Treatment of Castration-Resistant Prostate Cancer

Question 1

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 1

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 2

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 2

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 3

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 3

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 4

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 4

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 5

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 5

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 6

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 6

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 7

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 7

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 8

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 8

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 9

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 9

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 10

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 10

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 11

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 11

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 12

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 12

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 13

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 13

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 14

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 14

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 15

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 15

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 16

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 16

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 17

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 17

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 18

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 18

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 19

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 19

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 20

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 20

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.