BPH, Urinary Retention, and Prostate Cancer Flashcards
BPH vs. Prostate Cancer Prevalence
Both affect the prostate gland and cause the gland to increase in size.
BPH: Benign and does not spread throughout body and diagnosed in 1 out of 2 men in their 50s.
Prostate cancer: Malignant and will spread throughout the body and diagnosed in 1 out of 6 men
Symptom Comparison of BPH and Prostate Cancer
Enlarged prostate squeezes the urethra and inhibits urine flow.
Both BPH and Prostate Cancer symptoms:
- Urination urgency
- Trouble starting to urinate or need to push to release urine
- Weak urine stream
- Urine flow stops and starts
- Feeling bladder is never fully empty
Prostate Cancer additional symptoms:
- Painful or burning urination
- Blood in urine or semen
- Issues with erection and ejaculation
Diagnostics for BPH and/or Prostate Cancer
Prostate-specific antigen (PSA) test
Digital rectal exam (DRE)
Additional BPH tests:
- Urine flow
- Post-void residual volume in bladder test
Additional Prostate Cancer tests:
- Ultrasound
- Biopsy
General Pharmacotherapy in BPH Treatment (Mild to Moderate Symptoms vs Severe Symptoms)
Mild to Moderate Symptoms:
- Alpha-1 blockers—relax muscles in bladder to assist in urination (tamsulosin, alfuzosin, doxazosin) *SEE MALE REPRODUCTIVE HORMONES)
- 5-alpha-reducates inhibitors—shrink the prostate (dutasteride, finasteride) *SEE MALE REPRODUCTIVE HORMONES)
Severe Symptoms:
- Transurethral resection of the prostate (TURP)
- Transurethral incision of prostate
- Prostatectomy
Screening for Prostate Cancer
Optimal age: 55 y/o males and above
- Digital Rectal Exam (DRE)
- Prostate Specific Antigen (PSA): PSA may be altered by prostatic manipulation, ejaculation, 5α-reductase inhibitors, saw palmeto, and increased age. Normal range is <4ng /mL. MUST consider PSA VELOCITY (how quickly is the PSA rising?)
Common Sites of Metastatic Disease (4)
- Bone (90%)
- Lung (45%)
- Liver (25%)
- Adrenal glands
Goals of Prostate Cancer Therapy
Localized Disease (Stage 1-3A):
- Curable
- Reduce procedure related complications • Locally Advanced/
Metastatic Disease (Stage 3B- 4):
- Not curable
- Maintain quality of life, prolong survival
- Maximize symptom relief
Surgical Management in Prostate Cancer
Radical prostatectomy:
- Definitive surgery
- Side effects: impotence (20-50%), incontinence, stricture, fistula formation
Transurethral resection of the prostate (TURP):
- Used almost exclusively in locally advanced disease
- Side effects: UTI, retrograde ejaculation, impotence, ED
Prostate Cancer Risk Factors (4)
- Age: incidence dramatically increases in 6th decade
- Race: African Americans > Whites, Rare in Asian countries
- Family History: Mutations in androgen receptor gene; mutations in CYP17
- Diet: 2X increase w/ high meat and high fat content; associated with low vitamin D levels, lycopene and β-carotene
A 65-year-old African American male was diagnosed with prostate carcinoma 18 months ago. At the time he underwent surgery to remove the tumor.
What are his risk factors for prostate cancer?
Before surgery the patient’s PSA was 25 ng/mL (normal < 4.0 ng/mL). At a regular follow-up examination his only complaint is mild backache. His PSA is 100 ng/mL and the CT scan of pelvis shows several enlarged lymph nodes.
Does the patient’s disease require therapy at this time?
Patient was treated with leuprolide and flutamide and his PSA level fell to 8 ng/mL and remained stable for the next 18 months. His most recent clinic visit, however, revealed an increase in his PSA level to 75 ng/mL and a pelvic CT scan showed disease progression.
Is a change in therapy warranted at this time?
- Race and age
- Yes! Signs of metastatic disease
- Yes! Pt’s prostate cancer is now androgen-independent, i.e. no longer responsive to anti-androgen therapy! Begin treatment with chemotherapy
General Pharmacotherapy of Prostate Cancer (3)
- Prostate cancer is strongly androgen sensitive
- Blocking testosterone receptors inhibits or slows the cancer
Drugs that inhibit prostate cancer growth:
- 5α-reductase Inhibitors (finasteride - drug of choice for prostate cancer!) *SEE MALE REPRODUCTIVE HORMONES
- Androgen Receptor Antagonist (flutamide, bicalutamide) *SEE MALE REPRODUCTIVE HORMONES
- Gonadotropin-Releasing Hormone Agonists (leuprolide, goserelin) *SEE MALE REPRODUCTIVE HORMONES
Prostate Cancer Chemotherapy Options (Asymptomatic, First Line, Second Line)
- Asymptomatic
- Sipuleucel-T - First line chemotherapy
- Doetaxel (Taxotere®) 75mg/m 2 IV q21d + prednisone 5mg PO BID - Second line agents
- Cabazitaxel (Jevtana®) 25mg/m2 IV q21d + prednisone 5mg PO BID
- Abiraterone (Zytiga®) 1000mg PO daily + prednisone 5mg PO BID
Sipuleucel-T (MOA and Effects)
MOA: Autologous cellular immunotherapy. Leukapheresis collects the patient’s own cells. Patient cells are cultured with a recombinant antigen, PAP-GM-CSF.
PAP – prostatic acid phosphatase is an antigen expressed on 95% of prostate cancer cells.
GM-CSF – cytokine that activates the immune system.
The PAP-GM-CSF fused proteins specifically train and activate the collected antigen presenting cells. The activated patient cells are infused back into the patient where activated T-cells target and attack PAP antigen-expressing prostate cancer cells.
Effects: Prolonged survival by 4 months in clinical trials.
Sipuleucel-T (Toxicity)
- Requires premedication w/ acetaminophen and diphenhydramine (to prevent infusion hypersensitivity reaction)
- Expensive
ADRs:
Common—Chills, fatigue, fever, back pain, nausea, headache
Serious—Infusion related reactions (3.5%)
Taxanes (MOA)
MOA: Promote microtubule formation by inhibiting the disassembly of tubulin. Bind to the intermedia surface of the beta-tubulin to decrease depolymerization. Antagonizes the disassembly of tubulin. Promotes the microtubular polymerization and elongation (keeps microtubulin locked together and disrupts mitosis—cells cannot separate into daughter cells). Cell cycle arrest in mitosis.
