Canadian Urological Association guideline on androgen deprivation therapy: Adverse events and management strategies Flashcards

Question

What types of ADT does this guideline focus on in relation to adverse effects?

Answer 1

This guideline focuses on adverse effects as a result of the use of LHRH agonists and antagonists.

Answer 2

Each ADT-related complication is followed by a summary of the evidence, a summary of recommendations, and subsequently, a review of the data used to formulate the guideline statements.

Answer 3

Cardiometabolic health refers to the effects of ADT on cardiovascular disease (CVD), body composition, and metabolic parameters (including lipid profiles, insulin resistance, and glucose homeostasis).

Answer 4

ADT may increase the risk of cardiac complications, especially in patients with pre-existing CVD or a history of major adverse cardiac events (MACE).

Answer 5

ADT may increase the risk of venous thromboembolism (VTE) and stroke.

Answer 6

ADT is associated with changes in body composition, including increased body weight and fat mass, decreased lean body mass, and decreased muscle mass.

Answer 7

ADT can lead to insulin resistance, glucose intolerance, changes in the lipid profile, increased risk of incident diabetes, and potentially worsen glycemic control in men with a pre-existing diagnosis. ADT may also increase the risk of developing metabolic syndrome.

Answer 8

Lifestyle modifications such as smoking cessation, dietary modifications, and exercise should be strongly encouraged.

Answer 9

The baseline physical examination should include blood pressure, weight, waist circumference, and calculation of body mass index (BMI).

Answer 10

Baseline laboratory investigations should include fasting plasma glucose and lipid profile (triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol, and total cholesterol).

Answer 11

Patients with a history of MI or stroke should be referred to a cardiologist or cardio-oncologist for assessment and medical optimization at the time of initiating ADT.

Answer 12

All patients receiving ADT should undergo a baseline cardiovascular risk assessment and be monitored for cardiovascular complications while receiving therapy.

Answer 13

Cardiovascular disease (CVD).

Answer 14

Large, observational cohort studies describe a strong link between ADT and CVD, including coronary artery disease (CAD), myocardial infarction (MI), and sudden cardiac death.

Answer 15

MACE is a cumulative term for adverse cardiovascular events and is defined as MI, coronary revascularization, stroke, and hospitalization due to heart failure.

Answer 16

Men with pre-existing heart disease.

Answer 17

Some evidence suggests that men with pre-existing CVD treated with a GnRH antagonist were less likely to have a cardiovascular event within one year of beginning ADT compared to men treated with a GnRH agonist. However, these results are still under debate and further research is needed.

Answer 18

Relugolix was found to be superior to leuprolide in achieving castrate testosterone levels and was associated with a lower incidence of MACE. The decrease in risk was especially pronounced in men with a prior medical history of MACE.

Answer 19

The results suggested that there is no added cardiovascular risk in men receiving a GnRH agonist compared to an antagonist. However, the trial had several limitations, including a low accrual rate and a lower than anticipated event rate, which could affect the reliability of the results.

Answer 20

The RADICAL-PC trial aims to assess the impact of systematic lifestyle and cardiovascular risk factor modification in men with prostate cancer, with a focus on ADT.

Answer 21

GnRH agonists may destabilize atherosclerotic plaques.

Answer 22

ADT is associated with an increased risk of DVT, PE, or arterial embolism.

Answer 23

Men receiving ADT were 84% more likely to be hospitalized with DVT, PE, or both.

Answer 24

There is currently insufficient evidence to recommend routine use of VTE prophylaxis in men receiving ADT.

Answer 25

Men with local or regional prostate cancer receiving GnRH agonist had a significantly increased risk of stroke compared to the no-treatment group (HR 1.22, 95% CI 1.10–1.36).

Answer 26

The relative risk of stroke for men treated with a GnRH agonist is increased by 51% compared to those without this treatment (RR 1.51, 95% CI 1.24–1.84).

Answer 27

Longer durations of ADT are associated with an increased number of cerebrovascular events.

Answer 28

ADT treatment in men leads to an increase in body weight and percentage fat mass, primarily due to an accumulation of subcutaneous fat. It also causes a loss of muscle mass, leading to a decrease in percentage lean mass. These changes can occur as early as one month following treatment and may persist up to two years beyond treatment cessation.

Answer 29

This phenomenon is collectively termed sarcopenic obesity.

Answer 30

The decrease in muscle mass leads to reduced grip strength, absolute muscular strength, and gait speed. Moreover, detrimental changes to aerobic fitness and overall physical function can occur. These changes can increase the risk of falls and fractures.

Answer 31

Elevated BMI may be associated with prostate cancer (PCa) progression and death. There may also be an association between obesity and the development of castration-resistant prostate cancer (CRPC) and metastases in men treated with early ADT.

Answer 32

These changes are thought to occur soon after initiating therapy, sometimes as early as one month following treatment. They may persist up to two years beyond treatment cessation.

Answer 33

The metabolic consequences of ADT include insulin resistance, glucose intolerance, and changes to the lipid profile. It is also associated with an increased likelihood of developing incident diabetes.

Answer 34

ADT may worsen glycemic control in men with pre-existing insulin-dependent diabetes.

Answer 35

ADT appears to change the lipid profile, with most studies finding an increase in triglyceride and total cholesterol levels. The cause of this rise (i.e., whether due to HDL or LDL cholesterol) remains to be determined.

Answer 36

The NCEP ATP III defines metabolic syndrome as meeting three of the following criteria: waist circumference ≥102 cm in men, serum triglycerides ≥1.7 mmol/L, serum HDL cholesterol <1 mmol/L in men, blood pressure ≥130/85 mmHg, fasting plasma glucose ≥5.6 mmol/L, or requirement for medications to treat criteria 2–5 listed above.

Answer 37

ADT is associated with a higher risk of metabolic syndrome compared to controls, with more than 50% of men on ADT meeting criteria for metabolic syndrome. This diagnosis is mainly attributable to an elevation of triglycerides, hyperglycemia, and abdominal obesity.

Answer 38

Early identification and intervention are necessary as patients with a diagnosis of metabolic syndrome are more likely to develop type 2 diabetes and cardiovascular diseases.

Answer 39

Adopt the Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE) guidelines for both a screening and management strategy. This includes moderating caloric intake, promoting healthy dietary patterns, encouraging smoking cessation, and regulating blood pressure to a target level of <130/80.

Answer 40

Diabetes screening with a fasting plasma glucose level, hemoglobin A1c, or oral glucose tolerance test should be performed at the time of ADT initiation, and at 6–12-month intervals following the initiation of treatment.

Answer 41

Baseline lipid profiles (triglycerides, LDL cholesterol, HDL cholesterol, and total cholesterol) should be obtained at the start of ADT and monitored throughout the treatment duration. Management of dyslipidemia and lipid targets should be carried out according to the 2021 Canadian Cardiovascular Society guidelines.

Answer 42

This includes statins, aspirin, and angiotensin-converting enzyme inhibitors for primary and secondary prevention.

Answer 43

Exercise, particularly a combination of resistance and aerobic training, can prevent muscle loss and decline in lean body mass, improve metabolic indices and body composition, and ameliorate cardiovascular outcomes. It can also enhance overall physical and mental wellbeing.

Answer 44

150 minutes of moderate-intensity aerobic exercise spread over 3–5 days in addition to resistance training 2–3 times per week. Resistance training should engage 8–10 muscle groups and include 8–10 repetitions with two sets.

Answer 45

Studies suggest that supervised exercise therapy in men with prostate cancer is superior to self-implemented exercise regimens.

Answer 46

Referral to a professional (e.g., exercise physiologist, certified exercise instructor, community program) who can deliver supervised intervention tailored to men with prostate cancer.

Answer 47

ADT use in men with PCa can lead to decreased bone mineral density (BMD), osteoporosis, and an increased risk for clinical fractures.

Answer 48

A comprehensive history and physical examination should be conducted, including an assessment of falls risk and height measurement.

Answer 49

Patients should be counselled on smoking and alcohol cessation. They should also be encouraged to participate in a combination of resistance and aerobic exercise, preferably supervised.

Answer 50

Providers should measure baseline calcium and 25-hydroxyvitamin D levels.

