Carcinoma of the Prostate

Study guide:

Epidemiology: 

  • Most common cancer in men and the second leading cause of cancer death.

  • Most prostate cancer cases are adenocarcinomas (95%).

  • More common in African-American, followed by Caucasians and less common in southeastern and south-central Asia.

  • Usually prostate cancer is slow growing and identified in asymptomatic patients. ​

Risk factors:

  • Age.

  • Androgens:

    • Cancer of the prostate does not develop in males castrated before puberty.

  • Heredity:

    • Increased risk among first-degree relatives of patients with prostate cancer (especially from the father’s side).

    • Familial cases have gene alteration in chromosome 1, 17, and X.

  • Environment:

    •  The relationship between specific dietary components or cigarettes smoking and prostate cancer risk is unclear, yet it’s believed to exist based on studies of increased incidence in Japanese migrants to USA and westernization of Asian diet.

    • Acquired somatic mutations.

    • Diets high in saturated fats. 

Pathophysiology:

  • Unequal rates of cell division and cell death → uncontrolled neoplasia.

  • Further mutations → progression and metastasis.

  • Local invasion in the peripheral-zone tumors extend into the ejaculatory ducts and seminal vesicles while those in transitional-zone spread to the bladder neck.

  • Spread to lumbar spine results in osteoblastic metastasis that presents as low back pain and increased serum alkaline phosphatase levels, PSA, and prostatic acid phosphatase (PAP). 

  • 70% of prostate cancer cases arise in the peripheral zone, and are thus palpable on DRE, followed by the central zone, then the transitional zone.

Clinical Presentation:

Symptoms:

  • LUTS (less common than BPH due to peripheral location).

  • Symptoms of metastatic spread, e.g: back pain.​

  • Constitutional symptoms and symptoms of metastatic tumors.

Signs (seen in advanced disease):

  • Cancer cachexia

  • Bony tenderness

  • Adenopathy​​

  • Lower-extremity lymphedema or DVT

  • Overdistended bladder

Diagnosis:

  • Digital rectal exam: This will reveal asymmetry and irregular hard nodules.

  • Prostate specific antigen (PSA): 

    • Usually 4 ng/mL is the cutoff between normal and abnormal, however, cancer cannot be excluded if below the cutoff.

    • Used along with DRE for screening. Useful tool to monitor the progression post-treatment. 

    • Normal serum PSA increases with age due to BPH:

      • 2.5 ng/ml for ages 40-49

      • 7.5 ng/ml for ages 70-79

    • A serum PSA level of >10ng/ml is highly worrisome at any age.

      • In prostate cancer, PSA levels are elevated. However, there is a decrease in the number of free PSA (as oppose to BPH). The cancer cells make PSA in the bound form. 

    • Transrectal ultrasonography (TRUS): Used to assess the size of the prostate and to guide the biopsy.

    • Biopsy: obtained guided by TRUS, the best initial and most accurate test!

    • Gleason staging: Primary grade is assigned to the dominant pattern and a secondary grade to the next most frequent pattern. The two numerical grades are then added to obtain a combined Gleason score.

    • The higher the Gleason score, the worse the prognosis. 

    • CT & bone scan: to check for metastasis and determine the TNM grade.

Common sites for distant metastasis are bones, specifically lumbar spine and pelvis via vertebral venous plexus, and lymph nodes.

NO definitive screening test for prostate cancer. 

Management:

  • Radical prostatectomy, radical radiotherapy or brachytherapy (implantation of small radioactive particles into the prostate): for patient with higher than 10 years life expectancy.

  • Watchful waiting: for patients with less than 10 years life expectancy or life-limiting comorbidities.

  • Active surveillance: for patients with small asymptomatic foci, they will be followed up and biopsy will be obtained regularly to intervene when indicated.

  • Hormonal therapy (SE: osteoporosis, anemia, decreased libido, erectile dysfunction):

    • Orchiectomy used to be gold standard of locally advanced and metastasized cancer.

    • Androgen suppressing drugs used in locally advanced and metastasized cancer.

    • Antiandrogens (bicalutamide) to prevent further growth of the tumor.

    • Analogues of LHRH: currently the gold standard of locally advanced and metastasized cancer, it increases the testosterone level at first!

 

 

Prognosis: 

  • Estimated based on the pathologic TNM stage, margin status, Gleason grade, and serum PSA values.

  • Localized prostate cancer has generally good prognosis.

  • Metastatic cancer has no cure with median life expectancy of 1 to 3 years after diagnosis. 

Surgery is more likely to cause erectile dysfunction more than radiation therapy. 

For metastasized tumors the goal is to bring the testosterone to zero.  

Adopted from Master the Boards 3rd Edition.

References:​​

  • Kumar P, Clark M. Kumar & Clark's clinical medicine.

  • Walker B, Colledge N, Ralston S, Penman I. Davidson's principles and practice of medicine.

  • Le T, Bhushan V, Singh Bagga H. First aid for the USMLE step 2 CK. New York: McGraw-Hill Medical; 2010.

  • Le T, Bhushan V, Sochat M, Sylvester P, Mehlman M, Kallianos K. First aid for the® USMLE.

  • Fischer C. Master the boards.

  • Sattar H. Fundamentals of pathology. Chicago: Pathoma.com; 2011.

  • Agabegi S, Agabegi E, Ring A. Step-up to medicine. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2013. 

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Written by:      Lama Al Luhidan                                           


Reviewed by:  Bassam AlGhamdi
                         Roaa Amer ​

Format editor:  Adel Yasky