CONCEPTUAL SUMMARY
EPIDEMIOLOGY AND RISK FACTORS:
- Prostate cancer is the most common non-cutaneous cancer in men and a leading cause of cancer-related death.
- Risk factors include
- Screening is recommended via shared decision-making at age 50–69 for average-risk men; earlier (age 40–45) for high-risk men with a first-degree relative diagnosed with prostate cancer at an early age (especially before age 65).
PSA UNDERSTANDING:
Normal PSA ≤ 4 ng/dL — but prostate cancer can occur at PSA 2.5–4 ng/dL. PSA alone is NOT sufficient to diagnose prostate cancer — biopsy is required for confirmation. PSA velocity is most useful at lower PSA ranges (< 10), not when PSA is already very elevated. Not all prostate cancer cases have PSA > 10.
GLEASON/GRADE GROUPS:
Grade Group 1 = Gleason ≤ 6; Grade Group 2 = Gleason 3+4=7; Grade Group 3 = Gleason 4+3=7; Grade Group 4 = Gleason 8 (includes 3+5, 5+3, 4+4); Grade Group 5 = Gleason 9–10.
STAGING AND RISK STRATIFICATION:
Low risk: PSA < 10, Gleason ≤ 6 (Grade Group 1), Stage T1–T2a.
Intermediate risk: PSA 10–20, Gleason 7, or Stage T2b–T2c.
High risk: PSA > 20, Gleason ≥ 8 (Grade Group 4–5), or Stage T3–T4.
LOCALIZED DISEASE MANAGEMENT:
Very low or low risk with life expectancy > 10 years: active surveillance (minimizes treatment toxicity).
Low risk with life expectancy < 10 years: observation (less intensive monitoring).
Intermediate/high risk localized: radiation therapy ± ADT, or radical prostatectomy.
Radiation + short-term ADT is used for intermediate risk; radiation + long-term ADT for high risk.
Dutasteride and pumpkin seed extract are NOT proven treatments for prostate cancer prevention.
Finasteride reduces risk of low-grade prostate cancer by ~25% but may be associated with slightly increased relative risk of high-grade disease — benefits and risks must be discussed with patients on finasteride for BPH.
ADT MECHANISM AND RULES:
GnRH agonists (leuprolide, goserelin, triptorelin, histrelin): cause initial testosterone FLARE (LH surge before suppression) — bicalutamide must be co-administered for several weeks to prevent flare symptoms (bone pain, urinary obstruction).
GnRH antagonists (degarelix, relugolix): NO testosterone flare — rapidly suppresses testosterone; preferred in patients with pre-existing cardiovascular disease (relugolix showed CV benefit over leuprolide in HERO trial), urinary obstruction, or spinal cord compression risk.
Relugolix is the oral GnRH antagonist — shorter half-life makes it ideal for intermittent ADT. ADT must be CONTINUED even after progression to CRPC. Hot flashes are an ACUTE side effect — not a long-term metabolic complication. Long-term ADT complications: osteoporosis, insulin resistance, cardiovascular disease, metabolic syndrome, sexual dysfunction.
METASTATIC HORMONE-SENSITIVE PROSTATE CANCER (mHSPC):
Backbone is ADT + intensification. All improve OS over ADT alone: ADT + abiraterone + prednisone (LATITUDE/STAMPEDE), ADT + enzalutamide, ADT + apalutamide, ADT + docetaxel (CHAARTED — especially high-volume disease). High-volume mHSPC or symptomatic disease: docetaxel-containing regimens preferred. Triplet options: docetaxel + darolutamide + ADT, docetaxel + abiraterone + ADT (ARASENS and PEACE-1 trials). Docetaxel + enzalutamide: NOT an approved combination in any setting. Lutetium-177 PSMA: NOT approved for mHSPC.
