prostate%20cancer
PROSTATE CANCER

Prostate cancer is the cancer that occurs in the male's prostate.

It is the most common cancer in men >50 years of age.

Signs and symptoms include weak urinary stream, polyuria, nocturia, hematuria, erectile dysfunction, pelvic pain, back pain, chest pain, lower extremity weakness or numbness and loss of bowel or bladder control.

Diagnosis

Key Examinations for the Diagnosis of Prostate Cancer

  • Prostate-specific antigen (PSA) level
  • Digital rectal examination (DRE)
  • Prostate biopsy

Staging

  • Determines the extent of cancer upon diagnosis
  • Important factor in the choice of treatment and provides information about the prognosis of the disease

Tumor, Nodes and Metastasis (TNM) System

  • Developed by the American Joint Committee on Cancer (AJCC) and Union Internationale Contre le Cancer 
    T - Primary Tumor
    TX Primary tumor cannot be assessed
    T0 No evidence of primary tumor
    T1 Clinically inapparent tumor not palpable or visible by imaging
    T1a Tumor incidental histological finding in 5% or less of tissue resected
    T1b Tumor incidental histological finding in more than 5% of tissue resected
    T1c Tumor identified by needle biopsy (secondary to elevated PSA level)
    T2 Tumor confined within the prostate gland (by needle biopsy)
    T2a Tumor involves 1/2 of one lobe or less
    T2b Tumor involves >1/2 of one lobe but not both lobes
    T2c Tumor involves both lobes
    T3 Tumor extends through the prostatic capsule1
    T3a Extracapsular extension (unilateral or bilateral)
    T3b Tumor invades the seminal vesicle(s)
    T4 Tumor fixed or invades adjacent structures other than the seminal vesicles (bladder, rectum, levator muscles, and/or pelvic wall)
    N - Regional Lymph Nodes2
    NX Regional lymph nodes cannot be assessed
    N0 No regional lymph node metastasis
    N1 Regional lymph node metastasis present
    M - Distant metastasis3
    MX Distant metastasis cannot be assessed
    M0 No distant metastasis
    M1 Distant metastasis
    M1a Non-regional lymph node(s)
    M1b Bone(s)
    M1c Other site(s)
    1Invasion into the prostatic apex or capsule (but not beyond the prostatic capsule) is considered T2
    2Includes metastasis <0.2 cm considered pathologic N1
    3The most advanced category should be used when >1 metastasis site is present
    Adapted from: National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2016.

Staging

  • Should be based on the prostate-specific antigen (PSA) level, tumor grade, and positive prostate biopsies
    Stage Tumor Node Metastasis PSA Gleason Score
    I T1a-c N0 M0 PSA <10 Gleason <6
    T2a N0 MO PSA <10 Gleason <6
    T1-2a NO MO PSA X Gleason X
    IIA T1a-c N0 M0 PSA <20 Gleason 7
    T1a-c N0 MO PSA >10<20 Gleason <6
    T2a NO MO PSA <20 Gleason <7
    T2b NO MO PSA <20 Gleason <7
    T2b NO MO PSA X Gleason X
    IIB T2c N0 M0 Any PSA Any Gleason
    T1-2 N0 MO PSA >20 Any Gleason
    T1-2 NO MO Any PSA Gleason >8
    III T3a-b NO MO Any PSA Any Gleason
    IV T4 N0 M0 Any PSA Any Gleason
    Any T NI MO Any PSA Any Gleason
    Any T Any N MI Any PSA Any Gleason
    Adapted from: National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2016. NCCN website. 2016.; American Cancer Society. Prostate cancer staging. 2009.

Risk Stratification

  •  Based on the prostate-specific antigen (PSA) level, biopsy, Gleason score, and tumor, nodes and metastasis (TNM) classification
  • Helps in decision making for the management of patients diagnosed with prostate cancer
    Risk Group Stage Tumor PSA Gleason Score Others
    Clinically Localized
    Very Low I-IIA T1c <10 ng/mL Gleason ≤6 <3 positive prostate biopsy cores with <50% malignancy per core; PSA density <0.15 ng/mL/g
    Low I-IIB T1-T2a <10 ng/mL Gleason <7  
    Intermediate IIB T2b-T2c 10-20 ng/mL Gleason 7  
    High III T3a >20 ng/mL Gleason 8-10  
    Locally Advanced
    Very High III-IV T3b-T4 >20 ng/mL Gleason 8-10 Primary Gleason pattern 5 or >4
    Metastatic IV Any T, N1 or Any T, any N, M1      
    Adapted from: American Cancer Society. Prostate cancer staging. 2009; American Urological Association. Prostate cancer: guideline for the management of clinically localized prostate cancer: 2007 update. 2007. pp 9-10; European Association of Urology. Guidelines on prostate cancer. 2014. pp12-13; National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2016. NCCN website. 2016. pp ST-1-2.

