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.

Pharmacotherapy

Androgen Deprivation Therapy (ADT)

  • Treatment option for patients with disease progression despite surgical treatments and radiotherapy, or for symptomatic control of symptoms in patients who are against, with contraindications, or cannot tolerate surgical procedures
  • Recommended as first-line therapy in high-very high-risk and metastatic prostate cancer and as adjuvant therapy for patients with low-intermediate-risk prostate cancer
  • May be offered to intermediate-high risk and locally advanced prostate cancer patients prior to, during, or after external beam radiation therapy (EBRT) or in combination with radical radiotherapy
  • Prostate-specific antigen (PSA) levels should be measured every 3 months for patients under intermittent androgen deprivation therapy (ADT)
    • Restart androgen deprivation therapy (ADT) if prostate-specific antigen (PSA) measurements reach >10 ng/mL or if patients becomes symptomatic

Adrenal/Paracrine Androgen Synthesis Inhibitors

  • Eg Ketoconazole
  • Treatment option for patients with castration-resistant prostate cancer (CRPC) with or without visceral metastases
  • Mechanism of action: Anti-androgenic properties that block androgen production

Anti-Androgen Therapy

  • Eg Steroidal (Cyproterone acetate, Megestrol acetate, Medroxyprogesterone acetate); Non-steroidal or 1st-generation anti-androgens (Bicalutamide, Flutamide, Nilutamide)
  • Treatment option for patients with advanced disease, metastatic, or non-metastatic castration-resistant prostate cancer (CRPC)
    • May be given concomitantly with luteinizing hormone-releasing hormone (LHRH) analogs or orchiectomy for better androgen blockade (combined androgen blockade)
    • May be offered to patients with metastatic disease who prefer their sexual function restored even with more side effects
  • Mechanism of action: Blocks androgen receptors, thereby reducing the effect of endogenous hormones
  • Bicalutamide monotherapy may also help prevent non-metastatic bone fractures with its bone-protective properties, though monotherapy use is rare

Estrogens

  • Eg Diethylstilbestrol (DES)
  • Mechanism of action: Inactivates androgens, down-regulates luteinizing hormone-releasing hormone (LHRH) secretion, Leydig cell function direct suppression
  • Studies have shown that oral estrogen therapy has the same efficacy for castration as bilateral orchiectomy

Luteinizing Hormone-Releasing Hormone (LHRH) Analogs

  • Efficacy for castration is the same as orchiectomy
  • First-line agents used for androgen deprivation therapy (ADT) in prostate cancer
  • Luteinizing hormone-releasing hormone (LHRH) Agonist
    • Eg Goserelin, Histrelin, Leuprorelin (Leuprolide), Triptorelin
    • Mechanism of action: Stimulates luteinizing hormone-releasing hormone receptors, inducing a transient leutenizing hormone (LH) and follicle-stimulating hormone (FSH) surge, leading to androgen release inhibition
    • Induces the flare-up phenomenon, a sudden increase in testosterone, which may lead to increased bone pain, urethral obstruction, renal failure, spinal cord compression
  • Luteinizing hormone-releasing hormone (LHRH) Antagonist:
    • Eg Abarelix, Degarelix
    • Mechanism of action: Rapidly and directly inhibits androgen release thereby suppressing testicular androgen activity without the flare-up phenomenon

Chemotherapy

  • Eg Cabazitaxel, Carboplatin, Docetaxel, Doxorubicin, Etoposide, Estramustine, Mitoxantrone, Paclitaxel, Vinblastine, Vinorelbine
  • Recommended for patients with progressive disease despite medical and surgical castration (both hormone-resistant and/or castration-resistant metastatic prostate cancer)

Cabazitaxel

  • Alternative treatment to those intolerant or unresponsive to Docetaxel therapy
  • Patients given Cabazitaxel exhibited improvement in progression-free survival (PFS), prostate-specific antigen (PSA) response rate and overall survival in several studies
  • Given with concomitant steroids (daily Prednisone or Dexamethasone on day of chemotherapy)

Docetaxel

  • Recommended 1st-line treatment for men with symptomatic metastatic castration-resistant prostate cancer (CRPC)
  • Proven to improve prostate-specific antigen (PSA) response and time to recurrence and clinical progression
  • Should be reserved for prostate cancer patients with confirmed metastatic disease

Mitoxantrone

  • May be used for palliative therapy of the pain caused by bone metastasis of castration-resistant prostate cancer (CRPC)
  • Given concomitantly with corticosteroids