NON-METASTATIC CRPC (nmCRPC):
Rising PSA with castrate testosterone < 50 ng/dL but NO imaging evidence of metastases. Approved agents: darolutamide (ARAMIS trial), enzalutamide, apalutamide — all added to continued ADT. Abiraterone and docetaxel are indicated for METASTATIC settings only — not nmCRPC.
mCRPC TREATMENT SEQUENCE AND RULES:
First-line mCRPC (post-ADT):
abiraterone + prednisone or enzalutamide (or other AR inhibitors). Cross-resistance exists between abiraterone and enzalutamide (both target AR pathway) — sequencing one after the other shows diminished benefit; switching to chemotherapy (cabazitaxel) after one AR inhibitor is preferred (CARD trial).
Cabazitaxel: second-line after docetaxel — TROPIC trial showed OS benefit over mitoxantrone. Radium-223: ONLY for symptomatic bone-predominant mCRPC with NO visceral metastases. Do NOT combine radium-223 with abiraterone — ERA-223 trial showed increased fractures and deaths. Radium-223 is indicated for symptomatic disease only — do not use in asymptomatic patients.
PARP inhibitors: for BRCA1/2 or HRR gene mutations — olaparib (approved for any HRRm except PPP2R2A), rucaparib (BRCA1/2 only), talazoparib + enzalutamide (PALB2 and BRCA-mutated), niraparib + abiraterone (BRCA1/2). Talazoparib + enzalutamide: FDA approved for PALB2 mutation and BRCA mutations. Lutetium-177 PSMA: for PSMA-positive mCRPC that has progressed through a taxane AND a novel hormonal therapy (per VISION trial). Lower diarrhea risk compared to cabazitaxel (Thera-P trial). Sipuleucel-T: for asymptomatic or minimally symptomatic mCRPC, ECOG 0–1 — NOT for symptomatic disease. Mitoxantrone: NO overall survival benefit — palliative only; reserved for patients with no other treatment options.
AR INHIBITOR KEY DISTINCTIONS:
Abiraterone: inhibits CYP17 → requires prednisone (prevents mineralocorticoid excess and adrenal insufficiency). Key toxicities: hypokalemia (NOT hyperkalemia), hypertension, fluid retention, hepatotoxicity. Must be taken on an EMPTY STOMACH. Prednisone dose: 5 mg twice daily (NOT 20 mg). Seizures are NOT a side effect of abiraterone — they are associated with enzalutamide. Must perform cardiovascular workup before starting (hypertension, fluid retention risk).
Enzalutamide: strong CYP3A4 AND CYP2C9/2C19 inducer → decreases levels of warfarin, apixaban, rivaroxaban, tacrolimus. Key toxicities: fatigue, CNS effects, SEIZURES (contraindicated with seizure history). Apalutamide: key toxicities = rash and hypothyroidism (monitor TSH) + seizures. Darolutamide: LEAST CNS side effects, least drug interactions, limited BBB penetration — preferred in patients with CNS concerns or complex drug regimens.
CABAZITAXEL: G-CSF primary prophylaxis required in high-risk patients (elderly/frail). Myelosuppression is the dose-limiting toxicity.
BONE-MODIFYING AGENTS:
Denosumab 120 mg SQ every 4 weeks: SUPERIOR to zoledronic acid in delaying first skeletal-related event (SRE); does NOT require renal dose adjustment; higher risk of hypocalcemia — must supplement with calcium + vitamin D. Denosumab 60 mg SQ every 6 months: for osteoporosis prevention (ADT-induced) — NOT for SRE prevention. Zoledronic acid: requires renal dose adjustment; lower hypocalcemia risk compared to denosumab. Both agents require dental exam before starting and calcium + vitamin D supplementation. Alendronate: for osteoporosis prevention — NOT for SRE prevention in bone metastases.
SPECIAL SITUATIONS:
Neuroendocrine differentiation after long-term ADT: platinum-based chemotherapy (docetaxel + carboplatin) preferred — AR-targeted therapies are not effective. Visceral metastases: radium-223 and sipuleucel-T are contraindicated — chemotherapy or AR inhibitors required. PSA-only rise without radiographic/clinical progression: do NOT change therapy — continue current treatment and monitor (PSA rise alone is NOT sufficient to change treatment). Degarelix preferred acutely in symptomatic patients (spinal cord compression, urinary obstruction) because no testosterone flare.
