Transcript Screening for Ovarian Cancer - Ipswich-Year2-Med-PBL-Gp-2

Screening for Ovarian Cancer
Why screen for ovarian cancer?
• For advanced disease 5-year survival rates are
reported to be less than 30%, whereas for
patients diagnosed with stage I disease, the 5year survival is reported to be in excess of 90%
Why Not Screen for Ovarian Cancer
• The incidence and prevalence of ovarian cancer in the
general population is low -> low PPV and high false
positives
• False positives are followed up by invasive procedures with
a small, but significant risk of complications
• Up to 15% of women who undergo surgery for false
positive findings develop serious complications resulting in
morbidity and high cost of treatment
• The predictive value of either CA125 or transvaginal
ultrasonography (less than 3 percent) yields an
unacceptably high rate of false-positive results and
attendant morbidity and costs.
• The combination of annual CA 125 testing with
ultrasonography did not decrease mortality at 13 year
follow-up in a large randomized trial and screening caused
harm related to adverse effects from surgery for false
positive findings
Screening For Ovarian Cancer Using
CA 125
• CA 125 — Measurement of the serum
concentration of the CA 125 glycoprotein antigen
is the most widely studied biochemical method of
screening for ovarian cancer.
• Serum CA 125 values are elevated in
approximately 50 percent of women with early
stage disease and in over 80 percent of women
with advanced ovarian cancer
• a prospective study of asymptomatic
postmenopausal women found that an elevated
CA 125 concentration (≥30 U/mL) was a powerful
predictor of subsequent ovarian cancer risk (RR
35.9 at one year and 14.3 at five years)
Problems With Screening for Ovarian
Cancer using CA 125
• The specificity of CA 125 is limited. CA 125 levels are elevated in
approximately 1 percent of healthy women and fluctuate during the
menstrual cycle. CA 125 is also increased in a variety of benign and
malignant conditions, including:
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Endometriosis
Uterine leiomyoma
Cirrhosis with or without ascites
Pelvic inflammatory disease
Cancers of the endometrium, breast, lung, and pancreas
Pleural or peritoneal fluid due to any cause
• Mean CA 125 levels further vary with ethnicity and smoking status (lower
in non-White women and current smokers) and increase with age
• Studies of CA 125 in screening for ovarian cancer have focused upon
postmenopausal women, since menstrual cycle variations and the
prevalence of benign gynaecologic conditions in premenopausal women
would result in a substantially higher likelihood of false-positive tests.
Accumulated evidence suggests that annual CA 125 measurements alone
lack sufficient specificity for use in an average risk population of
postmenopausal women
Hereditary Breast-Ovarian Cancer
Syndrome
• The absolute risk of developing ovarian cancer over a lifetime
associated with the presence of a BRCA1 mutation is 35 to 45
percent, while it is less for those with BRCA2 mutations (15 to 25
percent)
• For women with a BRCA mutation, The American College of
Obstetricians and Gynecologists recommends periodic screening
with CA 125 and transvaginal ultrasonography beginning
between the ages of 30 and 35 years or 5-10 years earlier than
the earliest age of first diagnosis of ovarian cancer in the family.
• Risk-reducing salpingo-oophorectomy surgery—which removes
both of the ovaries and fallopian tubes—can reduce the risk of
ovarian and fallopian tube cancer by about 85% to 90% among
BRCA carriers. Women who have BRCA1 or BRCA2 mutations
should be offered risk-reducing salpingo-oophorectomy by age
40 or when childbearing is complete. The ideal time for this
surgery depends on the type of gene mutation.
Lynch II Syndrome
• Women with Lynch syndrome have a lifetime risk of
ovarian cancer that is 3 to 14 percent (compared with
1.5 percent in the general population) and develop
ovarian cancer at an earlier age than the general
population
• HNPCC is an autosomal dominant inherited
predisposition to develop colorectal and other cancers,
including ovarian resulting from failure of the DNA
mismatch repair system (MMR).
• Screening involves a detailed Hx, especially FHx of
colorectal, ovarian and other cancers, followed up by
PCR amplification of MMR genes (MLH1, MSH2
followed by others if first test is negative)
Ultrasonography
• Transvaginal ultrasonography has been evaluated
as a screening tool
Sensitivity (80 to 100%) and specificity (94-99%)
are operator dependent
• It has shown to be a poor screening tool for high
risk women, detecting cancers at stage III at the
earliest.
• Studies have found the method more useful in
screening lower risk women (with a family Hx of
ovarian cancer as opposed to familial types)
where early stage cancers are more likely to be
detected.
Multimodal Screening
• Combining CA 125 with transvaginal ultrasonography
• One UK study found elevated CA 125 (adjusted using an
algorithm to correct for stuff) followed by confirmatory
ultrasound had an 89.5% sensitivity, with 45% of cancers
detected at stages I & II. Specificity was 99.8%
• A UK study of Risk of Malignancy Index combined
ultrasound score, menopausal status and serum CA 125.
Three criteria are combined in a risk of malignancy index
(RMI) which is calculated using the product of the serum CA
125 level (U/ml), the ultrasound scan result (expressed as a
score of 0, 1 or 3) and the menopausal status (1 if
premenopausal and 3 if postmenopausal). Using an RMI
cut-off level of 200, the sensitivity was 85% and the
specificity was 97%.
• Patients with an RMI score of greater than 200 had, on
average, 42 times the background risk of cancer and those
with a lower value 0.15 times the background risk.
Ovarian Cancer Symptom Index
• The index is considered to be positive in women who
report pelvic or abdominal pain, bloating, increased
abdominal size, difficulty eating or early satiety
occurring more than 12 times a month, with symptoms
present for less than one year.
• A study found the combination of the symptom index,
CA 125 and HE4 serum markers as a first-line screen
had a sensitivity of 83.8 percent and specificity of 98.5
percent when two of the three tests were positive.
• If used for screening, a positive symptom index should
lead to transvaginal ultrasonography before surgical
referral.
When to Screen – Average Risk
• Screening for ovarian cancer with CA 125 or ultrasound
is NOT recommended for premenopausal and
postmenopausal women without a family history of
ovarian cancer .
• The predictive value of either test alone (less than 3
percent) yields an unacceptably high rate of falsepositive results and attendant morbidity and costs.
• The combination of annual CA 125 testing with
ultrasonography did not decrease mortality at 13 year
follow-up in a large randomized trial and screening
caused harm related to adverse effects from surgery
for false positive findings
When To Screen – Lower Risk Family Hx
• Women with a family history but without
evidence of a high-risk pattern.
• There is no evidence to support screening in
this group, and decisions regarding screening
should be based on individualised
considerations involving the patient and
clinician.
When To Screen – High Risk
• Women who are found to have BRCA1 and/or
BRCA2 or MMR gene defects.
• Even though evidence for screening
effectiveness has not been demonstrated, the
decision to screen this patient population is
based on their very high lifetime risk of
ovarian cancer.
• The optimal screening protocol, or frequency
for screening, has not been determined (Up To
Date 2011).