Overview
Prostate cancer
- Cancer of the prostate gland
- Adenocarcinoma accounts for > 90% of cases.
Epidemiology
- Worldwide:
- 2nd most common cancer diagnosis in men
- > 1.3 million cases diagnosed annually
- In the United States:
- 3rd leading cause of cancer in men
- Approximately 192,000 cases diagnosed annually
- Lifetime risk of a prostate cancer diagnosis is 11%.
- Lifetime risk of dying from prostate cancer is 2.5%.
- 5-year survival after diagnosis:
- Localized disease or regional spread: nearly 100%
- Distant metastatic disease: 31%
Risk factors
Inherent factors (major factors):
- Age
- Rare before 40 years of age
- Peaks between 65 and 74 years of age
- More common, and earlier onset, in African Americans
- Family history of prostate cancer, particularly in 1st-degree relatives who were diagnosed at < 65 years of age
- Family history of other heritable cancers
- Breast cancer, BRCA1 and BRCA2 gene mutations
- Melanoma
- Colorectal cancer, Lynch syndrome
- Ovarian cancer
- Pancreatic cancer
Medical factors:
- Obesity
- 5-alpha reductase inhibitors (e.g., finasteride)
- ↓ prostate-specific antigen (PSA) levels
- ↑ high-grade prostate cancer risk
- Trichomonas vaginalis infection
Social and environmental factors:
- High-fat, low-vegetable diet
- Cigarette smoking
- Exposure to Agent Orange
- Herbicide and defoliant chemical used during the Vietnam War between 1965 and 1972
- Associated with more aggressive cancer
- Exposure to chlordecone
- Insecticide used between 1973 and 1003 in the Caribbean
- Binds estrogen receptors, which may contribute to malignancy development
Related videos
Screening Rationale
Individualized screening
- Screening offers a small potential benefit in reducing the chance of death from prostate cancer.
- The potential benefit will take many years, even decades, while the harms take place soon after screening starts.
- Prostate cancer often has a slow growth rate, in which:
- Half of cases do not present clinically.
- Patients frequently die from other medical conditions.
- Each patient is encouraged to decide on the potential benefits and harms discussed based on his own values.
Benefits of screening
- Goals:
- Identify high-risk, localized prostate cancer that can be successfully treated
- Prevent prostate cancer-related morbidity and mortality, including advanced or metastatic disease
- Benefits of PSA-based screening:
- In men aged 55–69 years, screening may prevent 1.3 deaths from prostate cancer per 1,000 men screened over 13 years.
- Screening may prevent 3 cases of metastatic prostate cancer per 1,000 men.
- However, trials have not shown a reduction in all-cause mortality.
Risks of screening
- Harms of screening:
- Frequent false-positive results
- Leads to over-diagnosis (cancer diagnosed in men who otherwise would not have symptomatic cancer in their lifetime)
- Potential harms of diagnostic biopsy:
- Pain
- Infection
- Rectal bleeding
- Urinary obstruction
- Psychological harm
- Potential harms of cancer management:
- Erectile dysfunction (up to 50% of patients)
- Urinary incontinence
- Bowel dysfunction
- Psychological harm
Screening Recommendations
United States Preventive Service Task Force (USPSTF)
- Men aged 55–69 years should:
- Discuss potential benefits and harms with their clinician
- Consider age, family history, race/ethnicity, comorbid conditions, and life expectancy
- Make an individual decision about screening
- Men ≥ 70 years:
- Benefits do not outweigh the expected harms.
- Should not be routinely screened for prostate cancer
- Men who do not express a preference for screening should not be screened.
American Cancer Society
- Screening should not take place without a discussion about the harms and benefits.
- This discussion should occur at:
- 50 years of age for men with an average risk of prostate cancer and life expectancy ≥ 10 years
- 45 years of age for men with a high risk of prostate cancer (African Americans and those with a 1st-degree relative diagnosed with prostate cancer at < 65 years)
- 40 years of age for men with a higher risk (> 1 1st-degree relative who had prostate cancer at < 65 years)
Screening Strategy: PSA
Prostate-specific antigen is currently the only recommended screening method for prostate cancer.