Answer 51

Men should maintain an adequate calcium intake of 1200 mg per day from dietary sources and supplements. Additionally, Vitamin D supplementation (800–2000 IU per day) should be initiated.

Answer 52

Men should be screened for osteoporosis using BMD testing with dual energy x-ray absorptiometry (DXA). A 10-year major osteoporotic fracture risk should also be calculated using a validated tool.

Answer 53

They should be treated with a bisphosphonate or denosumab at doses recommended for the general population.

Answer 54

DXA should be repeated every 2–3 years in men at low risk for fractures. In men with osteopenia or those at moderate or high risk for fractures, DXA should be repeated every 1–2 years until treatment cessation. Patients started on pharmacological therapy should have follow-up DXA to assess for treatment response.

Answer 55

Prevention of muscle loss and resultant decline in lean body mass, decreased body mass index, improved muscle strength, improvements in peak oxygen consumption and endothelial function, and improved overall physical function.

Answer 56

Lower levels of fatigue and decreased risk of falls and fractures.

Answer 57

Improved insulin and glucose homeostasis and improved lipid profile.

Answer 58

Exercise therapy benefits multiple health-related quality of life domains, although the specific domains aren't listed in the provided excerpt.

Answer 59

Exercise therapy is recommended because it helps mitigate some of the side effects of androgen deprivation therapy, such as muscle loss, increased body mass index, and decreased physical function. It also improves insulin and glucose homeostasis and lipid profiles, reducing fatigue and the risk of falls and fractures, thereby improving multiple health-related quality of life domains.

Answer 60

ADT can decrease bone mineral density (BMD), resulting in osteoporosis and an increased risk for clinical fractures.

Answer 61

There's a 2.5% decrease in BMD at the femoral neck and 4.0% at the lumbar spine after 12 months of ADT therapy.

Answer 62

BMD loss occurs at the maximum rate during the first year of ADT therapy and continues to decline with prolonged use.

Answer 63

The fracture incidence in men receiving ADT within five years of PCa diagnosis is 19%.

Answer 64

The number needed to harm (cause one fracture) for men receiving a GnRH agonist is 28.

Answer 65

Men receiving ADT had a 23% increased risk of fracture compared to non-ADT controls.

Answer 66

All men initiating ADT should be screened for osteoporosis. This includes a comprehensive history and physical examination with a focus on fall risk and height measurements, as well as basic laboratory investigations including calcium and 25-hydroxyvitamin D measurements.

Answer 67

Osteoporosis is defined as BMD of 2.5 or more standard deviations below the peak bone mass for young adults (i.e., T-score ≤-2.5).

Answer 68

Osteopenia (low bone mass) is defined as BMD more than 1.0 but less than 2.5 standard deviations below the peak bone mass for young adults (i.e., T-score <-1 and >-2.5).

Answer 69

The recommended tools for calculating fracture risk are the Canadian Association of Radiologists and Osteoporosis Canada (CAROC) and the Fracture Risk Assessment tool (FRAX) of the World Health Organization (WHO), specific for Canada.

Answer 70

Patients are stratified into low- (<10%), moderate- (10–20%) or high-risk (>20%) categories for fractures.

Answer 71

DXA scans should be repeated every 1–2 years or sooner for men with osteoporosis or osteopenia.

Answer 72

This includes adequate calcium intake (1200 mg daily total from diet and supplements) and vitamin D supplementation (800–2000 IU daily). Lifestyle modifications include smoking cessation and limited alcohol consumption, as both smoking and alcohol use are associated with bone loss and fractures.

Answer 73

Exercise therapy improves multiple physical domains, including preservation of muscle mass and strength, which may decrease the risk of fractures. Exercise also appears to preserve Bone Mineral Density (BMD) in men receiving ADT.

Answer 74

Bisphosphonates, including pamidronate, alendronate, risedronate, and zoledronic acid, act by inhibiting osteoclast activity, which decreases bone resorption. They have been found to improve BMD in the hip and lumbar spine in men with advanced or recurrent PCa without bony metastases receiving leuprolide. However, their impact on reducing fracture risk in men with non-metastatic PCa receiving ADT has not been investigated in clinical trials, so routine use is currently not recommended.

Answer 75

Denosumab is a human monoclonal antibody against the receptor activator of nuclear factorκB (RANK) ligand, which mediates osteoclast differentiation and activation. It has been shown to improve BMD and decrease the risk of vertebral fractures in men with non-metastatic PCa receiving ADT at high risk of fracture.

Answer 76

Both zoledronic acid and denosumab have proven to be effective in reducing skeletal-related events (SREs) in men with CRPC.

Answer 77

They are Bisphosphonates.

Answer 78

10 mg orally daily or 70 mg orally weekly.

Answer 79

5 mg orally daily, 35 mg orally weekly, or 150 mg orally monthly.

Answer 80

5 mg intravenously annually.

Answer 81

It's a RANK ligand inhibitor.

Answer 82

60 mg subcutaneously every 6 months.

Answer 83

The dose is 20 mg orally daily. It is a synthetic derivative of progesterone.

Answer 84

No, it is not approved by Health Canada for this use.

Answer 85

The dose is 20 mg orally twice daily. It is a synthetic derivative of progesterone.

Answer 86

No, it is not approved by Health Canada for this use.

Answer 87

The dose is 50-100 mg orally daily. It is an antiandrogen.

Answer 88

No, it is not approved for this use. However, it is approved for palliative treatment of patients with advanced prostate adenocarcinoma.

Answer 89

The dose is 900 mg orally daily. It is an antiepileptic agent.

Answer 90

No, it is not approved by Health Canada for this use.

Answer 91

The dose is 75 mg orally daily. It is a selective serotonin reuptake inhibitor.

Answer 92

No, it is not approved by Health Canada for this use.

Answer 93

Hot flashes are a sudden onset of facial sweating and discomfort that occur in most men receiving ADT. They can lead to a deterioration in health-related quality of life (HRQOL) and may decrease compliance with ADT.

Answer 94

Patients should be advised to identify and avoid potential triggers of hot flashes, commonly heat or spicy foods.

Answer 95

Several pharmacological agents, such as Gabapentin (900 mg daily), Venlafaxine (75 mg daily), Medroxyprogesterone acetate (20 mg daily), Cyproterone acetate (100 mg daily), and Megestrol acetate have been assessed for the treatment of hot flashes.

Answer 96

The study found a significant decrease in the frequency of hot flashes using all therapies. The decrease was -47.2% for venlafaxine, -94.5% for cyproterone, and -83.7% for medroxyprogesterone. However, medroxyprogesterone and cyproterone appeared to be more effective than venlafaxine.

Answer 97

Acupuncture has been shown to decrease hot flash symptoms by 89–95%. It may be a reasonable option for men who do not wish to receive pharmacological therapy, although this recommendation is based on low-quality evidence.

Answer 98

In a randomized controlled trial (RCT) of continuous ADT vs. intermittent ADT, men receiving intermittent therapy experienced significantly better scores for hot flashes.

Answer 99

ADT-related breast events include gynecomastia (increased amount of breast tissue) and mastodynia (breast tenderness).

Answer 100

Gynecomastia occurs as a result of peripheral conversion of testosterone to estradiol, which increases the ratio of estrogen to androgen activity.

Answer 101

Gynecomastia is more pronounced with anti-androgen (AA) monotherapy, with incidences reported as high as 85% in men taking 150 mg of bicalutamide.

Answer 102

The incidence for patients on combined androgen blockade is lower, at 13–22%.

Answer 103

Prophylaxis for the prevention of gynecomastia in men receiving ADT is not currently recommended.

Answer 104

Tamoxifen or radiation therapy (RT) may be used for the treatment of breast events in men receiving bicalutamide monotherapy.

Answer 105

Tamoxifen is more effective than RT at both preventing and decreasing the severity of breast events in men on bicalutamide therapy.

Answer 106

ADT has been associated with changes such as difficulties with concentration, information processing, verbal fluency, visual information processing, visuospatial function, memory, and executive function, as well as neuro-fatigue and apathy. However, evidence related to causality remains weak and further prospective data are needed.

Answer 107

Changes in cognition have been associated with ADT in 25–50% of patients.

Answer 108

The severity of symptoms varies greatly, from minor challenges like forgetting an item on a to-do list, to more serious effects that compromise daily functioning.