PRACTICE QUESTIONS — PROSTATE CANCER
DR is a 71-year-old male with chronic kidney disease requiring dialysis. PSA = 9 ng/mL with abnormal DRE. Biopsy reveals low-risk prostate adenocarcinoma. 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
Explanation: DR has low-risk prostate cancer with a life expectancy < 10 years — observation (watchful waiting) is most appropriate. Observation is distinguished from active surveillance: observation is appropriate for men with shorter life expectancy (< 10 years) or significant comorbidities where treatment would not improve survival. Active surveillance (option A) is preferred for younger men with longer life expectancy who may eventually need treatment based on disease progression. Dutasteride (option B) has not been shown beneficial for treatment of prostate cancer. Radiation + short-term ADT (option C) is not indicated for low-risk disease.
[/expand]DR is a 40-year-old male with a past medical history of seasonal allergies. PSA = 9 ng/mL with abnormal DRE. Biopsy reveals very low-risk prostate adenocarcinoma. He prefers to minimize adverse effects. What is the most appropriate treatment option?
A. Active surveillance
B. Radical prostatectomy + short-term ADT
C. Radiation therapy + short-term ADT
D. Observation
Explanation: DR has very low-risk prostate cancer with a life expectancy > 20 years (age 40). Active surveillance is the preferred management — it monitors the cancer closely without immediate treatment, minimizing toxicity while preserving quality of life. This is the guideline-preferred approach for very low-risk disease with long life expectancy. Observation (option D) is less intensive and more appropriate for short life expectancy — not for a 40-year-old. Radical prostatectomy + ADT (option B) and radiation + ADT (option C) are appropriate for higher-risk disease — overtreatment for very low-risk disease in a young man.
[/expand]AC is a 65-year-old male with poorly controlled type 2 diabetes. PSA = 33 ng/dL, abnormal DRE, T2b adenocarcinoma, and bone metastases to ribs. No other distant metastases. In addition to starting ADT, which is the most appropriate treatment option?
A. Abiraterone + prednisone
B. Sipuleucel-T
C. Cabazitaxel + prednisone
D. Enzalutamide
Explanation: AC has newly diagnosed metastatic hormone-sensitive (castrate-naive) prostate cancer — ADT intensification is required. Both abiraterone and enzalutamide are recommended options. However, this patient has poorly controlled diabetes — abiraterone requires co-administration with prednisone (corticosteroid), which worsens glycemic control. Enzalutamide is the preferred option to avoid the negative effects of steroids on poorly controlled diabetes. Sipuleucel-T (option B) is not appropriate for hormone-sensitive disease — it is for asymptomatic/minimally symptomatic CRPC. Cabazitaxel (option C) is only indicated after docetaxel-containing regimens — not as initial treatment.
[/expand]RC is a 62-year-old on adjuvant leuprolide for high-risk prostate cancer post-EBRT. PSA has risen from 2.4 → 4.7 → 25 ng/mL. Testosterone < 20 ng/dL. CT scan shows NO metastatic disease. Which is the most appropriate change in RC's treatment?
A. Stop leuprolide, start docetaxel + prednisone
B. Stop leuprolide, start relugolix
C. Continue leuprolide, add darolutamide
D. Continue leuprolide, add abiraterone + prednisone
Explanation: RC has non-metastatic castration-resistant prostate cancer (nmCRPC) — rising PSA with castrate testosterone but NO metastases on imaging. For nmCRPC, darolutamide (ARAMIS trial), enzalutamide, or apalutamide added to continued ADT are the approved options. ADT must be CONTINUED — never stopped when progressing to CRPC. Relugolix (option B) is an alternative ADT but does not address the CRPC progression; switching ADT agents alone is insufficient. Docetaxel and abiraterone (options A and D) are indicated for METASTATIC disease — not nmCRPC.
[/expand]AB has mCRPC with progression on leuprolide → then ADT + enzalutamide for 2 years. He now has rising PSA, worsening back pain, progressive skeletal metastases, and a new liver lesion (visceral metastasis). ECOG 1. His biggest concern is getting his back pain under control quickly. In addition to continuing ADT, what is the most appropriate modification?
