Tumor Markers Useful tool or part of the problem? Dr. Grant MacLean

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

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

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

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

Jen had presented with a pelvic mass. Ca 125 = 1000 Lap: Fallopian tube ca (Adeno Ca) With chemo: Ca 125 down to 10 (N<37)

Jen 9 months later Anxious, fatigued Ca 125 = 200 Now frightened Diagnosis? Plan?

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 (N<4) CA 19.9 = 1700 (N<37) Diagnosis? Plan?

screening diagnosis monitoring therapy remission follow-up

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

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

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?

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.

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?

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?

Diagnosis: CA 125 +ve CEA +ve CA 19-9 What does it mean? Where is the primary?

Serum tumor markers may be a helpful piece of the puzzle but are seldom diagnostic Exceptions: AFP, BHCG, PSA

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

James: CEAN AFPN BHCG300

Response to therapy? Early rise Fall usually means response beware heterogeneity “normal” does not mean remission palliative therapy – treat the symptom or the number?

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

Most valuable uses of serum tumor marker: Are we using a useful therapy? Is this toxicity justifiable? Not all symptoms are cancer progression

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

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”

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!

Follow-up monitoring: o If useful salvage therapy eg: CEA to detect solitary resectable met o If useful lead-time, and useful therapy eg: germ cell cas o But it can create anxiety false reassurance false hope

And the dilemma – what next?

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

Serum Tumor Markers - When not helpful oProvoking anxiety o“Palliative chemotherapy” oTreat the symptom not the number oThe false reassurance of “normal”

Serum Tumor Markers highlight communication gaps oDoes the patient understand? oDoes the Oncologist understand? oIs the Oncologist accessible to the family physicians who knows the patient best, and who wonders “why?” or “what next”?

Gary: Had obstructive jaundice after stenting: CA 19.9 = 1700 normal.

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

Serum Tumor Markers A help? or a problem?