Prostate Specific Antigen and Prostatic Carcinoma Notes

Prostate Gland

  • Walnut-sized gland located just below the neck of the bladder.
  • Surrounds the urethra.
  • Produces secretions that support spermatozoa.

Prostate Gland Functions

  • Controls urination.
  • Forms part of the semen.
  • Surrounds the urethra, the passage through which urine exits the bladder.
  • Normal prostate enlargement is called "benign prostate hypertrophy."
  • Both benign prostate hypertrophy and prostate cancer can impinge upon the urethra, leading to difficulty with urination.

Common Prostate Problems

  • Benign Prostatic Hyperplasia (BPH)
  • Prostatitis
  • Prostate cancer

Benign Prostatic Hyperplasia (BPH)

  • Typically develops after age 40; affects 80% of men by age 80.
  • BPH is a benign condition that causes the prostate to swell, interfering with urine flow.
  • Symptoms:
    • Frequent urination (several times an hour).
    • A sense of urgency.
    • A long wait for urine to flow.
    • Frequent awakening at night to urinate.
    • Interruption of the urine stream (starting and stopping).
    • A constant feeling of fullness in the bladder.
  • BPH develops from the inside out, squeezing the urethra as inner prostate cells grow.
  • It is NOT cancer (benign).

Hyperplasia vs. Hypertrophy

  • Hyperplasia: Increased number of cells.
  • Hypertrophy: Cells get larger.

Serum PSA levels in BPH

  • Serum PSA levels are in part determined by the volume of epithelial cells present.
  • Large prostate glands generally contain more epithelial cells than small glands, thus contributing more PSA molecules to serum.

Prostatitis

  • Inflamed and swollen prostate.
  • Mainly caused by bacterial infection.
  • Symptoms:
    • Pain in the joints.
    • Pain in the muscles.
    • Pain in the lower back.
    • Aches, fever, and chills.
    • Urinary trouble (including blood in the urine).
  • Bacterial prostatitis is not contagious; treatment involves antibiotics.
  • Infected prostate may cause pain with urination.

Prostate Cancer

  • Malignant growth of cells in the prostate gland.
  • Cancer is a cellular disease involving disordered and abnormal cell growth.
  • In prostate cancer, cells grow out of control and form tumors.
  • If the tumor is within the gland, the cancer is localized and curable.
  • If the cancer escapes the gland, it is considered incurable; early detection is crucial.

Prostate Cancer Statistics and Detection

  • Second leading cause of cancer death in males in the U.S.
  • The cause is unknown.
  • Risk factors have been identified.
  • Often detected as a hard nodule during a routine rectal examination.
  • The PSA blood test is a screening test.
  • Diagnosis depends on the presence of cancer cells in a prostate biopsy.
  • Can be life-threatening or may exist for years without health problems.
  • Treatment depends on the growth and location of the tumor, as well as the age and health of the patient.
    Treatment options include observation, radiation therapy, surgery, hormonal therapy, and chemotherapy.

Risk Factors for Prostate Cancer

  • Age: Increases with age; extremely rare under 40, common in men over 80.
  • Heredity (genetic background): Black American males have a higher risk than Japanese-American males; more common among family members of prostate cancer patients; no specific prostate cancer gene has been identified to date.
  • Hormonal influences: Testosterone stimulates the growth of prostate cancer cells.
  • Environmental factors: Cigarette smoking and high saturated fat diets may increase risk.

Symptoms of Prostate Cancer

  • Early stages: Usually no symptoms.
  • Later stages:
    • Hard prostate nodules detected during a rectal examination (DRE).
    • Diminished urine flow and difficulty urinating.
    • Burning and bleeding with urination, and blood in the semen (hemospermia).
    • Enlarging prostate gland can completely block the flow of urine, resulting in a painfully obstructed and enlarged bladder (anuria).

Diagnosis of Prostate Cancer

  • Screening includes detecting a lumpy or large prostate gland during a rectal examination and an elevated PSA blood test.
  • Diagnosis is confirmed by prostate biopsy, where tissue samples are examined under a microscope.

Five Procedures to Help Diagnose Prostate Cancer

  • Digital Rectal Examination (DRE)
  • PSA (Prostate Specific Antigen) test
  • Transrectal Ultrasonography
  • Biopsy
  • Bone scan
  • Ultrasonography is an excellent method for biopsy guidance.

Digital Rectal Examination (DRE)

  • A doctor feels the outer lobes of the prostate for hardness or nodules by inserting a gloved, lubricated finger into the rectum.

Transrectal Ultrasonography (TRUS)

  • Ultrasonic waves are used to visualize the prostate.
  • A probe is inserted into the rectum to detect abnormalities, especially those too small to feel.
  • Usually done when DRE or serum PSA is abnormal.

