Download Ovarian Cancer Screening

Ovarian Cancer Screening
Dr Karen Mizia
SAN Ultrasound for Women
0562/SAH/1112/SAH
Learning Objectives
• Review the current evidence with regard to ovarian cancer screening
• How to assess the importance of an ovarian mass
• When to refer
Ovarian Cancer
• High mortality rate
• Stage I 90% 5 year survival
• Stage III or IV 30% survival
• Leading cause of death from gynaecological malignancy
• Relatively uncommon with an incidence of 10 in 100 000
• Aim to improve mortality rate with screening
Ovarian Cancer Screening Trials
PLCO (USA)
UKC-TOCS (UK)
Multi-centre (Japan)
University of Kentucky
(USA)
Ovarian Cancer Screening Trials
PLCO (USA)
UKC-TOCS (UK)
Multi-centre (Japan)
University of Kentucky
(USA)
• Randomised controlled trial of 78,216 women aged 5574
• Annual screening with TVUS and serum Ca-125 for 4
years or their usual gynae care
• US screen positive: ovarian volume > 10 cc, any cyst >
10 cc, any cyst with any solid area
• Physician informed of abnormal results within 3 weeks
• Treatment left to the discretion of the treating doctor
• 71% of OvCa detected by TVUS alone were stage I-II
• Ratio of surgeries to screen detected OvCa 19.5:1
• No evidence of a shift to earlier stage disease with
screening
• Survival rates similar
Ovarian Cancer Screening Trials
PLCO (USA)
UKC-TOCS (UK)
Multi-centre (Japan)
University of Kentucky
(USA)
• 202 638 post menopausal women aged 50-74 years randomly
assigned to:
• No treatment
• Annual Ca125 with TVUS as a second line
• TVUS annually
• US Screen positive: complex ovarian mass, simple cyst >60 cc,
ascites
• Abnormal primary screen repeat TVUS 6-8 weeks  abnormal
scan  referred for clinical assessment
• Clinical assessment then involved further Ca125, TVUS with
Colour Doppler studies, CT/MRI
• In TVUS arm:
• Surgeries to screen detected OvCa 18.8:1
• 50% had stage I or II (26% in control arm)
• Multimodal arm:
• Surgeries to screen detected OVCa 2.8:1
• 47% has stage I or II
• Mortality result pending
Ovarian Cancer Screening Trials
PLCO (USA)
UKC-TOCS (UK)
Multi-centre (Japan)
University of Kentucky
(USA)
• Prospective randomised trial
• 41 688 asymptomatic post menopausal women
• Screen arm (annual pelvic exam, TVUS and Ca125) or
control
• US screen positive: malignant impression, > 4 cm
• Management at discretion of oncologist
• TVUS associated with increase in early stage (63% vs
38%)
• Mortality result pending
Ovarian Cancer Screening Trials
PLCO (USA)
UKC-TOCS (UK)
Multi-centre (Japan)
University of Kentucky
(USA)
• 41 413 women aged over 50 or above 25years with
family history
• Case control: screening group compared to matched
controls in the same hospital
• Screen positive  repeat screen 4 weeks  Ca125 
repeat TVUS with colour Doppler and tumour indexing
 laparoscopic tumour removal within 8 weeks
• 68% stage I or II (27% controls), higher sub-stage shift
• 12 interval cancers
• 5 year survival 75% vs 53%
No current benefit to screening the
asymptomatic women
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RANZCOG
RCOG
ACOG
American Task Force
US Preventative Services Task Force
National Comprehensive Cancer Network
Canadian Task Force on the Periodic Health Exam
National Cancer Institute
National Breast and Ovarian Cancer centre
Australian Society of Gynaecology Oncologists
So a patient walks in…
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History
Family history
Serum biomarkers
Ultrasound
• Age: mean is 63 years
• In early age group benign more likely
than malignant
• Reproductive age more likely functional
cyst, epithelial ca rare but borderline and
sex cord stromal ca can occur
• Symptoms
• Most cysts asymptomatic
• Pain, pressure, bloating, frequency, early
satiety (PPV 1%)
• Bimanual
• Inaccurate for detecting and
characterising cysts
• Firmness and nodularity on POD
So a patient walks in…
• History
• Family history
• Serum biomarkers
• Ultrasound
Past History
Relative risk
Infertility
2.8
Nulliparous
1.6
Breast feeding
0.81
Oral contraceptive pill
0.65
Tubal ligation
0.59
Nagell and Hoff (2014) Transvaginal ultrasounograhpy in ovarian cancer: current
perspectives, International Journal of Women’s Health, 6,25-33
So a patient walks in…
• History
• Family history
• Serum biomarkers
• Ultrasound
• Genetic predisposition:
• family cancer syndromes have 3050% lifetime risk