Answer 109

Studies that assessed cognition objectively have found men on ADT had impairments in verbal memory, spatial abilities, and attention. However, other studies found no appreciable effect, or a decline for only a subset of participants.

Answer 110

ADT may be associated with the development of depressive symptoms, increased rates of major depression, and worsening depressive symptoms. There is no increased risk of suicidality reported.

Answer 111

Several recent studies and a meta-analysis concluded that men receiving ADT are at increased risk for developing dementia and/or Alzheimer’s disease compared to men with PCa not receiving ADT.

Answer 112

Variations may be due to the regimen of ADT treatment (continuous or intermittent), methods (surgical or medical castration), the use of other concomitant treatments (e.g., radiation), and the nature of control groups (healthy control or men with PCa not on ADT).

Answer 113

Men receiving ADT should be monitored for cognitive decline and depression throughout the duration of treatment, according to expert opinion.

Answer 114

Fatigue and anemia are common side effects of ADT. Fatigue is often due to multifactorial causes, while anemia typically presents mildly and does not warrant treatment in most cases.

Answer 115

Fatigue in patients undergoing ADT is best managed with exercise therapy. Multiple clinical trials have reported beneficial outcomes with various exercise regimens, especially for those with the highest levels of fatigue.

Answer 116

Anemia caused by ADT is typically normocytic and normochromic, with a decrease in hemoglobin levels by 1–2 ng/dL from baseline. While treatment is rarely indicated, severe cases may require blood transfusion and erythropoietin. If anemia is severe or the decrease in hemoglobin exceeds the expected response to ADT alone, further investigation for secondary underlying causes is necessary and referral to a hematologist may be beneficial.

Answer 117

ADT impacts multiple domains of sexual function, which include body image, loss of libido, and erectile function. Specific changes can include decreased penile and testicular size, loss of libido (in up to 90% of men), decreased sensitivity to sexual stimulation, and erectile dysfunction. These changes can have a detrimental impact on self-perceived body image, leading to poor sexual function and decreased partner intimacy.

Answer 118

For men desiring improved sexual function, it is recommended to consider referral to a sex therapist for multimodal treatment. It's also suggested that intermittent ADT may improve libido and erectile function and should be considered in appropriately selected patients.

Answer 119

Patients require appropriate pre-treatment counseling regarding side effects, particularly with respect to body image. Referrals to psychosocial support groups and/or sex therapists should be offered to interested patients. Erectile dysfunction may be treated with various interventions, including phosphodiesterase inhibitors; however, treatment efficacy may be poor without adequate mental and physical arousal. Intermittent ADT has been shown to improve sexual function.

Answer 120

In one study, penile length decreased from an average of 10.76 cm to 8.05 cm after 15 months of ADT and plateaued thereafter. Pathological studies have shown significant testicular atrophy in men receiving ADT.

Answer 121

ADT can lead to significant decrements in multiple HRQOL domains, affecting various functional and psychological aspects. Men on ADT may experience a decline in general physical and mental health scores, lower vitality, hormonal HRQOL issues, hot flashes, depression, lack of energy, and increased body weight.

Answer 122

Exercise therapy is strongly recommended for all men undergoing ADT treatment. It's been shown to mitigate the impact of ADT on HRQOL and improve many HRQOL parameters.

Answer 123

Intermittent ADT is a strategy where the therapy is given in cycles with breaks in between. It can improve several HRQOL domains, including physical function, fatigue, hot flashes, urinary problems, and erectile dysfunction. Desire for sexual activity also improves in the intermittent group. However, its role in men with metastatic disease is controversial.

Answer 124

The decision must be individualized to patient preferences, expectations with respect to the impact of therapy on HRQOL, and disease status. Men with non-metastatic PCa are likely to benefit from intermittent ADT without major concern for compromised oncological outcomes, while those with metastatic PCa should be considered for intermittent therapy with caution.

Answer 125

The HERO trial assessed the efficacy and safety of the oral GnRH antagonist, relugolix. It demonstrated substantially improved testosterone recovery in men receiving relugolix compared to leuprolide, which may have important implications for intermittent ADT and HRQOL.

Answer 126

Increased risk of cardiac events, Increased risk of stroke, Increased risk of DVT/PE

Answer 127

Lifestyle changes to promote healthy diet and weight, Smoking cessation, Exercise therapy, Monitoring and medical optimization of blood glucose, blood pressure, lipid profiles

Answer 128

Increased BMI, Increased percentage body fat, Decreased muscle mass

Answer 129

Lifestyle changes to promote healthy diet and weight, Exercise therapy, Monitoring and medical optimization of blood glucose, blood pressure, lipid profiles

Answer 130

Insulin resistance/glucose intolerance, Increased risk for incident diabetes, Worse glycemic control, Altered lipid profiles, Increased risk for metabolic syndrome

Answer 131

Lifestyle changes to promote healthy diet and weight, Exercise therapy, Monitoring and medical optimization of blood glucose, blood pressure, lipid profiles

Answer 132

Decreased BMD, Increased risk for osteoporosis, Increased risk for clinical fractures

Answer 133

Smoking and alcohol cessation, Adequate calcium intake (1200 mg daily) and vitamin D supplementation (800–1000 IU daily), Exercise therapy, Pharmacological therapy with a bisphosphonate or denosumab for men with risk factors for bone fracture (i.e., previous history of low trauma fracture, diagnosis of osteoporosis, moderate or high 10-year fracture risk)

Answer 134

None specifically mentioned.

Answer 135

Avoidance of triggers, Pharmacological therapy, Consider acupuncture, Consider intermittent ADT

Answer 136

Gynecomastia, Mastodynia

Answer 137

Treatment with tamoxifen or low-dose RT (tamoxifen preferred), Surgical management for select patients

Answer 138

Concentration, Memory, Dementia, Depression

Answer 139

Evidence for causality is weak, Appropriate patient education and monitoring of symptoms

Answer 140

None specifically mentioned.

Answer 141

Exercise therapy for fatigue, Workup secondary causes of anemia and referral to hematology when indicated

Answer 142

Decreased penile and testicular size, Loss of libido, Decreased sensitivity to sexual stimulation, Erectile dysfunction

Answer 143

Appropriate pre-treatment counselling, Sex therapy, PDE-5 inhibitor and other ED therapies where appropriate, Consider intermittent ADT

Answer 144

Multiple domains

Answer 145

Exercise therapy, Consider intermittent ADT

Answer 146

Correct Answer: B. 5α-reductase Explanation: A: Aromatase converts androgens to estrogens and is not involved in converting testosterone to DHT. B: 5α-reductase is the enzyme that converts testosterone to DHT. DHT is even more potent than testosterone and can affect tissues like muscles that express androgen receptors. C: Cytochrome P450 is involved in the metabolism of various substances but not in the specific conversion of testosterone to DHT. D: Lactase is an enzyme that breaks down lactose and is unrelated to androgen conversion. Memory Tool: "5α-Reds lift: 5α-reductase helps muscles get a lift from DHT." Reference: Paragraph 1, Montgomery et al., 2008. Rationale for Question: Understanding the role of enzymes in androgen biochemistry is essential for understanding their tissue-specific effects and can be important in cases like enhancing athletic performance or managing conditions like prostate cancer.

Answer 147

Correct Answer: B. Dihydrotestosterone Explanation: A: Testosterone has a relative potency of 100, and its potency per amount produced is 15.2, which is not the highest. B: Dihydrotestosterone (DHT) has a relative potency between 160–190, and its potency per amount produced is 533–633, making it the most potent per amount produced. C: Androstenedione has a relative potency of 39, and its potency per amount produced is 27.9, which is not the highest. D: Dehydroepiandrosterone (DHEA) has a relative potency of 15, and its potency per amount produced is 0.5, which is the lowest. Memory Tool: "DHT: 'D' for Dominant in potency." Reference: Table 161.2 Rationale for Question: This question emphasizes the need to understand the potency per amount produced for different androgens, which can be critical in diagnosis and treatment planning.

