2022 Canadian Urological Association (CUA)- Canadian Uro Oncology Group (CUOG) guideline: Management of castration-resistant prostate cancer (CRPC)

Question 1

What is the definition of castration-resistant prostate cancer (CRPC)?

A. A continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases despite castrate levels of testosterone
B. A continuous rise in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases despite high levels of testosterone
C. A reduction in serum prostate-specific antigen (PSA) levels, the progression of pre-existing disease, and/or the appearance of new metastases despite castrate levels of testosterone
D. A continuous rise in serum prostate-specific antigen (PSA) levels, the reduction of pre-existing disease, and/or the disappearance of new metastases despite castrate levels of testosterone

Answer 1

A
Explanation: CRPC is defined by disease progression (rising PSA levels, progression of pre-existing disease, appearance of new metastases) despite castrate levels of testosterone.

Question 2

What factors go beyond PSA levels to associate with the prognosis of CRPC?

A. Performance status, presence of visceral metastases, presence of bone pain, extent of disease on bone scan, serum lactate dehydrogenase and alkaline phosphatase levels
B. Performance status, absence of visceral metastases, presence of bone pain, extent of disease on bone scan, serum lactate dehydrogenase and alkaline phosphatase levels
C. Performance status, presence of visceral metastases, absence of bone pain, extent of disease on bone scan, serum lactate dehydrogenase and alkaline phosphatase levels
D. Performance status, presence of visceral metastases, presence of bone pain, absence of disease on bone scan, serum lactate dehydrogenase and alkaline phosphatase levels

Answer 2

A
Explanation: The prognosis of CRPC is associated with factors such as performance status, presence of visceral metastases, presence of bone pain, extent of disease on bone scan, and serum lactate dehydrogenase and alkaline phosphatase levels. These factors go beyond just the PSA levels.

Question 3

Which of the following is NOT a common morbidity associated with bone metastases in men with CRPC?

A. Pain
B. Pathological fractures
C. Spinal cord compression
D. Bone marrow proliferation

Answer 3

D
Explanation: Bone metastases in men with CRPC can produce significant morbidity, including pain, pathological fractures, spinal cord compression, and bone marrow failure. Note the condition is bone marrow failure, not proliferation.

Question 4

What is the general recommendation regarding the continuation of ADT in patients with CRPC?

A. ADT should be discontinued as it is ineffective in CRPC
B. ADT should be continued for the remainder of a patient’s life
C. ADT should be replaced with first-generation androgen receptor antagonists
D. ADT should be continued only until first-generation androgen receptor antagonists are introduced

Answer 4

B
Explanation: Because the androgen receptor remains active in most patients who have developed castration-resistant disease, it is recommended that ADT be continued for the remainder of a patient’s life.

Question 5

How often should imaging be performed for patients with a rapid PSADT (<10 months) or elevated PSA levels (>20)?

A. Every 1-2 months
B. Every 3-6 months
C. Every 6-12 months
D. Once a year

Answer 5

B
Explanation: Patients with a rapid PSADT (<10 months) or elevated PSA levels (>20) are at high risk for developing metastases earlier. Imaging in these patients should be performed every 3–6 months.

Question 6

What should be done for patients who have undergone total androgen blockade (TAB) and develop CRPC?

A. The anti-androgen (AA) should be discontinued to test for an anti-androgen withdrawal response (AAWD)
B. The anti-androgen (AA) should be continued and first-generation androgen receptor antagonists should be added
C. The anti-androgen (AA) should be replaced with a second-generation androgen receptor antagonist
D. The anti-androgen (AA) should be replaced with a different type of AA

Answer 6

A
Explanation: For patients who have undergone total androgen blockade (TAB), the anti-androgen (AA) should be discontinued to test for an anti-androgen withdrawal response (AAWD).

Question 7

What is the recommendation for men with high-risk nmCRPC (PSADT of less than 10 months and estimated life expectancy of greater than five years)?

A. These patients should be offered apalutamide, enzalutamide, or darolutamide
B. These patients should be offered only apalutamide
C. These patients should be offered only enzalutamide
D. These patients should be offered only darolutamide

Answer 7

A
Explanation: Men with high-risk nmCRPC, defined as a PSA doubling time (PSADT) of less than 10 months, with an estimated life expectancy of greater than five years should be offered apalutamide, enzalutamide, or darolutamide.

Question 8

What is the impact of apalutamide on median Metastases-Free Survival (MFS) in patients with nmCRPC at high risk for progression?

A. The median MFS was 40.5 months with apalutamide and 16.2 months with placebo
B. The median MFS was 16.2 months with apalutamide and 40.5 months with placebo
C. The median MFS was 30 months with apalutamide and 20 months with placebo
D. The median MFS was 20 months with apalutamide and 30 months with placebo

Answer 8

A
Explanation: The median MFS was 40.5 months with apalutamide and 16.2 months with placebo (hazard ratio [HR] for metastasis or death 0.28; 95% confidence interval [CI] 0.23–0.35; p<0.001).

Question 9

What were the results of the final analysis of the impact of darolutamide on survival rate in patients with nmCRPC at high risk for progression?