A. Stop enzalutamide, add mitoxantrone + prednisone
B. Continue enzalutamide, add abiraterone + prednisone
C. Stop enzalutamide, add docetaxel + prednisone
D. Stop enzalutamide, add abiraterone + prednisone
Explanation: AB has progressed on enzalutamide and now has visceral (liver) metastases and symptomatic disease requiring rapid response. Key decisions: (1) Adding abiraterone to enzalutamide (option B) is NOT recommended — no survival benefit demonstrated. (2) For visceral metastases with symptomatic disease where rapid response is needed, docetaxel provides faster tumor reduction than abiraterone. (3) Cross-resistance between enzalutamide and abiraterone (both AR pathway agents) further reduces the value of switching to abiraterone. (4) Mitoxantrone (option A) has no OS benefit and is reserved as a last resort when no other options are available.
[/expand]PC has mCRPC with no targetable mutations. Prior therapies include apalutamide, abiraterone + prednisone, and docetaxel + prednisone × 10 cycles. He has extensive bone metastases, NO visceral disease, requires morphine for bone pain, ECOG 1, and significant fatigue and neuropathy from docetaxel. He wishes to avoid highly toxic therapy. In addition to continuing ADT, which is the most appropriate treatment option?
A. Cabazitaxel
B. Radium-223
C. Enzalutamide
D. Pembrolizumab
Explanation: PC has symptomatic bone-predominant mCRPC with NO visceral metastases — the precise indication for radium-223. He has received multiple prior therapies (2 AR inhibitors + docetaxel) and desires a less toxic option. Radium-223 targets bone metastases with an alpha-emitter, improves OS, reduces SREs, and has a favorable toxicity profile (myelosuppression being the primary concern, not neuropathy/fatigue). Cabazitaxel (option A) is an option but carries significant toxicity (neutropenia, diarrhea, neuropathy) — not aligned with PC's preference for less toxic therapy. Enzalutamide (option C) is not appropriate after progression on apalutamide — cross-resistance within the same class. Pembrolizumab (option D) is only for dMMR/MSI-H disease — no such mutation is indicated here.
[/expand]LL has mCRPC with new skeletal metastases. His oncologist is adding enzalutamide to his ADT. What supportive care medication is most appropriate to initiate in LL?
A. Denosumab 120 mg every 4 weeks
B. Calcium + vitamin D 500 mg–400 IU twice daily
C. Alendronate 70 mg every 4 weeks
D. Denosumab 120 mg every 4 weeks AND calcium + vitamin D 500 mg–400 IU twice daily
Explanation: LL has mCRPC with bone metastases — denosumab 120 mg SQ every 4 weeks is the preferred bone-modifying agent for prevention of skeletal-related events. Crucially, calcium + vitamin D supplementation MUST be added to prevent denosumab-induced hypocalcemia — this is a mandatory co-administration. Option A alone is incomplete without supplementation. Option B alone is insufficient for SRE prevention in active bone metastases. Alendronate (option C) is for osteoporosis prevention (ADT-induced bone loss) — it is NOT indicated for prevention of SREs in patients with bone metastases.
[/expand]LB is a 60-year-old male with a history of MI 3 months ago and biochemical recurrence after EBRT. No metastatic disease. He is hesitant to pursue ADT due to fear of adverse cardiac effects. Which option 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
Explanation: LB has biochemical recurrence (castrate-sensitive) with a short PSA doubling time — ADT is an appropriate treatment choice. Given his recent MI and cardiac concerns: relugolix (oral GnRH antagonist) is preferred over leuprolide based on the HERO trial, which showed relugolix had significantly lower rates of major adverse cardiovascular events compared to leuprolide. GnRH antagonists do not cause testosterone flare. Relugolix's short half-life makes it ideal for intermittent ADT (can be stopped and restarted easily). Continuous leuprolide (option A) carries unnecessary cardiac risk. Intermittent leuprolide (option C) still uses a GnRH agonist — carries cardiac risk and flare risk.
[/expand]AC is a 65-year-old male with hypertension (controlled with amlodipine). Prostate cancer is metastatic to the liver and spine. ECOG 0. PSA = 87 ng/dL. In addition to starting ADT, which is the most appropriate treatment option?