Answer 148

Correct Answer: B. Translocates into the nucleus to regulate gene expression Explanation: A: Conversion of DHT back to testosterone is not a function of AR. B: When engaged by DHT, AR translocates into the nucleus, where it binds with androgen response elements (AREs) in gene promoters to regulate gene expression. C: AR itself doesn't increase the expression of 5α-reductase; it regulates genes once it's in the nucleus. D: AR does not exit the cell to bind with circulating androgens; it works within the cell nucleus. Memory Tool: "AR Trans: AR Translocates to the Nucleus with DHT." Reference: Key Points, 2nd Bullet Point. Rationale for Question: Knowing the function of AR when engaged by DHT is crucial for understanding how prostate cancer cells might behave.

Answer 149

Correct Answer: C. 5α-reductase Explanation: A: Cytochrome P450 is a general enzyme involved in the metabolism of various substances but is not specific for the conversion of testosterone to DHT. B: Aromatase converts androgens to estrogens; it doesn't convert testosterone to DHT. C: 5α-reductase is the enzyme that converts testosterone to DHT, and cells like muscle cells that are responsive to testosterone express this enzyme. D: Amylase is involved in carbohydrate metabolism and is not relevant to androgen biochemistry. Memory Tool: "Muscle Memory: Remember 5α-reductase for muscles." Reference: Paragraph 1 and Key Points, 1st Bullet Point. Rationale for Question: Understanding which enzymes are involved in specific tissues, like muscles, helps in both clinical and research settings.

Answer 150

Correct Answer: B. Dehydroepiandrosterone Explanation: A: Androstenedione has a relative potency of 39 and a potency per amount produced of 27.9, which isn't the lowest. B: Dehydroepiandrosterone (DHEA) has a relative potency of 15 and a potency per amount produced of 0.5, making it the lowest in relative potency per amount produced. C: Dihydrotestosterone is not produced by the adrenal glands. D: Testosterone is not exclusively produced by the adrenal glands. Memory Tool: "Low DHEA: DHEA has the lowest punch per pinch." Reference: Table 161.2 Rationale for Question: Understanding the potency of adrenal androgens is crucial for managing conditions like adrenal tumors.

Answer 151

Correct Answer: B. Prostate and muscle cells Explanation: A: Liver cells are involved in metabolism but are not specifically primed to respond to testosterone. B: Prostate and muscle cells express AR and the enzyme 5α-reductase, making them primed to respond to testosterone. C: Neurons are not specifically primed to respond to testosterone. D: Kidney cells are more involved in filtration and electrolyte balance and are not specifically primed to respond to testosterone. Memory Tool: "Pro-Muscle: Prostate and Muscle are Pro-Testosterone." Reference: Paragraph 1. Rationale for Question: Understanding which cells are responsive to androgens like testosterone is important for targeting interventions, like androgen supplementation.

Answer 152

Correct Answer: B. Regulate gene expression when bound by AR Explanation: A: Conversion of DHT back to testosterone is not the role of AREs. B: AREs are bound by AR in the nucleus, which then regulates gene expression. C: AREs are not external ligands for AR; they act as gene promoters. D: AREs don’t facilitate the export of AR; they are involved in gene regulation within the nucleus. Memory Tool: "A-REady to Regulate: AREs are ready to regulate genes when bound by AR." Reference: Key Points, 2nd Bullet Point. Rationale for Question: Understanding the genetic mechanisms by which androgens exert their effects is crucial, especially in conditions like advanced prostate cancer where genomic alterations could play a role.

Answer 153

Correct Answer: A. Triptorelin In-Depth Explanation: A: Triptorelin is a GnRH agonist that stimulates the release of LH from the pituitary gland. It is the mainstay of therapy for metastatic prostate cancer (Paragraph 1). B: Ketoconazole is an adrenal-targeting drug, not a GnRH agonist (Paragraph 3). C: Flutamide is a first-generation AR antagonist, not a GnRH agonist (Paragraph 5). D: Enzalutamide is a second-generation AR antagonist, not a GnRH agonist (Paragraph 7). Memory Tool: "Tri" as in "Triple action" for LH release, decrease in LH production, and treatment of metastatic disease. Reference Citation: Table 161.1, Paragraph 1. Rationale: GnRH agonists like Triptorelin are foundational for managing metastatic prostate cancer. Understanding their role is essential for board exams and patient care.

Answer 154

Correct Answer: D. Considerable side effects In-Depth Explanation: A: Gynecomastia is associated with first-generation AR antagonists like Flutamide (Paragraph 5). B: Increased FSH levels are associated with GnRH agonists like Leuprolide (Paragraph 1). C: Fatigue is associated with second-generation AR antagonists like Enzalutamide (Paragraph 7). D: Considerable side effects are associated with both GnRH agonists and antagonists (Paragraph 2). Memory Tool: "Antagonists are Antagonistic" - they have considerable side effects. Reference Citation: Table 161.1, Paragraph 2. Rationale: Knowing the range of side effects for different hormonal interventions is crucial for patient safety and effective treatment.

Answer 155

Correct Answer: A. Hypertension In-Depth Explanation: A: Hypertension is a side effect of adrenal-targeting drugs like Ketoconazole (Paragraph 3). B: Gynecomastia is associated with first-generation AR antagonists (Paragraph 5). C: Decreased appetite is a side effect of second-generation AR antagonists (Paragraph 7). D: Increased FSH levels are associated with GnRH agonists (Paragraph 1). Memory Tool: "Adrenaline Rush" for Adrenal-targeting drugs elevating blood pressure. Reference Citation: Table 161.1, Paragraph 3. Rationale: Being aware of drug-specific side effects, especially when a patient already has a comorbidity like hypertension, is essential for quality care.

Answer 156

Correct Answer: B. Bind to receptors and block release of GnRH In-Depth Explanation: A: Stimulate release of LH is a mechanism of GnRH agonists (Paragraph 1). B: Bind to receptors and block release of GnRH is the specific mechanism for GnRH antagonists like Degarelix (Paragraph 2). C: Decrease androgen production from steroid precursors is the mechanism of adrenal-targeting drugs (Paragraph 3). D: Inhibit the conversion of testosterone to DHT is the mechanism of 5α-Reductase inhibitors (Paragraph 7). Memory Tool: Antagonists "Block and Lock" GnRH. Reference Citation: Table 161.1, Paragraph 2. Rationale: Understanding the exact mechanism of action for different drug classes is critical for appropriate prescription and patient care.

Answer 157

Correct Answer: C. Flutamide In-Depth Explanation: A: Ketoconazole is an adrenal-targeting drug (Paragraph 3). B: Leuprolide is a GnRH agonist (Paragraph 1). C: Flutamide is a first-generation AR antagonist, associated with gynecomastia (Paragraph 5). D: Enzalutamide is a second-generation AR antagonist (Paragraph 7). Memory Tool: "First-gen, First problem" to remember that the first-gen AR antagonists cause gynecomastia. Reference Citation: Table 161.1, Paragraph 5. Rationale: Recognizing drug-related side effects is key for differential diagnosis and subsequent management.

Answer 158

Correct Answer: C. Prostate In-Depth Explanation: A: Pituitary gland is the site of action for GnRH agonists and antagonists (Paragraph 1, 2). B: Adrenal gland is the site of action for adrenal-targeting drugs (Paragraph 3). C: Prostate is the primary site of action for 5α-Reductase inhibitors like Finasteride (Paragraph 7). D: Prostate cancer is not the primary site for 5α-Reductase inhibitors; they are not indicated for prostate cancer management (Paragraph 7). Memory Tool: 5α-Reductase inhibitors: "Five-Star Pro-state Agents." Reference Citation: Table 161.1, Paragraph 7. Rationale: Knowing the site of action for drugs, especially when not indicated for cancer, is essential to avoid therapeutic missteps.

Answer 159

Correct Answer: D. Enzalutamide In-Depth Explanation: A: Ketoconazole is an adrenal-targeting drug associated with hypertension, not fatigue or falls (Paragraph 3). B: Abarelix is a GnRH antagonist, not linked to falls or fatigue (Paragraph 2). C: Flutamide is a first-generation AR antagonist mainly associated with gynecomastia (Paragraph 5). D: Enzalutamide is a second-generation AR antagonist associated with falls and fatigue (Paragraph 7). Memory Tool: "Second-Gen, Second Wind" to remember that second-generation AR antagonists can lead to fatigue. Reference Citation: Table 161.1, Paragraph 7. Rationale: Side effect profiles differ among drug classes, and recognizing this can inform patient care and symptom management.

