Management
Correct Answers
- C) Leuprolide + Docetaxel
- B) Add abiraterone + prednisone
- B) Hypokalemia
- C) Neutropenia
- C. Radiation therapy + short term androgen deprivation therapy
- A. Active surveillance
- D. Enzalutamide
- C. Darolutamide
- Continue leuprolide, add darolutamide
- C. Stop enzalutamide, add Docetaxel + prednisone
- Radium-223
- D. Denosumab 120 mg every 4 weeks and calcium plus vitamin D 500mg-400 IU twice daily
- Intermittent ADT with leuprolide
- Docetaxel + darolutamide
- Cabazitaxel + prednisone
- Lutetium-177 PSMA
- A. Olaparib
- Docetaxel + darolutamide
- Talazoparib + enzalutamide
- A, D, E, G (BRCA 1, MYC, FOXA1, SRD5A1)
- C. 42 years old man whose father diagnosed with prostate cancer at 57 years old
- C. Normal PSA </= 4 ng/dl but prostate cancer may occur at PSA 2.5-4ng/dl
- C. In men who are taking finasteride for BPH, the potential benefits and risks should be discussed
- C. 4
- B. Insulin resistance
- E.Degarelix
- A. Abirateron+prednisolone
- C. Patient should do cardiovascular work up and tests prior to therapy
1. Definition
- Prostate cancer is a malignant tumor of the prostate gland, arising primarily from prostate epithelial cells (most often adenocarcinoma).
- It is the most common non-cutaneous cancer in men and a leading cause of cancer-related death.
2. Risk Factors
- Age: Incidence rises after 50 years.
- Race/Ethnicity: Higher risk in African-Caribbean men; lower in Asian men.
- Family history: BRCA1/2, HOXB13 mutations.
- Genetics: gBRCA2 especially linked to aggressive disease.
- Lifestyle: High-fat diet, obesity, low physical activity.
3. Pathophysiology
- Driven by androgen signaling (testosterone → dihydrotestosterone → androgen receptor activation).
- Disease progression:
- Localized (organ-confined).
- Locally advanced (capsular penetration, seminal vesicle involvement).
- Metastatic (bone is the most common site, especially axial skeleton).
- Castration-resistant prostate cancer (CRPC): Tumor grows despite castrate levels of testosterone (<50 ng/dL).
4. Clinical Features
- Early stages often asymptomatic (detected via PSA screening or digital rectal exam).
- Later: urinary obstruction, hematuria, bone pain (metastasis), weight loss.
5. Diagnosis & Staging
- PSA (Prostate Specific Antigen): Used for screening, monitoring, recurrence.
- Biopsy: Confirmatory, graded with Gleason Score / ISUP Grade Groups.
- Staging: TNM system + PSA + Gleason score.
- Imaging: MRI, bone scan, PSMA PET-CT (in advanced cases).
6. Pharmacologic Management
a. Hormonal Therapy (Androgen Deprivation Therapy – ADT)
- LHRH agonists: leuprolide, goserelin.
- LHRH antagonists: degarelix, relugolix (oral).
- Antiandrogens: bicalutamide, flutamide, nilutamide (used less often now).
- Next-generation androgen receptor inhibitors (ARIs): enzalutamide, apalutamide, darolutamide.
- CYP17 inhibitor: abiraterone (blocks androgen synthesis, given with prednisone).
b. Chemotherapy
- Docetaxel: Standard in metastatic hormone-sensitive & castration-resistant disease.
- Cabazitaxel: Second-line after docetaxel.
c. Targeted / Radiopharmaceuticals
- PARP inhibitors: olaparib, rucaparib (for BRCA-mutated disease).
- Radium-223: Alpha-emitter for bone-predominant metastatic CRPC (not for visceral mets).
- PSMA-directed therapy: Lutetium-177-PSMA (recently approved).
- Sipuleucel-T: Autologous cellular vaccine (limited use).
- Checkpoint inhibitors: Pembrolizumab (MSI-H/dMMR tumors).
7. Supportive & Palliative Considerations
- Bone health: ADT → osteoporosis → denosumab or zoledronic acid for bone metastases.
- Hot flashes, metabolic syndrome, CV risk: Associated with ADT.
- Pain management: Opioids, bisphosphonates, palliative RT.
8. Monitoring & Pharmacist Role
- PSA & Testosterone levels (treatment response, progression).
- Adherence to oral agents (e.g., abiraterone, enzalutamide, relugolix).
- Drug interactions:
- Abiraterone: CYP3A4 substrate, requires prednisone.
- Enzalutamide/apalutamide: strong CYP inducers (affects anticoagulants, anticonvulsants).
- Toxicity monitoring:
- Docetaxel → neutropenia, neuropathy.
- Abiraterone → hypertension, hypokalemia, liver toxicity.
- Enzalutamide/apalutamide → seizures, fatigue, hypertension.
- Patient education: Oral drug timing (e.g., abiraterone taken fasting), side-effect management.
Key Takeaway for Oncology Pharmacists:
Prostate cancer management centers on androgen suppression and evolves with resistance. Pharmacists play a crucial role in monitoring hormone therapy, managing toxicities, preventing bone complications, and ensuring safe use of next-generation oral targeted therapies.
PROSTATE CANCER HORMONAL AGENTS (ANDROGEN DEPRIVATION THERAPY - ADT)
| GENERIC | BRAND | MOA | ADRs | BBW / WARNINGS | CONTRANDICATIONS | NOTES |
|---|---|---|---|---|---|---|
| Leuprolide | Lupron Depot, Eligard | GnRH Agonist (LHRH Agonist) | Hot Flashes, Gynecomastia, Impotence, Peripheral Edema, Bone Pain, Injection Site Pain, QT Prolong, DLD | Osteoporosis Risk, Tumor Flare | Pregnancy, Breastfeeding | SC or IM; ADT Tx = ↓ Testosterone; S/E: Hypogonadism, Hot Flashes, ↓ Libido, Impotence, Gynecomastia, Hair Thinning, Peripheral Edema |
| Goserelin | Zoladex | GnRH Agonist | ||||
| Histrelin | Supprelin | GnRH Agonist | ||||
| Triptorelin | Trelstar | GnRH Agonist | Osteoporosis Risk | Hypersensitivity Reactions | ||
| Degarelix | Firmagon | GnRH Antagonist | ||||
| Bicalutamide | Casodex | Anti-Androgen | Hot Flashes, Gynecomastia, Peripheral Edema, CVD, N/V/D | Hepatotoxicity | Pregnancy, Breastfeeding | ONLY used in combo with GnRH agonist; PO; Tumor Flare Sx = Bone pain or urinary problems; Prophylaxis = Give Anti-Androgens for several weeks with GnRH agonist initiation |
| Flutamide | Anti-Androgen | |||||
| Nilutamide | Xtandi | Anti-Androgen | Mono Tx OK | |||
| Enzalutamide | Xtandi | Anti-Androgen | ||||
| Abiraterone | Zytiga | Androgen Biosynthesis Inhibitor | Edema, HTN, ↓ K+ |
Prostate Cancer High-Yield Review Table (BCOP/BPS Focus)
| Category | Key Points (High-Yield for Exam) |
|---|---|
| Definitions | CRPC = progression despite castrate testosterone <50 ng/dL. PSA-only relapse → consider salvage RT ± ADT. |
| ADT (Androgen Deprivation Therapy) | GnRH agonists: leuprolide, goserelin (cause tumor flare → prevent w/ bicalutamide). GnRH antagonists: degarelix, relugolix (no flare, less CV risk). Complications: osteoporosis, metabolic syndrome, CV risk, hot flashes. |
| First-Line mHSPC | All improve OS: • ADT + abiraterone (LATITUDE/STAMPEDE, best OS) • ADT + enzalutamide • ADT + apalutamide • ADT + docetaxel (CHAARTED: high-volume disease). |
| AR Pathway Inhibitors | Abiraterone: blocks CYP17 → give w/ prednisone; risks: HTN, hypokalemia, ↑LFTs. Enzalutamide: seizures, strong CYP inducer (↓ warfarin, DOACs, tacrolimus). Apalutamide: rash, hypothyroidism, seizures. Darolutamide: least CNS side effects, fewer DDIs. |
| Chemotherapy | Docetaxel: OS benefit in mHSPC & mCRPC; monitor neutropenia, neuropathy. Cabazitaxel: post-docetaxel (TROPIC trial), requires G-CSF prophylaxis in high-risk. |
| Bone-Targeted Therapy | Denosumab: superior to zoledronic acid in delaying SREs; no renal adjustment, but higher hypocalcemia risk. Zoledronic acid: renal adjustment needed. Monitor Ca²⁺, vit D, dental exam (risk of ONJ). |
| Radiopharmaceuticals | Radium-223: only for symptomatic bone-only mCRPC, no visceral mets. Do not combine with abiraterone (↑ fractures, ERA-223 trial). Monitor CBC. |
| Immunotherapy | Sipuleucel-T: OS benefit in asymptomatic/minimally symptomatic mCRPC, ECOG 0–1. No benefit if symptomatic. |
| Molecular Therapies | PARP inhibitors (olaparib, rucaparib): for BRCA1/2 or HRR mutations after AR-targeted therapy. Pembrolizumab: MSI-H/dMMR tumors (tumor-agnostic approval). |
| Treatment Sequencing | Avoid sequencing abiraterone ↔ enzalutamide (cross-resistance). After AR inhibitor → chemo or PARPi (if mutation). After docetaxel → cabazitaxel, PARPi, radium-223 (if eligible). |
| Supportive Care | ADT → osteoporosis → DEXA q1–2 yrs, calcium/vit D, bisphosphonate/denosumab if high risk. Hot flashes: gabapentin, SSRIs/SNRIs (venlafaxine, paroxetine). Pain: opioids/NSAIDs first-line; radiation or radium-223 for persistent pain. |
| Special Scenarios | Neuroendocrine differentiation → platinum chemo (docetaxel/carboplatin). PSA rise only → do not change therapy until radiographic/clinical progression. CV risk → prefer GnRH antagonist (degarelix/relugolix). |
Pharmacist Takeaways
- Always continue ADT even when cancer becomes CRPC.