A. After a median followup time of 29 months, the median survival rate at three years was 83% in the darolutamide cohort and 77% in the placebo group
B. After a median followup time of 29 months, the median survival rate at three years was 77% in the darolutamide cohort and 83% in the placebo group
C. After a median followup time of 29 months, the median survival rate at three years was 70% in the darolutamide cohort and 80% in the placebo group
D. After a median followup time of 29 months, the median survival rate at three years was 80% in the darolutamide cohort and 70% in the placebo group

Answer 9

A
Explanation: After a median followup time of 29 months, the median survival rate at three years was 83% in the darolutamide cohort and 77% in the placebo group (HR 0.69; 95% CI 0.53–0.88; p=0.003).

Question 10

What is the recommendation for maintaining ADT in the nmCRPC state?

A. ADT should be maintained and first-generation androgen receptor antagonists should be discontinued if patients are receiving these agents
B. ADT should be discontinued and first-generation androgen receptor antagonists should be continued if patients are receiving these agents
C. Both ADT and first-generation androgen receptor antagonists should be maintained
D. Both ADT and first-generation androgen receptor antagonists should be discontinued

Answer 10

A
Explanation: ADT should be maintained in the nmCRPC state. First-generation androgen receptor antagonists (i.e., bicalutamide, flutamide, etc.) should be discontinued if patients are receiving these agents.

Question 11

How often should patients who are untreated for nmCRPC be followed with regular imaging?

A. Every 1-3 months
B. Every 3-6 months
C. Every 6-12 months
D. Once a year

Answer 11

C
Explanation: Patients who are untreated for nmCRPC should be followed with regular imaging every 6–12 months depending on PSADT.

Question 12

What is the recommendation for men with high-risk nmCRPC who are felt to be unsuitable or refuse approved therapies?

A. Observation or use of first-generation androgen receptor antagonists may be attempted
B. These patients should be offered apalutamide, enzalutamide, or darolutamide regardless of their suitability or willingness
C. These patients should be offered only apalutamide
D. These patients should be offered only enzalutamide

Answer 12

A
Explanation: In men with high-risk nmCRPC who are felt to be unsuitable or refuse approved therapies, observation or use of first-generation androgen receptor antagonists may be attempted.

Question 13

In the chemo-naive setting, is abiraterone acetate recommended for asymptomatic or minimally symptomatic mCRPC?
a) Yes, it is recommended as a first-line therapy
b) No, it is not recommended
c) It is only recommended for symptomatic mCRPC
d) The recommendation depends on the individual patient’s condition

Answer 13

a) Yes, it is recommended as a first-line therapy
Explanation: Abiraterone acetate 1000 mg/day plus prednisone 5 mg twice daily is recommended for first-line therapy for asymptomatic or minimally symptomatic mCRPC.

Question 14

What is the role of enzalutamide in the chemo-naive setting for asymptomatic or minimally symptomatic mCRPC?
a) It is not recommended
b) It is recommended as a first-line therapy
c) It is only recommended after other therapies have failed
d) It is recommended as a second-line therapy after abiraterone acetate

Answer 14

b) It is recommended as a first-line therapy
Explanation: Enzalutamide 160 mg per day is recommended as first-line therapy for asymptomatic or minimally symptomatic mCRPC.

Question 15

In the post-docetaxel setting, how is abiraterone acetate used?
a) It is not recommended
b) It is recommended in patients progressing on or after docetaxel-based chemotherapy
c) It is recommended as a first-line therapy
d) It is recommended only for patients who have not responded to enzalutamide

Answer 15

b) It is recommended in patients progressing on or after docetaxel-based chemotherapy
Explanation: Abiraterone acetate 1000 mg per day plus prednisone 5 mg twice daily is recommended in patients progressing on or after docetaxel-based chemotherapy.

Question 16

What is the recommended first-line systemic chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC)?

Answer 16

Docetaxel 75 mg/m2 intravenous (IV) every three weeks with 5 mg oral prednisone twice daily.

Question 17

What were the three treatment arms in the TAX-327 study?

Answer 17

1) Docetaxel 75 mg/m2 IV every three weeks; 2) Docetaxel 30 mg/m2 weekly for five of six weeks; 3) Control therapy with mitoxantrone.

Question 18

What survival advantage did docetaxel (every three weeks) show compared to mitoxantrone-prednisone in the TAX-327 study?

Answer 18

Median survival was 18.9 months with docetaxel compared to 16.5 months with mitoxantrone-prednisone.

Question 19

Median survival was 18.9 months with docetaxel compared to 16.5 months with mitoxantrone-prednisone.

Answer 19

Quality of life response was defined as a sustained 16-point or greater improvement from baseline on two consecutive measurements. It was higher with docetaxel given every three weeks (22% vs. 13%) or weekly (23% vs. 13%) compared with mitoxantrone.

Question 20

What is recommended for patients who do not respond to first-line ADT or who progress clinically or radiologically without significant PSA elevations?

Answer 20

These patients may have neuroendocrine differentiation. A biopsy of accessible lesions should be considered. If confirmed, these patients should be treated with combination chemotherapy, such as cisplatin/etoposide or carboplatin/etoposide.

Question 21

What is the recommended second-line systemic chemotherapy for mCRPC patients progressing on or following docetaxel?

Answer 21

Cabazitaxel.

Question 22

What were the results of a phase 3 study comparing cabazitaxel to mitoxantrone in patients previously treated with docetaxel?

Answer 22

The study showed a statistically significant survival advantage for the cabazitaxel group, with a median survival of 15.1 months compared with 12.7 months in the mitoxantrone group.