Biopsy

  • A small piece of tissue is cut away and sent to the laboratory for histological examination by a pathologist.

Further Tests After Prostate Cancer Confirmation

  • X-ray tests to determine the presence or absence of spread (metastasis) of the cancer.
  • Nuclear medicine bone scans and plain bone x-rays to look for metastasis, as prostate cancer can spread to the bone.
  • Lymph nodes may also be sampled by biopsy.

Prostatic Specific Antigen (PSA)

  • A glycoprotein produced only by the prostate gland.
  • Involved in the liquefaction of the semen.
  • Plasma concentrations may rise in men with prostate carcinoma or benign prostatic hypertrophy (BPH).
  • Used as an aid in the diagnosis and monitoring of prostatic cancer.

Prostatic Acid Phosphatase (PAP)

  • An enzyme produced by the prostate gland.
  • May be found in increased amounts in men who have prostate cancer.
  • PAP measurements were once used as a marker for prostatic cancer, but PSA levels are now used as a better marker.

Factors that Increase PSA

  • Older men
  • BPH
  • Lower urinary tract infections
  • After trauma to the prostate

PSA Blood Levels

  • Most PSA circulates in the plasma bound to α1-antichymotrypsin (ACT), but a small fraction circulates as free PSA.
  • Patients with prostate cancer usually have a higher ratio between ACT-bound PSA and free PSA than patients with BPH.
  • Useful in diagnosing and monitoring response to therapy.

PSA Serum Levels

  • Most men have PSA blood levels between 0 - 4.0
    g/ml.
  • 4 - 10
    g/ml may indicate BPH or cancer.
  • Above 10
    g/ml usually indicates malignant cancer.

Summary of PSA Levels

  • 0 – 4.0
    g/ml: Normal serum levels.
  • 4.0 – 10.0
    g/ml: BPH, Prostatitis, or early stages of prostatic cancer.
  • >10.0
    g/ml: Malignant cancer.

Observation

  • Decisions regarding treatment options are based on the patient's age, overall health, and whether the cancer is localized or metastatic.
  • Many patients may neglect observation until symptoms develop due to the slow-growing nature of prostate cancer.
  • The sooner treatment is started, the better.

Radiation Therapy

  • Involves exposing cancer areas to an external beam of radiation.
  • Rapidly dividing cancer cells are more vulnerable to radiation than surrounding normal cells.
  • Usually given over 6 to 7 weeks.
  • Can also be administered using radioactive pellets or "seeds" implanted into the prostate gland.
  • Side effects include difficulties with urinary control and bowel dysfunction.

Surgery

  • Prostatectomy is more often performed in younger patients when the cancer has not spread beyond the prostate gland.
  • Adverse reactions include urinary incontinence, loss of sexual function (impotence), anesthesia risks, and bleeding.

Hormonal Treatment

  • Employed for patients with metastatic prostate cancer.
  • Testosterone, the male hormone, stimulates the growth of prostate cancer cells.
  • Treatments suppress the production or action of testosterone.
  • Methods include:
    • Oral estrogen medication.
    • Injectable leuprolide (LUPRON), LHRH analogue.
    • Orchiectomy (surgical removal of the testicles).
    • Flutamide (antiandrogen drug, competes with testosterone).
    • LHRH: luteinizing hormone-releasing hormone
  • LUPRON, an injectable agent, impairs brain signals to the testicles to produce testosterone.

Testosterone and DHT

  • Testosterone is converted to dihydrotestosterone (DHT) by the 5α-reductase enzyme.
  • DHT binds with a specific protein and moves to the nucleus, influencing the growth of the cell.

Chemotherapy

  • Used for patients with advanced cancer.
  • Chemotherapy regimens tried have not been shown to be beneficial.
  • A new chemotherapy agent, suramin, is being studied.
  • Newer treatments include "cryotherapy," which involves freezing the prostate tissue to kill the cancer.

Prevention of Prostate Cancer

  • No specific measures are known to prevent prostate cancer.
  • Early detection is the most important prevention measure.
  • Yearly rectal examinations after age 40 are important.
  • The earliest sign is the discovery of an abnormal gland during a rectal examination.
  • The PSA blood test is another important screening tool for early detection.

Screening Guidelines

  • Treatment methods have significant potential for side effects.
  • Results of screening tests must be reviewed between the doctor and patient.
  • The American Cancer Society recommends annual screening by both rectal examination and PSA measurement starting at 50 years of age.
  • Initial screening is recommended at age 40 years for those men at special risk.
  • Screening tests are not free from controversy; 40% of U.S. men in their 40s have at least evidence of tiny areas of undetected prostate cancer.