- Abiraterone = hypokalemia, fluid retention, hepatotoxicity.
- Enzalutamide = fatigue, CNS effects, seizures risk, CYP inducer.
- Docetaxel/Cabazitaxel = neutropenia (DLT).
- Radium-223 = bone-only disease, symptomatic, no visceral mets.
- Bone-modifying agents (zoledronic acid/denosumab) required with bone mets.
- Genomic testing critical for PARP inhibitor eligibility.
- ADT basics: agonists vs antagonists, testosterone flare, side effects.
- mHSPC: intensify therapy (docetaxel, abiraterone, enzalutamide, apalutamide).
- mCRPC: continue ADT, add systemic therapy.
- Targeted therapy: Radium-223, PARP inhibitors.
- Supportive care: bone protection, monitoring electrolytes, DDIs.
- ADT: long-term metabolic, CV, and bone complications.
- AR inhibitors: enzalutamide (DDIs, seizures), apalutamide (rash, hypothyroidism), darolutamide (fewer CNS effects).
- Abiraterone: always with prednisone, monitor K⁺, LFTs, BP.
- Docetaxel/cabazitaxel: neutropenia (DLT), supportive care essential.
- Radium-223: bone-only mCRPC, monitor CBC, avoid with chemo.
- Supportive care: bone health, hot flashes, pain management.
- Sequencing: Avoid back-to-back AR inhibitors; consider chemo or PARP inhibitor if biomarker-driven.
- Biomarkers: BRCA/HRR → PARP inhibitors; MSI-H → pembrolizumab.
- Supportive care: G-CSF with cabazitaxel, bone protection, CV monitoring with ADT.
- Special populations: Neuroendocrine → platinum; CKD → avoid zoledronic acid.
- Exam nuance: Don’t switch therapy on PSA rise alone.
Q1. First-Line for mHSPCA
66-year-old male is newly diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC). He has good performance status. Which regimen has the strongest survival benefit?
- A) Leuprolide alone
- B) Leuprolide + Bicalutamide
- C) Leuprolide + Docetaxel
- D) Leuprolide + Mitoxantrone
Answer: C) Leuprolide + Docetaxel
Explanation: CHAARTED and STAMPEDE trials demonstrated improved overall survival when docetaxel is added to ADT in fit patients with mHSPC. Mitoxantrone provides palliative benefit only. Leuprolide alone or with bicalutamide is inferior to intensified regimens.
Q2. Castration-Resistant Progression
A patient on leuprolide develops PSA progression and new bone metastases. Testosterone remains <50 ng/dL. What is the next step?
- A) Switch to another LHRH agonist
- B) Add abiraterone + prednisone
- C) Discontinue ADT and observe
- D) Add dutasteride
Answer: B) Add abiraterone + prednisone
Explanation: He has metastatic castration-resistant prostate cancer (mCRPC). ADT must be continued; systemic intensification with abiraterone, enzalutamide, or docetaxel is indicated. Switching LHRH agonists has no benefit.
Q3. Abiraterone Monitoring
Which lab abnormality is most associated with abiraterone therapy?
- A) Hyperkalemia
- B) Hypokalemia
- C) Hypercalcemia
- D) Hyponatremia
Answer: B) Hypokalemia
Explanation: Abiraterone inhibits CYP17 → mineralocorticoid excess → hypokalemia, hypertension, fluid retention. Prednisone is co-administered to prevent adrenal insufficiency. Monitor K⁺, LFTs, BP.
Q4. Docetaxel Dose-Limiting Toxicity
Which is the primary dose-limiting toxicity of docetaxel?
- A) Peripheral neuropathy
- B) Cardiotoxicity
- C) Neutropenia
- D) Stomatitis
Answer: C) Neutropenia
Explanation: Docetaxel’s most common dose-limiting toxicity is neutropenia. Neuropathy is possible but not dose-limiting. Pharmacists should monitor CBC and consider G-CSF in high-risk patients.
Q5. Radium-223 Indication
Which patient is the best candidate for radium-223?
- A) mCRPC with bone metastases, no visceral metastases, symptomatic
- B) mCRPC with liver metastases
- C) Biochemical recurrence without metastases
- D) mHSPC with lymph node involvement only
Answer: A) mCRPC with bone metastases, no visceral disease
Explanation: Radium-223 is an alpha-emitter used in symptomatic bone-predominant mCRPC, not visceral disease. Improves survival and reduces skeletal events.
Q6. Cabazitaxel Consideration
A patient previously treated with docetaxel develops progression. Which statement about cabazitaxel is correct?
- A) It is less myelosuppressive than docetaxel
- B) It improves OS vs mitoxantrone in post-docetaxel mCRPC
- C) It requires dose adjustment for renal impairment
- D) It should be avoided if prior ADT failure only
Answer: B) It improves OS vs mitoxantrone in post-docetaxel mCRPC
Explanation: TROPIC trial showed cabazitaxel + prednisone improved survival after docetaxel. It is more myelosuppressive, often requiring G-CSF prophylaxis. No renal adjustment needed.
Q7. Bone Health
Which agent is recommended for prevention of skeletal-related events in mCRPC with bone metastases?
- A) Zoledronic acid
- B) Zoledronic acid + Denosumab
- C) Finasteride
- D) Aspirin
Answer: A) Zoledronic acid or Denosumab (both acceptable)
Explanation: Either bisphosphonate (zoledronic acid) or RANKL inhibitor (denosumab) reduces skeletal-related events (fractures, spinal cord compression). Monitor renal function with zoledronic acid and calcium with denosumab
Q8. Genomic Testing
Why is genomic testing (e.g., BRCA1/2, HRR mutations) important in advanced prostate cancer?
- A) Predicts PSA relapse
- B) Determines eligibility for PARP inhibitors
- C) Guides selection of LHRH agonist vs antagonist
- D) Determines need for prophylactic bisphosphonates
Answer: B) Determines eligibility for PARP inhibitors
Explanation: Olaparib and rucaparib are approved for mCRPC with BRCA1/2 or homologous recombination repair (HRR) mutations. Pharmacists play a key role in identifying candidates for molecular testing.
Q1. Epidemiology
Which of the following is the strongest non-modifiable risk factor for prostate cancer?
