gmacleantumormarkers

8/3/2019 GMacLeanTumorMarkers

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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, metastasiscan induce immune response

expressed early in malignant

transformationshed by cancer cells into serum


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Monoclonal antibodies can be developed

and used to detect these mucin antigens onthe 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 = 1000Lap: Fallopian tube ca (Adeno Ca)

With chemo: Ca 125 down to 10 (N


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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, possiblesmall mass in head of pancreas, possible small

lesions in liver

CEA = 20 (N


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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 benigndisease

Normal in 85% of patients with poorlydifferentiated cancer at presentation

Only a small percentage have resectable

disease

Is the patient fit for partial hepatectomy?


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Tumor Markerssome key facts:

Lack of specificity

Cancer heterogeneity

False negativesBenign 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?

CEAsmall % have resectable diseaseIn the patient otherwise fit enough to

withstand the next steps?

Living with the fearand who willmanage the anxiety?


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Diagnosis:

CA 125 +ve

CEA +ve

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 therapytreat the symptomor 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 = 350normal 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 cureDoes not mean complete remission

May not even mean improvement

If we use the number to reassure, wehave 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 cancereg: CA125 or CEA

Multiple markers elevated

Marker falling, mass increasing

There is a role for clinical judgement!


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Follow-up monitoring:

o If useful salvage therapy

eg: CEA to detect solitary resectable met

o If useful lead-time, and useful therapyeg: germ cell cas

o But it can create

anxiety

false reassurance

false hope


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And the dilemmawhat next?


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Serum Tumor Markers -

When most helpful

o Gestational Trophoblastic Neoplasia

o Chemotherapy of Germ cell cas

o Monitoring pts with germ cell cas

o Monitoring chemotherapy for ovarian ca

o Seeking surgically resectable relapse


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Serum Tumor Markers -

When not helpful

o Provoking anxiety

o Palliative chemotherapy

o Treat the symptom not the number

o The false reassurance of normal


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Serum Tumor Markers highlight

communication gaps

o Does the patient understand?

o Does the Oncologist understand?o 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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