Prostate Cancer

Aka: Prostate Cancer, Malignant Neoplasm of the Prostate, Prostate Cancer Risk Factor

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II. Epidemiology

  1. Histologic evidence of Prostate Cancer on autopsy
    1. Men over age 50 years: 30%
    2. Men over age 80 years: 70%
  2. Clinical Incidence
    1. Incidence (2024 in U.S.): 299,000 new cases
    2. Incidence tripled in 10 years prior to 1997 (PSA detection)
    3. Lifetime diagnosis occurs in 17% of men (1 in 6)
      1. Prostate Cancer diagnosis after age 65 years old in 60% of cases
      2. Prostate Cancer deaths are in over age 75 years old in 70% of cases
  3. Mortality
    1. Second leading cause of cancer death in men (Second to Lung Cancer)
    2. However, only 3% of men die of Prostate Cancer (35,250 deaths in 2024, U.S.)

III. Risk Factors

  1. Age (Incidental finding on Autopsy)
    1. Age 50 years: 30% incidence Prostate Cancer
    2. Age 60 years: 35% incidence Prostate Cancer
    3. Age 70 years: 40% incidence Prostate Cancer
    4. Age 80 years: 55% incidence Prostate Cancer
    5. Age over 90 years: 100% incidence Prostate Cancer
  2. Ethnicity
    1. Black Men: 64 per 100,000 (confers twice risk of caucasian men)
    2. Caucasian Men: 26 per 100,000 (confers twice risk of asian men)
    3. Lower risk ethnicity: Asian and hispanic
  3. Family History (Relative Risk of Prostate Cancer)
    1. Consider genetic marker testing in strong Family History (e.g. BRCA1, BRCA2, Lynch Syndrome)
    2. First degree relative with Prostate Cancer: Relative Risk of 2.5 to 3
    3. Brother with Prostate Cancer before age 63: Relative Risk of 4
    4. Sister with Breast Cancer: Relative Risk of 2
    5. Other Family History that increases Prostate Cancer risk
      1. More than one first degree relative is affected
      2. Affected relative was under age 55 at diagnosis
  4. Nutritional Supplements
    1. Vitamin E Supplementation (400 units/day)
      1. Prostate Cancer risk increases 1 new case in 625 men
      2. Klein (2011) JAMA 306:1549-56. [PubMed]
    2. Omega 3 Fatty Acid Supplementation
      1. Prostate Cancer increased risk in some studies (preliminary)
      2. Brasky (2013) J Natl Cancer Inst 105:1132 [PubMed]
      3. Brasky (2011) Am J Epidemiol 173(12): 1429–39 [PubMed]
  5. Factors not with additional cancer risk
    1. Ejaculation frequency not associated with cancer risk
    2. Leitzmann (2004) JAMA 291:1578-86 [PubMed]

IV. Screening

  1. See Prostate Specific Antigen
    1. Includes screening protocols, Shared Decision Making and PSA interpretation
  2. Indications
    1. No screening is recommended as of 2012 by AAFP and USPTF
    2. Other organizations (ACS, ACP, AUA) recommend offering screening via Shared Decision Making
      1. See Prostate Specific Antigen (PSA) for Informed Consent scripting
  3. Timing (if screening is performed)
    1. Start screening (some recommend every other year)
      1. Normal risk: Starting at age 50 years old (ACP, ACS) or age 55 (AUA)
      2. High Risk: Starting at age 40 years old (AUA) or 45 years old (ACS)
        1. Examples: Black men, first degree relative with Prostate Cancer <65 years old
    2. Stop screening
      1. Stop screening by age 70 years old OR
      2. Less than 10 to 15 years Life Expectancy (ACS/AUA)
        1. See Charlson Comorbidity Index (CALE)
    3. Frequency of testing
      1. Every 1-2 years
    4. References
      1. Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]
  4. Testing
    1. Prostate Specific Antigen
      1. See Prostate Specific Antigen (PSA)
      2. Recheck elevated PSA (>4 ng/ml) in 3 months
        1. Transient PSA increase (e.g. due to BPH, Prostatitis) will normalize on recheck in 25 to 40% of patients
        2. Antibiotics are not recommended for elevated PSA unless symptomatic Prostatitis is present
    2. Digital Rectal Exam (evaluate for asymmetry, nodularity)
      1. Findings
        1. Test Sensitivity: <60%
        2. Test Specificity: >83%
        3. Positive Predictive Value: <28%
      2. Summary: Poor efficacy with high False Positive and False Negative Rate
        1. Hoogendam (1999) Fam Pract 16(6): 621-6 [PubMed]
      3. Digital Rectal Exam may be predictive in those with elevated PSA level
        1. Nodule or irregularity on DRE is associated with Grading Group >=2 when PSA elevated
        2. Halpern (2018) J Urol 199(4):947-53 +PMID: 29061540 [PubMed]
  5. Additional Testing to consider on consistently elevated PSA (to further risk stratify to those who need biopsy)
    1. Multiparametric MRI (see below)
    2. PSA Kinetics
    3. Biomarkers
      1. Blood Biomarkers (e.g. 4Kscore, isoPSA, Proclarix)
      2. Urine Biomarkers (e.g. PCA3, MPS, SelectMDx)
      3. Farha (2022) Ther Adv Urol 14:17562872221103988 +PMID: 35719272 [PubMed]
    4. MyProstateScore (MPS)
      1. Consider in patients referred for Prostate biopsy
      2. Estimates risk of Prostate Cancer using 2 urinary biomarkers
        1. Prostate Cancer Antigen 3 (PCA3)
        2. TMPRSS2:ERG Gene Fusion
      3. Cost of $760 is not covered by Medicare or medicaid
        1. However private insurance may cover
      4. References
        1. Balloga (2022) Am Fam Physician 105(5): 542-3
    5. Prostate Cancer Risk Calculator
      1. https://www.prostatecancer-riskcalculator.com/

