tumor markers general

1. TUMOR MARKERS
• Tumor markers are substances present in and
produced by a tumor or produced by the host
in response to a tumor. Measured qualitatively
or quantitatively by chemical, immunological
methods.
• Tumor markers can contribute to cancer
management as screening tests for malignancy
in asymptomatic patients, diagnostic aids,
prognostic indicators, therapy predictors,
and/or post treatment monitoring.

2. Most Frequently Used Tumor
Markers
◻ Cancer antigen 125 (CA125)
◻ Alpha-fetoprotein (AFP)
◻ Human chorionic gonadotropin (hCG)
◻ Cancer antigen 19-9 (CA19-9)
◻ Carcinoembryonic antigen (CEA)
◻ Prostate-specific antigen (PSA)

3. Cancer antigen 125 (CA125)
◻ Screening for Ovarian Cancer The American
College of Obstetricians and Gynecologists
recommends that risk-reducing salpingo-
oophorectomy (ie, total removal of the ovaries and
fallopian tubes) should be offered by age 40 years
for BRCA1 or BRCA2 mutation carriers.
◻ For women who decline this operation, the
National Comprehensive Cancer Network (NCCN)
view is that while there may be circumstances
where offering screening with transvaginal
ultrasound and/or CA125 may be helpful.

4. Cancer antigen 125 (CA125)
◻ Diagnosis CA125 measurement in isolation is
not recommended for diagnosis due to its low
sensitivity and specificity for ovarian cancer.
◻ CA125 concentrations greater than 95 U/L in
postmenopausal women can discriminate such
masses with a positive predictive value of 95%
◻ If CA125 is 35 U/L or higher, an ultrasound
scan of the abdomen should be arranged to
enable calculation of the RMI (U × M ×
[CA125]
cutoff RMI value of 200 )

5. Cancer antigen 125 (CA125)
◻ Algorithm can be embedded in specialist
software Risk of malignancy algorithm
(ROMA) scoring system that includes CA125,
HE4, and menopausal
◻ Copenhagen Index (CPH-I), which includes
serum HE4, serum CA125, and age without
menopausal status or ultrasound
◻ Clearly there are significant drawbacks to the
first-line use of CA125 in the early detection of
ovarian cancer, but it is the best serum marker
available.

6. Cancer antigen 125 (CA125)
◻ Prognosis Five-year survival rates in patients with a
preoperative CA125 concentration > 65 U/L have been
found to be significantly lower than those for patients
with CA125 < 65 U/L.
◻ Following primary treatment with surgery and/or
chemotherapy, a nadir CA125 concentration (eg, to ≤5
U/L) and a more rapid rate of decrease (eg, ≥50%
during the initial two cycles of platinum-based
chemotherapy) are generally associated with more
favorable prognosis.
◻ Generally, a prolonged CA125 half-life and/or failure to
fall to within reference limits is predictive of poor
response to treatment and a higher rate of relapse.

7. Cancer antigen 125 (CA125)
◻ Monitoring Current ESGO recommendations
are that CA125 follow-up should be continued
in patients after complete response on primary
treatment for ovarian cancer
◻ The UK-based Medical Research
Council/European Organization for Research
and Treatment of Cancer (MRC-EORTC)
conducted a randomized trial to evaluate the
utility for such monitoring of CA125
(concluded routine CA125 monitoring is not
necessary )

8. Cancer antigen 125 (CA125)
◻ SUMMARY: CA125 is the most widely used
serum tumor marker for all epithelial ovarian
cancers but is most sensitive for serous
adenocarcinomas.
◻ Because many benign conditions are
associated with increased CA125, careful
interpretation of results in the clinical context is
paramount.
◻ The serum markers of choice for ovarian germ
cell tumors are AFP, hCG, and LDH while for
granulosa cell tumors, inhibin is the

9. Alpha-fetoprotein (AFP)
◻ AFP is an oncofetal antigen that is
appropriately increased in pregnant women
and most frequently inappropriately increased
in patients with germ cell tumors and HCC .
◻ Screening for HCC high-risk patients include
men and women with established cirrhosis due
to HBV or HCV infection or genetic
hemochromatosis, men with alcohol-related
cirrhosis( AFP and ultrasound)

10. Alpha-fetoprotein (AFP)
◻ Diagnosis For liver lesions more than 2 cm in size
where USS results are typical of HCC and AFP is
greater than 200 ng/ml a diagnosis of HCC can
be made without proceeding to biopsy.
◻ The AASLD guidelines no longer recommend AFP
testing as part of diagnostic evaluation because
AFP concentrations may be raised in
nonmalignant conditions and may be within
normal limits in a substantial number of HCC
patients, and because imaging is more definitive,
as is also recognized by the NCCN.

