Blood test for Cancer

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Blood tests for cancer are substances /molecular changes detected in abnormal amounts in the blood produced either by tumor or by the other cells in the body in response to the disease or related to the presence or progress of a tumor

The may be of following types:

  • Diagnostic markers
  • Prognostic markers
  • Therapy selection & response markers
  • Recurrence and metastasis markers

What are Ideal Criterion for Cancer Blood Test?

  • Detectable early in malignant disease
  • Specific for type and site
  • Production by all patients with a specific malignancy
  • Correlates quantitatively with the tumor load, biological behavior, progression
  • Responds rapidly to a change in size
  • Standardized reproducible quantitative assay

None of the Tumor Markers fulfills all the above criterion.

What is the alarming blood level of various blood tests for Cancer?

Tumor Marker Level above which benign disease is unlikely
CEA >10ng per mL
CA 19.9 >1,000 units per mL
AFP >500 ng per mL.
Β-hCG >30mlU per mL
CA 125 >200 units per mL
PSA >10ng per mL

 

Blood Test for Prostate Cancer – Prostate Specific Antigen

What is Prostate Specific Antigen (PSA)?

It is a glycoprotein expressed by prostate cancer cells, both normal and neoplastic. It is a tumor marker used  for screening of prostate cancer and to assess the extent of prostate cancer and volume of the disease. It is also used to assess the response to treatment.

  • The most notable marker in the kallikrein family is hK3, also known as PSA.
  • PSA is a 33-kD glycoprotein that acts as a serine protease.
  • The serum half-life of PSA is 2 to 3 days.
  • Prostate cancer cells do not make more PSA but rather make less PSA than normal prostatic tissue.
  • Elevated serum PSA levels are probably a product of disruption of cellular architecture within the prostate gland.

Factors Influencing the Serum Level of Prostate-Specific Antigen

  • PSA expression is strongly influenced by androgens.
  • Bimodal peaks between 0 and 6 months and after 10 years, correlating directly with testosterone levels.
  • Serum PSA becomes detectable at puberty with increases in luteinizing hormone and testosterone.
  • In the absence of prostate cancer, serum PSA levels vary with age, race, and prostate volumE.
  • In men without BPH, the rate of change in PSA is 0.04 ng/mL per year, 0.07 to 0.27 ng/mL per year in men with BPH who are between the ages of 60 and 85 years.
  • PSA increases 4% per milliliter of prostate volume.
  • Blacks without prostate cancer have higher PSA values than whites.
  • Prostatic inflammation (acute and chronic) and urinary retention can cause PSA elevations to variable degrees.
  • DRE as performed in an outpatient setting can lead to increases in serum PSA.
  • The presence of prostate disease (prostate cancer, BPH, and prostatitis) is the most important factor affecting serum levels of PSA.
  • Finasteride (5 mg) and other 5α-reductase inhibitors for treatment of BPH  lower PSA levels by an average of 50% after 6 months of treatment. If PSA does not decrease by 50% or if there is a rise in PSA when the patient is taking finasteride, the patient should be suspected of having occult prostate cancer and undergo further testing

What conditions may cause the PSA elevation other than prostate cancer?

Other than prostate cancer, there are some benign conditions that may cause PSA elevation.

  • BPH
  • Lower tract endoscope manipulation
  • Transrectal & transperineal prostate Bx
  • Acute urinary retention
  • Digital rectal examination
  • Prostate massage
  • Acute prostatitis

So if you get your PSA checked and find the level higher than normal, it is not always a thing to be worried as one of the above causes can be the cause for the same.

How much elevation of PSA is considered to be significant?

The value for normal range of PSA is highly controversial. Previously, levels above 4 ng/ml were considered to be abnormal but fixing this as the upper limit doesn’t seem to be correct as the levels of PSA increase with age in an individual, due to the increasing size of prostate gland.

Different normal reference ranges have been identified based on several studies-

  • 40 to 49 years – 0 to 2.5 ng/mL
  • 50 to 59 years – 0 to 3.5 ng/mL
  • 60 to 69 years – 0 to 4.5 ng/mL
  • 70 to 79 years – 0 to 6.5 ng/mL

What is PSA Density?

Thers is a direct relationship between PSA density (PSAD) and the likelihood of cancer. For men with a PSA between 4.0 and 10.0 ng/mL and a normal digital rectal examination, a PSAD greater than 0.15 has been suggested as discriminatory for the presence of cancer.

The major determinant of serum PSA in men without prostate cancer is the transition zone epithelium, not the epithelium of the peripheral zone of the prostate. Adjusting PSA for transition zone volume may help distinguish between BPH and prostate cancer. PSA/transition zone volume was the parameter with the highest overall validity (sensitivity and specificity) for prostate cancer

How much PSA levels can be considered safe?

