Onco 1: Prostate Flashcards
risk factors for prostate cancer
- Black
- immediate family hx
- age
- genetics:
- BRCA-2 mutation
- Lynch syndrome
prostate cancer screening
- consider harm of dx and overtreatment (chance of false positive)
- don’t screen pts over 70 (5 year suvival rate is already so good)
presentation of localized prostate cancer
NOT locally invasive
asymptomatic
presentation of locally invasice prostate cancer
not localized
urinary s/s
presentation of advanced prostate cancer
- back painn, cord compression
- lower extremity edema
- pathologic fractures
- anemia
- wt loss
prostate cancer prognosit factors
- prostate speific antigen (PSA)
- tumor size and exxtent
- hostologic grade (gleason score)
PSA level indications
- PSA > 10: 67% chance of prostate cancer
- normlaly <4, though pts cna develop prostate cnacer even withnormla PSA levles
gleason socre
scores cancer cells
- score 1: nearly normal cells
- 5: high grade tumor
scores are added together
- total 2-4 less aggressive
- 7-10 more aggressive
T, N, M staging for tumors
- T = tumor size
- N = node (lymph)
- NX: not assessed
- N0: negative
- N1:positive - M = metastass
- M0: no metastases
- M1: metastases
goal of prstate cnacer therapy for localized or locally invasive cancer
- conrol disease and symptoms
- decreased morbidity and mortality
curative
goal of prstate cnacer therapy for advanced or metastatic cancer
- palliative
- increased qol
- prolonged survival
treatment for localized/locally invasive postate cancer and low risk for recurrence
- observation
- very low risk and expected survival >20 (or low risk and >10): surveillance and can consider radiaiton
treatment for localized/locally invasive postate cancer and intermediate risk for recurrence
- 5-10 years expected survivail: observation or radiation
- > 10 yrs: surgery or radiation
- ADT is an option if pt also unfavorable
treatment for localized/locally invasive postate cancer and high and very high risk for recurrence
- < 5 years AND asymp: observation or ADT or radiation
- > 5 yrs OR symptomatic
- radiation + ADT (+/- abiraterone in very high risk)
- surgery + pelvic lymph node dissection (+/- radiation +/- ADT)
treatment for regional postate cancer
- < 5 years AND asymp: observation or ADT
- > 5 yrs OR symptomatic
- radiation + ADT (+/- abiraterone in very high risk)
- ADT +/- abiraterone
- surgery + pelvic lymph node dissection (+/- radiation +/- ADT) in select pts
treatment for advanced postate cancer and castrate naive/sensitive
- nonmetastatic: monitoring or ADT
- metastatic: ADT plus one of the following
- abiraterone
- enzalutamide
- apalutamide
- docetaxel 6 cycles
treatment for advanced postate cancer and castrate resistant and recurrent (and non-metastatic)
ADT +
- PSADT >10 months: monitoring or other seocndary therapy*
- PSADT < 10 months: apalutamide, enzalutamide, darolutamide, or secondary therapy
PSADT (PSA doubling time)
*othersecondary therapy: first gen antiandrogen, cs, antiandrogen withdrawal, ketoconazole +hydrocortisone
casstrate resistant definition
serum < 50 but disease progresssion
treatment for advanced adenocarcinoma postate cancer and castrate resistant and metastatic
- no prior docetaxel or hormone: aberaterone, docetaxel, enzalutamide
- no prior docetaxel, prior hormone: docetaxel (olaparib if BRCA mutation)
- prior docetaxel, no prior hormone: abieraterone, cabazitaxel, enzalutamide
- prior docetxel, prior hormone: cabazitaxel, docetaxel rechallenge
second line is the oppossite you did for first line (chemo vs hormone)
- Radium 223 INSTEAD of chemo if sympotatic bone metastaes
- Sipulecel-T in spcial cases