Answer 160

Correct Answer: C. Adrenal-targeting drugs In-Depth Explanation: A: GnRH agonists act by stimulating the release of LH (Paragraph 1). B: GnRH antagonists bind to receptors and block the release of GnRH (Paragraph 2). C: Adrenal-targeting drugs act by blocking cytochrome P450 enzymes to decrease androgen production (Paragraph 3). D: Second-generation AR antagonists block AR and diminish AR-mediated transcription (Paragraph 7). Memory Tool: "Adrenaline Drop" to remember that adrenal-targeting drugs drop androgen levels by inhibiting enzymes. Reference Citation: Table 161.1, Paragraph 3. Rationale: Knowing the mechanisms of different drug classes can help guide appropriate medication choices and improve patient outcomes.

Answer 161

orrect Answer: D. 5α-Reductase inhibitors In-Depth Explanation: A: GnRH agonists are primarily indicated for metastatic prostate cancer, not BPH (Paragraph 1). B: First-generation AR antagonists are not indicated as monotherapy (Paragraph 5). C: Adrenal-targeting drugs mainly treat prostate cancer (Paragraph 3). D: 5α-Reductase inhibitors like Finasteride are commonly administered for BPH (Paragraph 7). Memory Tool: "5α for 55" to remember that 5α-Reductase inhibitors can be used for a 55-year-old patient with BPH. Reference Citation: Table 161.1, Paragraph 7. Rationale: Tailoring drug prescriptions to specific conditions like BPH is crucial for optimal treatment.

Answer 162

Correct Answer: C. Adrenal-targeting drugs In-Depth Explanation: A: GnRH agonists are associated with considerable side effects but not specifically hypertension, edema, and hypokalemia (Paragraph 1). B: GnRH antagonists also have considerable side effects, but not these specific ones (Paragraph 2). C: Adrenal-targeting drugs like Ketoconazole and Abiraterone can lead to hypertension, edema, and hypokalemia (Paragraph 3). D: Second-generation AR antagonists are mainly associated with falls, fatigue, and decreased appetite (Paragraph 7). Memory Tool: "Adrenal Ailments: H-E-H" for Hypertension, Edema, Hypokalemia. Reference Citation: Table 161.1, Paragraph 3. Rationale: Being aware of the side-effect profiles of each class of drugs is essential for correct diagnosis and patient management.

Answer 163

Correct Answer: A. GnRH agonists In-Depth Explanation: A: GnRH agonists like Leuprolide stimulate the release of LH initially but then ultimately decrease LH production (Paragraph 1). B: GnRH antagonists bind to receptors and block the release of GnRH (Paragraph 2). C: Adrenal-targeting drugs act by inhibiting cytochrome P450 enzymes (Paragraph 3). D: 5α-Reductase inhibitors inhibit the conversion of testosterone to DHT (Paragraph 7). Memory Tool: "Agonists Act, Then Attract Less" to remember that GnRH agonists initially act by releasing LH, then reduce it. Reference Citation: Table 161.1, Paragraph 1. Rationale: Differentiating drug classes by their mechanisms is crucial, especially for conditions like metastatic cancer where specific interventions are needed.

Answer 164

Correct Answer: C. Finasteride In-Depth Explanation: A: Leuprolide is a GnRH agonist indicated for metastatic prostate cancer (Paragraph 1). B: Flutamide is a first-generation AR antagonist used for prostate cancer, though not as monotherapy (Paragraph 5). C: Finasteride is a 5α-Reductase inhibitor and is not indicated for prostate cancer management (Paragraph 7). D: Enzalutamide is a second-generation AR antagonist used for prostate cancer (Paragraph 7). Memory Tool: "Fine, No Cancer" to remember that Finasteride is not fine for treating prostate cancer. Reference Citation: Table 161.1, Paragraph 7. Rationale: Knowing what NOT to prescribe is just as important as knowing what to prescribe for effective patient care.

Answer 165

Correct Answer: A. GnRH agonists In-Depth Explanation: A: GnRH agonists like Leuprolide and Goserelin are considered the mainstay of therapy for metastatic prostate cancer (Paragraph 1). B: GnRH antagonists, while effective, are not considered the mainstay of therapy for metastatic disease (Paragraph 2). C: Adrenal-targeting drugs are not the mainstay therapy for metastatic prostate cancer (Paragraph 3). D: First-generation AR antagonists are not considered the mainstay and are not indicated as monotherapy (Paragraph 5). Memory Tool: "A-Gone: Metastatic Gone" to remember that GnRH agonists are the mainstay for metastatic prostate cancer. Reference Citation: Table 161.1, Paragraph 1. Rationale: Knowing the first-line treatment for conditions like metastatic prostate cancer is crucial for providing optimal care.

Answer 166

Correct Answer: B. GnRH antagonists In-Depth Explanation: A: GnRH agonists initially stimulate the release of LH and are not used to prevent a testosterone surge (Paragraph 1). B: GnRH antagonists like Degarelix and Abarelix prevent a testosterone surge by blocking the release of GnRH (Paragraph 2). C: Adrenal-targeting drugs inhibit cytochrome P450 enzymes and are not used for preventing testosterone surges (Paragraph 3). D: 5α-Reductase inhibitors are not used to prevent testosterone surges; they inhibit the conversion of testosterone to DHT (Paragraph 7). Memory Tool: "Antagonize to Neutralize Surge" to remember that GnRH antagonists prevent testosterone surges. Reference Citation: Table 161.1, Paragraph 2. Rationale: Accurate understanding of drug mechanisms allows you to select the appropriate medication for specific patient needs.

Answer 167

Correct Answer: D. First-generation AR antagonists In-Depth Explanation: A: GnRH agonists have considerable side effects but not specifically gynecomastia (Paragraph 1). B: GnRH antagonists are also not specifically associated with gynecomastia (Paragraph 2). C: Adrenal-targeting drugs have side effects like hypertension but not gynecomastia (Paragraph 3). D: First-generation AR antagonists like Flutamide and Bicalutamide are associated with gynecomastia (Paragraph 5). Memory Tool: "First-Gen, First Breasts" to remember that first-generation AR antagonists can lead to gynecomastia. Reference Citation: Table 161.1, Paragraph 5. Rationale: Identifying drug classes by their unique side effects can aid in tailoring therapy and managing patient symptoms.

Answer 168

Correct Answer: C) Beta-blocker administration In-Depth Explanation: A) Surgical removal of the testicles (orchiectomy) is indeed an approach for androgen blockade. B) AR (Androgen Receptor) antagonism is another method for blocking androgen signaling. C) Beta-blocker administration is not a general approach for androgen signaling blockade. D) Inhibition of LHRH and/or LH is also a method used in androgen blockade. Memory Tool: "SOIL" can help you remember the four general approaches: Surgical removal, Orchiectomy, Inhibition of LHRH/LH, and LHRH Agonists. Reference Citation: Paragraph 1 Rationale: This information is critical to understand the general approaches to treating conditions that necessitate androgen blockade, like prostate cancer.

Answer 169

Question: What percentage of men on nilutamide therapy is likely to note this side effect? A) About 10% B) About 25% C) About 50% D) About 75% Correct Answer: B) About 25% In-Depth Explanation: A) Incorrect. The side effect is observed in about 25% of men. B) Correct. About one-quarter of men (or about 25%) on nilutamide therapy note this side effect. C) Incorrect. The rate is about 25%, not 50%. D) Incorrect. The rate is about 25%, not 75%. Memory Tool: Remember the word "Quarter-Nilu" to associate one-quarter (25%) with Nilutamide. Reference Citation: Paragraph 2 Rationale: Understanding the side effects of specific drugs is essential for patient management and counseling.

Answer 170

Correct Answer: D) 61% In-Depth Explanation: A) Incorrect. The trial noted 52% metastatic, not 20%. B) Incorrect. 41% is not mentioned in the STAMPEDE trial. C) Incorrect. While 52% metastatic is noted in one STAMPEDE trial, the question asks for the percentage in another. D) Correct. 61% of the patient population had metastatic disease. Memory Tool: "STAMPEDE Sixty-one" can help you remember that 61% had metastatic disease in one of the STAMPEDE trials. Reference Citation: Table 161.3 Rationale: For comprehensive care and evidence-based practice, being familiar with landmark clinical trials is crucial.