- A) High-fat diet
- B) Advancing age
- C) Obesity
- D) Smoking
Answer: B) Advancing age
Explanation: Age is the primary risk factor. Diet/obesity may contribute but are modifiable. Smoking has only a weak association.
Q2. Screening
According to guidelines, PSA-based screening is most appropriate in:
- A) Men aged 30–40 years with no risk factors
- B) Men aged 50–69 years with shared decision-making
- C) All men over 75 years
- D) All African American men regardless of age
Answer: B) Men aged 50–69 years
Explanation: Routine PSA screening is controversial; USPSTF/ASCO recommend shared decision-making in average-risk men 50–69. High-risk men (family history, African American) may start earlier.
Q4. Initial Therapy
Which management strategy is most appropriate for a low-risk localized prostate cancer patient with life expectancy >10 years?
- A) Radical prostatectomy
- B) Radiation therapy + ADT
- C) Active surveillance
- D) Docetaxel chemotherapy
Answer: C) Active surveillance
Explanation: Low-risk localized disease is often managed with surveillance to avoid overtreatment. Surgery/radiation reserved for higher-risk or progression.
Q5. mHSPC Treatment
Which regimen showed overall survival benefit in CHAARTED and STAMPEDE trials?
- A) ADT alone
- B) ADT + Docetaxel
- C) ADT + Mitoxantrone
- D) ADT + Bicalutamide
Answer: B) ADT + Docetaxel
Explanation: Docetaxel added to ADT improved OS in metastatic hormone-sensitive prostate cancer (mHSPC).
Q6. ADT Mechanism
Leuprolide is best described as:
Answer: C) LHRH agonist
Explanation: LHRH agonists (leuprolide, goserelin) cause an initial testosterone surge (“flare”), unlike antagonists (degarelix, relugolix).
Q7. ADT Flare Prevention
Which drug can be co-administered with leuprolide to reduce testosterone flare?
- A) Finasteride
- B) Bicalutamide
- C) Abiraterone
- D) Apalutamide
Answer: B) Bicalutamide
Explanation: Non-steroidal anti-androgens (bicalutamide, flutamide, nilutamide) block AR to prevent flare when starting LHRH agonists.
Q8. CRPC Management
Which therapy is appropriate for a patient with mCRPC after progression on leuprolide?
- A) Switch to goserelin
- B) Add abiraterone + prednisone
- C) Stop ADT and observe
- D) Add dutasteride
Answer: B) Add abiraterone + prednisone
Explanation: In mCRPC, ADT is continued, but AR-pathway inhibitors (abiraterone, enzalutamide, apalutamide) or chemo are added.
Q9. Abiraterone Toxicity
The most common metabolic complication of abiraterone therapy is:
- A) Hyperkalemia
- B) Hypokalemia
- C) Hypercalcemia
- D) Hyponatremia
Answer: B) Hypokalemia
Explanation: Due to mineralocorticoid excess. Requires prednisone supplementation and monitoring.
Q10. Enzalutamide Drug Interactions
Enzalutamide is a:
- A) CYP3A4 substrate only
- B) CYP3A4 inhibitor
- C) Strong CYP3A4 inducer
- D) P-gp substrate only
Answer: C) Strong CYP3A4 inducer
Explanation: Enzalutamide induces CYP3A4, 2C9, 2C19 → ↓ levels of many drugs (warfarin, apixaban, tacrolimus). Pharmacist vigilance is crucial.
Q11. Docetaxel Toxicity
What is the primary dose-limiting toxicity of docetaxel?
- A) Stomatitis
- B) Neutropenia
- C) Neuropathy
- D) Diarrhea
Answer: B) Neutropenia
Explanation: Severe neutropenia is the DLT. Requires CBC monitoring; may need G-CSF.
Q12. Cabazitaxel Indication
Cabazitaxel is primarily used in:
- A) First-line mHSPC
- B) Post-docetaxel mCRPC
- C) Localized high-risk prostate cancer
- D) PSA-only relapse
Answer: B) Post-docetaxel mCRPC
Explanation: TROPIC trial showed cabazitaxel + prednisone improved OS vs mitoxantrone in docetaxel-pretreated mCRPC.
Q13. Radium-223 Use
Which is a contraindication for radium-223?
Answer: B) Concurrent docetaxel therapy
Explanation: Combination increases mortality/toxicity. Radium-223 indicated for symptomatic bone-only mCRPC (no visceral mets).
Q14. Bone-Modifying Agents
Which statement is correct?
- A) Denosumab requires renal dose adjustment
- B) Zoledronic acid can cause hypocalcemia
- C) Both reduce risk of visceral metastases
- D) Neither requires calcium/vitamin D supplementation
Answer: B) Zoledronic acid can cause hypocalcemia (and renal toxicity)
Explanation: Denosumab (RANKL inhibitor) is safe in renal dysfunction but higher risk of hypocalcemia. Both require calcium/vitamin D supplementation.
Q15. Genomic Testing
Which therapy is guided by BRCA1/2 mutation testing in mCRPC?
- A) Mitoxantrone
- B) Olaparib
- C) Abiraterone
- D) Enzalutamide
Answer: B) Olaparib
Explanation: PARP inhibitors (olaparib, rucaparib) are approved for mCRPC with BRCA1/2 or HRR mutations.
Q16. ADT Adverse Effect
Which of the following is a long-term complication of androgen deprivation therapy (ADT)?
- A) Leukopenia
- B) Osteoporosis
- C) Ototoxicity
- D) Pulmonary fibrosis
Answer: B) Osteoporosis
Explanation: ADT lowers testosterone → ↓ bone mineral density, ↑ fracture risk. Pharmacists should ensure calcium/vitamin D supplementation and consider bisphosphonate/denosumab.
Q17. Apalutamide Safety
Which adverse effect is most characteristic of apalutamide compared with other AR inhibitors?
- A) Seizures
- B) Rash and hypothyroidism
- C) Diarrhea
- D) Infusion reactions
Answer: B) Rash and hypothyroidism
Explanation: Apalutamide frequently causes rash and thyroid dysfunction; monitor TSH. Enzalutamide carries higher seizure risk.
Q18. Relugolix Advantage
Which advantage does relugolix (oral GnRH antagonist) have over leuprolide?
- A) Lower risk of hot flashes
- B) No testosterone flare
- C) Reduced fatigue
- D) Improved fertility preservation
Answer: B) No testosterone flare
Explanation: GnRH antagonists (degarelix, relugolix) achieve rapid testosterone suppression without initial flare seen with GnRH agonists.
Q19. PSA-Only Relapse
A 70-year-old man has PSA relapse (biochemical recurrence) after prostatectomy, no radiographic metastases. Next best step?
- A) Start docetaxel immediately
- B) Observation or salvage radiation ± ADT
- C) Start abiraterone
- D) Radium-223
Answer: B) Observation or salvage radiation ± ADT
Explanation: For PSA-only relapse, treatment is not systemic chemo but local salvage therapy or observation depending on risk.
Q20. Drug Interaction
Which drug interaction is most clinically significant with enzalutamide?
- A) Warfarin
- B) Allopurinol
- C) Digoxin
- D) Amlodipine
Answer: A) Warfarin
Explanation: Enzalutamide is a strong CYP2C9 and CYP3A4 inducer, which can ↓ warfarin, apixaban, rivaroxaban, tacrolimus levels. Close INR and drug monitoring needed.
Q21. Steroid Use with Abiraterone
Why is prednisone required with abiraterone?
- A) To reduce GI upset
- B) To prevent CYP interactions
- C) To replace cortisol and prevent mineralocorticoid excess
- D) To prevent seizures
Answer: C) To replace cortisol and prevent mineralocorticoid excess
Explanation: Abiraterone blocks CYP17 → ↓ cortisol → ↑ ACTH → mineralocorticoid excess. Prednisone replaces cortisol and suppresses ACTH.
Q22. Bone Pain Management
A man with prostate cancer and multiple bone metastases develops severe pain. First-line systemic agent for bone pain palliation?
- A) Radium-223
- B) Denosumab
- C) Opioids
- D) Cabazitaxel
Answer: C) Opioids
Explanation: For acute severe bone pain, analgesics (NSAIDs, opioids) are first-line. Radium-223 and denosumab reduce events but not immediate pain.