Background
- A protein produced by normal and neoplastic prostate cells
- In healthy individuals, a small proportion will enter the bloodstream.
Causes of elevated serum PSA in prostate cancer
- An increased number of cells producing PSA, despite the fact that malignant cells generally make less PSA
- Disruption in the normal architecture and basement membrane, allowing a higher proportion of PSA to enter the bloodstream
Interpretation of results
- There is no perfect PSA cut-off value that avoids all false positives or all false negatives.
- False-positive rate: approximately 70%
- Benign causes of elevated PSA levels (contributing to false-positive rate)
- Benign prostatic hyperplasia
- Prostatitis
- Urinary retention
- Urologic procedures (cystoscopy, transurethral resection of the prostate)
- Benign causes of elevated PSA levels (contributing to false-positive rate)
- False-negative rate: approximately 15%
- False-positive rate: approximately 70%
- Positive: PSA ≥ 4 ng/mL
- Most widely accepted standard, which tries to balance the trade-offs between sensitivity and specificity
- Test characteristics at this cut-off level:
- For detection of any prostate cancer: sensitivity = 21%; specificity = 91%
- For detection of high-grade cancer: sensitivity = 51%
- Different cut-off levels for decision-making: age-specific reference ranges since PSA levels tend to increase with age
- Negative: PSA < 4 ng/mL
- Follow-up is needed
- For patients on a 5-alpha reductase inhibitor (ARI):
- Correction factor must be applied for accurate interpretation since ARIs lower PSA values.
- If there is an increase in PSA level, they should be referred to urology.
Follow-up
- Retesting should be performed every 1–2 years if the level is < 4 ng/mL.
- Interval recommendations vary between organizations.
- Can be individualized based on PSA level and the patient’s risk factors
- Consider repeat testing in 6–8 weeks if the level is between 4 and 7 ng/mL to rule out benign causes.
- If the PSA is still elevated, or > 7 ng/mL on the initial screen, refer to urology.
- Further urologic workup can include:
- Free:total (f/t) PSA ratio (f/t PSA < 10%–15% suggests cancer)
- PSA density (ratio of PSA level to prostate volume measured on transrectal ultrasound)
- Molecular and genomic analysis
- Magnetic resonance imaging (MRI) of the prostate
- Prostate biopsy
Screening Strategy: Digital Rectal Examination
- No longer recommended for asymptomatic patients
- Low sensitivity and specificity
- Does not provide additional information to a PSA test
References
- American Cancer Society (2019). Recommendations for Prostate Cancer Early Detection. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/acs-recommendations.html
- United States Preventive Services Task Force (2018). Prostate Cancer: Screening. https://www.uspreventiveservicestaskforce.org/uspstf/announcements/final-recommendation-statement-screening-prostate-cancer
- Jahn, J., Giovannucci, E., Stampfer, M. (2015). The High Prevalence of Undiagnosed Prostate Cancer at Autopsy: Implications for Epidemiology and Treatment of Prostate Cancer in the Prostate-Specific Antigen-Era. Int J Cancer, 137(12): 2795–2802.
- Hoffman, R.M. (2020). Screening for prostate cancer. UpToDate. Retrieved December 20, 2020, from https://www.uptodate.com/contents/screening-for-prostate-cancer
- Sartor, A.O. (2020). Risk factors for prostate cancer. UpToDate. Retrieved December 20, 2020, from https://www.uptodate.com/contents/risk-factors-for-prostate-cancer
- Mark, J.R. (2019). Prostate cancer. MSD Manual Professional Version. https://www.msdmanuals.com/professional/genitourinary-disorders/genitourinary-cancer/prostate-cancer
- Tracy, C.R., Brooks, N.A., and Said, M. (2020). Prostate cancer. Medscape. https://emedicine.medscape.com/article/1967731-overview