Level of more than 4 ng/ml is seen in around 70% of the cases of prostate cancer. Levels of PSA between 4 to 10 ng/ml could be overlapping for benign and malignant causes. In such cases, PSA velocity and Percent-Free PSA may be helpful to differentiate between the two.

PSA velocity

It is the change in PSA values over time. PSA levels that continue to rise over time are more in favour of prostate cancer as compared to ones that are stable. It increases the specificity of a single PSA measurement for early cancer detection. Current recommendation include collection of PSA velocity over not less than 18 months and the use of three values to calculate PSA velocity.

  • Normal levels are around 0.75 ng/ml/year.
  • Rate of change in serum PSA more than 0.75 ng/mL per year was a specific marker for the presence of prostate cancer.
  • Men with prostate cancer have more rapid rises in PSA than men without prostate cancer.
  • Cancer detection rate was 47% among men with a PSA velocity of more than 0.75 ng/mL per year compared with 11% among men with a PSA velocity of less than 0.75 ng/mL per year.

Percent Free PSA

It is free PSA, expressed as a ratio with total PSA. It has been approved for early detection in patients with PSA between 4 & 10 ng/ml. In the PSA range of 4 to 10 ng/ml, the lower value of percentage free PSA goes in favor of prostate cancer compared to benign causes.

  • 5% to 35% of PSA exists as fPSA.
  • Prostate cancer cells do not produce more PSA than benign prostate epithelium, the PSA produced from malignant cells escape proteolytic processing.
  • The difference in the ratio of free to total PSA (percentage of free PSA or %fPSA) is greatest when comparing men without prostate cancer who have prostate enlargement (BPH) with those with prostate cancer and no prostate enlargement.
  • The role for %fPSA is more applicable to PSA levels less than 10 ng/mL.
  • %fPSA –done in men with benign DRE and minimal PSA elevations, within the diagnostic gray zone of 4 to 10 ng/mL.
  • %fPSA can help counsel men with PSA elevation between 4 and 10 ng/mL.

Is PSA elevated in all the cases of prostate cancer?

Usually basement membrane breach causes PSA elevation in most of the cases of prostate cancer. But some very early disease may no cause it to be significantly elevated. Also, most cases of prostate cancer are adenocarcinoma, but in a less common variant called small cell carcinoma, the PSA elevation may be too less as compared to the disease bulk and stage.  So the PSA elevation may not always correlate with the disease volume and spread in such cases.

What are the clinical applications of PSA?

Screening

Along with other investigations, it is a part of screening workup for prostate cancer in high risk individuals. Different studies have suggested different cutoffs for the PSA levels that are considered to be above the normal range to be considered for further diagnostic tests.

Monitoring treatment response

It helps in monitoring the response to treatment in prostate cancer. If it is well controlled on a particular therapy, it is an indicator of response to treatment. And if it increases while on treatment, it may indicate loss of response to the same, which then has to be correlated with imaging to see the disease extent and compare with the previous imaging findings.

Detection of early recurrence

If a patient has been treated previously, and is on follow up with regular monitoring of PSA, if the levels start rising thereafter, it may be an indicator of disease relapse or recurrence, and he needs to undergo further testing to confirm the same.

It is specific for prostate cancer.  Level of more than 4 ng/ml is seen in around 70% of the cases of prostate cancer. But some non-malignant prostate abnormalities could cause PSA elevation. Levels of PSA between 4 to 10 ng/ml could be overlapping for benign and malignant causes. In such cases, PSA velocity and Percent-Free PSA may be helpful to differentiate between the two.


Blood Test for Colon Cancer – Carcinoembryonic Antigen (CEA)

It is a 200 kDa. Glycoprotein with physiological function of role in cell adhesion and initiation of apoptosis. It’s half life is 3 days and normal values range from 0-3.5 ng/mL to 0-5.0 ng/mL. It is mainly used for colorectal cancer.

Can CEA elevation be seen Conditions other than Colorectal Cancer?

Yes, sometimes CEA may be elevated in other cancers, and even in non-malignant conditions as discussed below-

Malignant Causes

  • Gastric Cancer
  • Breast Cancer
  • Lung Cancer
  • Melanoma, pancreatic Cancer

Non-Malignant Causes    

  • Hepatitis
  • Cirrhosis
  • Alcoholic liver disease
  • Obstructive jaundice
  • Ulcerative colitis
  • Crohn’s disease
  • Pancreatitis
  • Renal disease & Chronic smokers

What are the Clinical Applications of CEA?

  1. Screening: Due to it’s low sensitivity, it has a limited role in screening of colorectal cancer.
  2. Diagnosis – It may sometimes be normal in cases of colorectal cancer (false negative) and sometimes be elevated in conditions other than colorectal cancer (false positive), as listed above. So these factors limit it’s use as a diagnostic test.
  3. Prognosis – High preoperative CEA value is an indicator of poor prognosis.
  4. Monitoring response to treatment
  5. Detection of early recurrence

Blood Test for Ovarian Cancer – CA 125

CA-125 is a mucin like molecule produced by mesothelial cells of peritoneum and tissues of mullerian origin. It is not found in normal ovary and it’s physiological function is unknown.