A. Abiraterone + prednisone
B. Lutetium-177 PSMA
C. Docetaxel + darolutamide
D. Docetaxel + enzalutamide
Explanation: AC has high-volume metastatic hormone-sensitive prostate cancer (mHSPC) with symptomatic disease (back pain). For high-volume mHSPC, docetaxel-containing triplet regimens are preferred. Docetaxel + darolutamide + ADT is an approved combination (ARASENS trial). Abiraterone + prednisone (option A) is an option for lower-volume or asymptomatic disease, but AC has high-volume disease and symptoms — docetaxel provides faster relief. Lutetium-177 PSMA (option B) is NOT approved for mHSPC — it is for mCRPC that has progressed through a taxane and novel hormonal therapy. Docetaxel + enzalutamide (option D) is NOT an approved combination in any prostate cancer setting.
[/expand]AB has mCRPC previously treated with ADT + docetaxel × 6 cycles then ADT + abiraterone + prednisone for 2 years. He now has progressive skeletal metastases and new small liver metastases, rising PSA, and increased back pain. ECOG 0. What is the most appropriate next line of treatment for AB?
A. Enzalutamide
B. Radium-223
C. Mitoxantrone + prednisone
D. Cabazitaxel + prednisone
Explanation: AB has progressed on docetaxel and abiraterone (both prior lines) and now has visceral (liver) metastases. The CARD trial compared cabazitaxel versus an alternate novel hormonal therapy (enzalutamide or abiraterone) in patients who had previously received docetaxel and one AR-targeted therapy — cabazitaxel showed superior OS. Enzalutamide (option A) would be an AR pathway agent sequenced after abiraterone — cross-resistance makes this less effective, and CARD trial supports cabazitaxel over this approach. Radium-223 (option B) is contraindicated with visceral (liver) metastases. Mitoxantrone (option C) has NO OS benefit and is the last resort.
[/expand]GC has mCRPC previously treated with leuprolide + apalutamide then docetaxel. Most recent PSMA PET scan shows progressing disease in lungs and bones. In addition to continuing leuprolide, which is the most appropriate next line of treatment?
A. Enzalutamide
B. Radium-223
C. Mitoxantrone + prednisone
D. Lutetium-177 PSMA
Explanation: GC meets criteria for lutetium-177 PSMA: PSMA-positive disease that has progressed through a taxane (docetaxel) AND a novel hormonal therapy (apalutamide). Per the VISION trial criteria, lutetium-177 PSMA-617 is the appropriate next step. Enzalutamide (option A) is NOT appropriate after progression on apalutamide — same AR-inhibitor class, cross-resistance expected. Radium-223 (option B) is NOT appropriate when there is visceral/lung disease — it is for bone-only disease. Mitoxantrone (option C) provides palliative benefit only with no OS advantage.
[/expand]GC (same patient with mCRPC, irritable bowel disease, progressed on apalutamide and docetaxel, PSMA-positive disease in lungs and bones). He is a truck driver and prefers a treatment with the least risk of diarrhea. What is the most appropriate next treatment?
A. Enzalutamide
B. Radium-223
C. Cabazitaxel
D. Lutetium-177 PSMA
Explanation: Both lutetium-177 PSMA and cabazitaxel are appropriate options here, but GC has irritable bowel disease and a professional need to minimize diarrhea. The Thera-P trial showed lutetium-177 PSMA had lower incidence of diarrhea compared to cabazitaxel, making it the preferred choice for this specific patient. Additionally, enzalutamide (option A) is contraindicated after apalutamide progression (same class). Radium-223 (option B) is contraindicated with visceral (lung) metastases.
[/expand]RC is a 65-year-old male with mCRPC and BRCA1 mutation. Prior therapies: leuprolide + abiraterone + prednisone, leuprolide + radium-223, and leuprolide + docetaxel + prednisone × 3 cycles. Worsening bone and liver metastases. ECOG 1. In addition to continuing ADT, which is the most appropriate treatment option?
