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. ​

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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. 

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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.

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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.

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Signs (seen in advanced disease):

• Cancer cachexia

• Bony tenderness

• Adenopathy​​

• Lower-extremity lymphedema or DVT

• Overdistended bladder

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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.