Answer 171

Correct Answer: D) 95% In-Depth Explanation: A) Incorrect. The decrease is approximately 95%, not 50%. B) Incorrect. The decrease is approximately 95%, not 75%. C) Incorrect. The decrease is approximately 95%, not 85%. D) Correct. Orchiectomy leads to an approximate 95% decrease in serum testosterone within 6 hours. Memory Tool: Remember "Orchi-95" to associate orchiectomy with a 95% decrease. Reference Citation: Key Points, Bullet Point 2 Rationale: This information is key for patient counseling and making informed decisions about treatment options.

Answer 172

Correct Answer: C. Inhibition of insulin secretion Explanation: A, B, and D are established mechanisms for androgen blockade. C is incorrect as insulin secretion inhibition does not play a role in androgen blockade. Memory Tool: Remember the acronym "SOIL" for Surgical Orchiectomy, Inhibition of LHRH, and AR antagonism. 'Insulin' doesn't fit. Reference Citation: Paragraph 1. Rationale: Understanding the mechanisms of androgen blockade is crucial for the appropriate management of prostate cancer patients.

Answer 173

Correct Answer: A) NCIC PR.7 In-depth Explanation: A: Correct. NCIC PR.7 showed that intermittent ADT was not inferior to continuous ADT in terms of overall survival (Table 161.3). B: Incorrect. SWOG-9346 concluded that noninferiority was not established between intermittent and continuous ADT (Table 161.3). C: Incorrect. GETUG-AFU15 involved ADT and docetaxel; it didn't compare intermittent and continuous ADT (Table 161.3). D: Incorrect. LATITUDE involved high-risk metastatic cases and compared ADT plus abiraterone to ADT plus placebo (Table 161.3). Memory Tool: NCIC PR.7 = "Non-Continuous Is Comparable, Provided Results 7" Specific Reference Citation: Campbell's Urology, Table 161.3 Rationale: Understanding landmark trials informs evidence-based treatment choices.

Answer 174

Correct Answer: C. Reduced production of aldosterone and cortisol Explanation: Aminoglutethimide inhibits a very proximal step in adrenal function, blocking the production of both aldosterone and cortisol. This is equivalent to a total adrenalectomy medically, and thus, cortisone and fludrocortisone replacement is required. Memory Tool: Think "Amino-NO-glutethimide" because it stops (NO) the adrenal glands from making aldosterone and cortisol. Rationale: Understanding the side effects of medications used in androgen blockade is crucial for patient management. Reference: Paragraph 5, Mechanisms of Androgen Blockade (Campbell's Urology).

Answer 175

Correct Answer: C. Abiraterone plus prednisone significantly extends radiographic progression-free and overall survival. Explanation: The LATITUDE trial concluded that abiraterone plus prednisone (along with traditional ADT) was superior in extending median radiographic progression-free (33.0 vs. 14.8 months) and overall survival (not reached vs 34.7 months, HR = 0.62). Memory Tool: Think "Latitude gives you more room to move" — more room for survival and freedom from progression. Rationale: Choosing an evidence-based treatment approach improves outcomes for high-risk prostate cancer patients. Reference: Paragraph 6 and Table 161.3, Mechanisms of Androgen Blockade (Campbell's Urology).

Answer 176

Correct Answer: B. Docetaxel significantly improves overall survival and failure-free survival. Explanation: The STAMPEDE trial demonstrated that adding docetaxel to standard hormone therapy improved overall survival by 24% and failure-free survival by 40% for men with newly diagnosed metastatic prostate cancer. Memory Tool: Think of a "stampede" as an overwhelming force, just like the added benefit of docetaxel in treatment. Rationale: Being aware of recent trials like STAMPEDE can help in optimizing treatment plans for high-risk prostate cancer patients. Reference: Table 161.3, Mechanisms of Androgen Blockade (Campbell's Urology).

Answer 177

Correct Answer: B. Adding chemotherapy to ADT improves overall survival. Explanation: The CHARTEED trial showed that the addition of chemotherapy (docetaxel) to ADT improved overall survival in patients with metastatic hormone-sensitive prostate cancer. This is especially true for patients with high-volume disease. Memory Tool: Think "CHART the course with ED (Early Docetaxel)" to remember the CHARTEED findings. Rationale: Inclusion of evidence-based treatments like those suggested by CHARTEED can provide better outcomes. Reference: Table 161.3, Mechanisms of Androgen Blockade (Campbell's Urology).

Answer 178

Correct Answer: B) ALP levels serve as a surrogate for volume of skeletal metastases Explanation: A) Incorrect. While ALP is often a marker for liver function, in this context it is a surrogate for skeletal metastases. B) Correct. ALP is the strongest predictor for overall survival and acts as a surrogate for the volume of skeletal metastases in patients with prostate cancer. C) Incorrect. ALP levels are actually the strongest predictor for overall survival in this case. D) Incorrect. ALP in this case is not an indicator for blood calcium levels. Memory Tool: Think of ALP as "A Link to Prognosis" in metastatic prostate cancer. Reference Citation: Paragraph 2; Campbell's Urology Rationale: Monitoring ALP levels in metastatic prostate cancer patients on ADT is essential for assessing prognosis. Understanding this aspect is vital for medical professionals.

Answer 179

Correct Answer: B) Ensure adequate intake of calcium and vitamin D3 In-Depth Explanation: A) Treatment of osteoporosis begins with recognition, but the text suggests proactively ensuring calcium and vitamin D3 intake for all men starting ADT. (Line: "Treatment of osteoporosis begins with recognition.") B) All men starting ADT should ensure adequate intake of calcium and vitamin D3 to mitigate the risk of fracture. (Line: "To mitigate risk of fracture, all men starting ADT (regardless of fracture risk) should ensure adequate intake of calcium and vitamin D3.") C) Prophylactic radiation therapy is used to prevent or reduce painful gynecomastia, not to mitigate the risk of fracture. (Line: "Prophylactic radiation therapy (10–15 Gy, single fraction) has been used to prevent or reduce painful gynecomastia.") D) Treatment of hot flashes is not related to the mitigation of fracture risk. (Line: "Treatment of hot flashes should be reserved for those men who find them particularly bothersome.") Memory Tool: Think of the "D3-Bone Connection" to remember that Vitamin D3 and calcium are essential for bone health in men on ADT. Reference Citation: General text for each answer choice. Rationale: Recognizing and mitigating the risks associated with long-term ADT, such as fracture risk, are crucial in comprehensive patient care.

Answer 180

Correct Answer: B) A significant castrate-resistant cell population is present. In-Depth Explanation: A) This choice is incorrect as an incomplete or sluggish response to ADT is evidence of a significant castrate-resistant cell population. (Line: "an incomplete or sluggish response is evidence of a significant castrate-resistant cell population.") B) An incomplete or sluggish response to ADT implies that there is a significant castrate-resistant cell population in the patient. (Line: "an incomplete or sluggish response is evidence of a significant castrate-resistant cell population.") C) The vignette does not provide information regarding the patient's adherence to the treatment regimen. D) While duration may influence ADT response, an incomplete or sluggish response specifically indicates a castrate-resistant cell population. (Line: "an incomplete or sluggish response is evidence of a significant castrate-resistant cell population.") Memory Tool: Remember "CRISP" for "Castrate-Resistant Incomplete or Sluggish Response to Prostate treatment" to recall the significance of incomplete or sluggish response. Reference Citation: General text for the explanation of each answer choice. Rationale: Understanding the implications of an incomplete or sluggish response to ADT is crucial for treatment adjustment and future management.

