Update on Cancer Tumor Markers.pptx

Appropriate Use and
Understanding of Tumor
Markers
Malcolm Brigden M.D.
Internet Sourcing and Hematology/Oncology
Slide Bank

Faculty/Presenter Disclosure
Relationships with commercial interests:
Grants/Research Support: None
Speakers Bureau/Honoraria: None
Consulting Fees: None
Perhaps I should get around more!

Disclosure of Commercial Support
Potential for conflict(s) of interest:
None

Some Other Disclosures-A
However, since nowadays everyone likes to disclose
something
• I do not like raisins in salads
• Similarly I own no green shirts
• There are many days when I wish I had a better
sense of humor
• My wife is the best thing that ever happened to me

Some specific CME disclosures-B
Le Temps Perdu - with apologies to Marcel Proust
Hippocrates (father of CME)
“Life is short the art is
long, occasion sudden,
experience fallible,
judgment difficult"
बालस्तवत क्रीडासक्तः तरुणास्तवत तरुणीसक्तः
व्र्द्धस्तावत चिन्तासक्तः परमे ब्रह्मचण कोचपनसक्तः
Balasthavath Kreeda aasaktah
tarunasthaavath taruneesaktah
vriddhasthaavath chintaasaktah
Parame brahmani kopinasaktah
As medical students we were playful in our
studies and wasted precious time
As young doctors, we were preoccupied with
family, spouse and finances
As older docs, we have enough worries, and
things seem to go in more slowly!
Alas, when are we to gain a proper update of
our knowledge!!

• To enhance and update participants’
understanding of the role of tumor markers in
cancer care including impact on screening,
diagnosis treatment and follow-up
• To understand the pros, cons and limitations of
tumor marker testing
• To provide various case scenarios which
hopefully will facilitate realistic applications

But First-Two Cases Scenarios for You to
Ponder during the Course of the
Presentation

Case scenario to ponder-Jen
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)
Clinical and CT remission

Jen- 9 months later
Anxious, fatigued, systemic symptoms
Ca 125 = 225
Now frightened -Am I relapsing?
What do you tell her?
Investigation/treatment plan?

Case scenario to ponder-Gary
Gary age 65- 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)
What do you tell him?
Investigation/treatment plan?

Topics to be covered
• Definition of tumor markers
• Classification of tumor markers
• Ideal characteristics of tumor markers
• Statistical consideration with tumor markers
• Assay technology for tumor markers
• Potential uses for tumor markers
• Individual tumor markers
• Various case scenarios
• Final conclusions

• A tumour marker is a biochemical indicator
selectively produced by certain tissues and
released into blood –detectable in blood or in
other body fluids.
• Any macro-molecule, regardless of function can
be called tumor marker
• One useful classification considers tumor
markers according to structure

Classification of tumor markers
according to structure
1- Oncofetal Proteins
2- Tumor Associated Antigens
3- Hormones
4- Hormonal Receptors
5- Enzymes
6- Cytokines
7- Oncogenes
8- Carbohydrate Related Antigens
9- Amino Sugar Derivatives

Types Examples
Protein / Glycoprotein CA125, CA15-3, CA19-9
Enzymes PSA, LDH
Oncofetal antigens CEA, AFP
Hormones hCG, calcitonin, gastrin, prolactin
Receptors ER, PR, EGFR
Oncogenes Ras, Myc, Bcr-Abl
Tumor suppressor
genes
BRCA1, p53, Rb

An Ideal Tumour Marker Should be….
Highly specificfor malignancy i.e. not detectable in benign
disease or healthy subjects
Highly sensitivefor malignancy i.e. detectable when only a
few cancer cells are present
Also
o Might be specific to a particular organ or cancer type
o Correlates with the tumour stage or tumour volume
o Correlates with the prognosis
o Reliably predicts recurrence
But such an ideal tumour marker doesn´t exist!!

