Role of tumor markers
No tumor marker has demonstrated a survival benefit in randomized controlled trials of screening in the general population.
Nevertheless, tumor markers can play a crucial role in detecting disease and assessing response to therapy in selected groups of patients.
Normalization of tumor marker values may indicate cure despite radiographic evidence of persistent disease.
In this circumstance, residual tumor is frequently nonviable.
Conversely, tumor marker levels may rise after effective treatment (possibly related to cell lysis), but the increase may not portend treatment failure.
However, a consistent increase in tumor marker levels, coupled with lack of clinical improvement, may indicate treatment failure.
Following tumor marker response is particularly useful when other evidence of disease is not readily accessible.
Cancer antigen (CA) 27.29
Carcinoembryonic Antigen(CEA)
Carcinoembryonic antigen(CEA), an onco-fetal glycoprotein, is expressed in normal mucosal cells and over-expressed in adenocarcinoma, especially colorectal cancer.
Non-neoplastic conditions associated with
cigarette smoking, peptic ulcer disease, inflammatory bowel disease, pancreatitis, hypothyroidism, biliary obstruction, and cirrhosis
>10 ng/mL are rarely due to benign disease
Fewer than 25% of patients with disease confined to the colon have an elevated CEA level.
Sensitivity increases with advancing tumor stage
elevated in 50% with extension to lymph nodes,
75 % with distant metastasis.
The highest values (>100 ng/mL) occur with metastasis.
Carcinoembryonic Antigen(CEA)
CEA is not useful in screening for colorectal cancer or in the diagnostic evaluation.
should be ordered only after malignancy has been confirmed.
CEA levels typically return to normal within four to six weeks after successful surgical resection
The major role for CEA levels is in following patients for relapse after intended curative treatment of colorectal cancer.
monitoring CEA levels every two to three months for at least two years in patients with stage II or III disease who are surgical candidates.
if CEA elevation is confirmed, patients should undergo imaging of potential recurrence sites
Cancer Antigen(CA) 19-9
Elevated levels of CA 19-9, an intracellular adhesion molecule, occur primarily in patients with pancreatic and biliary tract cancers.
sensitivity and specificity of 80 ~90% for pancreatic cancer
sensitivity of 60 ~ 70% for biliary tract cancer
Benign conditions associated
cirrhosis, cholestasis, cholangitis, and pancreatitis also result in CA 19-9 elevations.
values are usually less than 1,000 units/mL
CA 19-9 has no value in screening because positive predictive value is less than 1%.
However, the positive predictive value of levels over 1,000 units/mL is 97% when CA 19-9 testing is used in clinical situations that are consistent with pancreatic cancer (e.g., jaundice associated with a pancreatic mass).
CA 19-9 levels above 1,000 units/mL predict the presence of metastatic disease.
Alpha-Fetoprotein
Alpha-fetoprotein (AFP) is the major protein of fetal serum but falls to an undetectable level after birth.
associated with AFP elevations are
hepatocellular carcinoma
nonseminomatous germ cell tumors
Cirrhosis, viral hepatitis, Pregnancy may have abnormal AFP values,
usually less than 500 ng/mL.
AFP levels are abnormal in 80% of patients with hepatocellular carcinoma and exceed 1,000 ng/mL in 40% of patients with this cancer.
Although randomized controlled trials have not shown mortality risk benefit, the use of AFP in hepatocellular carcinoma screening continues to be debated.
In patients with a hepatic mass and risk factors for hepatocellular carcinoma, an AFP level above 500 ng/mL is often used in place of biopsy to diagnose hepatocellular carcinoma.
Beta Subunit of Human Chorionic Gonadotropin
b-hCG normally is produced by the placenta.
pregnancy, germ cell tumors, and gestational trophoblastic disease.
Both AFP and b-hCG play crucial roles in the management of patients with nonseminomatous germ cell tumors.
The AFP or b-hCG level is elevated in 85% of patients with these tumors, but in only 20% of patients with stage I disease. Hence, these markers have no role in screening.
In patients with extragonadal disease or metastasis at the time of diagnosis, highly elevated AFP or b-hCG values can be used in place of biopsy to establish a diagnosis of nonseminomatous germ cell tumor.