Hormone Therapy

  • Second-generation anti-androgens, eg Abiraterone acetate, Apalutamide, Enzalutamide
  • Recommended for patients with progressive disease despite medical and surgical castration

Abiraterone acetate

  • May be used for patients with metastatic castration-resistant prostate cancer (CRPC) pre or post Docetaxel therapy
  • Also used in the treatment of metastatic, high-risk, castration-sensitive prostate cancer
  • Administered together with Prednisone or Prednisolone; combination should not be given with anti-androgen
  • Increased median survival, provided pain palliation, showed prostate-specific antigen (PSA) level decrease, and delayed radiographic progression in studies done to prove the efficacy of Abiraterone in patients with metastatic CRPC who were given Docetaxel-containing regimens
  • Mechanism of action: Inhibits the enzyme CYP17 in turn suppressing testosterone production
  • Administered together with Prednisone or Prednisolone

Apalutamide

  • Treatment option for patients with non-metastatic CRPC
  • Mechanism of action: Acts as an androgen receptor inhibitor thereby inhibiting AR nuclear translocation, DNA binding & AR-mediated transcription

Enzalutamide

  • May be used for patients with both metastatic and non-metastatic CRPC
    • Treatment option for patients with metastatic CRPC pre- or post-Docetaxel
    • Compared with placebo, treatment with Enzalutamide showed significant lower risk of metastasis or death in patients with non-metastatic CRPC with a rapidly increasing level of PSA
  • Mechanism of action: Potent competitive inhibitor of androgen binding to androgen receptors, inhibits nuclear translocation of activated receptors and the association of the activated androgen receptor with DNA despite androgen receptor over-expression and prostate cancer cell resistance to anti-androgens

Immunotherapy

Pembrolizumab

  • Anti-PD1 antibody used for patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair (MMR)-deficient solid tumors that have progressed on prior treatment & with no satisfactory alternative treatment options

Sipuleucel-T

  • Cancer vaccine produced from the combination of autologous antigen-presenting blood mononuclear cells and recombinant human fusion protein
  • Studies have shown that Sipuleucel-T may help extend mean survival with reduction in mortality risk
  • May be given to metastatic castration-resistant prostate cancer (CRPC) patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, life expectancy of >6 months, absent hepatic metastases, and minimal or absent symptoms

Recommended Therapy for Castration-Resistant Prostate Cancer (CRPC)

  • For CRPC patients without metastasis, may continue ADT & start Apalutamide or other secondary hormone therapy if PSADT ≤10 months

Regimens for Metastatic Castration-Resistant Prostate Cancer (CRPC) if without Visceral Metastasis

  • Abiraterone acetate with Prednisone
  • Cabazitaxel + Prednisone: Given if with prior Docetaxel therapy
  • Docetaxel
  • Plus radiotherapy with Radium-223 if with bone metastasis
  • Other secondary hormone therapy
    • First-generation anti-androgens
    • Anti-androgen withdrawal
    • Ketoconazole +/- Hydrocortisone
    • Corticosteroids
    • DES or other estrogens
  • Recommended subsequent therapies include Docetaxel (if previously given Enzalutamide or Abiraterone), Radium-223 (if with bone metastasis), Pembrolizumab (MSI-H or dMMR), Enzalutamide (if not previously given), Abiraterone acetate with Prednisone (if not previously given), Sipuleucel-T (if not given previously), Cabazitaxel or Mitoxantrone with Prednisone (if previously given Docetaxel), & other secondary hormone therapy
    • May propose a Docetaxel rechallenge in patients who responded to previous Docetaxel regimen
  • If with disease progression, may initiate therapy with agents not previously given

Regimens for Metastatic Castration-Resistant Prostate Cancer (CRPC) if with Visceral Metastasis

  • Recommended subsequent combination regimens for patients with small cell CRPC include Cisplatin/Etoposide, Carboplatin/Etoposide, & Docetaxel/Carboplatin
  • Recommended 1st-line therapies for CRPC patients with adenocarcinoma include Docetaxel, Enzalutamide, Abiraterone with Prednisone, Mitoxantrone with Prednisone, & other secondary hormone therapy
    • If with disease progression, Docetaxel, Pembrolizumab (MSI-H or dMMR), Enzalutamide (if not previously given), Abiraterone acetate with Prednisone (if not previously given), Cabazitaxel or Mitoxantrone with Prednisone (if previously given Docetaxel) & other secondary hormone therapy may be considered
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