Prostate Cancer Flashcards by Kim Nguyen

Goals of therapy: localized disease

control disease and symptoms; decrease morbidity and mortality

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Goals of therapy: advanced or metastatic disease

palliation- symptom relief; improve QoL, prolong survival

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Factors to consider for prostate cancer treatment

comorbidities, symptoms, recurrence risk, life expectancy, disease stage (clinically localized and regional disease treatment is based on risk stratification rather than stage)

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Generally speaking, if the prostate cancer is localized and hasn’t metastasized yet, what do you do?

Observation or active surveillance

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Castrate level/goal for serum testosterone

Serum testosterone <50ng/dl

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Gold standard treatment for advanced prostate cancer

ADT

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Medical castration for ADT

LHRH agonist +/- antiandrogen: combined androgen blockade

LHRH antagonist

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Castration-sensitive prostate cancer treatment

combined modality approach as initial therapy for castration sensitive or naiïve prostate cancer for select high-risk and metastatic patients

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Castration-sensitive prostate cancer regimens

ADT + abiraterone OR apalutamide OR enzalutamide
ADT with docetaxel x6 cycles AND abiraterone OR darolutamide

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Castration resistant prostate cancer (CRPC) definition

Definition: serum testosterone <50ng/dl AND disease progression

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How to approach treating CRPC

Continue ADT and maintain castrate levels while adding on other therapies
Therapy based on whether patient has nonmetastatic or metastatic disease

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CRPC: patient has M0 disease (not metastatic)…treatment is based on what?

PSA doubling time within 10 months

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If PSA doubling time in M0 CRPC is >10 months, what do you do?

Monitor or give secondary hormone therapy

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If PSA doubling time in M0 CRPC is ≤10 months, what do you do?

Add on apalutamide, enzalutamide, darolutamide, or other secondary hormone therapy

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CRPC: patient has M1 disease (metastatic)…what is treatment based on?

Histology and prior therapy

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CRPC with M1 disease treatment: no prior docetaxel/no prior novel hormone therapy

Abiraterone
Docetaxel
Enzalutamide

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CRPC with M1 disease treatment: prior novel hormone therapy and no prior docetaxel

Docetaxel

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CRPC with M1 disease treatment: prior docetaxel and no prior novel hormone therapy

abiraterone, cabazitaxel

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CRPC with M1 disease treatment: prior docetaxel and hormone therapy

Cabazitaxel, docetaxel rechallenge

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First-line treatment options: visceral metastases

Consider docetaxel if patient hasn’t received and patient is fit for chemo

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First-line treatment options: no visceral metastases

treat based on prior therapy

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First-line treatment options: symptomatic bone metastases

Radium-223

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First-line treatment options: asymptomatic or minimally symptomatic, no liver metastases, life expectancy >6 months, good ECOG performance status

Sipuleucel-T

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LHRH agonists

Gosrelin, leuprolide, triptorelin, histrelin

LHRH agonist place in prostate cancer therapy

ADT

LHRH agonist acute AEs

tumor flare, hot flashes, ED, edema, gynecomastia, injection site reactions

LHRH agonist long-term AEs

osteoporosis, clinical fracture, obesity, insulin resistance, increased risk of DM, Cv events, HLD

Initial tumor flare when using LHRH agonists is caused by what?

Surge in LH/FSH release and increases testosterone production (presents as increased bone pain or increased urinary symptoms but resolves in 2 weeks)

LHRH agonist monitoring and management

Baseline bone mineral density test before starting long-term ADT calcium and Vitamin D supplementation

LHRH antagonists used in prostate cancer

Degarelix, relugolix

2nd generation antiandrogens used in prostate cancer

Apalutamide, darlutamide, enzalutamide

Apalutamide AEs

Fatigue, HTN, rash, diarrhea, nausea, arthralgias, fracture risk, peripheral edema SEIZURES!!!!!!!! D/C PERMANENTLY IN PATIENTS WHO DEVELOP A SEIZURE DURING TREATMENT

Apalutamide place in therapy

Secondary hormonal therapy for M0 and PSADT ≤10 months

Darlutamide place in therapy

Same as apalutamide

Darlutamide AEs

Fatigue, HTN, rash No increase in seizures

Darlutamide dose adjustment

300mg BID with food if CrCl 15-29ml/min

Enzalutamide AEs

Diarrhea, fatigue, HA, myalgias, edema Increased risk of seizures

Enzalutamide dose adjustments

Strong CYP2C8 inhibitor: 80mg PO QD Strong CYP3A4 inducers: 240mg PO QD

Docetaxel place in prostate cancer therapy

CRPC treatment option

Docetaxel AEs

Myelosuppression Alopecia Edema Peripheral neuropathy Hypersensitivity reaction

Docetaxel and hepatic impairment

CAUTION! Use not recommended with Tbili > ULN, or AST and/or ALT >1.5x ULN concomitant with alk phos >2.5x ULN

Abiraterone place in prostate cancer therapy

CRPC treatment option

Abiraterone AEs

Diarrhea Edema Hypokalemia HTN Hepatotoxicity Hypertriglyceridemia

Abiraterone should be given with what?

Steroids (like prednisone) to minimize signs of mineralocorticoid excess

Are the 2 formulations of abiraterone interchangeable?

Abiraterone monitoring

LFTs, potassium and phosphate levels, BP on monthly basis

Radium-223 place in prostate cancer therapy

Symptomatic bone metastases and no visceral metastases prior to and after docetaxel therapy

Radium-223 AEs

Peripheral edema, nausea, myelosuppression

Is radium-223 used in combo with chemo?

Sipuleucel-T place in prostate cancer therapy

Asymptomatic or minimally symptomatic, no liver metastases, life expectancy >6 months, ECOG performance status in M1 CRPC

Sipuleucel-T AEs

Infusion reaction Chills Fever Fatigue HA

Cabazitaxel place in prostate cancer therapy

Second-line therapy in CRPC

Cabazitaxel AEs

Febrile neutropenia Hypersensitivity reaction Mucositis Edema

Cabazitaxel clinical pearl

Poor affinity for MDR proteins → confers activity in resistant tumors and has activity in docetaxel resistance

Lu-177-PSMA-617 place in therapy

Second-line therapy in CRPC PSMA-positive M1 CRPC

Lu-177-PSMA-617 AEs

Fatigue Dry mouth Nausea Myelosuppression

Denosumab place in prostate cancer therapy

Androgen deprivation-induced bone loss in prostate cancer (general osteoporosis/bone loss)

Denosumab dosing difference

Dosing in cancer is different than for osteo