Yes I'm Afraid We Have to go There-
Statistics
• There are lies, damned lies and statistics."
• Facts are stubborn things, but statistics
are pliable.” - both from Mark Twain
• There are known knowns; there are things we know we
know. We also know there are known unknowns; that is
to say we know there are some things we do not know.
But there are also unknown unknowns - the ones we
don't know we don't know.” - from the unjustly maligned
Donald Rumsfeld

Some Statistical Terms Defined
– 100% sensitive: Always positive in patients with the disease
– 100% specific: Always negative in individuals who do not have
the disease I.e. finds only the disease
– Positive Predictive Value of a Tumour Marker:
The probability with which a tumour exists within the
patient group in the case of positive test results
– Negative Predictive Value of a Tumour Marker:
The probability with which no tumour exists within the
patient group in the case of negative test results
– Specificity of an individual Tumour Marker:
The percentage of normal persons or persons with benign
conditions for whom a negative result is obtained. The greater
the specificity, the fewer the false-positives.

Marker Cut-off Value Defined
• The concentration of a tumour marker which
differentiates healthy subjects from diseased subjects
• Usually taken as the mean concentration of a control
group plus 2 standard deviations (or the 95th
percentile)
• Testing specificity should be 95% ( 5% or less false
positives)
• Accordingly the cutoff value chosen for individual
tumor markers should be optimized for sensitivity and
specificity

0.0 100 ng/mL
Prostate cancer
2.0
100% sensitivity…..
(no false negatives)
Sensitivity- 2.0 ng/mL Cut-off value (PSA)

Healthy
0.0 100 ng/mL
Prostate cancer
2.0
But only 70% specificity!
(30% false positives)
Specificity- 2.0 ng/mL Cut-off value (PSA)

Healthy
0.0 100 ng/mL
10.0
100% specificity
(no false positives)….
Specificity- 10.0 ng/mL Cut-off value (PSA)

Healthy
0.0 100 ng/mL
Prostate
cancer
10.0
100% specificity
But only 70% sensitivity
(30% false negatives)!
Sensitivity- 10.0 ng/mL Cut-off value (PSA)

Healthy
0.0 100 ng/mL
Prostate cancer
At 4.0 ng/mL, 95% specificity
and 95% sensitivity
4.0
Specificity and Sensitivity-4.5 ng/mL Cut-off value (PSA)

Quiz question?
Your patient with ovarian cancer who is between cycle 3-4
of carbo platinum taxol therapy has 2 consecutive C-125
measurements of:
June 2014: 350 July 2014: 250
You can now tell the patient with some confidence?
1) there has been a significant decrease in your marker level
2) your marker level has decreased but we can’t yet be certain
of its significance
3) this result looks good but we need to see a further trend
4) this result by itself is probably not interpretable and we need
both trend plus additional values
5) some other statistical mumbo-jumbo

Intra/Interindividual Biologic Variation-Much Larger
Than We Typically Consider

Correctly Interpreting Serial Results in Individual
Patients -RCV
When is a change in serial
results truly significant ?
• The significant % change
required between two 2 serial
test results is the reference
change value (RCV)
• Inter and intra-individual
biologic variation may be
solely responsible for the
magnitude of the RCV
• RCV values can be at 95% or
99% probability level
• RCV should be reported each
laboratory result-but often are
not even published by lab

Correctly Interpreting Serial Results
in Individual Patients-2
Rough rules of thumb incorporating known values
for RCV in relation to interpreting tumor marker
results
• Any individual value should increase or decrease by
more than 50%of the original if it is to truly represent a
significant change i.e. simple biological variation may be
solely responsible for any lesser degree of change
between 2 sequential test results
• Obviously if there is a continued trend upwards or
downwards over several sequential values, RCV
becomes less significant

The Dreaded Tumor Marker
Spurious Surge
• In the literature, also called flare, spiking or pseudo-progression
• Tumor on therapy associations: germ cell tumors, hepatocellular
,breast, prostate, pancreatic gastric, and ovarian cancer
• Not uncommon - may be seen in up to 30% with some tumor types
• Typical magnitude of increase - 20-30% but may be higher
• More likely to be seen early on in therapy (first 1-3 months)
• May last 2-3 months, but typically around 1 month
• Lack of familiarity with this occurrence may lead to potential
abandonment of beneficial therapy
• Most likely mechanism - release of markers by dying cells
• Paradoxical PSA flare may also be seen following brachytherapy
• Paradoxically delayed tumor marker decreases may also be noted

Some Paradoxical Tumor
Marker Responses

• Assay technology and laboratory testing for
tumor markers

Quiz question?
Based on the published literature, which
European country appears to have the
greatest incidence of gender confusion on
the part of physicians?

