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 
     Clinical T (cT)
    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 capsule
    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)
     Pathological T (pT)
     T - Primary Tumor
     T2  Confined in the organ
     T3    Positive extension extraprostatically
     T3a  Unilateral or bilateral extraprostatic extension
     T3b  Tumor invades seminal vesicle(s)
     T4  Fixed tumor or invades adjacent structures other than the seminal vesicles (ie external sphincter, rectum, bladder, levator muscles, &/or pelvic wall)
    N - Regional Lymph Nodes
    NX Regional lymph nodes cannot be assessed
    N0 No regional lymph node metastasis
    N1 Regional lymph node metastasis present
    M - Distant metastasis1
    M0 No distant metastasis
    M1 Distant metastasis
    M1a Non-regional lymph node(s)
    M1b Bone(s)
    M1c Other site(s) with or without bone disease
    1The most advanced category (M1c) should be used when >1 metastasis site is present
    Adapted from: National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2018.

Staging

  • Should be based on the prostate-specific antigen (PSA) level, tumor grade, and positive prostate biopsies
    Stage Tumor Node Metastasis PSA Grade Group
    I cT1a-c N0 M0 PSA <10 1
    cT2a N0 MO PSA <10 1
    pT2 NO MO PSA <10 1
    IIA cT1a-c N0 M0 PSA  ≥10<20 1
    cT2a N0 MO PSA ≥10<20 1
    pT2 NO MO PSA ≥10<20 1
    cT2b NO MO PSA <20 1
    cT2c NO MO PSA <20 1
    IIB T1-2 N0 M0 PSA <20 2
     IIC T1-2 N0 MO PSA <20 3
    T1-2 NO MO PSA <20 4
    IIIA T1-2 NO MO PSA ≥20 1-4
    IIIB T3-T4 N0 M0 Any PSA 1-4
     IIIC Any T N0 MO Any PSA 5
     IVA Any T N1 M0 Any PSA Any
    IVB   Any T  Any N  M1  Any PSA  Any
    Adapted from: National Comprehensive Cancer Network. NCCN guidelines: prostate cancer. Version 3.2018. NCCN website. 2018.; American Cancer Society. Prostate cancer staging. 2018.

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 Clinical Stage   PSA   Grade Group or Gleason Score   Others
    Clinically Localized
    Very Low T1c <10 ng/mL Grade group 1/Gleason score ≤6 <3 prostate biopsy fragments/cores positive, with ≤50% cancer in each fragment/core & PSA density <0.15 ng/mL/g
    Low T1-T2a  & <10 ng/mL  & Grade group 1/Gleason score ≤6    
    Intermediate T2b-T2c  or 10-<20 ng/mL  or Grade group 2-3    
       Favorable  T2b-T2c  or  10-20 ng/mL  or  Grade group 2/Gleason score 3+4=7  & percentage of positive biopsy core <50% 
        Unfavorable  T2b-T2c  or  10-20 ng/mL or Grade group 2/Gleason score 3+4=7 or Grade group 3/Gleason score 4+3=7     
    High T3a or  >20 ng/mL  or Grade group 4/Gleason score 8 or Grade group 5/Gleason score 4+5=9    
    Locally Advanced
    Very High T3b-T4  
      Primary Grade group 5 or Grade group 4 or 5/Gleason score 8-10 in >4 cores   Primary Gleason pattern 5 or >4
     Regional  Any T, N1, M0             
    Metastatic Any T, any N, M1            
    National Comprehensive Cancer Network. NCCN guidelines: prostate cancer version 3.2018. NCCN website. 2018. pp PROS-2 Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO). Clinically localized prostate cancer guideline: Risk stratification, shared decision making, and care options: 2017 update. 2017. pp 683-685; European Association of Urology. Guidelines on prostate cancer. 2014. pp12-13

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
  • ProPSA (part of the Prostate Health Index) & prostate specific antigen 3 (PCA3) are newly developed, US FDA-approved biomarkers to detect prostate cancer
  • 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

Gallium 68-Prostate Specific Membrane Antigen (PSMA) PET/CT Scan

  • A new PET tracer which demonstrates high sensitivity with histopathological diagnosis
  • Can be utilized in staging prostate cancer

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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