Q23. Hot Flashes from ADT
Which non-hormonal option is most effective for hot flashes from ADT?
- A) Gabapentin
- B) Tamoxifen
- C) Dutasteride
- D) Ketoconazole
Answer: A) Gabapentin
Explanation: SSRIs (venlafaxine, paroxetine) and gabapentin are most studied for ADT-related hot flashes. Hormonal agents (megestrol) sometimes used but riskier.
Q24. Cabazitaxel Precaution
Which supportive care measure is recommended with cabazitaxel?
- A) Antihistamine premedication only
- B) Primary prophylaxis with G-CSF in high-risk patients
- C) Warfarin bridging
- D) Leucovorin rescue
Answer: B) Primary prophylaxis with G-CSF in high-risk patients
Explanation: Cabazitaxel has high risk of severe neutropenia → G-CSF prophylaxis is recommended in older or frail patients.
Q25. Radium-223 Monitoring
What is the primary lab monitoring requirement for radium-223?
- A) Liver function tests
- B) Platelet count and ANC
- C) Serum magnesium
- D) Serum uric acid
Answer: B) Platelet count and ANC
Explanation: Radium-223 can cause myelosuppression; monitor CBC before each dose.
Q26. Darolutamide Safety
Compared with enzalutamide, darolutamide is associated with:
- A) More CNS side effects
- B) Fewer CNS side effects and drug interactions
- C) More hepatotoxicity
- D) More seizures
Answer: B) Fewer CNS side effects and drug interactions
Explanation: Darolutamide has limited BBB penetration → less fatigue, dizziness, seizures risk; fewer CYP interactions.
Q28. Chemotherapy Choice
A 72-year-old with mHSPC has CHF and poor ECOG (PS 2). Which systemic therapy is least appropriate?
- A) Leuprolide alone
- B) Abiraterone + prednisone
- C) Enzalutamide
- D) Docetaxel
Answer: D) Docetaxel
Explanation: Frail patients (PS ≥2, comorbidities) should avoid docetaxel; oral AR-pathway inhibitors are safer.
Q29. Tumor Flare Symptoms
A patient starting leuprolide reports worsening bone pain and urinary obstruction in first 2 weeks. Cause?
- A) Drug interaction
- B) Tumor flare due to initial testosterone surge
- C) Chemotherapy toxicity
- D) Infection
Answer: B) Tumor flare due to initial testosterone surge
Explanation: GnRH agonists → initial ↑ LH/testosterone → tumor flare; prevent with bicalutamide.
Q30. Proven Survival Benefit
Which of the following agents has proven survival benefit in mCRPC?
- A) Mitoxantrone
- B) Abiraterone
- C) Ketoconazole
- D) Estramustine
Answer: B) Abiraterone
Explanation: Abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, and PARP inhibitors improve OS. Mitoxantrone, estramustine, ketoconazole provide palliation only.
Q31. Cardiovascular Risk
Which ADT agent is associated with a lower cardiovascular risk in patients with pre-existing heart disease?
- A) Leuprolide
- B) Goserelin
- C) Degarelix
- D) Bicalutamide
Answer: C) Degarelix
Explanation: GnRH antagonists (degarelix, relugolix) are associated with lower CV events compared to GnRH agonists in patients with CVD.
Q32. Sipuleucel-T
Sipuleucel-T is best indicated in:
- A) Asymptomatic or minimally symptomatic mCRPC, ECOG 0–1
- B) Symptomatic mCRPC with visceral metastases
- C) Biochemical recurrence only
- D) First-line metastatic castration-sensitive disease
Answer: A) Asymptomatic or minimally symptomatic mCRPC, ECOG 0–1
Explanation: Proven OS benefit but not effective for symptomatic disease; immune response takes time.
Q33. PARP Inhibitor Eligibility
Which biomarker predicts benefit from olaparib or rucaparib in prostate cancer?
Answer: B) BRCA1/2 or HRR mutations
Explanation: PARP inhibitors are effective in patients with homologous recombination repair defects.
Q34. Pembrolizumab
Which biomarker predicts response to pembrolizumab in prostate cancer?
- A) HER2 amplification
- B) Microsatellite instability-high (MSI-H) or dMMR
- C) KRAS mutation
- D) Androgen receptor overexpression
Answer: B) MSI-H/dMMR
Explanation: Pembrolizumab is approved in MSI-H/dMMR solid tumors, including prostate cancer.
Q35. Common Lab Change with Abiraterone
Which lab abnormality is most commonly associated with abiraterone use?
- A) Hyperkalemia
- B) Hypokalemia
- C) Hypercalcemia
- D) Hyponatremia
Answer: B) Hypokalemia
Explanation: Mineralocorticoid excess causes hypokalemia, hypertension, edema.
Q37. Radium-223 Contraindication
Radium-223 is contraindicated in patients with:
- A) Symptomatic bone-only metastases
- B) Concurrent chemotherapy (docetaxel)
- C) Bone marrow suppression
- D) Castration-sensitive prostate cancer
Answer: B) Concurrent chemotherapy (docetaxel)
Explanation: Combination ↑ risk of fractures and deaths (per ERA-223 trial with abiraterone). Use sequentially, not together.
Q38. Bone-Protective Agents
Which of the following requires renal dose adjustment?
- A) Denosumab
- B) Zoledronic acid
- C) Radium-223
- D) Sipuleucel-T
Answer: B) Zoledronic acid
Explanation: Zoledronic acid (IV bisphosphonate) is renally cleared; denosumab is not, but hypocalcemia risk higher in CKD.
Q39. Castration-Resistant Definition
Castration-resistant prostate cancer is defined by progression despite:
- A) PSA ≥20 ng/mL
- B) Serum testosterone <50 ng/dL (or <1.7 nmol/L)
- C) At least 6 months of ADT
- D) 2 lines of therapy
Answer: B) Serum testosterone <50 ng/dL with disease progression
Explanation: CRPC occurs when PSA or radiographic progression happens despite castrate levels of testosterone.
Q40. Visceral Metastases
Which systemic agent is most appropriate for prostate cancer with liver metastases?
- A) Radium-223
- B) Sipuleucel-T
- C) Docetaxel
- D) Denosumab
Answer: C) Docetaxel
Explanation: Radium-223 and sipuleucel-T are only for bone-only disease. For visceral metastases (e.g., liver, lung), chemotherapy or AR inhibitors are required.
Q41. Sequencing Challenge
A patient with mCRPC progressed on docetaxel and later on enzalutamide. BRCA2 mutation is detected. Best next-line systemic therapy?
- A) Cabazitaxel
- B) Abiraterone + prednisone
- C) Olaparib
- D) Radium-223
Answer: C) Olaparib
Explanation: PARP inhibitors are recommended for HRR mutations (BRCA1/2, ATM) after progression on AR-targeted therapy. Cabazitaxel is an option, but olaparib is prioritized for biomarker-driven therapy.
Q42. Cross-Resistance
Why is enzalutamide followed by abiraterone considered less effective than switching drug class?
- A) They both inhibit CYP17
- B) They both target androgen receptor signaling, leading to cross-resistance
- C) They both cause seizures
- D) They both are contraindicated in elderly patients
Answer: B) They both target AR pathway → cross-resistance
Explanation: Clinical trials show diminished response when sequencing abiraterone ↔ enzalutamide, compared to switching to chemo (cabazitaxel).
Q43. Cabazitaxel Survival Benefit
Which trial established cabazitaxel’s survival benefit after docetaxel?
- A) TAX 327
- B) TROPIC
- C) CHAARTED
- D) LATITUDE
Answer: B) TROPIC trial
Explanation: TROPIC: cabazitaxel + prednisone vs mitoxantrone in post-docetaxel mCRPC → OS improvement.
Q44. Molecular Testing
Which patients with prostate cancer should undergo germline genetic testing?
- A) Only those with liver metastases
- B) All men with mCRPC
- C) Only patients with family history of breast cancer
- D) Only patients under 50 years
Answer: B) All men with mCRPC
Explanation: Guidelines recommend germline testing for HRR genes in all men with metastatic prostate cancer, regardless of age or family history.
Q45. Drug-Drug Interaction
A patient on enzalutamide develops atrial fibrillation and is started on apixaban. What is the concern?
