PHP528 prostate cancer

which type of cancer is normally asymptomatic?

local prostate cancer

which second generation anti androgen is once a day dosing which second generation anti androgen is twice a day dosing

- Enzalutamide - apalutamide - darolutamide

Treatment for localized disease (3)

- active surveillance (AS) or observation - radical prostatectomy - radiation therapy

Prostate cancer treatment options (5)

- active surveillance or observation - radical prostatectomy - radiation therapy - androgen deprivation therapy - chemotherapy/immunotherapy/targeted therapy

advanced/metastatic disease cancer symptoms (3)

- back pain - cord compression - pathologic fractures

LHRH antagonists drugs (2)

- degarelix - relugolix

Non-metastatic Castration-Resistant Prostate Cancer, continue ADT and add: (3)

- enzalutamide - apalutamide - darolutamide

LHRH agonist drugs

- goserelin - leuprolide - triptorelin

LHRH agonist drugs

- goserelin - leuprolide - triptorelin

Targeted therapy for metastatic Castration-Resistant Prostate Cancer (2 drugs) Poly ADP-ribose polymerase inhibitors(PARP inhibitors)

- olaparib - rucaparib

Immunotherapy for metastatic Castration-Resistant Prostate Cancer

- sipuleucel-T - Pembrolizumab

locally invasive prostate cancer symptoms (3)

- urinary hesitancy - dribbling - impotence

SE of 1) enzalutamide 2) apalutamide 3) darolutamide

1) fatigue, fall, hypertension, seizure 2) fatigue, rash, hypothyroidism 3) fatigue, rash, extremity pain

ADT associated osteoporosis prevention •_____________1200 mg daily and _____________ 800-1000 IU daily •Bone-Targeting Agents: o____________________ 70 mg PO weekly o_________________ acid 5 mg (Reclast®) IV annually o__________________ 60 mg (Prolia®) SQ q 6 months

ADT associated osteoporosis prevention •Calcium 1200 mg daily and Vitamin D3 800-1000 IU daily •Bone-Targeting Agents: oAlendronate 70 mg PO weekly oZoledronic acid 5 mg (Reclast®) IV annually oDenosumab 60 mg (Prolia®) SQ q 6 months

ADT side effects •Acute: (5) •Long-term: (5)

ADT side effects •Acute: oTumor flare (LHRH agonists), oGynecomastia, oHot flashes, oErectile dysfunction, oInjection site reaction •Long-term: oOsteoporosis, oFracture, oObesity, oInsulin resistance, oIncreased risk of diabetes and cardiovascular events

Active surveillance and observation •Monitor _______,______ and _____________ •Initiate therapy if a significant change occurs: oActive surveillance: ___________ intent for ____________ patients oObservation: ____________intent for __________ patients •Advantages: (2) o - •Disadvantages: o o o

Active surveillance and observation •Monitor PSA,DRE and symptoms •Initiate therapy if a significant change occurs oActive surveillance: Curative intent for younger patients oObservation: Palliative intent for older patients •Advantages: oAvoid side effects from unnecessary treatment oMaintain quality of life •Disadvantages: oMissed opportunity for cure oCancer may progress, more difficult surgery with larger cancer oAnxiety of living with an untreated cancer

Initial therapy for localized disease for younger patients with low risk and very low risk

Active surveillance or observation

Androgen Deprivation Therapy 1) ___________________ castration •(LHRH) •(LHRH) 2) _____________ castration •_______________: Removal of testicles Goal of therapy is to.....

Androgen Deprivation Therapy 1) chemical castration •Luteinizing hormone-releasing hormone (LHRH) agonists •Luteinizing hormone-releasing hormone (LHRH) antagonists 2) surgical castration •Orchiectomy: Removal of testicles Goal of therapy is to induce castrate levels of testosterone (< 50 ng/dl)

when is sipuleucel -T used

Asymptomatic or minimally symptomatic metastatic CRPC

RC is a 72 year old man with a history of prostate cancer currently managed with leuprolide, 5 months ago his PSA=5ng/mL, todays PSA level =15 ng/mL and testosterone is in castration level, CT scan shows no metastatic disease, the patient has non metastatic castration-resistant prostate cancer. Which is the most appropriate treatment option for RC? a) pembrolizumab B) bicalutamide C) apalutamide D) docetaxel

