Prostate Cancer

Risk factors for prostate cancer

  1. Being > 40, being black, a family history of relatives diagnosed at a young age, high fat intake
  2. BPH does NOT increase risk, it may delay the diagnosis though
  3. Smoking does NOT increase risk, it increases mortality though

ACS screening guidelines for prostate cancer

  1. Screening is suggested beginning at 50 for most people
    1. Age 45 (high risk) for blacks or ppl with a strong family history including a relative who got it who was under 65
  2. Screening should be offered if the patient’s life expectancy is greater than or equal to 10 years

Gleason’s score

  1. Takes 2 specimens and grades them on a scale of 1 (well differentiated) to 5 (poorly differentiated)
    1. Total of 2-4 (well differentiated, slower growth, better diagnosis)
    2. Total of 5-6 = moderate differentiation
    3. Total of 7-10 = poor differentiated, faster growing, poorer prognosis
      1. Higher the gleason score, the worse the prognosis

Treatment of prostate cancer

  1. Initial treatment is based off of disease stage, gleason score, presence of symptoms, life expectancy, co-morbidities, ability to tolerate SE
  2. Active surveillance (observation) is recommended in patients that are low risk & have a long life expectancy, but the patient must understand that the tumor is going to progress
    1. Adv: avoid SE of treatment, maintain QOL, decreased costs
    2. Disadv:  miss opportunity for cure, exposure to aggressive treatment (SE), anxiety/uncertainty, disease progression, may make surgery more difficult, requires more frequent dr. visits
  3. Radiation therapy is an option for patients who aren’t surgical candidates
    1. Radiation therapy allows higher doses & lowers the risk of late effects
    2. Adv:  No bleeding, anesthesia or blood transfusions, less urinary incontinence, temporarily preserve erectile function
    3. Disadv:  8-9 weeks of treatment, temporary bowel/bladder symptoms, may make surgery for recurrence more risky, ED increases over time
  4. Brachytherapy (aka radioactive seeding)
    1. Adv: treatment completed in 1 day, low risk of incontinence, better survival in comparison to surgery (good option for low-risk cancers), short term erectile function is preserved
    2. Disadv:  requires general anesthesia, acute urinary retention, progressive ED, can’t give very high doses
  5. Radical prostatectomy is reserved for patients w/ > 10 years of life expectancy, & patients with the disease confined to the prostate
    1. Complications: blood loss, stricture formation, incontinence, lymphocele, fistula formation, anesthetic risk, ED
  6. Hormone therapy
    1. Biclutamide is an antiandrogen agent that prevents the stimulatory effect of androgen (inhibits cell growth)
  7. Treatment of metastatic disease (after androgen deprivation therapy–ADT has already been completed)
    1. Bilateral orchiectomy (removal of testes)
      1. Causes an immediate drop in testosterone (w/in 12 hours), but it may cause impotence or hot flashes, inexpensive
      2. Preferred initial treatment if there is a risk for spinal cord compression or ureteral obstruction on account of the cancer
    2. LH-RH agonist +/- an antiandrogen agent
      1. LH-RH agonists (Goserelin, leuprolide, triprtorelin, degarelix) are expensive
        1. SE:  hot flashes, injection site reactions, sexual SE, HA, weight gain, increased risk of diabetes & CV disease (increases cholesterol & TGs)
          1. Also tumor flare (results in bone pain & urinary sympmtoms) which is treated w/ the antiandrogen agent
          2. Also osteoporosis which is why Ca (1200 mg/day) , Vit D (800-1000 IU/day) +/- bisphosphonates are used as supplementation in ALL men > 50.
      2. Antiandrogen agents (bicalutamide, flutamine, nilutamide)
        1. Used (for 1 week) to prevent tumor flare
          1. Decreased survival when used alone
        2. Expensive; only use if several months of LH-RH agonist therapy didn’t help
        3. SE:  hot flashes, diarrhea, gynecomastia, LFT abnormalities
          1. Nilutamide also has SE of alcohol intolerance & visual disturbances
    3. 2nd line hormone therapy: ketoconazole or aminoglutethimide
      1. Both of these therapies require hydrocortisone replacement therapy
      2. Ketoconazole is a potent inhibitor of 3A4 & a weak inhibitor of 2C9 & 2C19
      3. Aminoglutethimide isn’t used that much due to its SE (think EPS–lethargy, dizziness, ataxia, confusion, depression, rashes)
    4. Hormone refractory prostate cancer:
      1. use docetaxel + either prednisone or estramustine
        1. Estramustine (IV or PO) = estradiol + alkylating agent (non-nitrogen mustard)
          1. SE:  N/V (dose limiting), gynecomastia, decreased libido, thromboemolicevents, increased CHF symptoms(usually occur within the first 2-12 months)
        2. Docetaxel SE:  nausea, complete alopecia, bone marrow suppression, fluid retention (dexamethasone to prevent this), peripheral neuropathy
      2. Alternative for patients failing docetaxel regimen:
        1. SE:  myelosuppression, N/V/D, hypersensitivity reactions (pre-medicate w/ benadryl, dexamethasone, & H2 antagonist)
        2. Metabolized by 3A4, don’t use w/ PVC products
      3. Androgen resistant metastatic prostate cancer:  may usesipuleucel-T (1st vaccine approved for the treatment of prostate cancer)
        1. SE:  infusion related reactions, back/joint/muscle pain
    5. Treatment for patients with prostate cancer in which bone metastases has occurred: use a bisphosphonate
      1. Use a bisphosphonate helps to prevent against pathological fractures, spinal cord compression, surgery, radiation therapy
      2. Radiation therapy or denosumab may also be tried

Treatment options based on the risk of recurrence

  1. Recurrence rate after prostatectomy:  45% w/in 2 years, 77% w/in 5 years, 96% w/in 10 years.
  2. If the patient had a prostatectomy, salvage therapy should be radiation +/- ADT (androgen deprivation therapy) therapy
  3. If the patient had radiation therapy, salvage therapy should be either a prostatectomy or ADT (androgen deprivation therapy) therapy
    1. Treatment depends on what their initial therapy was
    2. If the patient’s only sign of disease progression is a rising PSA, then observation may be a reasonable option

If the patient has either an abnormal digital rectal exam (DRE) or prostate specific antigen (PSA) screening then they should receive a transrectal ultrasound (TRUS)

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