Answer 181

Correct Answer: B) Gabapentin (900 mg) In-Depth Explanation: A) Venlafaxine is mentioned but not described as having a moderate decrease in hot flashes in the provided study. (Line: "A randomized trial of 311 men on ADT with hot flashes evaluated venlafaxine (75 mg/daily).") B) Gabapentin at a dose of 900 mg decreased hot flashes to a moderate degree according to a phase III trial. (Line: "the highest studied dose of gabapentin (900 mg) decreased hot flashes to a moderate degree.") C) Medroxyprogesterone acetate is mentioned but not in the context of a phase III trial decreasing hot flashes to a moderate degree. (Line: "A randomized trial of 311 men on ADT with hot flashes evaluated...medroxyprogesterone acetate (20 mg/daily).") D) Cyproterone acetate is mentioned but not in the context of a phase III trial decreasing hot flashes to a moderate degree. (Line: "A randomized trial of 311 men on ADT with hot flashes evaluated...cyproterone acetate (100 mg/daily).") Memory Tool: Think of "Gabapentin for Getting a Break" from hot flashes to remember that gabapentin can moderately decrease hot flashes. Reference Citation: Loprinzi et al., 2009 for gabapentin and general text for other options. Rationale: Hot flashes can be a bothersome side effect of ADT; knowing the treatment options backed by scientific evidence is essential.

Answer 182

Correct Answer: C) PSA In-Depth Explanation: A) Hemoglobin is associated with treatment response but is not described as a strong, independent predictor of survival after 7 months of ADT. (Line: "In castration-sensitive prostate cancer, treatment response is associated with bone metastases, symptoms, and serum ALP, hemoglobin, and LDH levels.") B) ALP is a surrogate for volume of skeletal metastases and a predictor for overall survival, but it is not specifically linked to survival after 7 months of ADT. (Line: "The strongest predictor for overall survival was ALP, a surrogate for volume of skeletal metastases.") C) PSA after 7 months of ADT was described as a strong, independent predictor of survival. (Line: "PSA after 7 months of ADT was a strong, independent predictor of survival.") D) LDH is associated with treatment response but is not described as a strong, independent predictor of survival after 7 months of ADT. (Line: "In castration-sensitive prostate cancer, treatment response is associated with bone metastases, symptoms, and serum ALP, hemoglobin, and LDH levels.") Memory Tool: Think "7th Heaven for PSA" to remember that PSA after 7 months is a key survival predictor. Reference Citation: Hussain et al., 2009 and general text for the explanation of each answer choice. Rationale: Knowing which biomarkers to watch can guide clinicians in evaluating the efficacy and potential durability of ADT treatment.

Answer 183

Correct Answer: D) All of the above In-Depth Explanation: A) Regular bone mineral density examinations are recommended for men on ADT. (Line: "patients should have regular bone mineral density examinations.") B) Adequate intake of calcium and vitamin D3 is recommended for all men starting ADT. (Line: "all men starting ADT should ensure adequate intake of calcium and vitamin D3.") C) Cessation of smoking is recommended for all men starting ADT. (Line: "be encouraged to quit smoking tobacco.") D) All of the mentioned measures should be considered to mitigate the risk of fractures. Memory Tool: Think "ABC of ADT Fracture Care" for "All Bone-exams, Calcium/Vitamin D3, and Cessation of smoking." Reference Citation: General text for the explanation of each answer choice. Rationale: Understanding preventive measures to mitigate the risk of fractures can help to manage the potential complications of long-term ADT.

Answer 184

Correct Answer: B) Time from castration-sensitive prostate cancer to castration resistance In-Depth Explanation: A) Overall survival is not specifically associated with BSI in the material provided. (Line: "Bone scan index (BSI), an automated method...") B) BSI has been directly and independently associated with the time from castration-sensitive prostate cancer to castration resistance. (Line: "has been directly and independently associated with time from castration-sensitive prostate cancer to castration resistance.") C) PSA levels are not specifically associated with BSI. (Line: "Bone scan index (BSI), an automated method...") D) Efficacy of ADT is not specifically associated with BSI. (Line: "Bone scan index (BSI), an automated method...") Memory Tool: Think "BSI to Bye-Bye Sensitivity" to remember BSI is linked with moving from castration-sensitive to castration-resistant prostate cancer. Reference Citation: Poulsen et al., 2016; Zacho et al., 2017, and general text for each answer choice. Rationale: Understanding the utility of BSI can guide clinicians in monitoring progression from castration-sensitive to castration-resistant prostate cancer.

Answer 185

Correct Answer: C) Gabapentin In-Depth Explanation: A) Venlafaxine was studied but was not specifically mentioned to decrease hot flashes to a moderate degree. (Line: "A randomized trial of 311 men on ADT with hot flashes evaluated venlafaxine...") B) Medroxyprogesterone was studied but was not specifically mentioned to decrease hot flashes to a moderate degree. (Line: "superiority to medroxyprogesterone and cyproterone.") C) Gabapentin at a dose of 900 mg decreased hot flashes to a moderate degree. (Line: "the highest studied dose of gabapentin (900 mg) decreased hot flashes to a moderate degree.") D) Cyproterone was studied but was not specifically mentioned to decrease hot flashes to a moderate degree. (Line: "superiority to medroxyprogesterone and cyproterone.") Memory Tool: Think "Cool it with Gabapentin" to remember that Gabapentin moderates hot flashes. Reference Citation: Loprinzi et al., 2009, and general text for each answer choice. Rationale: Hot flashes can be particularly bothersome, and knowing the moderate effectiveness of Gabapentin can help in patient management.

Answer 186

B) HSD3B1 In-Depth Explanation: A) ALP is a predictor for overall survival and volume of skeletal metastases, not specifically for resistance to ADT. (Line: "The strongest predictor for overall survival was ALP, a surrogate for volume of skeletal metastases.") B) Germline HSD3B1 variants are predictive biomarkers for response and ultimate resistance to ADT. (Line: "Collectively, the data suggest germline HSD3B1 variants are a predictive biomarker for response and ultimate resistance to ADT.") C) PSA is used for measuring the effectiveness of ADT but is not mentioned as a biomarker for resistance. (Line: "After initiation of ADT, the majority of prostate cancer patients exhibit a clinical response...") D) BSI is associated with time from castration-sensitive to castration-resistant prostate cancer but is not a biomarker for resistance to ADT. (Line: "Bone scan index (BSI), an automated method...") Memory Tool: Think "HSD3B1 Helps Screen Deception of ADT" to remember that HSD3B1 is useful in predicting resistance to ADT. Reference Citation: Text for each answer choice and line numbers. Rationale: Understanding biomarkers like HSD3B1 can offer insights into the patient's potential response to ADT, helping to tailor treatment plans.

Answer 187

Topic: Osteoporosis Management Vignette: You have a patient who is about to start ADT. What step is recommended for all men regardless of their fracture risk when initiating ADT? Multiple-Choice Options: A) Regular bone mineral density examinations B) Quit smoking tobacco C) Ensure adequate intake of calcium and vitamin D3 D) Engage in weight-bearing exercise

Answer 188

Correct Answer: B. Radiation and orchiectomy Explanation: A. Radiation alone showed a high frequency of progression (Line 2, Granfors et al., 1998) B. Radiation and orchiectomy showed significant improvements in clinical progression, overall mortality, and prostate cancer-specific mortality (Line 4-6, Granfors et al., 1998). C. Radiation combined with goserelin showed improvement, but in progression-free survival and overall survival, not in clinical progression, overall mortality, and prostate cancer-specific mortality (Line 9-11, Bolla et al., 2010). D. Bilateral surgical adrenalectomy had failure far outweighing success (Line 18, Huggins and Scott, 1945). Memory Tool: Think "RO" for Radiation and Orchiectomy to remember the superior treatment outcome. Rationale: Understanding the best treatment combination is essential for optimum patient care.

Answer 189

Correct Answer: C. ADT with abiraterone acetate Explanation: A. ADT alone is less effective compared to combinations (Line 32, Fizazi et al., 2017). B. ADT with goserelin is not specifically mentioned for mCSPC with high-risk features (Not in material). C. ADT with abiraterone acetate showed a significant improvement in overall survival, especially for high-risk mCSPC (Line 31-33, Fizazi et al., 2017). D. Docetaxel with ADT is a standard, but not specifically highlighted for superior overall survival in high-risk mCSPC (Line 39). Memory Tool: A.B.I. for A Better Improvement with ADT and Abiraterone in mCSPC. Rationale: Making evidence-based choices for mCSPC treatment is crucial.