C) apalutamide

BF is a 70 year old man in his usual health until recently he has been expereicing back pain and difficulty in urination. His PSA is 50 ng/mL, abnormal DRE, further workup shows that he has mestatatic prostate cancer, a bone scan reveals multiple metastatic bone lesions, CT scan shows additional distant metastatic disease to the lung and liver, BF was diagnosed with metastatic castration sensitive prostate cancer (m1CSPC). BF was started on ADT with leuprolide 7.5 mg IM q month, which of the following is the most appropriate option in addition to leuprolide a) carbazitaxel b) rucaparib c) docetaxel + darolutamide d) paclitaxel + pembrolizumab

C) docetaxel + darolutamide

degarelix SE

Hot flashes, LFT elevation, injection site reaction

Relugolix SE

Hot flashes, constipation, diarrhea, fatigue, muscular pain

Intermittent androgen deprivation •_______ for defined period of time, followed by break in ADT until ______ returns to _____________ level •Potential advantages: oDecreased ___________________ oDecreased _________ oMay delay _____________________________________ •Option for men with _________________disease

Intermittent androgen deprivation •ADT for defined period of time, followed by break in ADT until PSA returns to pre‐specified level •Potential advantages: oDecreased adverse effects oDecreased costs oMay delay androgen independence •Option for men with nonmetastatic disease

LHRH antagonist vs LHRH agonist why would LHRH antagonists be better than LHRH agonists? LHRH agonist •May require concomitant use of anti-androgen when initiating treatment due to testosterone flare •Delivered every 1, 3, 4, and 6 months •Useful for patient wants less frequent dosing

LHRH antagonist vs LHRH agonist - no tumor flare - ideal for patients who need rapid reduction in testosterone and disease response - lower risk for cardiovascular events comparing to LHRH agnoist LHRH agonist •May require concomitant use of anti-androgen when initiating treatment due to testosterone flare •Delivered every 1, 3, 4, and 6 months •Useful for patient wants less frequent dosing

Olaparib o300 mg PO ________ o__________________________________________ (BRCA1, BRCA2, CHEK2, ATM, PALB2...) oApproved for: rucaparib o600 mg PO ________ o___________ and __________ only oApproved for: SE o oGI: o

Olaparib o300 mg PO BID oHomologous Recombination Repair (HRR) genes (BRCA1, BRCA2, CHEK2, ATM, PALB2...) oApproved for: post androgen receptor-targeted therapy rucaparib o600 mg PO BID oBRCA1 and BRCA2 only oApproved for: post chemotherapy and androgen receptor-targeted therapy SE oFatigue/asthenia oGI: Nausea, vomiting, diarrhea oAnemia, thrombocytopenia

treatment for non metastatic castration resistant prostate cancer PSADT>10 months: PSADT<=10 months:

PSADT>10 months: monitoring or other secondary hormone therapy PSADT<=10 months: - apalutamide - darolutamide - enzalutamide

Radiation Therapy (2 types) advantages (3) disadvantages(3)

Radiation therapy - external beam radiation therapy - brachytherapy advantages - efficacy equal to prostatectomy - outpatient procedure - eliminates need for major surgery disadvantages - bowel complications - incontinence - erectile dysfunction

Radical prostatectomy Advantages - disadvantages - - - -

Radical prostatectomy Advantages - definitive therapy to remove primary tumor disadvantages - major inpatient surgery - incontinence - erectile dysfunction - bowel complications

Side effects associated with docetaxel and cabazitaxel (9)

Side effects associated with docetaxel and cabazitaxel •Neutropenia •Anemia •Diarrhea •Febrile neutropenia •Fatigue •Asthenia •Back pain •Abdominal pain •Peripheral neuropathy (docetaxel > cabazitaxel)

Treatment options for metastatic Castration-resistant Prostate Cancer oral agents: • • • • •Immunotherapy: o o •Targeted therapy: o o •M

Treatment options for metastatic Castration-resistant Prostate Cancer •Abiraterone •Enzalutamide •Docetaxel •Cabazitaxel •Immunotherapy: oSipuleucel-T oPembrolizumab •Targeted therapy: oOlaparib oRucaparib •Mitoxantrone

LHRH side effects Acute: Long term:

acute: tumor flare, hot flashes, gynecomastia, erectile dysfunction, injection site reaction. Long-term: osteoporosis, fracture, obesity, increased risk of diabetes and CV events

antiandrogens 1) first generation antiandrogens (3) 2) second generation antiandrogens (3)

antiandrogens 1) first generation antiandrogens (4) - flutamide - bicalutamide - nilutamide - prevents tumor flare when used with LHRH agonist 2) second generation antiandrogens (3) - apalutamide - darolutamide - enzalutamide

initial therapy for localized disease for younger patients with intermediate risk.