There were a total of 80
responses to the audit
questionnaire
England 60
Scotland 11
N Ireland 6
Wales 3
2012 UK National
Audit of Tumour
Marker Services

UK survey-Commonest reasons for
rejection of marker testing requests
• No or inappropriate clinical details given
• Multiple tumor markers requested - fishing/screening
expeditions
• PSA- in females
• CA 125- in males(17% of total requests)
• CA15-3- in males (26%of total requests)
• CA19-9 -but no suggestion of pancreatic disease in the
clinical details
• Thyroglobulin- in patients without known thyroid cancer
• CEA- in those with no history of colorectal cancer
• CA15-3 –but not for breast cancer follow up

Results of other tumor marker audits
• Greek hospital - only 10% of tumor marker
test requests appropriate, unjustified
expenses: $35,000/month
• Audit in Ireland - 30-50% of clinicians used
tumor markers to screen for malignancy
without an inappropriate index of suspicion

Summary:Some statistical/laboratory
considerations in relation to tumor markers
• Try to order testing from same laboratory
• Try to know the reference ranges and RCV95%
for each tumor marker test
• Never rely on results of a single test
• Remember the half-life of tumor markers and
possible spuriously surges when interpreting
clinically discrepant results

Tumor Marker Potential Usefulness in
Oncology
• Screening
• Diagnosis
• Staging
• Prognosis
• Monitoring
– During therapy
– During Remission and follow-up

Screening In General- Some Important Patient
Related Considerations
Anxious patients often seek screening for early diagnosis or
reassurance
Some angry patients want to know “why was I not screened
for this cancer in the first place?”
Other Considerations:
Is a negative marker result really reassuring?
What does a positive marker result indicate?
What is the lead time involved with possible early marker
elevation - and is it truly significant?
Can we actually treat the tumor better if we find it early?
Is the patient fit enough to withstand the next steps?
Can we manage any anxieties or fearsmarker testing creates?

Screening In General- Screening Versus
Case Finding
• Screening involves screening of all in a certain category
(for example, all adults of a certain age).
• Case finding involves screening a smaller group based
on the presence of risk factors or an individual patient’s
expressed concerns
– So, PSA’s on all comers over a certain age-screening
– But, PSA performed in the doctor's office because of family
history or other concerns - case finding
NB: The results of randomized screening studies
cannot automatically be extrapolated to case
finding scenarios

Tumor Markers and Screening
• Tumor markers play a limited role for tumor screening,
simply because….
– relatively low sensitivity
– lack of specificity and relation to tumor size
• Inappropriate for the detection of small in situ cancers
• Any practice of ordering a battery of marker tests in
carcinoma of unknown primary should be actively
discouraged.pro
• However there are a few situations where screening
with tumor markers may be appropriate
– calcitonin & medullary thyroid cancer

Tumor Markers and Screening-Unique
Situations
• UK consensus statement on ovarian cancer
recommends both CA 125 and pelvic ultrasound in
women >of 50 with unexplained abdominal/pelvic
symptoms.
• NCCN and hepatoma
recommends Q6 mth alpha-fetoprotein with abdominal
US for known Hep B or C related cirrhosis at high risk
for hepatocellular carcinoma
• PSA screening remains intensely debated with various
learned bodies advancing a variety of opinions
– In the great PSA debate, as mentioned, it is important to
discriminate between screening and case finding

More on CA-125 Screening
• It is useful for specific high risk group screening for
ovarian cancer, along with bi-annual examination &
ultrasound
– Family history of breast, ovarian, endometrial cancer
– History of removal of benign ovarian and breast tumour.
– Postmenopausal palpable ovary.
– Woman workers in asbestos industries.
• Reasonable sensitivity when used for appropriate
indications
– It can detect Ca. Ovary in 50% of Stage I and in 60% in Stage II.
– Its specificity increases if it is combined with ultrasound /clinical
exam or is serially determined over a period of time
46

St. Elsewhere's Case Presentation-A
A 69 year old non smoker female, had recurrent UTI’s.
The local practitioner ordered a CBC, LFT’s Cr,
which were normal, and a CEA, which
was 7.8 ( lab reference range0-2.5)
The patient subsequently referred to GI, Urology,
Hematology-Oncology

GI- performed colonoscopy and gastroscopy, both negative.
Urology- did a cystoscopy -found a benign urethral polyp.
Heme-Onc (under pressure from the sister) recommended:
CT chest, abdomen, pelvis, mammogram, and pelvic US
Also suggested : a GYN consult.
All of these studies/ consultations were negative!!