Cancer of the Prostate Risk Assessment (CAPRA)

  • A straightforward scoring system (0-10) that predicts likelihood of metastasis, cancer-specific mortality, and overall survival
  • Based on the patient’s age, prostate-specific antigen (PSA) levels, Gleason score, clinical stage, and percent of malignant biopsy cores
  • Also predicts disease recurrence after radical prostatectomy

Assessment

Gleason Score

  • Useful in determining tumor grade, prognostic risk, and management strategies
    Gleason Score Definition
    Gleason X Gleason score cannot be assessed
    Gleason <6 Well differentiated (slight anaplasia)
    Gleason 7 Moderately differentiated (moderate anaplasia)
    Gleason 8-10 Poorly differentiated/undifferentiated (marked anaplasia)

Physical Examination

Digital Rectal Examination (DRE)

  • Detects prostatic enlargement with volume of >0.2 mL
  • Abnormal DREs are associated with high Gleason scores and may be considered for prostate biopsy

Laboratory Tests

Prostate-Specific Antigen (PSA) Level

  • A kallikrein-like serine protease produced by prostatic epithelial cells
  • Risk for prostate cancer increases with increasing level of prostate-specific antigen (PSA) and may warrant a prostate biopsy
  • Predicts extension outside the prostate gland, seminal vesicle invasion, and lymphadenopathies
  • Baseline results should be obtained prior to starting treatment as it is also a good measurement for therapeutic efficacy

Prostate Biopsy

  • Most common method used in diagnosing prostatic carcinoma
  • Should only be offered if prostate-specific antigen (PSA) levels and digital rectal examination (DRE) highly suggest prostate cancer
  • Transrectal ultrasound (TRUS)-guided core-needle prostate biopsy is highly recommended for men with prostate-specific antigen (PSA) levels of >4 ng/mL
  • Indications:
    • Increased risk for prostate cancer and with prostate-specific antigen (PSA) levels of 2.5-4 ng/mL
    • Increased prostate-specific antigen (PSA) levels of >0.35 ng/mL within 1 year from baseline of <4 ng/mL
    • Increased prostate-specific antigen (PSA) levels of >0.75 ng/mL within 1 year from baseline of 4-10 ng/mL
    • Prostate-specific antigen (PSA) levels too high for age range
  • Obtaining a minimum of 10-12 cores are recommended
  • Should be done under antibiotic coverage
  • The perineal approach (transperineal 3D prostate mapping biopsy) is a useful option for special circumstances (eg rectal amputation)

Other Tests

Other Tumor Markers

  • Have been associated with prostate cancer diagnosis but are not routinely performed
  • Include apoptosis markers [eg B-cell lymphoma 2 (Bcl-2), BCL2 Associated X Protein (Bax)], proliferation rate markers (eg Ki67), p53 mutation/expression, p27, E-cadherin, deoxyribonucleic acid (DNA) plody, p16
  • An increase in serum acid phosphatase levels may indicate poor prognosis in patients with localized and disseminated disease

Imaging

  • Should be based on prostate-specific antigen (PSA) results, Gleason score, and patient’s health status

Plain Film Radiography

  • May be used to assess for presence of bone pathologies in symptomatic patients

Ultrasonography

  • Transrectal ultrasound (TRUS) may be used to assess the prostate gland if prostate-specific antigen (PSA) levels and digital rectal examination (DRE) results are inconclusive
  • Also used as a guide during transrectal prostate biopsies

Computed Tomography (CT) Scan

  • May be used to assess for presence of bone pathologies
  • May be used for lymph node staging in asymptomatic patients at intermediate-high risk [prostate-specific antigen (PSA) level >10 ng/ mL, Gleason score >8, or clinical stage >T3]

Magnetic Resonance Imaging (MRI)

  • Multiparametric MRI (mpMRI) by diffusion-weighted imaging or hydrogen 1 (H1)-spectroscopy may be done to assess if repeat prostate biopsy is needed in patients with negative results in transrectal ultrasound (TRUS)
    • Detects large and poorly differentiated tumors and extracapsular extension
  • Sensitivity at >2 cc: 67-75% for Gleason <6; 97% for Gleason 7; 100% for Gleason >8
  • Positive results may suggest repeat prostate biopsy

Radionuclide Bone Scan

  • Used to assess for possible bone involvement
  • May be performed for symptomatic patients with prostate-specific antigen (PSA) results of >10 ng/mL, Gleason score >8 and those with decreasing prostate-specific antigen (PSA) doubling time

Screening

Recommended for men:

  • 50 years of age at average risk for prostate cancer and with life expectancy of >10 years
  • 45 years of age at high risk for developing prostate cancer (eg African American descent, with 1st-degree relatives diagnosed with prostate cancer who are <65 years old)
  • 40 years of age with 1st-degree relatives diagnosed with prostate cancer who are <65 years old and with previous prostate-specific antigen (PSA level of >1 ng/mL)
  • With previous prostate-specific antigen (PSA) level of >2 ng/mL taken at 60 years old
  • With initial screening which includes prostate-specific antigen (PSA) and digital rectal examination (DRE)
  • With negative results but at risk for prostate cancer, repeat screening should be done depending on the prostate-specific antigen (PSA) result:
    • Prostate-specific antigen (PSA) <2.5 ng/mL = every 2 years
    • Prostate-specific antigen (PSA) >2.5 ng/mL = yearly
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