- A) Enzalutamide increases apixaban concentration → bleeding
- B) Enzalutamide decreases apixaban concentration → thrombosis risk
- C) Apixaban increases enzalutamide levels → seizures
- D) No significant interaction
Answer: B) Decreased apixaban concentration
Explanation: Enzalutamide is a strong CYP3A4 and P-gp inducer → lowers DOAC levels → reduced efficacy.
Q46. Radium-223 Use
A man with mCRPC, bone metastases, and rising PSA but asymptomatic is considered for radium-223. He is also receiving abiraterone. What is the correct approach?
- A) Start radium-223 with abiraterone
- B) Start radium-223 alone, stop abiraterone
- C) Delay radium-223 until symptomatic
- D) Add denosumab before starting radium-223
Answer: C) Delay until symptomatic
Explanation: ERA-223 trial showed ↑ fractures and deaths when radium-223 + abiraterone were combined. Use radium-223 only for symptomatic bone-predominant disease, no visceral mets, not combined with AR-targeted therapy.
Q47. Neuroendocrine Differentiation
Prostate cancer biopsy shows neuroendocrine differentiation after progression on long-term ADT. Best systemic therapy?
- A) Enzalutamide
- B) Docetaxel + carboplatin
- C) Abiraterone
- D) Radium-223
Answer: B) Docetaxel + carboplatin
Explanation: Treatment-resistant prostate cancers can transform to aggressive neuroendocrine histology → platinum-based chemo is preferred.
Q48. PSA vs Radiographic Progression
A patient with mCRPC on enzalutamide shows PSA rise, but scans show stable bone metastases, and patient is asymptomatic. Best next step?
- A) Switch to abiraterone
- B) Switch to docetaxel
- C) Continue enzalutamide and monitor
- D) Add sipuleucel-T
Answer: C) Continue enzalutamide and monitor
Explanation: PSA rise alone without radiographic or clinical progression does not require therapy switch; BPS often tests this nuance.
Q49. Bone-Modifying Agents
Which statement about denosumab vs zoledronic acid in prostate cancer is correct?
- A) Zoledronic acid is superior in preventing skeletal-related events (SREs)
- B) Denosumab is superior in delaying first SRE, but risk of hypocalcemia is higher
- C) Both require renal adjustment
- D) Denosumab cannot be used in CKD
Answer: B) Denosumab superior in delaying SREs, but ↑ hypocalcemia risk
Explanation: Denosumab delayed time to first SRE compared with zoledronic acid. Zoledronic acid requires renal adjustment; denosumab does not but ↑ hypocalcemia risk.
Q50. High-Yield Final
A patient with mHSPC (high-volume disease per CHAARTED) is started on ADT. Which combination improves overall survival the most?
- A) ADT + abiraterone
- B) ADT + enzalutamide
- C) ADT + apalutamide
- D) ADT + docetaxel
Answer: A) ADT + abiraterone
Explanation: All options improve OS in high-volume mHSPC, but LATITUDE and STAMPEDE trials showed ADT + abiraterone has one of the largest OS benefits. NCCN/EAU list ADT + abiraterone, enzalutamide, apalutamide, or docetaxel as preferred.
DR is a 71 yo Caucasian male with chronic kidney disease requiring dialysis. His primary care physician checked a prostate specific antigen (PSA) which resulted at 9 ng/ml and he had an abnormal digital rectal exam (DRE). Further imaging and biopsy reveal a low risk prostate adenocarcinoma. His life expectancy is 7 years.
What is the most appropriate treatment option for DR at this time?
- A. Active surveillance
- B. Active surveillance + dutasteride
- C. Radiation therapy + short term androgen deprivation therapy
- D. Observation
Correct answer = D.
BF is classified as low risk and has life expectancy <10 years, making observation the most appropriate option. Dutasteride has not been found to be beneficial for the treatment of prostate cancer. Radiation with long-term or short term ADT is not indicated for low risk disease. Active surveillance is preferred in younger men with longer life expectancy.
DR is a 40-year-old Caucasian male with a past medical history of seasonal allergies. His primary care physician checked a PSA which resulted at 9 ng/ml and he had an abnormal digital rectal exam (DRE). Further imaging and biopsy reveal a very low risk prostate adenocarcinoma. He prefers a treatment strategy that minimizes adverse effects.
What is the most appropriate treatment option for DR at this time?
- A. Active surveillance
- B. Radical prostatectomy + short term androgen deprivation therapy
- C. Radiation therapy + short term androgen deprivation therapy
- D. Observation
Correct answer = A (active surveillance)
BF is classified as very low risk and has life expectancy >20 years. Active surveillance is the preferred option for this risk category/life expectancy. Active surveillance minimizes toxicity of treatment. Observation is not appropriate for a young healthy patient. Adjuvant radiation is not indicated in very low risk disease.
AC is a 65-year-old male with poorly controlled type 2 diabetes and was undergoing regular prostate cancer screening. His most recent PSA was 33ng/dl with an abnormal DRE. Further workup revealed a T2b adenocarcinoma of the prostate and bone scan revealed multiple metastatic lesions to the ribs. CT shows no other sites of distant metastatic disease. In addition to continuing ADT.
Which of the following is the most appropriate treatment option for AC at this time?
- A. Abiraterone + prednisone
- B. Sipuleucel T
- C. Cabazitaxel + prednisone
- D. Enzalutamide
Correct answer = D
BF has newly diagnosed metastatic prostate cancer discovered during active surveillance (aka castrate naïve (or sensitive) prostate cancer). He is currently not on any hormonal therapy; therefore he does not have castration resistant prostate cancer. Sipuleucel-T is therefore not appropriate at this time. Cabazitaxel is only indicated after docetaxel-containing regimens. Of the options available, abiraterone and enzalutamide are both recommended options. This patient has poorly controlled diabetes so avoiding corticosteroids is best for this patient, making enzalutamide the preferred option.
RC is a 62 year old that presents to your clinic with a history of high risk prostate cancer status post EBRT, currently on adjuvant leuprolide. Six months prior PSA level was 2.4 ng/mL and testosterone levels less than 20ng/dL. Three months prior PSA of 4.7ng/ml. Today’s lab values are within normal limits except PSA level of 25 ng/ml and testosterone less than 20ng/dL. CT scan shows no metastatic disease.
Which is the most appropriate addition to RC’s ADT at this time?
- A. Docetaxel + prednisone
- B. Bicalutamide
- C. Darolutamide
- D. Abiraterone + prednisone
Correct answer = C
Based on laboratory and imaging data RC has non-metastatic castration resistant prostate cancer. Darolutamide is indicated in this setting supported by data from the ARAMIS trial. Docetaxel and abiraterone are indicated in the metastatic setting but not in the M0 or non-metastatic setting. Bicalutamide is an option in some castration sensitive patients that do not tolerate a LHRH agonist or antagonist but unfortunately RC has progressed to the castration recurrent setting (confirmed with testosterone <50 ng/mL).
RC is a 62-year-old that presents to your clinic with a history of high risk prostate cancer status post EBRT, currently on adjuvant leuprolide. Six months prior PSA level was 2.4 ng/mL and testosterone levels less than 20ng/dL. Three months prior PSA of 4.7ng/ml. Today’s lab values are within normal limits except PSA level of 25 ng/ml and testosterone less than 20ng/dL. CT scan shows no metastatic disease.
Which is the most appropriate change in RC’s treatment at this time?
- A. Stop leuprolide, start docetaxel + prednisone
- B. Stop leuprolide, start relugolix
- C. Continue leuprolide, add darolutamide
- D. Continue leuprolide, add abiraterone + prednisone
Correct answer = C (Continue leuprolide, add darolutamide)
Based on laboratory and imaging data, RC has non-metastatic castration resistant prostate cancer. Darolutamide is indicated in this setting, supported by data from the ARAMIS trial. Docetaxel and abiraterone are indicated in the metastatic setting but not in the M0 setting. ADT should be continued despite progression to castration-resistant disease. Relugolix is an alternative to leuprolide for ADT but is not indicated after progression on leuprolide as a single agent.
