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Prostate cancer

Last updated: October 26, 2021

Summarytoggle arrow icon

Prostate cancer is one of the most common cancers that affect men, especially those > 50 years of age. Typically, prostate cancer has an indolent course and is usually discovered while still localized in the prostate. This allows many patients to undergo monitoring for progression rather than active treatment, preventing unnecessary treatment-related adverse effects. Prostate cancer is typically diagnosed and monitored using prostate-specific antigen (PSA) testing, multiparametric MRI (mpMRI), and guided biopsy. Once the decision to treat has been made, therapeutic options include radical prostatectomy, radiation therapy, androgen deprivation therapy (ADT), and chemotherapy. Since all treatment options may adversely affect the patient's quality of life, shared decision-making with the patient is strongly encouraged in all current guidelines. Symptomatic management may be preferable in patients with significant comorbidities or limited life expectancy, as further treatment is unlikely to be life-prolonging.

  • 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.

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

References: [3][4]

Symptoms

Digital rectal examination (DRE) [6][7][8]

A DRE should be performed in individuals with elevated serum PSA levels; and as part of the comprehensive evaluation of male LUTS. DRE has a low positive predictive value for detecting prostate cancer and should not be performed as the sole screening modality.

  • May be normal in early disease or if the cancer is located in areas of the gland that are not palpable on DRE [9]
  • Features suggestive of prostate cancer include:
    • Localized indurated nodules on an otherwise smooth surface
    • Prostatomegaly, lobar asymmetry, obliteration of the sulcus
    • Hard nontender nodules

Most prostate cancers are located in the peripheral zone (posterior lobe) of the prostate. In contrast, BPH occurs in the transitional zone of the prostate.

Even patients with advanced prostate cancer may have a normal DRE; if clinical suspicion is high, continue diagnostic evaluation for prostate cancer!

Approach

The following content is related to diagnosing prostate cancer in symptomatic patients or those with a positive screening test. Screening for prostate cancer in asymptomatic individuals is detailed separately.

Prostate-specific antigen (PSA) levels

PSA is a serine protease produced only in the prostate gland and, therefore, is an organ-specific marker. It is not cancer-specific however, as levels may also be elevated in benign conditions. [10]

A PSA level ≤ 4 ng/mL does not exclude prostate cancer!

5-alpha reductase inhibitors (5-ARIs) can suppress PSA production, resulting in spuriously low PSA levels. This should be taken into consideration in patients on long-term 5-ARIs (e.g., for BPH). [15][16]

Inflammation, manipulation of the prostate, and other malignant and benign prostate diseases may lead to a false-positive PSA result!

Urinalysis [17][18]

Initial imaging

Prostate biopsy

Gleason score and grade groups are used to grade the metastatic potential of prostate adenocarcinoma based on gland-forming differentiation.

Evaluation of tumor extent [21][22][33]

mpMRI is the preferred method for detecting local tumor extent (including recurrent prostate cancer) and PET-CT is preferred to evaluate for metastatic disease. [34][35]Skeletal metastases are the most common nonnodal sites of metastasis in prostate cancer. Vertebral metastases commonly occur due to the spread of malignant cells through the Batson vertebral venous system. Skeletal metastases are predominantly osteoblastic but osteolytic metastases can also occur.

The TNM staging system is based on American Joint Committee on Cancer recommendations (see “Grading and staging” in “General oncology”). Broadly, prostate cancer is divided into the following clinical stages. [21][37][38]

Approach [21][33]

Management options for prostate cancer depend on the cancer stage, presence of high-risk features, and the patient's life expectancy. The impact of potential adverse effects of treatment on quality of life should be discussed with the patient prior to treatment initiation.

Watchful waiting [21]

  • Indications: recommended approach if all of the following apply
    • Limited life expectancy (≤ 5 years)
    • Slow-growing tumor (i.e., low-risk or intermediate-risk localized tumors)
    • Asymptomatic or minimal symptoms
  • Method
    • Regular monitoring with scheduled DRE and serum PSA levels (less intensive follow-up than active surveillance).
    • Initiate definitive management according to cancer stage only when symptoms occur.

Active surveillance [21][40]

Androgen deprivation [33][41]

Androgen deprivation therapy (ADT)

Androgen synthesis inhibitors and androgen receptor antagonists [42]

Initiate prophylaxis against treatment-induced osteoporosis and fractures in all patients on androgen deprivation and/or glucocorticoids.

First-generation antiandrogens (flutamide and bicalutamide) are used only for the short-term management of a testosterone flare. [43]

Radiation therapy [21][44]

Radical prostatectomy [21]

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

Chemotherapy [33]

Management of bone health [48][49][50]

Prostate cancer patients are at an increased risk of skeletal features due to osteoporosis (treatment-induced and age-related) and bone metastases. [33]

Prophylaxis against treatment-induced osteoporosis and fractures

Management of skeletal events [51]

Patients with known vertebral metastatic disease and new neurological symptoms must have an urgent MRI to rule out spinal cord compression.

  • Monitor serum total PSA levels. [52]
    • Every 6 months for the first 5 years, then annually for patients who have had definitive local therapy
    • Every 3–6 months for patients on ADT
  • Consider assessing PSA velocity (PSA doubling time); a significant rise or short doubling time suggests a recurrence. [11]
  • Arrange further studies for patients with abnormal PSA values.
  • Annual DRE: to monitor for prostate cancer recurrence and rectal cancer [46]

General principles [53]

Given the indolent nature of prostate cancer and the significant potential for treatment-related decline in quality of life, patients should be educated on the risks and benefits of participating in screening and undergoing treatment if cancer is detected. For patients with a limited life expectancy, neither screening nor treatment may be appropriate. [21][54]

  • PSA screening is controversial as it has:
    • A high false-positive rate [53]
    • A high detection rate of clinically insignificant cancers (leading to overdiagnosis) [53]
    • Minimal or no effect on prostate cancer-related mortality. [55][56][57]
  • Patient harm may occur as a result of testing and/or treatment initiated by a positive PSA screening test.

Because of the low benefit and potential risk associated with PSA screening, patients should be involved in the decision to screen for prostate cancer. [6]

Screening recommendations [58]

Recommendations for screening are based on age and life expectancy. Screening is not recommended for patients with a life expectancy < 10 years.

Screening recommendations by age group in prostate cancer [6][54][58]
Patient age Screening recommendation
< 40 years
  • Screening is discouraged.
40–54 years
55–69 years
  • Shared decision-making: Proceed with screening if the patient chooses this option.
≥70 years
  • Screening is not recommended.

Screening for prostate cancer is not recommended in patients with a life expectancy < 10 years. [54]

Screening modalities [58] [6]

  • The most important prognostic indicator for prostate cancer is the histological grade (i.e., grade group or Gleason score). [38]
  • Broadly, patients with cancer confined to the prostate and pretreatment PSA levels < 10 ng/mL have a favorable prognosis. [21][61]
Grade groups for prostate cancer [31][62]
Grade group

Gleason score [32]

5-year survival after radical prostatectomy
1 ≤ 6 96%
2 3 + 4 = 7 88%
3 4 + 3 = 7 63%
4 4 + 4 = 8 48%
5 9 or 10 26%

The differential diagnoses listed here are not exhaustive.

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