Tumor Markers Useful tool or part of the problem?

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Tumor MarkersUseful tool or part of the problem?

• Dr. Grant MacLean

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• Glycoconjugates on the cell surface
• involved in adhesion, motility, metastasis
• can induce immune response
• expressed early in malignant
• transformation
• shed by cancer cells into serum

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• Monoclonal antibodies can be developed
• and used to detect these mucin antigens on
• the cancer cell surface or in the serum

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• Pathologists can now help us with
• diagnostic dilemmas
• Eg Adeno ca, Unknown primary
• profile TTF1, CK-7, CK20

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• Focus on
• Serum Tumor Markers
• esp CEA
• CA 125
• CA 19.9
• also AFP, BHCG, PSA, CA15-3

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• Jen had presented with a pelvic mass.
• Ca 125 1000
• Lap Fallopian tube ca (Adeno Ca)
• With chemo Ca 125 down to 10 (Nlt37)

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• Jen 9 months later
• Anxious, fatigued
• Ca 125 200
• Now frightened

Diagnosis? Plan?
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• Gary presents with weight loss and jaundice.
• CT scan Gastric outline blurred, possible
  small mass in head of pancreas, possible small
  lesions in liver
• CEA 20 (Nlt4)
• CA 19.9 1700 (Nlt37)

Diagnosis? Plan?
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• screening
• diagnosis
• monitoring therapy
• remission
• follow-up

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• Anxious patients seek screening for
• early diagnosis
• reassurance
• Some angry patients want to know
• why was I not screened?

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CA 125 for Screening for Ovarian Cancer?

• FDA approval based on prediction of persistent ov
  ca at second look laparotomy
• 50 at 2nd look lap with residual disease had
  negative CA 125
• 50 with Stage I disease normal serum CA 125
• 11,283 women screened, 486 laps, to detect 5
  invasive cas and 8 borderline tumors

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CEA to screen for colon cancer, or relapse?

• Elevated in smokers
• Elevated in other cancers and benign disease
• Normal in 85 of patients with poorly
  differentiated cancer at presentation
• Only a small percentage have resectable disease
• Is the patient fit for partial hepatectomy?

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Tumor Markers some key facts

• Lack of specificity
• Cancer heterogeneity
• False negatives
• Benign diseases positive CA 125 or CEA
• Smokers have raised CEA
• Many men (20-40 !?) die with,
• not from, prostate ca.

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Screening

• Is a negative reassuring?
• What does a positive indicate?
• What is the lead time?
• Can we treat it better if we find it early?
• Can we manage the anxiety we create?

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Finding it early

• PSA do we need to treat?
• Is the lead time useful?
• CEA small have resectable disease
• In the patient otherwise fit enough to
  withstand the next steps?
• Living with the fear and who will manage the
  anxiety?

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Diagnosis

• CA 125 ve
• CEA ve
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• CA 19-9

What does it mean?
Where is the primary?
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• Serum tumor markers may be a helpful
• piece of the puzzle but are seldom
• diagnostic
• Exceptions AFP, BHCG, PSA

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• James, male, mid 30s
• - supra-clavicular lymph node
• - cough
• Clinically NAD except dull lung base
• CXR pleural effusion.

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• James
• CEA N
• AFP N
• BHCG 300

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Response to therapy?

• Early rise
• Fall usually means response
• beware heterogeneity
• normal does not mean remission
• palliative therapy treat the symptom
• or the number?

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• Stella presented with abdominal swelling.
• Limited lap widespread ovarian ca
• CA 125 300
• falling to 80 with chemo
• Yet the abdominal mass is increasing!?

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Most valuable uses of serum
tumor marker

• Are we using a useful therapy?
• Is this toxicity justifiable?
• Not all symptoms are cancer progression

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• Wendy had been on chemotherapy for
• Stage III ovarian cancer.
• CA 125 350
• normal after 3 treatments
• Prior to 5th chemo
• abdominal pain, vomiting,
• no bowel movement for 3 days.

Diagnosis? Plan?
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• At the end of therapy
• beware the misleading
• Does not mean cure
• Does not mean complete remission
• May not even mean improvement
• If we use the number to reassure, we
• have to manage the anxiety with the
• rising number

normal
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Beware the mysteries

• Elevated marker with NED
• eg BHCG with creatinine elevated
• Elevated marker with no cancer
• eg CA125 or CEA
• Multiple markers elevated
• Marker falling, mass increasing
• There is a role for clinical judgement!

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Follow-up monitoring

• If useful salvage therapy
• eg CEA to detect solitary resectable met
• If useful lead-time, and useful therapy
• eg germ cell cas
• But it can create

anxiety false reassurance false hope
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• And the dilemma what next?

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Serum Tumor Markers -

• When most helpful
• Gestational Trophoblastic Neoplasia
• Chemotherapy of Germ cell cas
• Monitoring pts with germ cell cas
• Monitoring chemotherapy for ovarian ca
• Seeking surgically resectable relapse

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Serum Tumor Markers -

• When not helpful
• Provoking anxiety
• Palliative chemotherapy
• Treat the symptom not the number
• The false reassurance of normal

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Serum Tumor Markers highlight communication gaps

• Does the patient understand?
• Does the Oncologist understand?
• Is the Oncologist accessible to the family
• physicians who knows the patient best, and
  who wonders why? or
• what next?

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• Gary
• Had obstructive jaundice
• after stenting
• CA 19.9 1700 normal.

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• Jen on clinical exam had diffuse
• Lymphadenopathy.
• Infectious mononucleosis
• On recovery, Ca 125 normal
• (200 20).

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Serum Tumor Markers

• A help?
• or
• a problem?