A. Olaparib
B. Sipuleucel-T
C. Mitoxantrone
D. Pembrolizumab
Explanation: RC has a BRCA1 mutation (HRR gene mutation) — this makes him an excellent candidate for a PARP inhibitor. Olaparib is FDA-approved for mCRPC with any HRR mutation (except PPP2R2A) per NCCN guidelines, supported by the PROfound trial showing PFS and OS benefit. Sipuleucel-T (option B) is NOT indicated in this advanced, symptomatic, visceral-metastatic setting. Mitoxantrone (option C) has NO OS benefit and is the last resort. Pembrolizumab (option D) is only for dMMR/MSI-H tumors — BRCA mutation does not indicate pembrolizumab.
[/expand]RC is a 65-year-old male with mCRPC and PALB2 mutation. Prior therapy: leuprolide + docetaxel × 6 cycles, then maintained on leuprolide. Now has rising PSA and new skeletal metastases. ECOG 1. Which of the following is the most appropriate FDA-approved treatment option?
A. Olaparib + abiraterone
B. Rucaparib
C. Niraparib + abiraterone
D. Talazoparib + enzalutamide
Explanation: RC has a PALB2 mutation. Among the PARP inhibitor options listed: talazoparib + enzalutamide is the ONLY FDA-approved combination for PALB2 mutations (in addition to BRCA mutations). Rucaparib (option B) is FDA-approved for BRCA1/2 mutations only — NOT PALB2. Olaparib + abiraterone (option A) and niraparib + abiraterone (option C) are FDA-approved combinations but specifically for BRCA1/2 mutations — not currently approved for PALB2.
[/expand]RB is a 65-year-old male with hypertension (controlled with amlodipine) and prostate cancer metastatic to the liver and spine with a BRCA2 mutation. ECOG 0, PSA = 87 ng/dL. In addition to starting ADT, which is the most appropriate treatment option?
A. Enzalutamide
B. Abiraterone + olaparib
C. Docetaxel alone
D. Docetaxel + darolutamide
Explanation: RB has high-volume mHSPC with symptomatic disease. Despite the BRCA2 mutation, the treatment remains within the mHSPC framework — PARP inhibitors are not approved for mHSPC (they are for mCRPC). Docetaxel + darolutamide is the appropriate high-volume mHSPC triplet regimen. Enzalutamide alone (option A) is less preferred for high-volume, symptomatic disease where docetaxel-based therapy provides faster clinical benefit. Abiraterone + olaparib (option B) is not a recommended mHSPC regimen. Docetaxel alone (option C) is inferior to docetaxel + a novel hormonal therapy combination in mHSPC.
[/expand]Which of the following patients is the most appropriate candidate to start prostate cancer screening?
A. 35-year-old whose father was diagnosed at age 55
B. 45-year-old whose father was diagnosed at age 70
C. 42-year-old whose father was diagnosed at age 57
D. 40-year-old whose father was diagnosed at age 67
Explanation: Guidelines recommend starting prostate cancer screening at age 40–45 for high-risk men, primarily defined as having a first-degree relative diagnosed at an early age (before age 65). A father diagnosed at age 57 is the strongest hereditary risk indicator — early diagnosis suggests a hereditary component, making his 42-year-old son the best screening candidate. Option A (35 years old) is too young even for high-risk screening. Options B and D have fathers diagnosed at ages 70 and 67 — these are late-onset diagnoses suggesting less hereditary influence.
[/expand]Which of the following is correct regarding PSA measurement?
A. All prostate cancer cases have PSA > 10
B. Measuring PSA velocity is useful for a patient with PSA = 20
C. Normal PSA ≤ 4 ng/dL but prostate cancer may occur at PSA 2.5–4 ng/dL
D. PSA level alone is enough to diagnose prostate cancer
Explanation: PSA ≤ 4 ng/mL was historically considered normal, but prostate cancer is well-established to occur within the 2.5–4 ng/mL range — PSA alone cannot exclude cancer. Option A is false — many prostate cancers are diagnosed with PSA < 10. Option B is false — PSA velocity is most useful in LOWER PSA ranges (< 10) to aid biopsy decisions, not when PSA is already very elevated. Option D is false — PSA is a SCREENING tool, not a diagnostic test; tissue biopsy is required for diagnosis.
