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Prostate cancer

Last updated: March 4, 2021

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Prostate cancer is the second most common cancer in men after skin cancer and the second leading cause of cancer death in men after lung cancer. The risk of developing prostate cancer increases with age. It is more common in African Americans. In early stages, prostate cancer generally causes no symptoms and is typically detected by screening. The preferred diagnostic procedures are digital rectal examination (DRE), PSA testing, and ultrasound-guided transrectal prostate biopsy. Bone metastases are common in advanced prostate cancer and can be diagnosed using a bone scan. Because most patients with prostate cancer are of advanced age, life expectancy and the histological evaluation of a tumor biopsy should be taken into account when planning treatment. Radical prostatectomy and radiotherapy are indicated in young patients. In older patients, “watchful waiting” (i.e., purely symptomatic treatment) and “active surveillance” (i.e., continuous restaging and initiation of curative measures if tumor progresses) are also a treatment option since localized prostate cancer typically has a slower growth rate and a better prognosis compared to other malignancies.

  • Incidence: following skin cancer (i.e., melanoma and nonmelanoma combined) most common cancer in men in the US [1]
  • Mortality: in 2020, second leading cause of cancer deaths in men in the US (after lung cancer)

Epidemiological data refers to the US, unless otherwise specified.

Risk factors [2][3]

Advanced age is the main risk factor for prostate cancer.
Sexual activity and benign prostatic hyperplasia (BPH) are not associated with prostate cancer.

Prostate cancer is commonly localized in the Peripheral zone (Posterior lobe).

Early-stage prostate cancer

  • Typically asymptomatic
    • Early prostate cancers are found during screening tests.
    • Some prostate cancers are found incidentally (incidental prostate cancer, e.g., in patients that require a transurethral resection due to BPH)

Advanced-stage prostate cancer

Constitutional symptoms

  • Fatigue
  • Loss of appetite
  • Weight loss

Urinary symptoms [7]

Metastatic disease

The differential diagnoses listed here are not exhaustive.

Approach to suspected prostate cancer

Screening and basic diagnostics [8]

Digital rectal examination (DRE) [9]

  • Low sensitivity (approx. 30%)
  • Good specificity (approx. 90%) : Irregular and nodular prostate is suspicious for malignancy, but not specific for cancer.
  • Indications
  • Physiological DRE findings
    • Smooth
    • Nonfirm
    • Symmetric
    • Roughly heart-shaped
    • Painless
  • Early stage prostate cancer DRE findings
    • Localized indurated nodules
    • Otherwise smooth
    • Nonfirm
    • Painless
  • Advanced stage prostate cancer DRE findings
    • Asymmetric areas
    • Frank nodules
    • Painless

Blood tests

Prostate-specific antigen (PSA) levels

  • Overview
    • Serine protease that splits the semenogelin-1 protein and thereby liquefies semen.
    • Only produced by the prostate gland: organ-specific marker
  • Indication
    • Suspected prostate cancer
    • Screening
      • Benefit is controversial
      • Usefulness should be evaluated on a case-by-case basis by the physician and patient.
    • Monitoring of metastasis or detection of cancer recurrence following treatment of PSA-positive prostate cancer
  • Interpretation

Normal PSA values do not exclude the diagnosis of prostate cancer.

Inflammation, manipulation of the prostate, and other malignant or benign prostate disease causing elevated enzyme levels may lead to false-positive PSA results.

Other blood tests


Confirmatory testing

Prostate biopsy

  • Indication
    • Histological confirmation of suspicious findings on DRE
    • Suspicious PSA levels or velocities
    • Clinically suspicious prostate cancer
  • Technique: ∼ 12 prostate samples are taken from different areas of the prostate guided by transrectal ultrasonography (TRUS) under local anesthesia and prophylactic antibiotics.
  • Interpretation: : When prostate cancer is present in the biopsy, the tumor is graded using the Gleason score.
    • Calculated based on the microscopic appearance of prostate cancer
    • Higher score indicates a worse prognosis (ranges from 2 to 10)
    • Score is established by adding the Gleason grades of the most prevalent and the second most prevalent differentiation pattern within the biopsy
    • Grade ranges from 1 to 5
      • Grade 1: well-differentiated, microscopically uniform glands without invasion into adjacent healthy prostate tissue
      • Grade 5: undifferentiated cancer cells with no glandular differentiation
  • Complications

The Gleason scoring system is used to grade the metastatic potential of adenocarcinoma of the prostate according to gland-forming differentiation.