Answer 190

Correct Answer: B. ADT concurrent with and after radiation Explanation: A. No proven role for presurgical hormonal therapy in combination with surgery (Line 34). B. ADT concurrent with and after radiation is the standard care for high-risk localized disease treated with radiation (Line 35). C. & D. These are standards for metastatic forms but not specified for high-risk localized disease (Line 37 & 39). Memory Tool: Remember "High Rad" for High-risk and Radiation + ADT. Rationale: Adhering to standard care guidelines improves treatment outcomes.

Answer 191

Correct Answer: B. Radiation and goserelin Explanation: A. Radiation and docetaxel isn't highlighted for dramatic improvements in the material (Not in material). B. Radiation and goserelin showed dramatic improvement in progression-free and overall survival (Line 10-11, Bolla et al., 2010). C. Radiation and orchiectomy showed improvements, but the focus was not on progression-free survival and overall survival (Line 4-6, Granfors et al., 1998). D. Radiation and abiraterone isn't specifically mentioned in relation to progression-free and overall survival (Not in material). Memory Tool: "Go Radiant!" - "GOserelin" makes "RADIation" more effective. Rationale: Knowledge of the long-term effects of treatments aids in better patient management.

Answer 192

Correct Answer: B. Allowed advanced CSPC with a variety of disease stages Explanation: A. Focused on high-risk disease was a feature of another landmark study (Line 31, Fizazi et al., 2017). B. STAMPEDE trial had looser inclusion criteria allowing advanced CSPC in different stages (Line 35-36, James et al., 2017). C. & D. These were not the unique features of the STAMPEDE trial (Not in material). Memory Tool: Think "STAMPEDE lets everyone in" to remember its diverse inclusion criteria. Rationale: Understanding the inclusion criteria of trials helps interpret the applicability of findings.

Answer 193

Correct Answer: C) Primary ADT significantly lowers the risk of all-cause mortality only in men with high risk of prostate cancer progression. In-depth Explanation: A) Incorrect. According to the material, primary ADT does not significantly improve overall survival for most men with clinically localized prostate cancer. B) Incorrect. Primary ADT did not alter the risk of prostate cancer-specific mortality according to a retrospective cohort study (Potosky et al., 2014). C) Correct. Primary ADT is associated with decreased risk of all-cause mortality only in men at high risk of prostate cancer progression. D) Incorrect. Primary ADT did not alter the risk of all-cause mortality for all men with localized prostate cancer. Memory Tool: Remember "High-C Primary ADT" to recall that Primary ADT is effective in lowering all-cause mortality for men at "High risk" of prostate "Cancer" progression. Reference Citation: (Potosky et al., 2014) Rationale: This question addresses the nuanced use of primary ADT in the context of age and risk stratification. Knowing when to administer primary ADT is essential for optimal patient care.

Answer 194

Correct Answer: C) Immediate ADT has an overall survival advantage in some patients with biochemically recurrent prostate cancer. In-depth Explanation: A) Incorrect. According to a study by Duchesne et al., immediate ADT has shown an overall survival advantage (HR=0.55, P=0.047). B) Incorrect. The same study suggests that immediate ADT can offer a survival advantage. C) Correct. The study suggests early ADT may be of value for some patients with recurrent disease. D) Incorrect. Immediate ADT has shown an overall survival advantage in the study. Memory Tool: Think "I-ADT can be ICY" where "I-ADT" stands for Immediate ADT and "ICY" stands for "Immediate Can Yield" benefits. Reference Citation: (Duchesne et al., 2016) Rationale: The question aims to clarify the timing of ADT initiation in the setting of biochemically recurrent prostate cancer, which is a topic often confronted in clinical practice.

Answer 195

Options: A) Recommend primary ADT to reduce all-cause mortality B) Recommend against primary ADT as it does not provide a survival benefit C) Recommend primary ADT to reduce prostate cancer-specific mortality D) The use of primary ADT is independent of age Correct Answer: B) Recommend against primary ADT as it does not provide a survival benefit Explanation: Primary ADT does not provide a survival benefit for most men with clinically localized prostate cancer, particularly those over 65 (Shahinian et al., 2006; Potosky et al., 2014). Memory Tool: Think "Primary ADT = Primarily Not Helpful" for localized prostate cancer in elderly men. Reference: Shahinian et al., 2006; Potosky et al., 2014 Rationale for the Question: This question tests your knowledge on the appropriate timing and efficacy of primary ADT, especially in older patients.

Answer 196

Correct Answer: B) 1.5 years Explanation: The median overall survival in the immediate ADT group was 7.6 years vs. 6.1 years in the delayed ADT group (Schroder et al., 2009). Memory Tool: Think "Immediate gives you a 'One-and-a-Half' year bonus" to remember the 1.5-year advantage. Reference: Schroder et al., 2009 Rationale for the Question: This question explores the difference in survival benefits between immediate and delayed ADT, a crucial clinical decision point.

Answer 197

Correct Answer: D Explanation: A: Incorrect. Immediate ADT may be considered, depending on multiple factors like PSA doubling times (Dale et al., 2009). B: Incorrect. The decision for immediate ADT depends on various factors like PSA levels, doubling times, and patient anxiety (Dale et al., 2009). C: Incorrect. PSA doubling time is one of the factors considered for initiation of ADT (Dale et al., 2009). D: Correct. Immediate ADT has shown an overall survival advantage (HR = 0.55, P = 0.047) (Duchesne et al., 2016). Memory Tool: "ADT ASAP" can improve overall survival in biochemically recurrent prostate cancer. Reference Citation: Duchesne et al., 2016 Rationale: Knowing when to initiate ADT in biochemically recurrent prostate cancer can significantly affect patient outcomes.

Answer 198

Correct Answer: C In-Depth Explanation for Each Answer: A) Incorrect. A retrospective study found that primary ADT did not alter the risk of all-cause mortality (Potosky et al., 2014). B) Incorrect. Primary ADT was also found not to alter prostate cancer-specific mortality (Potosky et al., 2014). C) Correct. Primary ADT was associated with a decreased risk of all-cause mortality only in men at high risk of prostate cancer progression. D) Incorrect. Up to 40% of men over 65 have received ADT, but it is not beneficial for overall survival (Shahinian et al., 2006). Memory Tool: Think "High Risk, High Reward" - Primary ADT is beneficial only for high-risk cases. Reference Citation: Potosky et al., 2014; Shahinian et al., 2006. Rationale: Knowledge about the limitations of Primary ADT is crucial for appropriate treatment planning and patient counseling.

Answer 199

Correct Answer: B In-Depth Explanation for Each Answer: A) Incorrect. The median overall survival for immediate ADT was 7.6 years versus 6.1 years for delayed ADT, which is not more than a 2-year difference (Schroder et al., 2009). B) Correct. The 10-year cumulative incidence of death was 55.6% in the delayed group and 52.1% in the immediate group, showing no significant difference (Schroder et al., 2009). C) Incorrect. The study was not designed or powered to show the superiority of immediate ADT. D) Incorrect. Noninferiority was not established in the study. Memory Tool: Think "Immediate or Delayed, Death’s Still Played" - Immediate vs. delayed ADT didn't significantly alter the 10-year death rate. Reference Citation: Schroder et al., 2009 Rationale: Understanding that noninferiority was not established helps in making evidence-based decisions on timing of ADT.

Answer 200

Correct Answer: D. Dehydroepiandrosterone Explanation: A: Testosterone, produced mainly by the testes, is one of the potent androgens that maintains prostate epithelium. It's not the answer. B: Dihydrotestosterone (DHT) is converted from testosterone and has a potency between 160-190, making it quite effective in maintaining prostate epithelium. C: Androstenedione, although weaker compared to testosterone, still has a relative potency of 39, which isn't insufficient for maintaining the prostate epithelium. D: Dehydroepiandrosterone (DHEA) is produced in the adrenal glands and has a relative potency of just 15, making it insufficient for maintaining prostate epithelium in castrated men, according to Walsh and Siiteri, 1975. Memory Tool: "D-Efficient: DHEA is deficient for the prostate." Reference: Paragraph 2, Walsh and Siiteri, 1975. Rationale for Question: The importance of knowing the relative potency and sources of different androgens is crucial for understanding the pathophysiology and treatment options for conditions like prostate cancer.

Canadian Urological Association guideline on androgen deprivation therapy: Adverse events and management strategies Flashcards

(225 cards)