Prostatic Specific Antigen (PSA)

What sample is needed for Prostatic Specific Antigen (PSA)?

1. This is done on the patient’s serum.
2. A random sample can be taken.
3. Take the sample before any prostatic procedure is done.
4. The sample is stable at 2 to 8 °C for 2 weeks.

What are the precautions for Prostatic Specific Antigen (PSA)?

1. Rectal examination may elevate a minimal level. Take the sample before the rectal examination.
2. Prostatic biopsy or transurethral resection of the prostate elevates the PSA level.
3. Ejaculation within 24 hours of the sample taking will lead to a high value.
4. If you have a history of urinary tract infection or prostatitis, your PSA will be elevated five times and remain elevated for at least six weeks.
5. Taking a history of medication like Proscar may increase the PSA value.

What are the indications for Prostatic Specific Antigen (PSA)?

1. This is a tumor marker for the diagnosis of prostatic carcinoma.
2. Prostatic Specific Antigen (PSA) and prostatic acid phosphatase increase the detection of prostatic carcinoma.
3. PSA is a good marker for monitoring the effectiveness of the treatment.
4. PSA is the early indicator of recurrence.

What is the importance of Prostatic Specific Antigen (PSA)?

1. Prostatic Specific Antigen (PSA) has no sensitivity and specificity for diagnosing prostatic carcinoma.
2. The ASCP manual claims that this test is highly specific, highly sensitive, and relatively low-cost.
   PSA with rectal examination may diagnose nearly 90% of cancers.
3. PSA is an important tumor marker for prostate cancer:
   1. It can diagnose.
   2. It can stage.
   3. It can monitor the treatment of prostate cancer.

How will you define Prostatic specific antigen (PSA)?

1. It is one of the most organic-specific tumor markers.
2. Prostatic Specific Antigen (PSA) can detect prostatic cancer in the early stage.
3. Early detection for prostatic cancer gives a life expectancy of 10 years.

What is the Prostatic Specific Antigen (PSA) structure?

1. Prostatic Specific Antigen (PSA) is a single-chain glycoprotein of 237 amino acids.
2. There are four carbohydrate side chains.
3. It has a molecular weight of 28,430.
4. The carbohydrate linkage occurs at amino acid 45 (asparagine), 69 (serine), 70 (threonine), and 71 (serine).
5. The Prostatic Specific Antigen (PSA) gene, KLK3, is located on chromosome 19q13.41.
6. Prostatic Specific Antigen (PSA) is produced by the epithelial cells of the acini and secreted into the lumen of prostatic ducts and seminal fluid.

7. Prostatic Specific Antigen (PSA) possesses chymotrypsin-like and trypsin-like activity.
8. Adding protease inhibitors may be important to prevent the autohydrolysis of PSA in solution.
9. Prostatic Specific Antigen (PSA) exists in two forms:
10. Free form. It is a free PSA in minor form.
11. Complexed form. It is complexed with protease inhibitor-α-antichymotrypsin or with α-macroglobulin

How will you discuss the pathophysiology of Prostatic Specific Antigen (PSA)?

1. PSA is a glycoprotein in the cytoplasm of prostate epithelial cells, ducts, and prostatic carcinoma.
2. PSA is a kallikrein-serine proteinase produced by the prostate epithelial cells and from malignant prostatic cells.
3. PSA is a single-chain glycoprotein found in high concentrations in the prostate.
4. Its molecular mass is 28.43 kD.
5. It consists of 237 amino acids.
   1. The gene coding is done, and it is present on chromosome 19.
   2. This is an antigenic protein.
   3. PSA possesses chymotrypsin and trypsin-like activity.
6. PSA is present in the blood in two forms:
   1. Free PSA.
   2. PSA bound to protein.
   3. In BPH, there is more free PSA, while in cancer, there is more bound PSA.
7. It is produced by the epithelial cells of acini and prostate gland ducts.
   1. PSA is secreted into the prostatic ducts.
   2. PSA cleaves seminal vesicle-specific proteins into small, low molecular-weight proteins in the seminal fluid.
   3. The above process leads to the liquefaction of the seminal coagulum.

8. The raised level of PSA with increasing age depends upon the following factors:
   1. Enlargement of the prostate.
   2. Inflammation of the prostate.
   3. The presence of microscopic foci of carcinoma is clinically insignificant.
   4. Leakage of PSA into the serum.
9. Levels> 4 ng/mL are found in over 80% of cancer cases.
10. The level of PSA also denotes the tumor burden.
11. Surgery, radiation, or hormone therapy are associated with decreased PSA levels.
    1. Later on, an increase in the PSA level indicates the recurrence of the tumor.
12. The US Preventive Services Taskforce recommendations are :
    1. No use of screening by doing PSA after the age of 75 years.
    2. They also say there is a limited value of PSA for screening under 75 years unless there is a strong family history.
    3. Their recommendation is PSA screening every four years instead of annual screening.
13. The American Urological Society and American Cancer Society have different recommendations.
    1. They recommend a yearly PSA screening test after the age of 50 years.
    2. In people with strong family histories and men, Afro-Americans advise PSA at the age of 40 years.
14. PSA has a long half-life of 2 to 3 weeks when serum comes to a normal level or baseline after any procedure on the prostate.
15. PSA levels may not be raised in the early stages of Prostatic carcinoma.
    1. PSA has a limited diagnosis value in the gray zone of 4 to 10 ng/mL.
    2. Benign prostatic hyperplasia shows values of 4 to 8 ng/mL.
    3. Levels>8 ng/mL are highly suggestive of prostatic cancer.
    4. Low level is due to benign prostatic hyperplasia or early prostatic cancer.
16. If Prostatic cancer is completely removed, then PSA will not be detected.
    1. Patients below 10 ng/mL have the local disease and respond well to local treatment.
    2. After complete curative surgery or radiation therapy, the PSA level will be 0 to 0.5 ng/mL.