AB has prostate cancer that initially progressed on ADT (leuprolide) and was changed to ADT + Enzalutamide. He did well for 2 years with this regimen and then presented with a rising PSA (14ng/dl, then 20ng/dl, over 3 months) and worsening back pain. Today, his PSA is 35ng/dl and a bone scan shows progression of skeletal metastases and a new liver lesion (concerning for metastasis). His ECOG PS is 1. Life expectancy is greater than 6 months. His biggest concern at this time is getting his back pain under control quickly. In addition to continuing ADT, what is the most appropriate modification to AB’s treatment regimen at this time?
- A. Stop enzalutamide, add Mitoxantrone + prednisone
- B. Continue enzalutamide, add Abiraterone + prednisone
- C. Stop enzalutamide, add Docetaxel + prednisone
- D. Stop enzalutamide, add Abiraterone + prednisone
Answer: C
AB now has metastatic CRPC with progression of his skeletal metastases and new liver metastasis.
- Mitoxantrone is used in patients who have no other treatment options for palliation of symptoms (typically after docetaxel which this patient has not had).
- Adding abiraterone to enzalutamide is not a recommended treatment option and has not shown a benefit.
- Docetaxel/prednisone and abiraterone/prednisone with ADT are both potential options, however for faster relief of symptoms and for visceral metastases, docetaxel is preferred over abiraterone.
PC has metastatic prostate cancer (somatic and germline testing both show no targetable mutations) and a history of hypertension and a bilateral orchiectomy. Prior lines of therapy include apalutamide, abiraterone + prednisone, and docetaxel + prednisone. He returns after 10 cycles of docetaxel for follow up. His PSA has been increasing over the last 2 months. Repeat staging scans show extensive worsening bone metastases and no visceral disease. He now requires scheduled morphine for bone pain. His ECOG performance status is 1. He has significant fatigue and neuropathy from docetaxel and wishes to avoid therapy with significant toxicity at this time. In addition to continuing ADT, which of the following is the most appropriate treatment option for PC at this time?
- A. Cabazitaxel
- B. Radium-223
- C. Enzalutamide
- D. Pembrolizumab
Correct answer = A. Sipuleucel T is not indicated in this setting.
Enzalutamide is not the best option for this patient who has a known seizure history and continued seizures despite therapy. Mitoxantrone has no overall survival benefit and is generally reserved for patients who cannot tolerate any other treatment option. This patient has a homolgous recombinant repair mutation making him a candidate for a PARP inhibitor. Rucaparib is only FDA indicated and NCCN guideline recommended for BRCA1/2 mutations. Olaparib is FDA indicated for any HRRm (and NCCN guidelines recommend for any HRRm except PP2R2A). The phase III PROfound trial included patients with ATM mutation in cohort A which showed a PFS and OS benefit. This is the most appropriate option for the patient based on available evidence.
LL has prostate cancer that progressed during adjuvant ADT with increasing PSA, testosterone <50 ng/dL, and bone scans showing new skeletal metastases. His oncologist is planning to add enzalutamide to his ADT at this time. The oncologist asks if there are any other supportive care medications that you would recommend.
What of the following agents is most appropriate to initiate in LL at this time?
- A. Denosumab 120 mg every 4 weeks
- B. Calcium plus vitamin D 500mg-400 IU twice daily
- C. Alendronate 70 mg every 4 weeks
- D. Denosumab 120 mg every 4 weeks and calcium plus vitamin D 500mg-400 IU twice daily
Correct answer = D
LL now has castrate resistant prostate cancer with bony disease so it is reasonable to initiate therapy for prevention of a skeletal-related event. Denosumab is a preferred agent for this indication. Alendronate is reasonable to prevent osteoporosis but is not indicated for prevention of skeletal-related events. Denosumab has been shown to delay time to first skeletal related events in patients with bone metastases from prostate cancer. Calcium plus vitamin D should be added to therapy to prevent hypocalcemia.
LB is a 60-year-old male with history of myocardial infarction 3 months ago and low risk prostate cancer treated with external beam radiation 6 months ago. He follows up with his oncologist regularly and his PSA has doubled in the last four months. He presents today to discuss recent imaging which shows no sites of metastatic disease. He is not a candidate for further local treatment and is hesitant to purse androgen deprivation therapy due to fear of adverse cardiac effects.
Which of the following options is most appropriate for LB?
- A. Continuous ADT with leuprolide
- B. Intermittent ADT with relugolix
- C. Intermittent ADT with leuprolide
- D. Treatment is not indicated at this time
Correct answer = B (Intermittent ADT with relugolix)
LB has a biochemical recurrence (castrate sensitive). Appropriate treatments include ADT and active surveillance. Due to his short doubling time, ADT is a good choice for him. Intermittent ADT is an option for biochemical recurrence. With regard to cardiac events, relugolix showed a benefit over leuprolide in the HERO trial, making it preferable for this patient. It is also a good option for intermittent ADT because of its short half-life.
AC is a 65-year-old male with history of hypertension (controlled with amlodipine). After initially presenting with back pain, imaging and biopsy revealed prostate cancer metastatic to the liver and spine. Current ECOG performance status is zero. All lab values are within normal limits except for a PSA of 87ng/dl. In addition to starting ADT, which of the following is the most appropriate treatment option for AC at this time?
- A. Abiraterone + prednisone
- B. Lutetium-177 PSMA
- C. Docetaxel + darolutamide
- D. Docetaxel + enzalutamide
Correct answer = C (Docetaxel + darolutamide)
This patient has m1CSPC – treatment options include docetaxel + abiraterone, docetaxel + darolutamide, abiraterone + prednisone, apalutamide or enzalutamide.
- Lutetium-177 PSMA is not approved for m1CSPC.
- Docetaxel + enzalutamide has not been approved as a combination regimen in any setting.
- This patient has high volume disease, making a docetaxel-containing regimen preferred.
- Additionally, he is having pain from his cancer, making docetaxel an attractive option to provide quick relief of his pain. He is otherwise healthy with minimal comorbidities making him a good candidate for docetaxel.
AB is a 60-year-old male with castration resistant prostate cancer that was initially treated with ADT + docetaxel x 6 cycles and at progression started on ADT + abiraterone + prednisone. He did well for 2 years with this regimen and then presented with a rising PSA (14ng/ml, then 20ng/ml, over 3 months) and increased back pain. Today, his PSA is 35ng/ml and imaging shows progression of skeletal metastases and several new small liver metastases. His ECOG PS is 0. In addition to continuing ADT
What is the most appropriate next line of treatment for AB?
- A. Enzalutamide
- B. Radium-223
- C. Mitoxantrone + prednisone
- D. Cabazitaxel + prednisone
Answer = D (Cabazitaxel)
Mitoxantrone has no overall survival benefit and should be reserved for patients with no other appropriate treatment options. Radium-223 is only indicated for pts with bone-only mets. Cabazitaxel and alternate novel hormonal therapy were compared in this setting in the CARD trial and cabazitaxel had superior survival benefit. Therefore, cabazitaxel is preferred over enzalutamide for this patient.
GC has metastatic castration resistant prostate cancer with no other comorbidities. He was initially treated with leuprolide and apalutamide and when he progressed, he was started on docetaxel. His most recent PSMA PET scan shows numerous sites of progressing disease in the lung and bones. In addition to continuing his leuprolide, which of the following is the most appropriate next line of treatment for AB?
- A. Enzalutamide
- B. Radium-223
- C. Mitoxantrone + prednisone
- D. Lutetium-177 PSMA
Answer = D (Lutetium-177 PSMA)
The patient meets criteria to receive this agent, as he has PSMA-positive disease that has progressed through a taxane and a novel hormonal therapy. Enzalutamide is not appropriate after progression on apalutamide. Radium-223 is not recommended with visceral disease. Mitoxantrone does not provide a survival benefit in this setting.
RC is a 65-year- old male with metastatic prostate cancer and tumor mutation testing revealed BRCA1 mutation. His previous lines of therapy include leuprolide + abiraterone + prednisone, leuprolide + Radium-223, and leuprolide + docetaxel + prednisone. He has received 3 cycles of docetaxel and his PSA has been increasing over the 2 months. Repeat staging scans show worsening bone and liver metastases. He now requires scheduled morphine for bone pain. His ECOG performance status is 1. In addition to continuing ADT, which of the following is the most appropriate treatment option for RC at this time?