We interrupt this case presentation to
put you in the driver seat!
You have seen the St. Elsewhere Team's progress
If you were in charge you would now:
1) order a PET CT scan since CT scan was not helpful
2) order CT colonoscopy as regular colonoscopy was unhelpful
3) visit the lab-chew out the pathologist in charge of biochemistry
4) reassure the patient and do nothing further
5) reassure the patient, repeat CEA in three months

She returned to the office 4 months later, and
a repeat CEA level was 2.3
Financial toll: Probably in the range of 50 K+
Emotional toll: Likely incalculable

ASCO Recommendations - Appropriate Use of CEA
-CEA testing should be used for
staging/prognosis, detecting recurrence,
monitoring therapy, and screening for
hepatic metastasis in patients with colon
cancer.
-CEA is not recommended for screening of
neoplastic diseases, because of low
sensitivity and specificity
J Clin Oncol. 2001;19:1865-1878.

Tumor Markers and Diagnosis
• Tumor marker determination is not the key
diagnostic examination, but can be
complementary to clinical findings, medical
imaging or further referral
– AFP & Hepatoma Guideline: Finding a hepatic mass
>2 cm with cirrhosis and AFP >200 ug/L and typical
imaging-biopsy not required for hepatoma Dx
– CA 125 Ovarian Ca Guideline:CA 125 >35 with
indeterminate pelvic mass merits referral to
gynecological specialist/surgeon

Tumor Markers and Staging
• Germ cell tumors- tumor markers and medical imaging are
complementary in pre-therapeutic and post-therapeutic
staging
• Represent an integral part of the testicular cancer staging
protocol

Tumor Markers and Prognosis
• The pre-therapeutic level of certain tumor markers may
provide prognostic information since related to metabolic
activity, tumor size, extent of invasion
• May help to avoid the under treatment of aggressive
disease and overtreatment of indolent disease
• Also allows refinement of therapeutic strategies by
selecting groups at increased risk of failure with standard
treatments
• Represents a significant current use for tumor markers
– CEA & colon cancer
– Beta-hCG alpha-fetoprotein LDH & germ cell tumors
– PSA & prostate cancer
– CA 125 &ovarian cancer
– Oncotype DX &breast cancer

Tumor Type Potential Prognostic Information
CEA - colon cancer
De novo patients – Absolute CEA level prior to surgery
(especially if fail to return to baseline) poor prognostic sign
Hepatic metastectomy candidates-CEA >100 worse long-
term prognosis postsurgery
PSA - prostate cancer
De novo patients- Partin Tables-PSA level at diagnosis with
Gleason score allows risk stratification for biologic
aggressiveness/ likelihood of metastatic disease
CA 125 -ovarian cancer De novo patients- Pre-chemotherapy CA125 levels, half-life,
and time to nadir each have shown univariate prognostic
value for overall survival
Beta-hCG, LDH,alpha-
fetoprotein- germ cell
De novo patients-Marker levels at presentation facilitate
stratification into high, intermediate and low risk groups
which help direct subsequent therapy
Oncotype DX -breast ca
De novo patients-Gene signature analysis of 21 genes allows
prognostication into low, intermediate and high risk groups in
hormone receptor positive node-negative patients and direct
need for chemotherapy

Tumor Markers and Monitoring During Treatment
• High markers level before treatment generally:
– Not only correlate with the therapeutic results but are sometimes
superior for the assessment of complete remission status
• Periodic reassessment of the appropriate markers during
therapy coupled with sequential imaging may allow more
effective monitoring of treatment success
– Beta hCG, alpha-fetoprotein and LDH and germ cell tumors
– CEA and colon cancer
– PSA and prostate cancer
– CA 125 and ovarian cancer
– CA 19-9 and pancreatic cancer
– CA 15-3 and breast cancer
• Interpretation of serial results must also always consider
tumor marker half-life and a possibility of spuriously spiking