• x1 relative 3.7%
• x2-3 relatives 5.5%
• Only 10% OvCa occur in patients
with a family history
• ACOG recommend period
screening
So a patient walks in…
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History
Family history
Serum biomarkers
Ultrasound
• Ca125
• Elevated in 50% of stage I, 90% stage III
• Not specific: elevated with other cancer,
benign disease
• Change over time
• HE4
• Improved sensitivity with Ca125
• Promising for triage not screening
• OvPlex
• Developed by HelathLinx Lmt
• Marketed as early detection test
• Measures ca125 and 4 other protein
biomarkers
• Company reports sensitivity 94.1% and
specificity 91.3%
Nossov et al (2008) the early detection of ovarian cancer from traditional methods
to proteomics, 199, 215-23
OvPlex
So a patient walks in…
• History
• Family history
• Serum biomarkers
• Ultrasound
• Some features seen on
ultrasound are diagnostic
Dermoid cyst
Endometrioma
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
So a patient walks in…
• History
• Family history
• Serum biomarkers
• Ultrasound
• International Ovarian Tumour
Association (IOTA)
• Compared simple ultrasound
rules, logistic regression models,
risk of malignancy index and
clinical skill
• 75% of masses defined as benign
or malignant with simple rules
• 93% sensitivity and 90%
specificity
IOTA simple rules
Benign
Malignant
 Unilocular cyst
 Irregular solid tumour
 Solid component where the largest is < 7 mm in
largest dimension
 Ascites
 Acoustic shadowing
 At least 4 papillary projections
 Smooth multilocular cyst < 100 mm in largest
dimension
 Irregular multilocular solid tumour at least 100 mm
in largest dimension
 No detectable blood flow on Colour Doppler
Imaging
 Very high colour component on Colour Doppler
Imaging
ONE OR MORE BENIGN, NO MALIGNANT FEATURES
= BENIGN
ONE OR MORE MALIGNANT, NO BENIGN FEATURES
= MALIGNANT
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
Ultrasonic features
Predictive value
For predicting a malignant tumour (M features)
M1—Irregular solid tumour
M2—Presence of ascites
M3—At least four papillary structures
96 (88 to 98); 64/67
97 (93 to 99); 157/162
88 (80 to 93); 75/85
M4—Irregular multilocular solid tumour with largest diameter
≥100 mm
84 (77 to 90); 103/122
M5—Very strong blood flow (colour score 4)
88 (82 to 92); 131/149
At least one M feature
87 (84 to 90); 340/389
For predicting a benign tumour (B features)
B1—Unilocular
99 (98 to 99); 673/681
B2—Presence of solid components, of which largest solid
component has largest diameter <7 mm
100 (90 to 100); 33/33
B3—Presence of acoustic shadows
95 (92 to 97); 223/234
B4—Smooth multilocular tumour with largest diameter <100
mm
99 (97 to 100); 190/191
B5—No blood flow (colour score 1)
98 (96 to 99); 615/629
At least one B feature
97 (96 to 98); 1083/1112
Rule 1: If one or more M features are present in absence of B feature, mass is classified as malignant.
Rule 2: If one or more B features are present in absence of M feature, mass is classified as benign.
Rule 3: If both M features and B features are present, or if no B or M features are present, result is inconclusive and
second stage test is recommended.
10% of multilocular cysts proved
to be malignant
functional
mucinous
cystadenoma
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
• Unilocular solid
• Borderline malignant serous
papillary cystadenoma
• Malignancy found in 37% of
solid masses
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
Malignancy found in 43% of
multilocular solid masses
Borderline serous papillary
adenocarcinoma
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
• Colour doppler flow image of
solid mass in 28 yo
• Dysgerminoma
• 65% of solid tumours proved to
be malignant
Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian
cancer, UOG, 6, 681-690
Learning Objectives
• Review the current evidence with regard to ovarian cancer screening
 No evidence to suggest routine population screening is helpful
• How to assess the importance of an ovarian mass
Consider the complexity
Combining markers with clinical suspicion improves detection when an
adnexal mass is detected improves sensitivity and specificity
• When to refer
Benign features conservative management or to gynaecologist
Malignant features, raised tumour markers or uncertain to gynae-oncologist