- A. Olaparib
- B. Sipuleucel T
- C. Mitoxantrone
- D. Pembrolizumab
Correct answer = A (Olaparib)
- Sipuleucel-T is not indicated in this setting.
- Mitoxantrone has no overall survival benefit and is generally reserved for patients who cannot tolerate any other treatment option.
- This patient has a homologous recombinant repair mutation making him a candidate for a PARP inhibitor. Olaparib is FDA indicated for any HRRm (and NCCN guidelines recommend for any HRRm except PPP2R2A).
- Pembrolizumab is only indicated for dMMR or MSI-high cancers. Olaparib is the most appropriate option for the patient based on available evidence.
RB is a 65-year-old male with history of hypertension (controlled with amlodipine). After initially presenting with back pain, imaging and biopsy revealed prostate cancer metastatic to the liver and spine with a BRCA2 mutation. Current ECOG performance status is zero. All lab values are within normal limits except for a PSA of 87 ng/dl. In addition to starting ADT, which of the following is the most appropriate treatment option for RB at this time?
- A. Enzalutamide
- B. Abiraterone + olaparib
- C. Docetaxel
- D. Docetaxel + darolutamide
Correct answer = D (Docetaxel + darolutamide)
This patient has m1CSPC – treatment options include docetaxel + abiraterone + prednisone, docetaxel + darolutamide, abiraterone + prednisone, apalutamide or enzalutamide. Abiraterone + olaparib is not recommended for m1CSPC. Enzalutamide is not appropriate because of the high volume disease and good performance status – he should receive a docetaxel-containing regimen. Additionally, he is having pain from his cancer, making docetaxel an attractive option to provide quick relief of his pain. Docetaxel alone has inferior OS compared to docetaxel + abiraterone or docetaxel + darolutamide. He is otherwise healthy with minimal comorbidities making him a good candidate for docetaxel + darolutamide.
GC has metastatic castration resistant prostate cancer with irritable bowel disease. He was initially treated with leuprolide and apalutamide and when he progressed, he was treated with docetaxel. His most recent PSMA PET scan shows numerous sites of progressing disease in the lung and bones. He is a truck driver and prefers a treatment with the least risk of diarrhea as it could significantly impact his ability to work. In addition to continuing his leuprolide.
What is the most appropriate next line of treatment for AB?
- A. Enzalutamide
- B. Radium-223
- C. Cabazitaxel
- D. Lutetium-177 PSMA
Answer = D (Lutetium-177 PSMA)
Radium-223 is only indicated for pts with bone-only metastases. Enalutamide is not appropriate after progression on apalutamide (same class). Therefore, Lu-PSMA 177 preferred over cabazitaxel for this patient due to lower incidence of diarrhea in the Thera-P trial.
RC is a 65-year-old-male with metastatic prostate cancer and tumor mutation testing revealed PALB2 mutation. He was diagnosed two years ago and initially treated with leuprolide + docetaxel x 6 cycles. He has been maintained on leuprolide since completing docetaxel. Most recent labs showed PSA was increasing and imaging showed several new skeletal metastases. His ECOG performance status is 1. In addition to continuing ADT, which of the following is the most appropriate FDA approved treatment option for RC at this time?
- A. Olaparib + abiraterone
- B. Rucaparib
- C. Niraparib + abiraterone
- D. Talazoparib + enzalutamide
Correct answer = D Talazoparib + enzalutamide
Of the options listed, talazoparib + enzalutamide is the only FDA approved for a PALB2 mutation, all others are for BRCA mutation only.
Which of the following genes are involved in prostate cancer (choose 4)?
Answer: A, D, E, G (BRCA 1, MYC, FOXA1, SRD5A1)
Explanation: Mutations in the BRCA1 (and BRCA2) DNA repair genes significantly increase the risk of aggressive prostate cancer. MYC is a potent oncogene that is frequently amplified in prostate cancer and drives tumor growth and progression. FOXA1 is a pioneer transcription factor that is often mutated in prostate cancer and plays a key role in regulating androgen receptor signaling. SRD5A1 (and SRD5A2) encode for the 5-alpha-reductase enzymes that convert testosterone to the more potent dihydrotestosterone (DHT), a primary driver of prostate cancer growth. ALK, MEK, and EGFR are more commonly associated with other cancers, such as lung cancer.
Which of the following patients is most candidate to start prostate cancer screening?
- A. 35 years old man whose father diagnosed with prostate cancer at 55 years old
- B. 45 years old man whose father diagnosed with prostate cancer at 70 years old
- C. 42 years old man whose father diagnosed with prostate cancer at 57 years old
- D. 40 years old man whose father diagnosed with prostate cancer at 67 years old
Answer: C
Explanation: Guidelines recommend initiating prostate cancer screening at age 40-45 for men at high risk, which is primarily defined as having a first-degree relative (father, brother) diagnosed with prostate cancer at an early age (typically under 65). A diagnosis in a father at age 57 is considered early and carries the strongest hereditary risk, making his 42-year-old son the best candidate for earlier screening. The other options involve older ages of diagnosis in the father (which suggests less hereditary influence) or a son who is too young (35) for screening to typically be recommended.
Which of the following is correct regarding PSA measurement?
- A. All Prostate cancer cases have PSA>10
- B. Measuring PSA velocity is useful for patient that has PSA=20
- C. Normal PSA </= 4 ng/dl but prostate cancer may occur at PSA 2.5-4ng/dl
- D. PSA level alone is enough to diagnose prostate cancer
Answer: C
Explanation: This is the only entirely correct statement. While a PSA level ≤ 4 ng/mL was historically considered normal, it is well-established that prostate cancer can be present at any PSA level, including within the "normal" range (e.g., 2.5-4 ng/mL). Option A is false; many prostate cancers are diagnosed with a PSA < 10. Option B is false; PSA velocity (the rate of change over time) is most clinically useful in the lower PSA ranges (e.g., < 10) to aid in the decision for biopsy, not when the PSA is already very high. Option D is false; PSA is a screening tool, not a diagnostic test. A diagnosis requires a prostate biopsy.
Which of the following is correct regarding prostate cancer prevention?
- A. Pumpkin seed extract is good for prevention
- B. Its recommended for patients >65 years old to take finasteride for prevention
- C. In men who are taking finasteride for BPH, the potential benefits and risks should be discussed
- D. Dutasteride use is associated with low grade prostate cancer
Answer: C
Explanation: This is a key point from large clinical trials like the Prostate Cancer Prevention Trial (PCPT). While finasteride (and dutasteride) reduce the overall risk of being diagnosed with prostate cancer by about 25%, they are associated with a slightly increased relative risk of being diagnosed with high-grade (Gleason 8-10) disease. Therefore, a thorough discussion of these potential benefits and risks is mandatory. Option A is unproven by robust scientific evidence. Option B is false; these medications are not recommended solely for prevention, especially in men over 65. Option D is misleading; the drugs are associated with a reduced diagnosis of low-grade cancer, not that their use causes it.
which of the following grades represented by Gleason pattern 3+5 ?
- A. 1
- B. 3
- C. 4
- D. 5
Answer: C
Explanation: The modern clinical classification uses Grade Groups (1-5), which simplify the older Gleason scoring system (6-10). The Grade Group is determined by the combined Gleason score:
- Grade Group 1: Gleason score ≤ 6
- Grade Group 2: Gleason score 3+4=7
- Grade Group 3: Gleason score 4+3=7
- Grade Group 4: Gleason score 8 (which includes patterns 3+5, 5+3, and 4+4)
- Grade Group 5: Gleason scores 9-10
Therefore, a Gleason pattern 3+5 = 8 corresponds to Grade Group 4.
Which of the following is not considered a long term side effect for LHRH agonists?
- A. Osteoporosis
- B. Insulin resistance
- C. Hot flushes
- D. Cardiovascular diseases
Answer: C
Explanation: LHRH agonists (e.g., leuprolide, goserelin) cause medical castration, leading to hypogonadism. Hot flushes (or flashes) are a very common acute side effect of this low-testosterone state, but they are not a long-term metabolic complication. In contrast, osteoporosis (due to bone mineral density loss), insulin resistance (which can lead to diabetes), and an increased risk of cardiovascular diseases are all well-established long-term consequences of androgen deprivation therapy (ADT).