11. Alpha-fetoprotein (AFP)
◻ AFP in Prognosis. In combination with other
factors, AFP concentrations may provide
prognostic information in untreated HCC
patients and in those being considered for liver
resection or transplantation(<1000ng/ml), with
high concentrations generally associated with
poor prognosis.

12. Alpha-fetoprotein (AFP)
◻ AFP in Post treatment Monitoring.
Measurement of AFP at follow-up visits is
recommended by the NACB, NCCN, and
others to monitor disease status after liver
resection or liver transplantation, for detection
of recurrence or after ablative therapies,
and/or during palliative treatment.

13. Alpha-fetoprotein (AFP)
◻ Measurements of hCG, AFP, and LDH are
integral to the management of patients with
GCTs(Germ Cell Tumors) .
◻ Plasma concentrations of AFP and hCG
should be measured in any male with a
suspicious lump in the testes and in any
patient with malignancy of unknown origin.

14. Alpha-fetoprotein (AFP)
◻ Serum or plasma concentrations of AFP and/or
hCG are increased in 80% to 85% of men with
NSGCT, while less than 25% of those with
seminomas have raised hCG and none have
raised AFP.
◻ Increased AFP precludes a diagnosis of
seminoma. Increased AFP in a patient diagnosed
with seminoma suggests that the AFP may not be
related to the tumor (eg, may be of liver origin) or
that yolk sac elements were overlooked.

15. Alpha-fetoprotein (AFP)
◻ criteria developed by the International Germ Cell
Cancer Collaborative Group (IGCCCG) for
Prognostic Categories for Nonseminomas
◻ Good- marker concentrations— all of AFP <1000
ng/ml and hCG <5000 U/L
◻ Intermediate- marker concentrations— any of AFP
≥1000 ng/ml and hCG >5000 U/L
◻ Poor -marker concentrations—any of AFP >10,000
ng/ml and hCG >50,000 U/L

16. Alpha-fetoprotein (AFP)
◻ Monitoring. Tumor markers should be measured
before and after surgical excision of GCTs because
calculation of the tumor marker half-life provides
helpful information about the success of treatment.
◻ Provided that disease is confined to the testis or ovary,
serum AFP and/or hCG should decline to normal with
apparent half-lives of 5 to 6 days for AFP and 1 to 2
days for hCG.
◻ Further treatment with chemotherapy or radiation is
required if AFP or hCG remain increased following
surgery or if imaging identifies residual or metastatic
disease.

17. The importance of careful monitoring of tumor
markers is illustrated in Fig.

18. Human chorionic gonadotropin
(hCG)
◻ Screening of women at high risk of developing
GTD (ie, women who have had a partial or
complete hydatidiform mole in a previous
pregnancy) is conveniently performed by
measuring hCG in urine or blood.
◻ Estimation of hCG serum concentrations may be
helpful in diagnosing molar pregnancies because
values greater than two multiples of the median for
the gestational date are suggestive of GTD

19. Human chorionic gonadotropin
(hCG)
◻ Prognosis is assessed according to the
International Federation of Gynaecology and
Oncology staging system for GTN,142 which
includes pretreatment hCG concentration as one
of the eight prognostic factors used for scoring.
◻ Women with scores of 7 or higher are at high risk
of recurrence and are treated with intravenous
multiagent chemotherapy until the hCG
concentration has returned to normal and then for
a further 6 consecutive weeks

20. Human chorionic gonadotropin
(hCG)
◻ Following a diagnosis of GTD and surgical
evacuation, if hCG has reverted to normal
within 56 days, then follow-up will be for 6
months from the date of uterine evacuation.
◻ If hCG has not reverted to normal within 56
days, then follow-up will be for 6 months from
normalization of the hCG concentration.

21. Cancer antigen 19-9 (CA19-9)
◻ Screening and Diagnosis. The low positive
predictive value of CA19-9 means it cannot be
used in screening, but in symptomatic patients, it
contributes to diagnosis with sensitivity of 80% .
◻ Because CA19-9 may be increased in biliary
infection (cholangitis), inflammation, or biliary
obstruction (of any etiology), the NCCN
recommends that it is best measured after biliary
decompression is complete and bilirubin is normal.

22. Cancer antigen 19-9 (CA19-9)
◻ Prognosis. Preoperative CA19-9 concentrations
correlate with both American Joint Cancer
Committee (AJCC) staging and disease burden,
so they can complement when assessing whether
a pancreatic tumor is resectable.
◻ with concentrations greater than 130 kU/L found in
one center to be strongly associated with the
identification of subradiographic unresectable
disease.

23. Cancer antigen 19-9 (CA19-9)
◻ Low postoperative CA19-9 concentrations at 3
months and before adjuvant chemotherapy
have also been shown to be independent
prognostic factor.
◻ normalization of CA19-9 following neoadjuvant
therapy associated with longer median survival
among both nonresected and resected groups
of patients.