Question 23

What can be considered for patients who have had a good response to first-line docetaxel?

Answer 23

Re-treatment with docetaxel can be considered.

Question 24

When is Radium-223 recommended for patients with mCRPC?

Answer 24

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 25

What is the mechanism of action of Radium-223 and its impact on patient survival?

Answer 25

Radium-223, an intravenous alpha-emitting agent, mimics calcium and preferentially targets bone metastases. It improves overall survival by 3.6 months and delays symptomatic skeletal-related events by 5.8 months.

Question 26

Why can’t PSA measurements be used to evaluate the effectiveness of Radium-223?

Answer 26

PSA measurements are not a good indicator of the effectiveness of Radium-223, given the drug’s mechanism of action. Alkaline phosphatase appears to be a better marker of activity.

Question 27

Which agent should always be used when using Radium-223 and why?

Answer 27

A bone-supportive agent (denosumab or zoledronic acid) should always be used when using Radium-223 to prevent an increased risk of fractures.

Question 28

When is 177Lu-PSMA-617 recommended for use in patients with mCRPC?

Answer 28

177Lu-PSMA-617 is recommended for patients with mCRPC and PSMA-expressing metastatic lesions who have progressed on at least one previous taxane chemotherapy and an androgen receptor-axis-targeted therapy (ARAT).

Question 29

177Lu-PSMA-617 is recommended for patients with mCRPC and PSMA-expressing metastatic lesions who have progressed on at least one previous taxane chemotherapy and an androgen receptor-axis-targeted therapy (ARAT).

Question 30

What are the benefits of 177Lu-PSMA-617 over cabazitaxel, according to the TheraP study?

Answer 30

The TheraP study showed that a significantly higher proportion of patients (66% vs. 37%) in the Lu-PSMA-617 arm had at least a 50% reduction in PSA from baseline. Grade 3–4 adverse events occurred less frequently in the 177Lu-PSMA-617 treatment group (33% vs. 53% in the cabazitaxel group).

Question 31

When is Radium-223 recommended for patients with mCRPC?

Answer 31

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 32

What were the clinical benefits of 177Lu vipivotide tetraxetan + SoC over SoC alone, according to the VISION trial?

Answer 32

The VISION trial demonstrated that 177Lu vipivotide tetraxetan + SoC prolonged median overall survival by 4 months, reduced risk of death by 38%, prolonged radiographic progression-free survival by 5.3 months, reduced risk of disease progression by 60%, and prolonged median time to first symptomatic skeletal event (SSE) or death by 4.7 months.

Question 33

What adverse events were noted in the Lu-PSMA-617 arm of the VISION trial?

Answer 33

Myelosuppression was noted in 47.4% (grade 3–5 in 23.4%) of patients in the Lu-PSMA-617 arm. Additional concerning adverse events included fatigue, xerostomia due to expression of PSMA in salivary glands, and nausea-vomiting.

Question 34

What is the recommended dosage of olaparib for patients with metastatic castration-resistant prostate cancer (mCPRC) and HRR mutation who have progressed on a previous androgen receptor-axis targeted therapy (ARAT)?

Answer 34

The recommended dosage of olaparib for such patients is 300 mg twice daily.

Question 35

Approximately what percentage of prostate cancers from patients with metastatic disease carry HRR gene mutations?

Answer 35

HRR gene mutations occur in approximately 20–30% of prostate cancers from patients with metastatic disease.

Question 36

What is the most commonly altered gene in prostate cancers with HRR mutations?

Answer 36

The most commonly altered gene is BRCA2.

Question 37

What renders a cancer susceptible to poly (ADP-ribose) polymerase (PARP) inhibition in a form of synthetic lethality?

Answer 37

Defective homologous recombination repair (HRR) renders a cancer susceptible to PARP inhibition.

Question 38

What were the radiographic progression-free survival (PFS) results for patients with BRCA1/2 or ATM mutations in the PROfound trial?

Answer 38

The radiographic PFS was significantly improved in the olaparib arm, with results favoring olaparib (7.39 months) versus the physician’s choice of enzalutamide/abiraterone (3.44 months), with a hazard ratio (HR) of 0.34.

Question 39

The radiographic PFS was significantly improved in the olaparib arm, with results favoring olaparib (7.39 months) versus the physician’s choice of enzalutamide/abiraterone (3.44 months), with a hazard ratio (HR) of 0.34.

Answer 39

The overall survival was significantly improved in the olaparib arm, with a median OS of 19.1 months versus 14.7 months in the physician’s choice arm. The hazard ratio was 0.69.

Question 40

What were the common adverse events reported in the olaparib arm of the PROfound study?

Answer 40

The common adverse events were anemia, fatigue, nausea, and diarrhea.

Question 41

What is the scope of approval for olaparib by Health Canada, the US Food and Drug Administration, and the European regulatory authority?

Answer 41

Health Canada approved olaparib for patients with deleterious or suspected deleterious germline or somatic BRCA1/2 or ATM mutations who have progressed following prior treatment with an NHT (i.e., abiraterone, enzalutamide, apalutamide, darolutamide). The U.S. FDA approved olaparib for prostate cancers harboring a broader spectrum of 11 additional genes directly or indirectly involved in HRR. The European authority approved olaparib only for BRCA1/2 alterations.