[/expand]Which of the following is correct regarding prostate cancer prevention?
A. Pumpkin seed extract is good for prevention
B. It is recommended for patients > 65 years to take finasteride for prevention
C. In men taking finasteride for BPH, the potential benefits and risks should be discussed
D. Dutasteride use is associated with low-grade prostate cancer
Explanation: Finasteride (and dutasteride) reduce the overall risk of prostate cancer diagnosis by ~25% but are associated with a slightly increased relative risk of HIGH-GRADE disease (Gleason 8–10) — therefore a thorough discussion of both benefits and risks is mandatory for patients already taking these drugs. Option A is not supported by robust clinical evidence. Option B is false — these medications are not recommended solely for prevention, especially in older men. Option D is misleading — dutasteride reduces detection of LOW-GRADE cancer rather than causing it; the concern is increased relative risk of high-grade disease when low-grade cancer is suppressed.
[/expand]Which grade group is represented by Gleason pattern 3+5?
A. 1
B. 3
C. 4
D. 5
Explanation:
Gleason 3+5 = Gleason score 8 = Grade Group 4.
The Grade Group to Gleason score mapping:
Grade Group 1 = Gleason ≤ 6;
Grade Group 2 = Gleason 3+4=7;
Grade Group 3 = Gleason 4+3=7;
Grade Group 4 = Gleason 8 (includes 3+5, 5+3, and 4+4);
Grade Group 5 = Gleason 9–10.
Which of the following is NOT considered a long-term side effect of LHRH agonists?
A. Osteoporosis
B. Insulin resistance
C. Hot flushes
D. Cardiovascular diseases
Explanation: Hot flushes (hot flashes) are an ACUTE side effect of the low-testosterone state produced by LHRH agonists — they are not a long-term metabolic complication. Long-term complications of ADT are the metabolic consequences of chronic testosterone suppression: osteoporosis (bone mineral density loss → fracture risk), insulin resistance (can lead to type 2 diabetes), and cardiovascular disease (increased risk of myocardial infarction, stroke, metabolic syndrome).
[/expand]A 57-year-old man presents with bone pain, constipation, multiple lytic lesions (ribs, vertebrae, humerus), PSA = 180 ng/mL, enlarged prostate causing complete rectal obstruction by external compression. Otherwise healthy. No spinal cord compression. Which is the preferred next step?
A. Biopsy of a malignant bone lesion
B. Radium-223
C. Leuprolide
D. Abiraterone + prednisone
E. Degarelix
Explanation: This patient has newly diagnosed metastatic prostate cancer presenting as a urological emergency — complete rectal obstruction requiring rapid testosterone suppression. Leuprolide (option C) and other GnRH agonists cause an initial TESTOSTERONE FLARE that can worsen obstruction, bone pain, and risk spinal cord compression — dangerous in this setting. Degarelix is a GnRH antagonist that suppresses testosterone RAPIDLY without any flare — it is the preferred agent for acute symptomatic presentations. Bone biopsy (option A) is unnecessary with such a classic presentation and PSA = 180. Radium-223 (option B) is for symptomatic bone-only mCRPC — not for newly diagnosed mHSPC. Abiraterone (option D) is for intensification AFTER ADT is established — not the immediate first step.
[/expand]KM is a 70-year-old male with high-risk prostate cancer post-EBRT + BT. He now has rising PSA (20 → 40 ng/mL over 6 months) and liver metastases. He takes levetiracetam 500 mg BID for seizures. In addition to starting ADT, what is the most appropriate treatment?
A. Abiraterone + prednisone
B. Enzalutamide
C. Docetaxel + darolutamide
D. Continue EBRT + BT
Explanation: KM has mCRPC with liver metastases (visceral disease). The first-line options for mCRPC include abiraterone or enzalutamide. However, KM takes levetiracetam for seizures — enzalutamide (option B) is CONTRAINDICATED in patients with a history of seizures due to its seizure risk. Therefore, abiraterone + prednisone is the safe and appropriate choice. Docetaxel + darolutamide (option C) is a triplet regimen approved for mHSPC — not the standard first-line choice for mCRPC specifically. Continuing radiation (option D) is ineffective for widespread visceral metastatic disease.