Tumor Markers and Monitoring During Remission
and Follow-up
May predict early recurrent/metastatic disease with a lead time over
clinical/radiological findings ie testicular cancer
– Possible local or limited metastasis
– Possible curable recurrence
Cancers where intense post treatment surveillance has produced
better outcomes:
– CEA and colon cancer
– Beta-hCG and AFP and germ cell tumors
Cancers where intense post treatment surveillance has not
necessarily produced better outcomes (But it's often done anyway)
– CA 15-3 in breast cancer
– CA 19-9 and pancreatic cancer
– CA 125 and ovarian cancer
Unfortunately for some incurable cancers such as ovarian cancer,
early marker detected recurrence has been associated with no
increased survival but actual adverse psychological outcomes

• Some Individual tumor markers

• CEA
• CA19-9
• CA15-3
• CA125
• PSA
• AFP
• bHCG
• LDH
• Thyroglobulin
• Chromogranin A
Colorectal
Pancreas
Breast
Ovary
Prostate
HCC, Germ cell
Germ cell
Lymphoma
Thyroid cancer
Neuroendocrine tumors

• CEA = carcinoembryonic antigen
• Glycoprotein involved in cell
adhesion
• Oncofoetal antigen later re-expressed
In tumors
• Practical use is in colon, lung
breast cancer and other G.I. cancers
BENIGN
• IBD
• Cirrhosis
• Hepatitis
• Pancreatitis
• Gastritis
• PUD
• Smoking(19%)
• COPD
•Renal failure
• Hypothyroidism
• NORMAL (3%)
MALIGNANT
• CRC
• Gastric ca
• Pancreatic ca
• Breast ca
• Lung ca
• Ovarian ca

Practical use in colorectal cancer
1.Screening – no role
2.Diagnosis – no role by itself
3. Prognosis / Staging
Preoperative elevated CEA is a negative prognostic factor
4.Detecting tumor recurrence
Stage II/III CRC – CEA q3 months x 5 years
Rising CEA should prompt reevaluation
5.Following response to treatment
Metastatic CRC – CEA q 1-3 months while on active treatment
along with appropriate imaging studies
Persistently rising CEA should prompt restaging
Caution if rise is within 4- 8 weeks of new treatment -always
consider possibility of spuriously spike

• Glycoprotein involved in adhesion
of colon, pancreas and gastric cells
to endothelium
• Practical use is in pancreatic cancer:
BENIGN
Cholecystitis
Pancreatitis
Cirrhosis
Liver failure
MALIGNANT
• Pancreatic
cancer
• Cholangio-
carcinoma
• Colorectal
cancer
• Gastric cancer
• Ovarian cancer
• Lung cancer

Practical use in pancreatic cancer:
1. Screening – no role
2. Diagnosis – no role by itself
3. Prognosis / staging – no role
• Also not used to determine operability
4. Detecting tumor recurrence
• Cannot provide definitive evidence of recurrence by itself
• May guide need for follow-up imaging +/- biopsy
5. Following response to treatment
• Present data insufficient to recommend routine CA19-9 alone
for following response
• Many use CA19-9 for locally advanced or metastatic
pancreatic cancer q1-3 months during active treatment in
conjunction with appropriate imaging studies

• A circulating MUC-1 (cell surface associated mucin)
antigen
• Not specific: Tumors of breast, ovary, uterus, lung,
pancreas, stomach, colon, liver, cirrhosis, hepatitis
• Practical use is usually in breast cancer

Practical use in breast cancer:
2. Diagnosis – no role
3. Staging / Prognosis – no role
Not currently recommended
75-90% with metastatic breast ca have elevated CA 15-3 levels
Monitor CA15-3 when on active treatment in conjunction with
appropriate imaging studies
NB: May also consider CEA determinations in metastatic breast ca

• Expressed in tissues derived from
coelomic and mullerian epithelia
• Practical use in epithelial ovarian cancer
and other gynecological malignancies
BENIGN
• Ascites
•Peritonitis
•Cirrhosis
•Endometriosis
•PID
•Heart failure
•Benign ovarian
tumors
MALIGNANT
• Epithelial ovarian
cancer
•Breast cancer
•Colorectal cancer
•Pancreatic
cancer

Practical use in epithelial ovarian cancer:
1. Screening
• Studies ongoing, but no role currently except unique circumstances
1. Diagnosis – limited role except unique circumstances
2. Prognosis / Staging – no definitively proven role
• No consensus, but frequently used in follow-up despite UK
randomized trial results of no increase in survival
• May help guide further imaging/tests
• Useful for advanced ovarian and other gynecological cancers on
active treatment in conjunction with appropriate imaging studies