Question 42

Figure 1

Answer 42

Management of CRPC

Question 43

What are the key points about Bone-supportive agents in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 43

Denosumab (120 mg SC) and zoledronic acid (4 mg IV) are recommended every four weeks to prevent disease-related skeletal-related events (SREs) in men with CRPC and bone metastases.

Question 44

What are the key points about Bone loss and ADT in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 44

Bone loss associated with androgen deprivation therapy (ADT) increases the risk of fracture. About 90% of patients with metastatic castration-resistant prostate cancer (mCRPC) will develop bone metastases, leading to local decreases in bone integrity and significant risk of SREs.

Question 45

What are the key points about Zoledronic acid in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 45

Zoledronic acid is a third-generation nitrogen-containing bisphosphonate. It reduced the rate of SREs by 36% in treated patients compared to placebo. It also increased the median time to first SRE. However, it should not be used in men with baseline creatinine clearance <30 mL/min.

Question 46

What are the key points about Denosumab in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 46

Denosumab is a fully humanized monoclonal antibody against RANK ligand. It has been shown to be effective in preventing bone loss and new vertebral fractures due to ADT. In mCRPC, denosumab has shown significant improvement in the time to the first SRE compared to zoledronic acid. No dose modification for renal function is necessary, but the risk of hypocalcemia is increased.

Question 47

What are the key points about Oral hygiene and dental evaluation in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 47

Good oral hygiene, baseline dental evaluation for high-risk individuals, and avoidance of invasive dental surgery during therapy are recommended to reduce the risk of osteonecrosis of the jaw (ONJ) for patients treated with bone-targeted therapies.

Question 48

What are the key points about Optimal duration in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 48

The optimal duration of zoledronic acid and denosumab in men with CRPC and bone metastases is undefined. The risk of ONJ appears to be related to time on bone-targeted therapy, so caution should be taken in using these agents beyond two years.

Question 49

What are the key points about Indications in the management of CRPC according to the 2022 CUA-CUOG guidelines?

Answer 49

Denosumab and zoledronic acid are not approved and not indicated for SRE prevention in the treatment of metastatic castration-sensitive prostate cancer or for bone metastases prevention.

Question 50

What are the potential benefits of systemic corticosteroid therapy in managing castration-resistant prostate cancer (CRPC)?

Answer 50

Corticosteroid therapy with low-dose prednisone or dexamethasone may offer improvements in PSA values and/or palliative outcomes in up to 30% of patients. This therapy is effective in both symptomatic and asymptomatic men. Steroids may also exert an anti-neoplastic effect on prostate cancer.

Question 51

When is Radium-223 recommended for patients with mCRPC?

Answer 51

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 52

What level and strength of recommendation is given to the use of corticosteroid therapy in CRPC according to the 2022 CUA-CUOG guidelines?

Answer 52

Level 3, Weak recommendation.

Question 53

How effective is palliative radiation in treating bone metastases from prostate cancer?

Answer 53

Most men will experience partial or complete pain relief from external beam radiation to a specific lesion. Bone metastases from prostate cancer are often radiosensitive.

Question 54

What are the comparative benefits of single fraction versus multiple fraction standard palliative radiotherapy (RT) for prostate cancer?

Answer 54

A single fraction of standard palliative RT is as effective as five or more fractions in providing palliation. However, more patients require retreatment for pain recurrence with single fraction radiation.

Question 55

What is Stereotactic body RT (SBRT) and when can it be considered in the management of CRPC?

Answer 55

SBRT is a more precise form of palliation delivered in five or fewer treatments. It can be considered particularly for oligometastatic disease where high-dose RT is currently being studied for improved oncological outcomes.

Question 56

What is the management approach for malignant spinal cord compression in the context of CRPC?

Answer 56

Malignant spinal cord compression is an oncological emergency that requires immediate diagnosis with an MRI. Options for treatment are debulking surgery + RT, vertebrectomy with stabilization and RT, or RT + steroids.

Question 57

What level and strength of recommendation is given to the immediate diagnosis and treatment of malignant spinal cord compression in CRPC according to the 2022 CUA-CUOG guidelines?

Answer 57

Level 1, Strong recommendation.

Question 58

When is Radium-223 recommended for patients with mCRPC?

Answer 58

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 59

When is Radium-223 recommended for patients with mCRPC?

Answer 59

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 60

When is Radium-223 recommended for patients with mCRPC?

Answer 60

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 61

When is Radium-223 recommended for patients with mCRPC?

Answer 61

Radium-223 is recommended for bone symptomatic mCRPC patients who have progressed following taxane chemotherapy or are unfit for chemotherapy and do not have visceral metastases.

Question 62

Vignette: A 65-year-old man is evaluated for castration-resistant prostate cancer (CRPC). Which of the following is crucial for determining his treatment plan?

Options:

A) Patient’s age
B) Presence or absence of radiographic metastases
C) Family history of prostate cancer
D) Blood testosterone levels

Answer 62

Correct Answer: B) Presence or absence of radiographic metastases

Explanation:

A) Age is important but not a critical determinant for therapy.
B) Correct. Determining the presence or absence of radiographic metastases is crucial for the treatment plan (Paragraph 2).
C) Family history is not a critical determinant.
D) Blood testosterone levels are not crucial in the context of CRPC.
Memory Tool: Radiographic Metastases = Road Map for CRPC Treatment.