Ovarian Cancer CA-125 Tumor Marker

Can CA-125 elevation be seen Conditions other than Ovarian Cancer?

Yes, sometimes CA-125 may be elevated in other cancers, and even in non-malignant conditions as discussed below-

Malignant Causes

  • Ovarian carcinoma
  • Primary peritoneal carcinoma
  • Endometrial carcinoma

Non-Malignant Causes

  • Acute hepatitis
  • Acute pancreatitis
  • Chronic liver disease
  • Cirrhosis
  • Congestive heart failure
  • Diverticulitis
  • Pericarditis
  • Systemic lupus erythematosus
  • Sarcoidosis
  • Endometriosis
  • Pelvic inflammatory disease
  • Adenomyosis
  • Benign ovarian neoplasm
  • Functional ovarian cyst
  • Menstruation
  • Uterine Myomata

What are the Clinical Applications of CA-125

  1. Screening – Due to it’s low sensitivity, it has a limited role in screening of ovarian cancer.
  2. Diagnosis – It may sometimes be normal in cases of ovarian cancer (false negative) and sometimes be elevated in conditions other than ovarian cancer (false positive), as listed above. So these factors limit it’s use as a diagnostic test.
  3. Prognosis – High preoperative CAA-125 value is an indicator of poor prognosis and an independent prediction of survival
  4. Monitoring response to treatment
  5. Detection of early recurrence

Blood Test for Pancreatic Cancer – CA 19-9

It’s half life is 1 to 3 days and normal  range is  0.37 to 0-100 U/L. It is mainly elevated in pancreaticobiliary tumors.

Can CA-19.9 elevation be seen Conditions other than Pancreatic Cancer?

Yes, sometimes CA-19.9 may be elevated in other cancers, and even in non-malignant conditions as discussed below-

Malignant Causes

  • Hepatocellular Carcinoma
  • Gastric Cancer
  • Colorectal Cancer

Non-Malignant Causes

  • Acute and chronic pancreatitis
  • Hepatocellular jaundice
  • Cirrhosis
  • Acute cholecystitis
  • Cystic Fibrosis

What are the Clinical Applications of CA-19.9

  1. Screening – Due to it’s low sensitivity, it has a limited role in screening of pancreatic cancer.
  2. Diagnosis – It may sometimes be normal in cases of pancreatic cancer (false negative) and sometimes be elevated in conditions other than pancreatic cancer (false positive), as listed above. So these factors limit it’s use as a diagnostic test.
  3. Monitoring response to treatment
  4. Detection of early recurrence

Blood Tests for Testicular Cancer

Human Chorionic Gonadotrophin (hCG)

It has.two subunits, Alpha & Beta Chain. Alpha chain is identical to alpha chain of TSH,FSH, & LH. Serum half-life is 18 to 36 hours. Normal reference range is 0 to 5 IU/L.

hCG elevation may be seen in following malignant and non-malignant conditions-

Malignant Causes

  • Gestational Trophoblastic Neoplasia (complete/partial molar pregnancy)
  • Germ cell Tumor of Ovary
  • Germ Cell Tumor of Testis
  • Carcinoma of liver, stomach, lung & pancreas.

Non-Malignant Causes 

  • Ectopic pregnancy
  • Pituitary adenoma
  • Pregnancy
  • After termination of pregnancy
  • Hypogonadal state
  • Marijuana use

Clinical applications of hCG

To monitor the response to treatment and in follow-up for-

  • Gestational trophoblastic tumor
  • With AFP in Non Seminomatous germ cell tumors (NSGCT) of testis, ovary, & other sites

Alfa Feto Protein (AFP)

It is a major protein in fetus and is undetectable after birth. Half life of AFP is 5 to 7 days. Normal values is less than 15 ng/mL.

AFP elevation may be seen in following malignant and non-malignant conditions-

Malignant Causes

  • Nnon Seminomatous Germ Cell Tumor of Testis, ovary, or other sites.
  • Hepatocellular Carcinoma (HCC)
  • Hepatoblastoma

Non-Malignant Causes (False Positive Elevation) 

  • Hepatitis
  • Cirrhosis
  • Biliary tract obustruction
  • Alcoholic liver disease
  • Ataxia telangiectasia
  • Hereditary tyrosinaemia
  • Wiscott – Aldrich syndrome
  • Physiological-Pregnancy,Infants

Clinical Applications of AFP

  • Screening of Hepatocullular Cancer (HCC) in High risk population (eg; China) and High risk disease groups (eg; Hemochromatosis, Hepatitis)
  • Diagnosis of HCC and Hepatoblastoma
  • Staging and Prognosis of Germ Cell Tumor

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