anywhere from active surveillance or observation

which second generation antiandrogen is a CYP2C19 inducer

apalutamide

Abiraterone acetate MOA

blocks cholesterol from making testosterone to decrease the over all testosterone and androgen production targets cyp17

patient has hypocalcemia from zoledronic acid. what supplements do you recommend?

calcium and vit D

initial therapy for localized disease for <5 yrs with high or very high risk

cancer is bigger here so we need to do surgery or radiation

RI is 75 year old male with chronic kidney disease requiring dialysis. his primary care physician checked a prstate specific antigen which resulted at 7ng/ml and he had an abnormal digital rectal exam. Further imaging and biopsy revealed a low risk prostate cancer with a gleason score 6. His life expectancy is estimated about 3 years. what is the most appropriate tratment options for RI at this time. a) leuprolide b) radical prostatectomy c) docetaxel d) observation

d) observation

MJ is a 75 year old man with a history of metastatic prostate cancer, he has been on leuprolide and tolerated the therapy well for the last 5 years. He returns for follow up today and his PSA has been increasing gradually, repeat staging scans show new liver and lung metastases, he has new abdominal pain requiring prn morphine. which is theh most appropriate treatment option for MJ (m1CRPC) a) cabazitaxel b) olaparib c) sipuleucel T d) docetaxel

docetaxel

metastatic Castration-Sensitive Prostate Cancer (m1CSPC) oThe term "castration-sensitive" is used to define patients who........ ADT plus: ______________________(LATITUTE trial) o___________________ (TITAN trial) o______________________ (ENZAMET trial) o_________________________________ (PEACE-1 trial) o__________________________________ (ARASENS trial)

metastatic Castration-Sensitive Prostate Cancer (m1CSPC) oThe term "castration-sensitive" is used to define patients who have not been treated with ADT and those who are not on ADT at the time of progression ADT plus: oAbiraterone (LATITUTE trial) oApalutamide (TITAN trial) oEnzalutamide (ENZAMET trial) oDocetaxel + Abiraterone (PEACE-1 trial) oDocetaxel + Darolutamide (ARASENS trial)

for Non-metastatic Castration-Resistant Prostate Cancer, treatment is initiated if (3)

oShort PSA doubling time (PSADT ≤ 10 months) oRapid PSA velocity oLong life expectancy

prostate cancer disease states prostate cancer -> 1) _____________________________________________ (CSPC) -> _________________ disease, __________________ _____________ disease/non metastatic, metastatic _________________ prostate cancer 2) ______________________________________________ (CRPC) -> ________________________________________(M0CRPC), ____________________________________________ (m1CRPC)

prostate cancer disease states prostate cancer -> 1) castrate sensitive prostate cancer (CSPC) -> localized disease, biochemical relapsed disease/non metastatic, metastatic castrate sensitive prostate cancer 2) castrate resistant prostate cancer (CRPC) -> non metastatic castrate resistant prostate cancer (M0CRPC), metastatic castrate resistant prostate cancer (m1CRPC)

intial therapy for localized disease in regional risk groups

radiation or surgery

when is pembrolizumab used?

solid tumors

to cure prostate cancer it is important to control _________________________

testoserone

two formulations of abiraterone acetate oZytiga®: - 1000mg PO daily, with _________________ - Must be taken on an ____________ stomach, either ____ hour before or ____ hours after a meal, food may increase ____________ folds oYonsa®: - _______________ formulation - 500mg PO daily, with _________________________ - May be taken with or without ___________

two formulations of abiraterone acetate oZytiga®: - 1000mg PO daily, with Prednisone - Must be taken on an empty stomach, either 1 hour before or 2 hours after a meal, food may increase AUC 5-10 folds oYonsa®: - Fine-particle formulation - 500mg PO daily, with Methylprednisolone - May be taken with or without food

Bone metastases in prostate cancer recommendation medication: (2)

zoledronic acid oIV q3-4 weeks oRenal dosing: CrCl > 60 ml/min = 4 mg, 50-60 ml/min = 3.5 mg 40-49 ml/min = 3.3 mg 30-39 ml/min = 3 mg •RANK ligand inhibitor: ◦Denosumab 120 mg SQ every 4 weeks