Reference: Paragraph 2 from provided material.

Rationale for this question: Understanding the critical determinants for CRPC treatment is essential for optimal patient management.

Question 63

Vignette: A 68-year-old man with metastatic CRPC (mCRPC) reports progression despite docetaxel treatment. What second-line chemotherapy can be considered?

Options:

A) Apalutamide
B) Cabazitaxel
C) Mitoxantrone
D) Abiraterone

Answer 63

Correct Answer: B) Cabazitaxel

Explanation:

A) Incorrect. Apalutamide is not approved for use in metastatic CRPC.
B) Correct. Cabazitaxel is a second-line option for patients who have had progressive disease during or after docetaxel treatment (Paragraph 9).
C) Incorrect. Mitoxantrone doesn’t prolong survival and is more palliative.
D) Incorrect. Abiraterone is hormonal therapy, not chemotherapy.
Memory Tool: Second place Cab (Cabazitaxel) comes after the Doc (Docetaxel).

Reference: Paragraph 9 from provided material.

Rationale for this question: Identifying appropriate second-line therapies for mCRPC is crucial for effective treatment planning.

Question 64

Vignette: A 70-year-old patient with mCRPC has never undergone chemotherapy. Which androgen receptor (AR) signaling inhibitor improves survival in this setting?

Options:

A) Enzalutamide
B) Apalutamide
C) Abiraterone
D) Orteronel

Answer 64

orrect Answer: A) Enzalutamide

Explanation:

A) Correct. Enzalutamide improves survival in men with mCRPC in the prechemotherapy settings (Paragraph 18).
B) Incorrect. Apalutamide is not approved for use in metastatic CRPC.
C) Incorrect. Abiraterone is not specifically an AR signaling inhibitor.
D) Incorrect. Orteronel is still in clinical development.
Memory Tool: Enza-Ends the debate for prechemo survival improvement.

Reference: Paragraph 18 from provided material.

Rationale for this question: Understanding which AR signaling inhibitors are effective in prechemotherapy mCRPC is important for patient survival.

Question 65

Clinical Vignette: A 66-year-old male patient with a history of prostate cancer presents with increasing PSA levels but no signs of radiographic metastases. What treatment option is most appropriate for him?

A. Apalutamide
B. Docetaxel
C. Abiraterone
D. Sipuleucel-T

Answer 65

Correct Answer: A. Apalutamide
In-depth Explanation:

A. Apalutamide: Correct. FDA approved for men with nonmetastatic (M0) CRPC to delay the onset of radiographic metastases.
B. Docetaxel: Incorrect. Standard first-line chemotherapy for metastatic CRPC (mCRPC), not indicated in nonmetastatic CRPC.
C. Abiraterone: Incorrect. Approved for mCRPC but not nonmetastatic CRPC.
D. Sipuleucel-T: Incorrect. Indicated for asymptomatic or minimally symptomatic mCRPC without visceral metastases.
Memory Tool: “A for Apalutamide, A for Absence of metastasis.”
Reference Citation: Paragraph 1 under Key Points: Clinical Considerations
Rationale for Question: Addresses the need to evaluate the type of CRPC (metastatic vs nonmetastatic) before choosing a therapy.

Question 66

Clinical Vignette: A patient with mCRPC did not respond well to a regimen of docetaxel. What is the most appropriate second-line chemotherapy option?

A. Cabazitaxel
B. Platinum agents
C. Mitoxantrone
D. Abiraterone

Answer 66

Correct Answer: A. Cabazitaxel
In-depth Explanation:

A. Cabazitaxel: Correct. Second-line chemotherapy option for patients with mCRPC who have had progressive disease during or after docetaxel treatment.
B. Platinum agents: Incorrect. Indicated in patients with small cell prostate cancer and perhaps in other subsets of mCRPC.
C. Mitoxantrone: Incorrect. Does not prolong survival, used to palliate symptoms.
D. Abiraterone: Incorrect. It is a hormonal therapy, not chemotherapy.
Memory Tool: “Second chance with Cabazitaxel.”
Reference Citation: Paragraph 2 under Key Points: Cytotoxic Chemotherapy
Rationale for Question: Focuses on second-line treatment options after first-line chemotherapy failure.

Question 67

Clinical Vignette: A patient with mCRPC tests negative for AR-V7. Which therapeutic strategy could be equally effective for this patient?

A. Taxane Chemotherapy
B. AR-directed therapy
C. Both A and B
D. Neither A nor B

Answer 67

Correct Answer: C. Both A and B
In-depth Explanation:

A. Taxane Chemotherapy: Incorrect alone. Effective in AR-V7(+) patients.
B. AR-directed therapy: Incorrect alone. Effective in AR-V7(–) patients.
C. Both A and B: Correct. AR-V7(–) men may benefit similarly from either AR-directed therapy or chemotherapy.
D. Neither A nor B: Incorrect.
Memory Tool: “AR-V7 negative? Either way, you have a play.”
Reference Citation: Paragraph 6 under Key Points: Next-Generation Hormonal Therapies
Rationale for Question: Differentiating treatment strategies based on biomarkers such as AR-V7.

Question 68

Clinical Vignette: A 70-year-old male patient with mCRPC has a negative bone scan but persistent elevated PSA levels. What is the most accurate imaging technique to use for metastasis detection?

