OVARIAN CANCER New NICE guidelines and the research behind them

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OVARIAN CANCERNew NICE guidelines and the
research behind them

• Journal Club 20/5/11
• Natalie Brown and Matthew Parkes

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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

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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

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Clinical question What are the symptoms and
signs of ovarian cancer?
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Recognition in primary care when to measure
CA-125

• Symptoms present particularly gt12 times per month
  (especially if gt50yo)
• 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

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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

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Investigation after CA-125 results in primary care

• If CA-125 gt 35, arrange USS abdomen and pelvis
• If USS suggestive of ovarian cancer, refer
  urgently (2ww)
• If normal USS consider other causes
• If CA-125lt35, consider other causes

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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 gt250

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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

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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

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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

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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

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Summary of holistic management

• Fertility
• Sexuality
• Genetics
• Physiotherapy

• Self-help strategies
• Counselling
• Support groups

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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 casecontrol studies should be
  conducted to compare the accuracy of CT versus
  MRI for staging in women with ovarian cancer.

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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

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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

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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

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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

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Were the controls recruited in an acceptable way?

• All controls have family histories consistent
  with inherited susceptibility for ovarian cancer

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Was exposure accurately measured to avoid bias?
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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

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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

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How precise are the results?

• Wide confidence intervals for results

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Do you believe the results?

• Unable to comment on quality and appropriateness
  of survey
• Measuring of serum markers appropriate

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Can the results be applied to the local
population?

• USA study
• Symptom reporting different across Atlantic?
• Tumour markers ? Universal across populations

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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.