OVARIAN CANCER
New NICE guidelines and the
research behind them
Journal Club 20/5/11
Natalie Brown and Matthew Parkes
Content
• Summary of NICE guidelines
• Critical appraisal of paper
– Anderson M, Goff B, Lowe K et al. Use of
symptom index, CA125 and HE4 to predict
ovarian cancer. Gynecol Oncol 2010 March
116(3): 378.
• Discussion
NICE guidelines: Ovarian Cancer
• The recognition and initial management of ovarian
•
•
cancer – published April 2011
Guidelines produced to focus on areas of uncertainty and
when wide variation in clinical practice
Statistics
– 5th most common cancer in women (1 in 20 cases of
cancer) and rising
– Leading cause of death from gynaecological cancer
(4,300 women die from ovarian cancer each year in
the UK)
– Overall 5 year survival 35%
– Approximately 6,700 new cases of ovarian cancer
were diagnosed every year in United Kingdom
between 2004 and 2007
Clinical question: What are the
symptoms and signs of ovarian cancer?
Recognition in primary care : when
to measure CA-125
• Symptoms present particularly >12 times per month
(especially if >50yo)
–
–
–
–
Persistent abdominal distension (‘bloating’)
Early satiety and/or loss of appetite
Pelvic or abdominal pain
Increased urinary urgency and/or frequency
• Alternatively, suspect in a woman over 50 who has
•
developed ‘IBS’ symptoms in the last year
Also measure if experiencing weight loss, change in
bowel habit or fatigue and ovarian cancer is suspected
When to avoid CA-125 in primary
care
• If a woman has ascites and/or an
abdominal or pelvic mass on clinical
examination that is ‘not obviously due to
uterine fibroids’
• Refer urgently (2 week referral) to
secondary care
Investigation after CA-125 results
in primary care
• If CA-125 > 35, arrange USS abdomen
and pelvis
– If USS suggestive of ovarian cancer, refer
urgently (2ww)
– If normal USS consider other causes
• If CA-125<35, consider other causes
Establishing the diagnosis in
secondary care
• Need to have USS or CA-125 if not already
done
• If under 40 years old, measure beta-hCG
and AFP to identify those who may not
have epithelial ovarian cancer
• Next calculate RMI score and refer to MDT
if score >250
Risk of malignancy index (RMI)
• RMI = score based on combination of USS
•
findings, menopausal status and CA-125 level
USS score; 1 point if one of the following
present, 3 points if 2-5 of the following present
–
–
–
–
–
Multilocular cysts
Solid areas
Metastases
Ascites
Bilateral lesions
RMI continued
• Menopausal status
– 1 point if pre-menopausal
– 3 points if post-menopausal
• CA-125
– Use the value itself
• Eg a post menopausal lady with ascites and solid
•
areas on USS, and CA-125 of 50 has an RMI of 3
x 3 x 50 = 300
If RMI is 250 or greater, must be referred to
specialist MDT
Further investigation in secondary
care
• If overall picture suggestive of ovarian
cancer, needs CT pelvis, abdomen +/thorax to assist with staging
• MRI not routinely advised
• Tissue diagnosis – generally recommend if
contemplating chemotherapy
– Percutaneous image guided biopsy
– Laparoscopic biopsy
Summary of clinical management
• Stage I
–
–
–
–
Oophorectomy
Retroperitoneal lymph node assessment
1a and 1b – no chemotherapy
1c and above – adjuvant chemotherapy
• Stage II-IV
– Surgical objective = complete removal of all
macroscopic disease
– Intraperitoneal chemotherapy only used in Trials at
present
Summary of holistic management
•
•
•
•
Fertility
Sexuality
Genetics
Physiotherapy
• Self-help strategies
• Counselling
• Support groups
Further research recommendations
• Further research should be undertaken on
the relationship between the duration and
frequency of symptoms in women with
ovarian cancer before diagnosis, the stage
of disease at diagnosis and subsequent
survival.
• Large multicentre case–control studies
should be conducted to compare the
accuracy of CT versus MRI for staging in
women with ovarian cancer.
Critical Appraisal of journal article
• Anderson M, Goff B, Lowe K et al. Use of
symptom index, CA125 and HE4 to predict
ovarian cancer. Gynecol Oncol 2010 March
116(3): 378.
• Using ‘CASP’ framework via BWH Trust
library homepage
Did the study address a clearly
defined issue?
• To evaluate to use of symptom index with
serum HE4 or Ca-125 alone and in
combination to predict ovarian cancer
Did the authors use an
appropriate method to answer
their question?
• Prospective case-control study
– 74 women with ovarian cancer
– 137 ‘healthy’ women as controls
Were the cases recruited in an
acceptable way?
• Cases were recruited from a group that
had positive imaging suggesting ovarian
cancer and were surveyed prior to surgery
and before receiving a definitive diagnosis
of ovarian cancer
Were the controls recruited in an
acceptable way?
• All controls have family histories consistent
with inherited susceptibility for ovarian
cancer
Was exposure accurately measured
to avoid bias?
What confounding factors have the
authors accounted for?
• Control group selection bias and the ability to
•
•
•
record and recall symptoms more specific to
ovarian cancer
Recall bias of patients awaiting surgery and
ability to remember recent symptoms than a
high risk control group
Study does not have detailed information for
imaging results
The study did not look at case notes to see if
symptoms had been clinically reported – only
took results from their own survey
What are the results?
• As a single marker CA-125 had the highest
•
•
•
overall sensitivity 81.1% and specificity of 95%
HE4 had the highest sensitivity in high risk
cases, overall sensitivity 77% and specificity
95%
Symptom index alone showed sensitivity of
63.5% and specificity of 88.3%
Any 2 of 3 above positive sensitivity 83.8% and
specificity of 98.5%
How precise are the results?
• Wide confidence intervals for results
Do you believe the results?
• Unable to comment on quality and
appropriateness of ‘survey’
• Measuring of serum markers appropriate
Can the results be applied to the
local population?
• USA study
• Symptom reporting different across
Atlantic?
• Tumour markers ? Universal across
populations
Do the results fit with other
available evidence?
HE4
- Consistent evidence across studies
suggesting HE4 better than Ca-125
- Also suggests that the combination of
HE4 and CA125 is more specific, but less
sensitive than either marker in isolation.