A. CT Scan
B. X-Ray
C. MRI
D. PSMA-PET/CT

Answer 68

Correct Answer: D. PSMA-PET/CT
In-depth Explanation:

A. CT Scan: Incorrect. Less sensitive in detecting bone metastases compared to PSMA-PET/CT.
B. X-Ray: Incorrect. Least sensitive imaging modality for detecting bone metastases.
C. MRI: Incorrect. While sensitive, it’s not as specific as PSMA-PET/CT.
D. PSMA-PET/CT: Correct. It offers the highest sensitivity and specificity for detecting prostate cancer metastases.
Memory Tool: “PSMA: Precise Scanning Makes A-difference.”
Reference Citation: Paragraph 3 under Key Points: Role of Imaging
Rationale for Question: Emphasizes the importance of using the most accurate imaging modality in complex cases.

Question 69

Clinical Vignette: A 65-year-old man with prostate cancer has only 2 bone metastases. What is the most suitable management strategy?

A. Androgen Deprivation Therapy (ADT) alone
B. Chemotherapy
C. ADT and Stereotactic Body Radiation Therapy (SBRT)
D. Palliative Care

Answer 69

Correct Answer: C. ADT and Stereotactic Body Radiation Therapy (SBRT)
In-depth Explanation:

A. ADT alone: Incorrect. Not aggressive enough for oligometastatic disease.
B. Chemotherapy: Incorrect. Generally not the first choice for oligometastatic disease.
C. ADT and SBRT: Correct. Combining ADT with SBRT is emerging as a management strategy for oligometastatic prostate cancer.
D. Palliative Care: Incorrect. Not appropriate for a patient with only 2 bone metastases and who can tolerate aggressive treatment.
Memory Tool: “Oligo, go big—ADT and SBRT.”
Reference Citation: Paragraph 4 under Key Points: Oligometastatic Disease
Rationale for Question: Discusses the role of multimodal therapy in the management of oligometastatic disease.

Question 70

Clinical Vignette: A 62-year-old male with high-risk localized prostate cancer has completed radical prostatectomy and is showing rising PSA. When should ADT be initiated?

A. Immediately
B. Wait until symptomatic
C. Upon detection of metastases
D. After salvage radiation therapy

Answer 70

Clinical Vignette: A 62-year-old male with high-risk localized prostate cancer has completed radical prostatectomy and is showing rising PSA. When should ADT be initiated?

A. Immediately
B. Wait until symptomatic
C. Upon detection of metastases
D. After salvage radiation therapy

Question 71

Vignette: You are contemplating hormonal therapy for a 65-year-old male patient with mCRPC who hasn’t received chemotherapy.

Question: Which among the following statements is true about Abiraterone in mCRPC?

Options:
A. Abiraterone is not approved for mCRPC.
B. Abiraterone is a CYP17 inhibitor that is approved for mCRPC both before and after chemotherapy.
C. Abiraterone is approved only for nonmetastatic CRPC.
D. Abiraterone is an AR signaling inhibitor.

Answer 71

Correct Answer: B. Abiraterone is a CYP17 inhibitor that is approved for mCRPC both before and after chemotherapy.

Explanation:

A: Incorrect. Abiraterone is approved for mCRPC both before and after chemotherapy.
B: Correct. Abiraterone is a CYP17 inhibitor and is approved for both settings.
C: Incorrect. Abiraterone is not approved for nonmetastatic CRPC.
D: Incorrect. Abiraterone is a CYP17 inhibitor, not an AR signaling inhibitor.
Memory Tool: “Abi Before & After Chem” – to remember Abiraterone is used before and after chemotherapy.

Reference: Paragraph 1, Next-Generation Hormonal Therapies key points

Rationale: Knowing the proper hormonal treatments for specific CRPC stages is essential for patient management.

Question 72

Question: In the evaluation of a patient with castration-resistant prostate cancer (CRPC), which of the following is NOT a critical determinant?

A. Radiographic metastases
B. Biochemical progression
C. PSA levels
D. Presence or absence of symptoms (e.g., pain)

Answer 72

Correct Answer: C. PSA levels

Explanation: Critical determinants for evaluating CRPC include the presence or absence of radiographic metastases (A), biochemical versus clinical progression (B), and the presence or absence of symptoms like pain (D). PSA levels (C) are not listed as a critical determinant.

Memory Tool: Think “RBiP” - Radiographic, Biochemical, Pain.

Reference: Paragraph 1, Clinical Considerations

Rationale: This question was chosen to test your understanding of what factors are critically important in evaluating CRPC.

Question 73

Question: Which immune checkpoint inhibitor has been approved for locally advanced or metastatic urothelial carcinoma that has progressed following platinum-based chemotherapy?
A. Pembrolizumab
B. Atezolizumab
C. Ipilimumab
D. None of the above

Answer 73

Correct Answer: A. Pembrolizumab

Explanation: Pembrolizumab is approved for patients with locally advanced or metastatic urothelial carcinoma that has progressed after platinum-based chemotherapy. Atezolizumab (B) is also used, but Pembrolizumab has more robust data for this indication. Ipilimumab (C) is not approved for this use.

Memory Tool: “Pemb-Uro” for “Pembrolizumab in urothelial carcinoma.”

Reference: Paragraph 4, Immune Checkpoint Inhibitors

Rationale: This question is designed to clarify your understanding of the specific indications for immune checkpoint inhibitors in bladder cancer.