Glycoprotein produced by both
normal and neoplastic prostate
tissue- a serine protease
There are 2 major circulating forms of PSA:
• Free
• Complexed to 1-antichymotrypsin
or 2-macroglobulin
This has led to other PSA manipulations
to try to improve diagnostic utility
• Free PSA
• PSA density
• PSA velocity
• Age-adjusted PSA cutoffs
BENIGN
• BPH
• Prostatic
infection
• Prostatic
inflammation
• Perineal trauma
or prostatic biopsy
MALIGNANT
• Prostate cancer

Practical use in prostate cancer:
1. Screening – remains controversial
2. Diagnosis – may be helpful to narrow differential diagnosis but
biopsy still standard
3. Prognosis / Staging – no role by itself
• Routinely used in follow-up after treatment for localized disease
• After surgery: PSA should be undetectable within 6 wks-any
increase represents relapse
• After XRT : PSA eventually nadirs-Any increase >2.0 above
nadir value represents relapse -or 3 consecutive increases from
nadir value
• Routinely used to assess treatment response
• Those patients with poorly differentiated or neuroendocrine
features may have low PSA in the face of progressive disease

Produced by fetal liver and yolk sac
• NORMAL VALUE: Below 16 ngm / ml
• HALF LIFE OF AFP – 5 to 7 days
Raised AFP in testicular carcinoma :
• Pure embryonal carcinoma
• Teratocarcinoma
• Yolk sac Tumor
• Combined tumors,
• AFP not raised pure choriocarcinoma ,
or seminoma
BENIGN
• Pregnancy
• Chronic liver
disease
• Cirrhosis
•Hepatitis
• EtOH
• Drugs
MALIGNANT
• Hepatocellular
carcinoma
• Germ cell tumors
• Gastric cancer

Practical use in hepatocellular carcinoma
1. Screening high risk patients
• AFP be used in conjunction with ultrasound every 6 months in
Hepatitis B,C at high risk of developing HCC
• Lead period -early detection which is ~ 6 months before clinical Dx
2. Diagnosis – high levels may be diagnostic, but only in high-risk
3. Staging / Prognosis - no role
• Used following definitive therapies to monitor for recurrence
• Used while patient on active treatment for HCC

• Produced by trophoblasts
during pregnancy
• It is a glycoprotein consisting
of - and -subunits
• Used in germ cell tumors
• Detection and follow-up of gestational
trophoblastic diseases (GTDs)
BENIGN
• Pregnancy
• Marijuana
• Pituitary
disorders
• Hypogonadal
states
MALIGNANT
• Germ cell tumors
• Gestational
trophoblastic
disease
• Trophoblastic
differentiation of
lung or gastric ca

bHCG-Continued
NORMAL VALUE: < 1 ng / ml
HALF LIFE of HCG: 24 to 36 hours
Frequency of raised  HCG - various germ cell tumors
100 % - Choriocarcinoma
60% - Embryonal carcinoma
55% - Teratocarcinoma
25% - Yolk Cell Tumour
7% - Seminomas

Practical use in NSGCT/Seminoma
2. Diagnosis measured prior to orchiectomy
• 80 to 85% of testicular tumours have positive markers
• Pure seminomas don’t have elevated AFP but 5-7% have
elevated beta-hCG
• LDH also used along with bHCG and AFP-is elevated in 40-
60% germ cell tumors
3. Prognosis/Staging – part of TNM staging criteria
4. Following response to treatment – measured before,
during and after treatment to determine response
5. Detecting tumor recurrence – measured routinely at
each follow-up visit

Large left paraaortic nodal mass due to
Germ cell tumor causing hydronephrosis

Other Considerations- Tumor Markers and GCT
• Only 10 to15% NSGCT have normal marker levels
• Degree of marker elevation is directly proportional to tumor burden
• Markers may confirm or question reported histology - AFP should
never be elevated in seminoma
• Markers often become positive earlier than follow-up X-Ray studies
• After orchiectomy, if markers remain elevated- means residual
disease .
• After lymphadenectomy, elevation of markers - means Stage III
disease
• After surgery or chemotherapy, negative tumor markers becoming
positive on follow up – means tumor recurrence

