutz-Jeghers syndrome

A

Germline mutations in the STK11 gene cause Peutz-Jeghers syndrome (PJS), an autosomal dominant gastrointestinal polyposis disorder which confers an increased risk of breast, gastrointestinal and gynaecological tumours. Patients with the condition manifest characteristic pigmented lesions on the lips and buccal mucosa, which should prompt clinicians to consider the underlying diagnosis. 20% risk of developing sex cord stromal tumours of ovary

94
Q

What are the characteristics of serous and mucinous borderline tumours?

A

Serous

  • 25-50% bilateral
  • micropapillary features present in 10-15%

Mucinous

  • 10% bilateral
  • May be associated with low grade appendiceal primary tumour
95
Q

Management of borderline ovarian tumours.

A

Management is surgical - usually excellent prognosis. The complete staging procedure for all ovarian cancer includes: total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) with peritoneal washing, omentectomy, and careful examination of peritneal surfaces and pelvic organs with resection of grossly visible metastases. Appendicectomy if mucinous histology (due to low grade mucinous appendiceal primary).

Consider fertility preserving procedures - in early stage disease there is no difference in progression free or overall survival with conservative surgery

  • USO
  • Cystectomy has a higher risk of recurrence compared to USO (23% vs 7%)
  • Generally no role for lymphadenectomy or adjuvant therapy.
96
Q

Describe the protective effect of COCP for ovarian cancer.

A
  • 20% risk reduction for every 5 years of use.
  • 50% risk reduction after 15 years use.
  • Effect continues after cessation of pill, up to 30 years. Though effect attenuates over time.
97
Q

What is the risk of malignant transformation in ovarian endometriosis?

A

2-3 fold increase in clear cell and endometioid ovarian ca and possible LGSC.

Absolute risk still low - 0.7-2.5%

98
Q

What can be used as chemoprevention for ovarian cancer in women with significant family history or BRCA positive?

A

COCP - significant reduction in risk of ovarian cancer and no increase in breast cancer risk up to 10 years after cessation of use.

  • BRCA1 breast Ca usually ER/PR negative (BRCA2 usually ER/PR pos)
99
Q

Borderline tumours involve mutations of which pathway?

A

BRAF/KRAS

100
Q

BOT - factors that increase risk of recurrence after primary surgery?

A

Invasive implants

DNA aneuploidy

micro papillary tumours

101
Q

Laparoscopy and BOT?

A

Risks:

Increased spill rate

Risk of port site metastasis, understating disease

Worsened survival

At present laparotomy recommended

102
Q

Definition borderline tumour

A

Tumours of low malignant potential with atypical epithelial proliferation but without stromal invasion. Noninvasive neoplasms that can have intraperitoneal spread.

103
Q

Six subtypes of borderline ovarian tumours

A

Serous (65-70%) Mucinous (11%), Less common: Endometrioid, clear cell, seromucinous, borderline Brenner tumor

104
Q

Describe malignant potential of borderline ovarian tumours

A

BOT can be associated with microinvasion, intraepithelial carcinoma, lymph node involvement, and non-invasive peritoneal implants

105
Q

Prognosis for BOT

A
  • majority of BOT are limited to the ovary(ies) at presentation
  • 75% being diagnosed at FIGO stage I, compared to only 10% of ovarian carcinomas diagnosed at an early stage.

10-year survival of 97% for all stages combined recurrences and malignant transformation can occur

  • The 5-year survival rates for: - stage I borderline: vary from 95–97%. - stage III: 50–86%. The 10-year survival rates range from 70–80%, owing to late recurrence
106
Q

Serous borderline tumours

A
  • Most common (50%) - Often bilateral (30%) - Share similar histological features to low grade serous carcinomas - May be a spectrum of cystadenomas - BOT - low grade serous adenoma - Can be associated with extra-ovarian lesions (also called implants), which can be invasive or non-invasive
107
Q

Mucinous borderline tumours

A
  • Second most common (11%) - Either intestinal (86%) or endocervical/mullerian - 10% associated with peritoneal pseudomyxoma - Can be indistinguishable from appendiceal tumours therefore also need to review appendix Tumors are usually large, unilateral, and cystic with a smooth ovarian surface, composed of multiple cystic spaces with variable diameter. The cysts are lined by columnar mucinous epithelium of gastric or intestinal differentiation, with papillary or pseudopapillary infoldings, and admixed goblet cells and neuroendocrine cells
108
Q

Risk factors for BOT

A
  • Younger age (>30% diagnosed under 40yrs) - Nulliparity - Protective: - Lactation No evidence of increased or decreased risk: - BRCA mutation - Contraceptive pill use
109
Q

Histological features of BOT

A

Histological features are defined by epithelial cellular proliferation greater than that seen in benign tumours. Borderline ovarian tumours have a stratified epithelium with varying degrees of nuclear atypia and increased mitotic activity; their lack of stromal invasion distinguishes them from invasive carcinomas

110
Q

Treatment for women with BOT: - Desire to retain fertility - No desire to retain fertility

A
  1. Retain fertility: - Early stage? - conservative surgery - Late stage? - If invasive implants then complete surgery and follow up. If no invasive implants then consider conservative surgery with close follow up Need to counsel re risk of recurrence and future fertility Consider complete surgery after family complete 2. No desire to complete fertility: - Complete surgery with close follow up Complete surgery: - exploration of the entire abdominal cavity with peritoneal washings - TAH-BSO - infracolic omentectomy - appendicectomy in the case of mucinous tumours Conservative surgery: Either cystectomy or USO + washings
111
Q

Tumour markers in BOT

A

Serum CA125 levels may be raised: - may have a high level in 75% of serous and 30% of mucinous borderline ovarian tumours.

CA19-9 levels are frequently raised in mucinous borderline ovarian tumours.

Other tumour markers such as CEA, CA15-3 and CA72-4 may help detection but are not specific and may be within normal limits or only minimally elevated.

RMI status often low as many borderline ovarian tumours occur in younger, premenopausal women,

112
Q

What to do if a BOT is identified after surgery

A

Referral to the regional cancer centre followed by discussion at MDM.

Further management is planned according to the histology, grade, stage,

DNA ploidy status (DNA aneuploidy carries higher risk of dying), fertility preferences and completeness of primary surgery.

113
Q

Recurrence rates for early stage BOT dependent on surgical management

A
  • Cystectomy 23% - USO 7%
114
Q

Fertility outcomes after treatment of borderline ovarian tumours

A

no adverse effect of pregnancy on the disease or vice versa. Spontaneous fertility rates reported in literature vary between 32–65%, with nearly half of the women treated conservatively conceiving spontaneously

Gynae-Oncology (14 decks)

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