Question 74

Clinical Vignette: A 65-year-old male is diagnosed with metastatic prostate cancer. He asks about the history of hormonal therapies in prostate cancer treatment.

Answer 74

Correct Answer: B. Hormonal therapy for prostate cancer was championed by Charles Huggins in 1941 and showed significant improvement in patients with metastatic cancer.

In-Depth Explanation:

A is incorrect because hormonal therapy was first championed by Charles Huggins in 1941, not the early 20th century. It is primarily for metastatic prostate cancer.
B is correct, as the vignette and key points indicate, Charles Huggins in 1941 reported significant improvement in patients with metastatic prostate cancer following castration.
C is incorrect; hormonal therapies are not a recent development and can be used independently of chemotherapy.
D is incorrect because hormonal therapies were introduced in 1941, not the 1980s, and they have shown significant effectiveness in treating metastatic prostate cancer.
Memory Tool: Think “Huggins in the 40s” to remember that Charles Huggins championed hormonal therapy in 1941.

Reference Citation: Paragraph 1, (Huggins, 1941)

Rationale: This information is essential for understanding the historical context and effectiveness of hormonal therapies in treating metastatic prostate cancer.

Question 75

Clinical Vignette: A 58-year-old male is found to have elevated acid phosphatase levels. What can be concluded regarding his prostate cancer status based on phosphatase levels?

Multiple-Choice Options:
A. Elevated phosphatase levels are specific to prostate tumors.
B. Elevated phosphatase levels can also be found in normal adult and hypertrophic prostates.
C. Elevated phosphatase levels are found only in infant prostates.
D. Elevated phosphatase levels indicate the presence of neoplastic cells of a more primitive type in the prostate.

Answer 75

Correct Answer: B. Elevated phosphatase levels can also be found in normal adult and hypertrophic prostates.

In-Depth Explanation:

A is incorrect because elevated phosphatase levels are not specific to prostate tumors and can also be found in normal adult and hypertrophic prostates.
B is correct. Huggins observed elevated phosphatase levels in prostate tumors, as well as in normal adult and hypertrophic prostates.
C is incorrect; little to undetectable enzyme levels are present in newborn infant prostate tissues.
D is incorrect; Huggins stated that prostatic carcinomas consist of adult epithelium, not neoplastic cells of a more primitive type.
Memory Tool: Think “P levels for Prostate, but not just for Prostate tumors” to remember that phosphatase levels can be elevated in other conditions.

Reference Citation: Paragraph 1, (Huggins, 1941)

Rationale: Understanding that phosphatase levels can be elevated in various prostatic conditions is critical for diagnosis and management.

Question 76

Clinical Vignette: A 72-year-old male with prostate cancer is prescribed hormonal therapy to reduce AR activity. His oncologist explains the function of the androgen receptor (AR). Which domains are key functional parts of the AR?

Multiple-Choice Options:
A. Ligand-binding, DNA-binding, and de novo steroidogenesis
B. Ligand-binding, DNA-binding, and transactivation
C. Ligand-binding, AR splice variants, and transactivation
D. Ligand-binding, DNA-binding, and amplification

Answer 76

Correct Answer: B. Ligand-binding, DNA-binding, and transactivation

In-Depth Explanation:

A is incorrect; de novo steroidogenesis is not a key functional domain of AR but a method of AR pathway adaptation.
B is correct, according to the key points, AR has three key functional domains: ligand-binding, DNA-binding, and transactivation.
C is incorrect; AR splice variants are not one of the key functional domains but rather a method of AR pathway adaptation.
D is incorrect; amplification is not a functional domain of the AR but another method of AR pathway adaptation.
Memory Tool: Think “L-D-T for AR” to remember Ligand-binding, DNA-binding, and Transactivation are the functional domains of AR.

Reference Citation: Key Points, (no author specified)

Rationale: Understanding the key functional domains of the AR is important for comprehending how hormonal therapy impacts prostate cancer.

Question 77

Clinical Vignette: A 55-year-old male with advanced castration-resistant prostate cancer (CRPC) undergoes an autopsy. What is likely to be found regarding AR pathway activation?

Multiple-Choice Options:
A. AR pathway activation is typically absent in advanced CRPC
B. AR pathway activation continues to be necessary and sufficient in advanced CRPC
C. AR pathway activation is replaced by other signaling pathways in advanced CRPC
D. AR pathway activation is sporadically seen but not considered necessary in advanced CRPC

Answer 77

Correct Answer: B. AR pathway activation continues to be necessary and sufficient in advanced CRPC

In-Depth Explanation:

A is incorrect; analyses of rapid/warm autopsies have demonstrated that AR pathway activation is still necessary in advanced CRPC.
B is correct, as indicated in the key points and material, men succumbing to advanced CRPC still have AR pathway activation.
C is incorrect; AR pathway activation is not replaced but continues to be active.
D is incorrect; AR pathway activation is not sporadic but is considered necessary and sufficient.
Memory Tool: Think “Always Reliable Pathway” to remember that AR pathway activation remains essential in advanced CRPC.

Reference Citation: Paragraph 1 and Key Points, (Rubin et al., 2000)

Rationale: Knowing that AR pathway activation continues in advanced CRPC can guide therapeutic decisions and expectations for disease progression.

