Prostate Cancer Flashcards
Goals of therapy: localized disease
control disease and symptoms; decrease morbidity and mortality
Goals of therapy: advanced or metastatic disease
palliation- symptom relief; improve QoL, prolong survival
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)
Generally speaking, if the prostate cancer is localized and hasn’t metastasized yet, what do you do?
Observation or active surveillance
Castrate level/goal for serum testosterone
Serum testosterone <50ng/dl
Gold standard treatment for advanced prostate cancer
ADT
Medical castration for ADT
LHRH agonist +/- antiandrogen: combined androgen blockade
LHRH antagonist
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
Castration-sensitive prostate cancer regimens
ADT + abiraterone OR apalutamide OR enzalutamide
ADT with docetaxel x6 cycles AND abiraterone OR darolutamide
Castration resistant prostate cancer (CRPC) definition
Definition: serum testosterone <50ng/dl AND disease progression
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
CRPC: patient has M0 disease (not metastatic)…treatment is based on what?
PSA doubling time within 10 months
If PSA doubling time in M0 CRPC is >10 months, what do you do?
Monitor or give secondary hormone therapy
If PSA doubling time in M0 CRPC is ≤10 months, what do you do?
Add on apalutamide, enzalutamide, darolutamide, or other secondary hormone therapy
CRPC: patient has M1 disease (metastatic)…what is treatment based on?
Histology and prior therapy
CRPC with M1 disease treatment: no prior docetaxel/no prior novel hormone therapy
Abiraterone
Docetaxel
Enzalutamide
CRPC with M1 disease treatment: prior novel hormone therapy and no prior docetaxel
Docetaxel
CRPC with M1 disease treatment: prior docetaxel and no prior novel hormone therapy
abiraterone, cabazitaxel
CRPC with M1 disease treatment: prior docetaxel and hormone therapy
Cabazitaxel, docetaxel rechallenge
First-line treatment options: visceral metastases
Consider docetaxel if patient hasn’t received and patient is fit for chemo
First-line treatment options: no visceral metastases
treat based on prior therapy
First-line treatment options: symptomatic bone metastases
Radium-223
First-line treatment options: asymptomatic or minimally symptomatic, no liver metastases, life expectancy >6 months, good ECOG performance status
Sipuleucel-T
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?
No
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?
NO
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