• Cytoplasmic enzyme present in
most body tissues
• Quite non specific, but mostly a
marker of cell turnover
• Practical use in lymphoma,
germ cell tumors
tumor burden in heme malignancies
BENIGN
• RBC hemolysis
• MI
• Hepatic disease
• Skeletal injury
MALIGNANT
• Germ-cell
tumors
• Lymphoma
• Fast growing
tumors (SCLC)
• Heme
malignancies

Practical use in lymphoma
1. Screening – no role by itself
2. Diagnosis – no role
3. Staging / Prognosis – used for prognosis
as item in IPI prognostic scoring system
Used routinely in follow-up after definitive treatment
Used while patients on active treatment for lymphoma,
other hematological malignancies

Tumor Marker Malignancy
Chromogranin A (CGA) Pheochromocytoma, carcinoid
Thyroglobulin Thyroid cancer
Immunoglobulins Multiple myeloma, LPL, other
lymphomas
Catecholamines /
vanillylmandelic acid
(VMA)
Adrenal tumors
S100 Melanoma

Thyroglobulin
Reference value
• 90% general population < 25 ng/ml
Indications: Differentiated thyroid cancer
Follow-up therapy
• After operation, TG should be undetectable
• High TG level indicates incomplete resection or
metastasis
Clinical follow-up
• Monthly assay for six months then every 3 months
• TG > 5 ng/ml requires a survey looking for recurrence or
metastasis

• Final conclusions and caveats

Some Final Marker Caveats -1
Beware the Communication Gaps
• Does the patient understand the individual marker
result significance?
• Does the Oncologist understand it also?
• Does the rest of the staff who might be questioned
by the patient understand?
• Is the Oncologist accessible to the family physician
who knows the patient best, and who may wonder
“why?” or “what next”?

Be Aware of Potential “Marker Mysteries”
• Elevated marker with no evident disease
eg: BHCG increase seen with creatinine elevation
• Elevated marker with no evident cancer
eg: spurious CA125 or CEA in non-malignant disease
• Multiple markers elevated- significance?
• Marker falling, but tumor volume increasing
• Marker rising, but disease clinically responding
There must always be a predominant role for
clinical examination and judgment!

Remember Markers May Not Always Be Helpful
• May provoke unnecessary anxiety
– CA 125 ,PSA, or CEA cripples-UK Ca 125 trial
• May lead to "unnecessary and unhelpful palliative
chemotherapy”
• Always treat the symptom and clinical condition- not
an isolated laboratory value
• Beware any false reassurance from “normal marker
results” when the clinical assessment might seem
contrary

Have You Finished Your Pondering of the
Original Two Cases?

Remember Jen?
Originally Fallopian tube ca
successfully treated with
normalization CA 125
Jen 9 months later
Anxious, fatigued
Ca 125 = 225
Now frightened –"Am I
relapsing?”
You might now?
1) H@P, repeat marker
2) H@P, repeat marker, CT
scan
3) Send straight to
exploratory laparotomy
4) Send back to gyne/onc’s
5) other

Final outcome - Case 1
Jen on your clinical exam, has diffuse
lymphadenopathy. Her CBC shows an
atypical lymphocytosis and you order
appropriate testing
Dx: Infectious mononucleosis
On recovery: Ca 125 normal
(225 20)

Remember Gary?
Presented -weight loss,
jaundice.
• CT scan: possible small
pancreatic mass, possible
small liver lesions
• CEA = 20 (N<4)
• CA 19.9 = 1700 (N<37)
You might now?
1) send immediately to
surgery
2) inform patient of ca
pancreas-time for
chemo
3) order G.I. consult, ERCP
4) order pancreatic MRI

Final outcome - Case 2
Gary:
Actually had benign obstructive
jaundice due to unsuspected stone in
common bile duct
After ERCP and basket removal:
CA 19.9 went from 1700 to normal.

Update on Cancer Tumor Markers.pptx

Update on Cancer Tumor Markers.pptx

Recommended

Recommended

More Related Content

Similar to Update on Cancer Tumor Markers.pptx

Similar to Update on Cancer Tumor Markers.pptx (20)

Recently uploaded

Recently uploaded (20)

Update on Cancer Tumor Markers.pptx