What is the normal Prostatic Specific Antigen (PSA)?

Source 1

Healthy male: % of the population	ng/mL
80%	<4.0
18%	4.1 to 10.0
2%	10.1 to 20
1%	>20

• To convert into SI units x 1.0 = µg/L

Source 3

• Men =  <4.0 ng/mL
• PSA value increases with age.

Another source

• Healthy Male less than 40 years of age = 0 to 2.5 ng/mL
• Healthy males above 40 years of age :
  • < 4.0 ng/mL in 96 %.
  • 4 to 10 ng/mL in 4 %
• Benign Prostatic Hyperplasia
  • <4 ng/mL in 90 %.
  • 4—10 ng/mL in 10 %.
  • > 10 ng/mL in 1 %
• Prostatic cancer :
  • < 4 ng/mL in 15 % .
  • 4 – 10 ng/mL in 20 %.
  • > 10 ng/mL in 65 %
• Free PSA = more in BPH.
• Bound PSA = more in cancers.
• Free PSA <25%, then more chances of cancer.

Source 4

• PSA : Men = 0 to 4.0 ng/mL or 0 to 4.0 µg/L
• 4.0 to 8.0 ng/mL suggests Benign prostatic hyperplasia or possible prostatic Cancer.
  • >4.0 ng/mL is reported in 8% of the cases with no malignancy or benign disease.
• >8.0 ng/mL is highly suggestive of prostatic cancer.

Another source

• The suggested age-specific  PSA reference ranges:
  1. 0 to 2.5 ng/mL for 40 to 49 years.
  2. 0 to 3.5 ng/mL for 50 to 59 years.
  3. 0 to 4.5 ng/mL for 60 to 69 years.
  4. 0 to 6.5 ng/mL for 70 to 79 years
• If prostatic cancer is completely removed, then no PSA will be detected.

What are the causes of increased prostatic specific antigen (PSA)?

1. Prostatic cancers.
2. Benign prostatic hyperplasia.
3. Prostatitis.
4. Prostatic infarction.
5. In the case of rectal manipulation of the prostate.

What is the relationship between free PSA and the possibility of cancer?

Free PSA %	The possibility of cancer in %
0 to 10	56
10 to 15	28
15 to 20	20
20 to 25	16
>25	8

What are the recommendations for Prostatic Specific Antigen (PSA)?

1. This has high specificity, high sensitivity, and low cost.
2. Men over 50 years are advised for early diagnosis:
   • PSA.
   • Rectal examination.
3. PSA correlates with pathological stages of tumor extension and metastasis.
   • A higher PSA level is associated with the advanced pathological stage.
   • Tumor confined to the prostate seldom has PSA >50 ng/mL.
   • PSA level <20 ng/mL rarely causes bone metastasis.

What is the interpretation of the Prostatic Specific Antigen (PSA)?

Prostatic Specific Antigen (PSA) level/DRE	Interpretations
PSA detects	Only 2% of healthy asymptomatic males
PSA = 4.0  to 10.0 ng/mL	20% of the patients with BPH
DRE (Direct rectal examination)	∼50% of confined prostatic cancer. It increases with raised PSA
PSA = <4.0 ng/mL	∼45% of cancers are confined, and 25% are unconfined cancers
PSA = >10 ng/mL	2% cases of BPH and 44% cases of prostatic cancers
Staging of patients with prostatic cancer
<4 ng/mL	There is prostate-confined cancer
<10 ng/mL	Bone metastasis is rare
>10 ng/mL	>50% have an extracapsular disease
>50 ng/mL	Most of the patients have positive lymph nodes
>100 ng/mL	Predicts bone metastasis with >90% accuracy Signs and symptoms are seen in >66%

What will be the response after the surgical treatment?

• After radical prostatectomy = The PSA level is below the detection limit.
  • This will drop after 2 to 3 weeks of the surgery.
  • Measure the PSA the first year after the surgery = every third month.
  • Measure the PSA the second year after the surgery = every fourth month.
  • Measure the PSA the third year after the surgery = every 6 months.
• After one year of the surgery, 50% of the cases show a rise in the PSA level, indicating positive biopsy and metastasis.
• Antiandrogen therapy includes:
  1. Bilateral Oophorectomy.
  2. LH- LH-releasing hormone analog-like diethylstilbesterol and Flutamide are given.

What is the interpretation of the PSA for prostatic cancers?

Chances for prostatic cancer	PSA level 0 to 2.0 ng/mL	PSA 2 to 4 ng/mL	PSA 4 to 10 ng/mL	PSA >10 ng/mL
Direct rectal examination = negative	1%	15%	25%	>50%
Direct rectal examination = positive	5%	20%	45%	>75%

• Importance: Tumor confined to the prostate is curable by surgery. Therefore, early detection is very important.

Questions and answers:

after the age of 50 years, PSA and rectal examination.”]

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