24. Cancer antigen 19-9 (CA19-9)
◻ Therapy Prediction. Postoperative CA19-9
concentrations may help to predict the benefit
of adjuvant therapy (usually gemcitabine-
based).
◻ In one study, patients with CA19-9
concentrations of 90 kU/L or less who received
gemcitabine-based adjuvant therapy had a
longer disease-free survival than those who
did not (26 months vs. 16.7 months),

25. Cancer antigen 19-9 (CA19-9)
◻ Monitoring. Rising CA19-9 concentrations
suggest progression and can be used,
together with radiographic and clinical data, to
influence decisions to initiate palliative
treatment in a patient whose disease
progresses after surgery or to change (or
discontinue) chemotherapy in patients
progressing during treatment.

26. Carcinoembryonic antigen (CEA)
◻ Diagnosis. Depending on the cutoff point
chosen, serum CEA will be increased in only
50% of patients at the time of diagnosis, and it
cannot be used in isolation to diagnose even
advanced disease of colorectal cancer .
◻ Markedly increased concentrations are
suggestive of metastatic disease (generally to
the liver) but do not necessarily indicate a
colorectal primary source.

27. Carcinoembryonic antigen
(CEA)
◻ Prognosis. A number of studies have shown
that increased preoperative CEA
concentrations at the time of initial
presentation of patients with colorectal cancer
are associated with adverse outcome.
◻ It is therefore generally recommended that
CEA be measured preoperatively in newly
diagnosed colorectal cancer patients to
provide both prognostic information and a
baseline value for interpreting subsequent
concentrations.

28. Carcinoembryonic antigen
(CEA)
◻ Monitoring. Metaanalyses of some randomized
controlled trials concluded that overall survival
was significantly improved only when CEA
testing was included in the intensive follow-up
arm.
◻ Now generally agreed that CEA testing should
be performed every 3 to 6 months for 5 years
following curative surgery for colorectal
cancer.
◻ An increase of 20% compared with the
previous CEA (provided CEA was >2.5 μg/L)
was considered to be significant.

29. Carcinoembryonic antigen
(CEA)
◻ Measurement of CEA is also recommended during
chemotherapy for metastatic disease, although
care in interpretation is required because CEA
concentrations may be affected by factors other
than tumor progression (eg, liver damage).
◻ CEA-defined responses agree well with radiologic
responses (the “gold standard”) in over 90% of
cases, enabling the conclusion that use of CEA is
as accurate as CT imaging for assessing the
response of colorectal cancer liver metastases to
chemotherapy.

30. Prostate-specific antigen (PSA)
◻ PSA in Screening for Prostate Cancer.
Screening asymptomatic men for prostate
cancer with PSA is highly controversial
◻ inability of PSA to differentiate aggressive
prostate cancers that require treatment from
indolent cancers that will not progress
◻ there are significant risks of overdiagnosis and
overtreatment of some men.

31. Prostate-specific antigen (PSA)
◻ PSA as an Aid to Diagnosis of Prostate
Cancer. Men with symptoms suggestive of
prostate cancer should be offered a PSA test
◻ Results above the upper limit of the reference
interval but less than 10 μg/L are considered
to be within a “gray zone” where additional
testing (eg, percent free PSA) may be
implemented in some centers before
proceeding to biopsy.

32. Prostate-specific antigen (PSA)
PSA in Prognosis and Therapy Prediction of
Prostate Cancer
The pretreatment serum PSA value correlates
with the risk of extraprostatic extension,
seminal vesicle invasion, and lymph node
involvement and is an independent predictor of
response to all forms of treatment.
Bone scans are generally not necessary in
patients with newly diagnosed prostate cancer
who have a PSA of less than 20.0 μg/L

33. Prostate-specific antigen (PSA)
◻ Following radical prostatectomy, PSA should
decrease to and remain at undetectable
concentrations, with measurable
concentrations indicative of residual disease or
possibly the presence of benign glands.
◻ The rate of fall is likely to be slower in patients
who have received radiotherapy, and PSA
rarely falls to less than 0.2 μg/L because not
all prostate tissue is ablated.

34. Prostate-specific antigen (PSA)
◻ In patients receiving hormonal therapy, a low
nadir after treatment has prognostic
significance and can be quantitatively linked to
survival.
◻ Those for whom the PSA nadir is greater than
0.2 μg/L within 8 months of endocrine therapy
have a 20-fold greater risk of cancer-specific
mortality than those with a PSA nadir of less
than 0.2 μg/L

35. CONCLUSION
here are tumor markers and tumor markers,
Their numbers increasing year after year.
But are they sensitive and, more importantly,
specific?
We should get our answers loud and clear.

36. THANK YOU