Prostatic Specific Antigen (PSA)

Sample

1. This is done on the serum of the patient.
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.

Precautions

1. Rectal examination may elevate a minimal level. Take the sample before the rectal examination.
2. Prostatic biopsy or transurethral resection of the prostate elevate the PSA level.
3. Ejaculation within 24 hours of the sample taking will lead to high value.
4. Take the history of urinary tract infection or prostatitis which will leave to an elevation of PSA. This will be five times and remains elevated for at least 6 weeks.
5. Take the history of medication like Proscar may increase the PSA value.

Indication

1. This is a tumor marker for the diagnosis of prostatic carcinoma.
2. PSA along with prostatic acid phosphatase increases the detection of prostatic carcinoma.
3. PSA is a good marker for the monitoring of the effectiveness of the treatment.
4. PSA is the early indicator of recurrence.

Important: PSA has no sensitivity and specificity for the diagnosis of prostatic carcinoma.

• While in the ASCP manual this test is claimed as highly specific, highly sensitive, and relatively low cost.
  PSA with rectal examination may diagnose nearly 90 % of the cancers.
• 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.

Pathophysiology

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

5. Raised level of PSA with increasing age depends upon the following factors:
   1. Enlargement of the prostate.
   2. Inflammation of the prostate.
   3. Presence of microscopic foci of carcinoma which are clinically insignificant.
   4. Leakage of PSA into the serum.
6. Level > 4 ng/mL are found in more than 80% of the cancer cases.
7. The level of PSA also denotes the tumor burden.
8. Surgery, radiation, or hormone therapy are associated with a decrease in PSA level.
   1. Later on, an increase in the PSA level indicates the recurrence of the tumor.
9. The US preventive services Taskforce recommendation are :
   1. No use of screening by doing PSA after the age of 75 years.
   2. They also say that there is a limited value of PSA for screening under the age of 75 years unless there is strong family history.
   3. Their recommendation is PSA screening every 4 years instead of annual screening.
   4. While the American urological society and American cancer society have a different recommendation.
      1. They recommend an annual PSA screening test after the age of 50 years.
      2. In the people with strong family history and men Afro-American, advise PSA at the age of 40 years.
10. 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.
11. PSA levels may not be raised in the early stages of Prostatic carcinoma.
    1. PSA has a limited value of diagnosis in the gray zone of 4 to 10 ng/mL
    2. Benign prostatic hyperplasia show values of 4 to 8 ng/mL.
    3. Level > 8 ng/mL are highly suggestive of prostatic cancer.
    4. Low level is due to benign prostatic hyperplasia or early prostatic cancer.
12. If Prostatic cancer is completely removed, then PSA will not be detected.
    1. Patients with a level 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 between 0 to 0.5 ng/mL.

NORMAL

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 and no benign disease.
• >8.0 ng/mL are highly suggestive of prostatic cancer.

If prostatic cancer is completely removed, then no PSA will be detected.

• • 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

Increase PSA has been seen in:

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

Relationship of free PSA for 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

Recommendation for PSA

1. This has high specificity, high sensitivity, and low cost.
2. Men over the 50 years are advised for early diagnosis:
   • PSA.
   • Rectal examination.
3. PSA correlates with pathological stages of tumor extension and metastasis.
   • Higher PSA level is associated with the advanced pathological stage.
   • Tumor confined to the prostate has seldom PSA >50 ng/mL.
   • PSA level <20 ng/mL has rarely bone metastasis.
4. After  surgical treatment the response will be:
   • After radical prostatectomy = PSA level be below the detection limit.
     • This drop will take 2 to 3 weeks after the surgery.
     • Measure the PSA first year after the surgery = every third month.
     • Measure the PSA second years after the surgery = every fourth month.
     • Measure the PSA 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.
5. Antiandrogen therapy includes:
   1. Bilateral Oophorectomy.
   2. LH- releasing hormone analog-like diethylstilbesterol and Flutamide is given.
6. Importance: Tumor confined to the prostate is curable by the surgery, therefore early detection is very important.

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