V. Imaging

  1. Multiparametric MRI (mpMRI)
    1. Protocols are experimental in 2022 and are not wide spread
    2. Cost is estimated at <$500
    3. May assist in risk stratification of whether biopsy is indicated
    4. May assist in directing targeted biopsy
    5. Stabile (2020) Nat Rev Urol 17(1): 41-61 [PubMed]

VI. Diagnosis

  1. Transrectal Ultrasonography-guided Prostate biopsy
    1. Prostate Biopsy indications
      1. PSA >4 ng/ml or
      2. PSA 2.5 to 4.0 ng/ml and Prostate Cancer Risk Factor or
      3. Free PSA <8% of total PSA or
      4. Rapid PSA increase in one year
        1. Baseline PSA <4 ng/ml and PSA increase by more than 0.35 ng/ml in last year or
        2. Baseline PSA 4-10 ng/ml and PSA increase by more than 0.75 ng/ml in last year
    2. Biopsy cores (12 cores are standard)
      1. Twelve cores are significantly more sensitive than 6 without increased complication risk
      2. However, even 12 cores sample only 1% of the Prostate, and 20% False Negative Rate
      3. Eichler (2006) J Urol 175(5): 1605-12 [PubMed]

VII. Classification

  1. See Prostate Cancer Staging (TNM)
  2. See Prostate Cancer Histologic grading (Gleason Score)

VIII. Complications: Metastasis

  1. Spine Metastasis (90% of Prostate Cancer metastasis)
    1. Involves Vertebral Column in 85% of cases
    2. Most often affects Lumbar Spine
    3. Identified 19 months from initial diagnosis
    4. Recurrence is common (45% risk within 2 years)
  2. Lung Metastasis (50% of Prostate Cancer metastasis)
    1. Identified 35 months from initial diagnosis
  3. Liver Metastasis (25% of Prostate Cancer metastasis)
  4. Brain Metastasis (rare)
    1. Identified 60 months from initial diagnosis
    2. Poor prognosis (average survival 7.6 months)
  5. References
    1. Benjamin (2002) Am Fam Physician 65(9): 1834-40 [PubMed]

IX. Management

  1. See Prostate Cancer Management

X. Prevention: Possibly Protective Factors

  1. Exercise (walking)
  2. Soy Protein
  3. Flaxseeds (Phytoestrogens)
  4. Lycopones (tomatoes)
  5. Selenium
  6. Green Tea
  7. Vitamin D Supplementation
  8. Calcium Supplementation
  9. Garlic
  10. PC-SPES
  11. Grape seed extract
  12. Zinc

XI. References

  1. Cooner (1994) Am Fam Physician
  2. Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]
  3. Wilbur (2008) Am Fam Physician 78(12): 1377-84 [PubMed]
  4. Xu (2024) Am Fam Physician 110(5): 493-9 [PubMed]

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