Question 78

Clinical Vignette: A 60-year-old male with prostate cancer is found to have a high expression of AR-V7. What can be inferred about his disease prognosis?

Multiple-Choice Options:
A. The patient has a better prognosis due to AR-V7’s protective effect.
B. The patient is likely to have a poor prognosis associated with castration resistance.
C. AR-V7 expression has no significant impact on the patient’s prognosis.
D. AR-V7 expression indicates that the patient will respond well to first-line hormonal therapy.

Answer 78

Correct Answer: B. The patient is likely to have a poor prognosis associated with castration resistance.

In-Depth Explanation:

A is incorrect; AR-V7 has been strongly associated with castration resistance and overall poor patient survival, not a protective effect.
B is correct; according to the material, high expression of AR-V7 is strongly associated with castration resistance and poor patient survival.
C is incorrect; AR-V7 expression significantly impacts prognosis, specifically indicating a poor prognosis.
D is incorrect; AR-V7 expression actually makes it less likely that the patient will respond well to first-line hormonal therapy.
Memory Tool: Think “V for Very Bad” to remember that AR-V7 is associated with a very bad prognosis due to castration resistance.

Reference Citation: Paragraph 1, (Antonarakis et al., 2014)

Rationale: Knowing the prognostic implications of AR-V7 expression can influence treatment decisions and inform clinicians about likely patient outcomes.

Question 79

Clinical Vignette: A 68-year-old male with prostate cancer is showing resistance to hormonal therapy. Which of the following are methods of AR pathway adaptation to hormonal therapy?

Multiple-Choice Options:
A. Mutation, amplification, de novo steroidogenesis, and AR splice variants
B. Ligand-binding, DNA-binding, and transactivation
C. Amplification, phosphatase levels, and transactivation
D. De novo steroidogenesis, DNA-binding, and amplification

Answer 79

Correct Answer: A. Mutation, amplification, de novo steroidogenesis, and AR splice variants

In-Depth Explanation:

A is correct; according to the key points, mutation, amplification, de novo steroidogenesis, and AR splice variants are methods of AR pathway adaptation.
B is incorrect; these are functional domains of AR, not adaptation mechanisms.
C is incorrect; phosphatase levels and transactivation are not methods of AR pathway adaptation.
D is incorrect; DNA-binding is a functional domain of AR and not a method of adaptation.
Memory Tool: Remember “M.A.D.A.” for Mutation, Amplification, De novo steroidogenesis, and AR splice variants as the adaptation methods.

Reference Citation: Key Points, (no author specified)

Rationale: Understanding AR pathway adaptation mechanisms is crucial for managing treatment resistance in prostate cancer.

Question 80

Clinical Vignette: A urology fellow is studying the history of prostate cancer treatment. In discussing the pioneering work of Charles Huggins, what key observations did he make regarding prostate cancer epithelium?

Multiple-Choice Options:
A. Prostate carcinomas consisted of a malignant type of adult epithelium.
B. Prostate carcinomas were primarily neoplastic cells of a more primitive type.
C. Prostate carcinomas mostly consisted of hypertrophic prostate tissues.
D. Prostate carcinomas primarily consisted of cells similar to those in newborn infant prostate tissues.

Answer 80

Correct Answer: A. Prostate carcinomas consisted of a malignant type of adult epithelium.

In-Depth Explanation:

A is correct; Huggins observed that prostatic carcinomas consisted of a malignant type of adult epithelium.
B is incorrect; Huggins specifically said the cells were not of a more primitive type.
C is incorrect; while Huggins did discuss hypertrophic prostate tissues, this was not his key observation regarding prostate carcinomas.
D is incorrect; Huggins found little to undetectable enzyme in newborn infant prostate tissues, indicating the cells in prostate carcinomas are different.
Memory Tool: Remember “Huggins = Malignant Adult” to recall that Charles Huggins identified the epithelium in prostate carcinomas as a malignant type of adult epithelium.

Reference Citation: Paragraph 1, (Huggins, 1941)

Rationale: Understanding the historical observations can provide context for current prostate cancer pathology and treatment.

Question 81

Clinical Vignette: A 63-year-old male with advanced prostate cancer is considering undergoing castration as part of his treatment. What clinical improvements might he expect after the procedure?

Multiple-Choice Options:
A. Weight loss, increased sexual capacity, and lower red blood cell count
B. Weight gain, improvement of pain symptoms, and upward red blood cell count
C. Weight gain, increased sexual capacity, and edema of lower extremities
D. Weight loss, worsening of pain symptoms, and downward red blood cell count

Answer 81

Correct Answer: B. Weight gain, improvement of pain symptoms, and upward red blood cell count

In-Depth Explanation:

A is incorrect; Huggins observed weight gain, not weight loss, and a loss of sexual capacity, not an increase.
B is correct; according to Huggins, patients experienced weight gain, significant improvement of pain symptoms, and an upward trend in red blood cell count.
C is incorrect; while weight gain and edema of the lower extremities were observed, sexual capacity was lost, not increased.
D is incorrect; the observations indicated improvements in symptoms, not worsening.
Memory Tool: Think “WPU for Wellbeing” to remember Weight gain, Pain improvement, and Upward red blood cell count are likely benefits.

Reference Citation: Paragraph 1, (Huggins, 1941)

Rationale: Understanding the potential clinical benefits after castration can help in patient counseling and informed decision-making.