  • In confirmed prostate cancer to assess the extent of the disease
  • Should be performed, if advanced cancer is suspected by either PSA levels > 10 ng/mL or a Gleason score ≥ 7



Complications following surgery or radiotherapy

Radiotherapy-specific risks

We list the most important complications. The selection is not exhaustive.

Survival rates of prostate cancer patients [12]
SEER Stage Description 5-year relative survival rate
  • Nearly 100%
  • Nearly 100%
  • 31%


  • The treatment plan is based upon:
  • Results of imaging studies, PSA levels, and the Gleason score are taken into consideration when evaluating the different treatment options.

Management of localized disease

Active surveillance [13]

  • Regular follow-ups with cancer restaging instead of treatment
  • Preferred option for most early-stage cancers)
  • Treatment is only started if the tumor progresses.

Watchful waiting [13]

  • Less intensive type of follow-up than active surveillance
  • Best approach in a number of different cases, including:
    • Elderly patients with slow-growing tumors
    • Life-limiting comorbidity
    • Life expectancy < 10 years due to other causes
  • Systemic or local treatment to relieve symptoms is initiated if symptomatic progression of the tumor occurs.

Radiation therapy [14]

Radical prostatectomy [14]

Radical prostatectomy involves removal of the vas deferens, resulting in infertility.

Antiandrogen therapy [14]

Management of disseminated disease

Management of castration-resistant prostate cancer (CRPC)

  1. Key Statistics for Prostate Cancer. Updated: January 5, 2017. Accessed: March 5, 2017.
  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. Prostate Cancer Risk Factors. Updated: June 9, 2020. Accessed: November 9, 2020.
  4. Jahn JL, Giovannucci EL, Stampfer MJ. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate-specific Antigen-era. International Journal of Cancer. 2015; 137 (12): p.2795-2802. doi: 10.1002/ijc.29408 . | Open in Read by QxMD
  5. Philip J, Mathew J. Penile metastasis of prostatic adenocarcinoma: Report of two cases and review of literature.. World J Surg Oncol. 2003; 1 (1): p.16. doi: 10.1186/1477-7819-1-16 . | Open in Read by QxMD
  6. Screening Tests for Prostate Cancer. Updated: August 1, 2019. Accessed: November 6, 2020.
  7. Jones D, Friend C, Dreher A, Allgar V, Macleod U. The diagnostic test accuracy of rectal examination for prostate cancer diagnosis in symptomatic patients: a systematic review. BMC Fam Pract. 2018; 19 (1). doi: 10.1186/s12875-018-0765-y . | Open in Read by QxMD
  8. Insurance Coverage for Prostate Cancer Screening. Updated: April 14, 2016. Accessed: February 15, 2017.
  9. Filella X, Alcover J, Molina R, Rodríguez A, Carretero P, Ballesta AM. Free and Total PSA in the Diagnosis of Prostate Cancer. Tumor Biology. 1997; 18 (6): p.332-340. doi: 10.1159/000218047 . | Open in Read by QxMD
  10. Prostate cancer types. Updated: November 5, 2020. Accessed: November 6, 2020.
  11. Wernert N. The peripheral zone of the prostate is more prone to tumor development than the transitional zone: Is the ETS family the key?. Molecular Medicine Reports. 2011 . doi: 10.3892/mmr.2011.647 . | Open in Read by QxMD
  12. Watchful Waiting or Active Surveillance for Prostate Cancer. Updated: March 11, 2016. Accessed: February 15, 2017.
  13. Initial Treatment of Prostate Cancer, by Stage. Updated: March 11, 2016. Accessed: February 15, 2017.
  14. Stephenson AJ, Eastham JA. Role of Salvage Radical Prostatectomy for Recurrent Prostate Cancer After Radiation Therapy. J Clin Oncol. 2005; 23 (32): p.8198-8203. doi: 10.1200/jco.2005.03.1468 . | Open in Read by QxMD
  15. Survival Rates for Prostate Cancer. Updated: January 9, 2020. Accessed: November 9, 2020.