Prostate Cancer

    .  Source: MKSAP 17




    • 2nd most common malignancy worldwide
    • Majority do not die from it.
    • Risk Factors:
      • Black/Hispanic  (Asian lowest risk)
      • Age
      • History of Prostate Ca in 1st degree relative.
      • High Fat Low Fibre increases diet
      • Prostatitis
    • Vasectomy does not increase risk



    • 5-alpha-reductase
      • Decreases incidence of prostate Ca (shrinks prostate), but no survival benefit shown.
      • Gynecomastia, erectile dysfunction, poor libido



    • Data:  Screening does not improve Prostate Ca mortality.
    • PSA screening no longer recommended (does not improve mortality), but identifies lots of biologically indolent prostate ca.
      • DRE, similar problem to PSA, (worse at finding prostate cancers).
      • Currently no recommendation exists from USPSTF and AUA on DRE (poor research data, no benefit shown)
    • If find asymmetric prostate or have symptoms...
      • Checking PSA is no longer screening, but can help with diagnosis (and biopsy). 



    • Same as BPH (more likely BPH statistically)
      • Urinary hesitancy
      • Incomplete bladder emptying
      • Decreased stream
      • Nocturia.
    • These symptoms more likely represent BPH, but excluding prostate Ca is important. 
      • Checking PSA in this context is NOT screening!  May help diagnostically.
    • More specific symptoms:
      • Erectile Dysfunction (invasion of neurovascular bundle?)
      • Bone Pain (metastasis)
      • Cord Compression



    • If have symptoms
      • Do PSA and DRE (can trend PSA to ensure not going up)
      • If PSA elevated OR DRE abnormal --> transrectal biopsy to determine BPH vs. Prostate Ca.
        • Then stage --> is it organ confined? locally advanced? is it curable by surgery/rads?
      • Free PSA also thought to improve on total PSA, but not many studies.
    • Transrectal Biopsy (Definitive)
      • Take cores from multiple areas (including the nodule that is palpated)
      • This is simple office procedure (no analgesia or anesthesia)
      • Can do on ASA (bleeding risk low).
      • Negative biopsy does not exclude prostate cancer, if still suspecting (PSA level, symptoms, palpation etc..)
        • Need to observe closely and repeat biopsy!
    • Transrectal U/S
      • Images prostate... not part of initial routine workup.
      • Done as part of staging evaluation (how locally advanced it is)
      • Can be done to guide the biopsy to palpable site
    • Diffuse Metastatic Workup?
      • Hard to say when to do.
      • Risk factors are: high PSA, gleason score (8-10 is highest risk, 7 intermediate), # of cores involved
      • Gleason ≥ 8, High PSA, or T3/4 Status:
        • Need Bone Scan + Consider CT
    • Pathology
      • Gleason Score - Two most prevalent differentiation patterns from all the biopsy cores added together to give a score.  Each score represents architectural pattern and addition gives composite score. 
      • Correlated closely with prevlaence of non-organ-confined disease and outcomes after local therapy.
      • Gleason Risk
        8-10 High Risk
        7 Intermediate Risk
        < 6 Low Risk
    • Staging
      • 2010 - AJCC Revised TNM to incorporate Gleason Score (Histologic Grading)
      • Gleason Score
        • Early Stage - Minimal Cores, Low PSA, Low Gleason
      • General T-Staging
        • T-Stage Easy To Remember
          T1 Not palpable or visible on imaging (PSA identified)
          T2 Felt on DRE
          T3 Extending through capsule (Invading Seminal Vesicles only)
          T4 Locally Advanced Invasing (Bladder Pelvic Muscles, etc..)
    • Treatment
      • Options:
        • Observation
        • Active surveillance
        • Radiation therapy
        • Brachytherapy
        • Radical prostatectomy.



    • Use Partin's Tables (Google it!) to help identify risk of local recurrence & spread.
    • Options:
      • Observation
      • Active Surveillance
      • Radiation Therapy
      • Brachytherapy
      • Radical Prostatectomy
    • Active Surveillance
      • Post-poning definitive local therapy
      • Follow PSA, DRE, repeat biopsy
      • Appropriate for Low Risk Prostate Ca (Gleason ≤6, Low PSA < 20, limited cores) with life expectancy > 10yrs
        • No trials comparing active surveillance vs. initial definitive local therapy (as of 2015)
      • If PSA goes up or progression:
        • Definitive Local Therapy


    • Local Therapy (no trials comparing these modalities)
      • May be the only necessary action (especially if organ confined disease)


    Definitive Local Therapy Notes S/E
    Radial Prostatectomy

    - Indicated if < 70yo (high morbidity)

    - if Node Positive: ADT

    Urinary incontinence (60-70% @2mo)

    Sexual Dysfunction (worse than rads)

    External-Beam Radiotherapy

    - Equivalent to surgery, but no 

      comparative head-to-head trials

    Urinary: irritation (urgency/frequency/dysuria)

    Bowel Symptoms (frequency/urgency/diarrhea - 10-20%)

    Brachytherapy   Worse urinary irritation than radiation


    • Intermediate-to-high risk disease treated with surgery who have positive LNs should be treated with adjuvant androgen deprivation therapy (ADT)
    • "Low Risk" defined by:
      • PSA < 20 ng/mL (ug/L)
      • T1 or T2
      • Gleason < 8
    • Androgen Deprivation Therapy 
      • 80-90% response
      • Indications: (generally)
        • Newly diagnosed high-risk disease receiving radiation therapy
        • Metastatic hormone-sensitive cancer
      • Options:
        • GnRH agonist
        • Antiandrogen Agent
        • Bilateral orchiectomy (if very elderly, is alternative to ADT)
      • S/E:
        • Fatigue, Loss of muscle, osteoporosis, dyslipidemia, hyperglycemia, sexual dysfunction.
        • "intermittent ADT" insufficient evidence if sacrificing efficacy.


    Post-Treatment F/U

    • History & Physical + Serum PSA
    • After radial prostatectomy PSA should be undetectable (PSA > 0.2 ug/L or ng/mL = active cancer).
    • After radiotherapy PSA usually drops down to nadir (but still detectable).  A rise > 2 ng/mL or ug/L = recurrence.



    • Biochemical Recurrence: Rising PSA level --> treat with ADT
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