[/expand]A patient is starting abiraterone. What is the most important counseling point?
A. Take 4 tablets (250 mg each) after lunch
B. Abiraterone is taken with prednisone 20 mg twice daily
C. Patient should complete cardiovascular workup and tests prior to therapy
D. Side effects may include seizures and osteoporosis
Explanation: Abiraterone inhibits androgen synthesis and causes secondary mineralocorticoid excess → hypertension, hypokalemia, and fluid retention — all cardiovascular risks. Baseline cardiovascular assessment (BP, electrolytes, ECG) is mandatory before starting therapy. Option A is incorrect — abiraterone must be taken on an EMPTY STOMACH (at least 1 hour before or 2 hours after eating) to ensure proper absorption. Option B is incorrect — the co-administered steroid is prednisone 5 mg TWICE DAILY (not 20 mg); 20 mg would cause significant glucocorticoid excess and toxicity. Option D is incorrect — seizures are a toxicity of ENZALUTAMIDE, not abiraterone. Osteoporosis is a long-term ADT effect, not specifically caused by abiraterone itself.
[/expand]Which genes are involved in prostate cancer? (Choose 4)
A. BRCA1
B. ALK
C. MEK
D. MYC
E. FOXA1
F. EGFR
G. SRD5A1
Explanation:
- BRCA1 (and BRCA2) DNA repair gene mutations significantly increase the risk of aggressive prostate cancer.
- MYC is a potent oncogene frequently amplified in prostate cancer, driving tumor growth and progression.
- FOXA1 is a pioneer transcription factor often mutated in prostate cancer, playing a key role in regulating androgen receptor signaling.
- SRD5A1 (and SRD5A2) encode 5-alpha-reductase enzymes that convert testosterone to the more potent dihydrotestosterone (DHT) — the primary driver of prostate cancer growth (these are the targets of finasteride and dutasteride).
- ALK, MEK, and EGFR are more commonly associated with other cancers (NSCLC primarily).
A patient progressed on ADT + enzalutamide for mCRPC. BRCA2 mutation confirmed. He has been treated with 3 prior lines of therapy including docetaxel. He has a homologous recombination repair (HRR) mutation (ATM mutation, not BRCA). He has a seizure history and continued seizures despite antiepileptic therapy. What is the most appropriate treatment option?
A. Olaparib
B. Sipuleucel-T
C. Mitoxantrone
D. Rucaparib
Explanation: This patient has an HRR mutation (ATM mutation) and has progressed on AR-targeted therapy and docetaxel — he is a candidate for a PARP inhibitor. Olaparib is FDA-approved and NCCN-recommended for any HRR mutation (except PPP2R2A) in mCRPC, supported by the PROfound trial which included ATM mutation patients in cohort A showing PFS and OS benefit. Enzalutamide is inappropriate given the seizure history. Sipuleucel-T (option B) is not indicated in this symptomatic, heavily treated setting. Mitoxantrone (option C) has no OS benefit. Rucaparib (option D) is only approved for BRCA1/2 mutations — NOT ATM or other HRR mutations.
[/expand]A patient with mCRPC on enzalutamide shows a rising PSA but CT scans show stable bone metastases and he is asymptomatic and feeling well. What should be the next step?
A. Switch to abiraterone
B. Switch to docetaxel
C. Continue enzalutamide and monitor
D. Add sipuleucel-T
Explanation: PSA rise alone WITHOUT radiographic or clinical progression is NOT an indication to change therapy in mCRPC. This is a high-yield exam point. Therapy should be continued until there is confirmed radiographic progression (new lesions on bone scan or CT) OR clinical progression (new or worsening symptoms). Switching to abiraterone (option A) after enzalutamide has cross-resistance concerns and is premature with stable imaging. Switching to docetaxel (option B) is appropriate at confirmed progression — not for PSA rise alone. Adding sipuleucel-T (option D) is not appropriate in this late-line setting.
[/expand]