A 57-year-old man presents to his local ED with bone pains and constipation.On imaging he is found to have multiple lytic lesions involving two ribs,three vertebrae,and his left humerus.He has no spinal cord compression on MRI but CT of the abdomen and pelvis shows an enlarged prostate with external compression of the rectum causing complete obstruction. Prostate-specific antigen (PSA) is 180 ng/mL. He is otherwise healthy.
Which of these options is the preferred next step for him?
- A.Biopsy of a malignant bone lesion
- B.Radium-223
- C.Leuprolide
- D.Abiraterone+prednisone
- E.Degarelix
Answer: E
Explanation: This patient has newly diagnosed, metastatic prostate cancer presenting with a urological emergency (complete rectal obstruction). The absolute priority is to rapidly lower testosterone to alleviate symptoms and shrink the tumor. Standard LHRH agonists (like Leuprolide - C) cause an initial "testosterone flare" that can worsen symptoms catastrophically (e.g., increased pain, spinal cord compression). Degarelix is a GnRH antagonist that suppresses testosterone levels rapidly without a flare, making it the preferred initial agent in this acute, symptomatic setting. After acute control with Degarelix, treatment would typically be switched to a long-term LHRH agonist and other therapies. A bone biopsy (A) is unnecessary with such a high PSA and classic findings. Radium-223 (B) and Abiraterone (D) are treatments for castration-resistant prostate cancer (CRPC), not for initial hormone-sensitive treatment
KM is a 70-year-old male with very high risk prostate cancer that was initially treated with EBRT+BT after 2 years. He then presented with a rising PSA (20 ng/ml, then 40ng/ml, over 6 months) and increased back pain. Imaging shows liver metastases. He take levitracetam 500 mg twice daily for his seizures, in addition to starting ADT, what is the most appropriate of treatment for KM?
- A. Abirateron+prednisolone
- B. Enzalutamide
- C. Docetaxel+Daroulutamide
- D. Continue EBRT+BT
Answer: A
Explanation: The rising PSA despite ongoing ADT and the presence of liver metastases define metastatic castration-resistant prostate cancer (mCRPC). The first-line treatment options for mCRPC include Abiraterone (+ Prednisone) or Enzalutamide. However, Enzalutamide (B) is contraindicated in patients with a history of seizures due to its associated risk of causing seizures. The patient takes levetiracetam for seizures, making Enzalutamide an unsafe choice. Therefore, Abiraterone + Prednisolone (A) is the most appropriate and safest option. Docetaxel+Darolutamide (C) is a complex regimen not indicated here, and continuing radiotherapy (D) is ineffective for widespread visceral metastases.
Patient will start abirateron what to tell him?
- A. You should take 4 tablets(250 mg) after lunch
- B. Abirateron is taken with prednisolone 20 mg twice daily
- C. Patient should do cardiovascular work up and tests prior to therapy
- D. Side effects may include seizures & osteoporosis
Answer: C
Explanation: Abiraterone inhibits adrenal and tumoral androgen synthesis and can cause a syndrome of secondary mineralocorticoid excess, leading to hypertension, hypokalemia (low potassium), and fluid retention. These side effects pose significant cardiovascular risks. Therefore, a baseline cardiovascular assessment, including blood pressure monitoring and electrolyte checks, is mandatory before and during therapy. Option A is false; Abiraterone must be taken on an empty stomach (at least 1 hour before or 2 hours after food) to ensure proper absorption. Option B is false; the concomitant steroid is prednisone 5 mg twice daily (or prednisolone), not 20 mg. Option D is false; seizures are a known side effect of Enzalutamide, not Abiraterone. Osteoporosis is a side effect of ADT in general, not specifically caused by Abiraterone itself.
Q42. Cross-Resistance
Why is enzalutamide followed by abiraterone considered less effective than switching drug class?
- A) They both inhibit CYP17
- B) They both target androgen receptor signaling, leading to cross-resistance
- C) They both cause seizures
- D) They both are contraindicated in elderly patients
Answer: B) They both target AR pathway → cross-resistance
Explanation: Clinical trials show diminished response when sequencing abiraterone ↔ enzalutamide, compared to switching to chemo (cabazitaxel).
Q43. Cabazitaxel Survival Benefit
Which trial established cabazitaxel’s survival benefit after docetaxel?
- A) TAX 327
- B) TROPIC
- C) CHAARTED
- D) LATITUDE
Answer: B) TROPIC trial
Explanation: TROPIC: cabazitaxel + prednisone vs mitoxantrone in post-docetaxel mCRPC → OS improvement.
Q44. Molecular Testing
Which patients with prostate cancer should undergo germline genetic testing?
- A) Only those with liver metastases
- B) All men with mCRPC
- C) Only patients with family history of breast cancer
- D) Only patients under 50 years
Answer: B) All men with mCRPC
Explanation: Guidelines recommend germline testing for HRR genes in all men with metastatic prostate cancer, regardless of age or family history.
Q45. Drug-Drug Interaction
A patient on enzalutamide develops atrial fibrillation and is started on apixaban. What is the concern?
- A) Enzalutamide increases apixaban concentration → bleeding
- B) Enzalutamide decreases apixaban concentration → thrombosis risk
- C) Apixaban increases enzalutamide levels → seizures
- D) No significant interaction
Answer: B) Decreased apixaban concentration
Explanation: Enzalutamide is a strong CYP3A4 and P-gp inducer → lowers DOAC levels → reduced efficacy.
Q46. Radium-223 Use
A man with mCRPC, bone metastases, and rising PSA but asymptomatic is considered for radium-223. He is also receiving abiraterone. What is the correct approach?
- A) Start radium-223 with abiraterone
- B) Start radium-223 alone, stop abiraterone
- C) Delay radium-223 until symptomatic
- D) Add denosumab before starting radium-223
Answer: C) Delay until symptomatic
Explanation: ERA-223 trial showed ↑ fractures and deaths when radium-223 + abiraterone were combined. Use radium-223 only for symptomatic bone-predominant disease, no visceral mets, not combined with AR-targeted therapy.
Q47. Neuroendocrine Differentiation
Prostate cancer biopsy shows neuroendocrine differentiation after progression on long-term ADT. Best systemic therapy?
- A) Enzalutamide
- B) Docetaxel + carboplatin
- C) Abiraterone
- D) Radium-223
Answer: B) Docetaxel + carboplatinExplanation: Treatment-resistant prostate cancers can transform to aggressive neuroendocrine histology → platinum-based chemo is preferred.
Q48. PSA vs Radiographic Progression
A patient with mCRPC on enzalutamide shows PSA rise, but scans show stable bone metastases, and patient is asymptomatic. Best next step?
- A) Switch to abiraterone
- B) Switch to docetaxel
- C) Continue enzalutamide and monitor
- D) Add sipuleucel-T
Answer: C) Continue enzalutamide and monitor
Explanation: PSA rise alone without radiographic or clinical progression does not require therapy switch; BPS often tests this nuance.
Q49. Bone-Modifying Agents
Which statement about denosumab vs zoledronic acid in prostate cancer is correct?
- A) Zoledronic acid is superior in preventing skeletal-related events (SREs)
- B) Denosumab is superior in delaying first SRE, but risk of hypocalcemia is higher
- C) Both require renal adjustment
- D) Denosumab cannot be used in CKD
Answer: B) Denosumab superior in delaying SREs, but ↑ hypocalcemia risk
Explanation: Denosumab delayed time to first SRE compared with zoledronic acid. Zoledronic acid requires renal adjustment; denosumab does not but ↑ hypocalcemia risk.
Q50. High-Yield Final
A patient with mHSPC (high-volume disease per CHAARTED) is started on ADT. Which combination improves overall survival the most?
- A) ADT + abiraterone
- B) ADT + enzalutamide
- C) ADT + apalutamide
- D) ADT + docetaxel
Answer: A) ADT + abiraterone
Explanation: All options improve OS in high-volume mHSPC, but LATITUDE and STAMPEDE trials showed ADT + abiraterone has one of the largest OS benefits. NCCN/EAU list ADT + abiraterone, enzalutamide, apalutamide, or docetaxel as preferred.