Beta Subunit of Human Chorionic Gonadotropin
AFP > 10,000 ng/mL or b-hCG > 50,000 mIU /mL at initial diagnosis portend a poor prognosis, with a five-year survival rate of 50%.
Following AFP and b-hCG levels is imperative in monitoring response to treatment in patients who have nonseminomatous germ cell tumors.
AFP and b-hCG levels that do not decline as expected after treatment have a significantly worse prognosis, and changes in therapy should be considered.
The b-hCG level is used to diagnose gestational trophoblastic disease, a rare neoplastic complication of pregnancy.
Cancer Antigen(CA) 125
CA 125 is a glycoprotein normally expressed in coelomic epithelium during fetal development. This epithelium lines body cavities and envelopes the ovaries.
associated with epithelial ovarian cancer.
CA 125 levels are elevated in about 85% of women with ovarian cancer, but in only 50% of those with stage I disease.
Insensitivity in early-stage disease and low disease prevalence limit the usefulness of CA 125 in ovarian cancer screening.
CA 125 has been used as an adjunct in the diagnosis of pelvic masses. In postmenopausal women with asymptomatic palpable pelvic masses, CA 125 levels higher than 65 units/mL have a positive predictive value of 98% for ovarian cancer.
Because premenopausal women have more benign causes of elevated CA 125 levels, testing for the marker is less useful in this population.
After definitive treatment of ovarian cancer, CA 125 levels should be obtained every three months for two years, and with decreasing frequency thereafter.
Prostate-Specific Antigen(PSA)
(PSA) is a glycoprotein produced by prostatic epithelium.
PSA can be elevated
Prostate cancer, prostatitis, benign prostatic hypertrophy, and prostatic trauma, as well as after ejaculation
In men with prostatitis, PSA levels return to normal within eight weeks of symptom resolution.
Waiting 48 hours after ejaculation to measure the PSA level has been recommended.
Digital rectal examination does not elevate PSA levels above normal values.
In prostate cancer,
the positive predictive value of PSA levels greater than 4 ng/mL is 20 to 30% and
rises to 50% when PSA levels exceed 10 ng/mL
Prostate-Specific Antigen(PSA)
Prostate cancer screening remains controversial.
Limitations of screening include
uncertainty about outcome benefit after treatment of localized prostate cancer,
potential identification of clinically insignificant tumors,
attendant morbidity of treatment.
Prostate-Specific Antigen(PSA)
If PSA testing is undertaken
an age of 40 years has been suggested for initiation of screening in black men and in all men with a family history of prostate cancer.
In patients without established risk factors and a minimum life expectancy of 10 years, screening could begin at age 50.
If elevated PSA values are confirmed, patients should be referred for biopsy.
PSA levels predict the presence of metastatic disease.
Patients with newly diagnosed prostate cancer and PSA levels below 20 ng/mL rarely have osseous metastasis and do not need bone scanning.
computed tomographic scanning is unnecessary with PSA levels below 25 ng/mL.
if a prostate nodule is detected, the bone scan is widely positive, and the PSA level exceeds 100 ng/mL, treatment is often instituted without performance of biopsy.
After treatment of prostate cancer, PSA levels should be obtained every six months for five years, and then annually.
In men who have undergone radical prostatectomy, any detectable PSA is significant.
After radiotherapy, a PSA nadir is not reached for one to two years. Three consecutive elevations of the PSA level indicate biochemical relapse in previously irradiated patients.
Cancer of Unknown Primary
Intuitively, a panel of tumor markers should help to establish the origin of the tumor.
Unfortunately, most tumor markers are too nonspecific for this purpose.
with adenocarcinoma in older men, significant PSA elevations have sufficient specificity to make the diagnosis of prostate cancer.
In poorly differentiated tumors, AFP and b-hCG levels should be ordered.
Marked elevations of these tumor markers signify the presence of an extragonadal germ cell tumor.
In women with peritoneal carcinomatosis or malignant ascites, treatment for ovarian cancer is instituted if the CA 125 level is elevated.
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