treatment for advanced small cell or neuroendocrine postate cancer and castrate resistant and metastatic
- chemo
- cisplatin/etoposide
- carboplatin/etoposide
- docetaxel/carboplatin
- cabazitaxel/carboplatin - supportive care
if unsure if small cell or adenocarcinoma, treat as adeno
secondary hormone therapies for the treatment of prostate cancer
- second gen antiandrogen: only for M0 and PSADT < 10 months (except enzalutamide whcih you can use in M1 too)
- androgenn metabolizm inhibitor (abiraterone): M1 only
- other (M0 or M1)
- first gen antiandrogen
- CS: hydrocortisone, prednisone, dexamethasone
- antiandrogen withdrawal
- ketoconazole + hydrocortisone
Second gen anti-androgen agents
- apalutamide
- darolutamide
- enzalutamide
first gen anti-androgen agents
- nilutamide
- flutamide
- bicalutamdie
ADT
andrgeon deprivation therapy
- surgical castration (has been replaced with medical)
- medical castration: LHRH agonist OR LHRH antag
LHRH agonsit MOA
- mimic endogenous LHRH
- release LH, FSH
- long term LHRH agonism -> downregulation
- overall decrease in testosterone production
gaol serum testosterone after treatmetn
<50 after a month
LHRH agonist agents
- goserelin
- leuprolide
- triptorelin
- histerelin
dosing ranges form q1mo to q24mo depending on agent and dose
acute LHRH agonist ADR
- tumor flare: give antiandrogen before and for 2-4 weeks during LHRH agonist admin to reduce tuor falre
- hot flash
- ED
- edema
- gynecomasstia
- inj site reaction
long term LHRH agonist (and LHRH antag) ADR
- osteoporosis: obtain a baseline dexa
- clincal fracture
- obestiy
- inuslin resistance, increased risk of DM
- CV events
- HLD
supportive care in prostate cancer
- get that dexa scan at baseline adn yearly
- Ca 1000-2000mg QD
- Vit D 400-800 IU QD
prevention of skeletal related events (SRE) and possible antiumor effect
- zoledronic acid
- denosumab
preferred osteoporisis treatment in prostate cnacer pts
zoledronic acid
androgen depreivation-induced bone loss in prostate cnacer treatment
denosumab
LHRH antag MOA
- bind reversibly to LHRH receptors
- decrease in FSH and LH
- decrease in testosterone
LHRH antag agents
- degarelix Qmo
- relugolix QD
advantages of LHRH antags
- fastser decrease in testoerone than agonits (goal levels at day 7 vs 28)
- no tumor flare
disadvantages of LHRH antag
- cost
- dosing schedule
antiandrogen MOA
- inhibit androgen reuptake and/or androgen binding in target tissues
- competitive inhibitor for bidning fo dihydroxytestoerone adn testosterone
antiandrogen first gen ADR
- diarrhea
- gynecomastia
- elevated LFT
- hot flash
monitor:
- LFT Qmo then periodically
- testpsterone, PSA
- pulmonary function (nilutamide only)
combined androgen blockade
- LHRH agonsit or antag + atiandrogen
- associate diwth more ADR
- per NCCN: no benefit over casstration alone
can consider after several months of not at goal
prostate cancer: hormon therapy and relapse
most pts initially respond but almost all relapse 2-4 yrs after starting therapy
- tumor coposed of hormon independent cells
- tumor stimulated by extratesticular androgens which are intracellularly conerted to dihydroxytestosterone
apalutamide ADR
- fatigue
- HTN
- rash
- sezures
- nausea, diarrhea
- arthralgias
- fracutre risk
- peripheral edema
- seizures (super rare, but if it happens, dc): SPARTAN trial
darolutamide admin
PO BID with food
renal dose adjust
darolutamide ADR
- fatigue
- HTN
- rash
- no seziure risk (ARAMIS tiral)
better tolerated than apalutamide
enzalutamide DDI
- dose reduce if conmittant strong CYP2C8 inibitor
- dose increase if conmitant strong CYP3A4 inducer
enzalutamide ADR
- diarrhea
- fatigue
- HA
- myalgias
- edema
- increased seizure risk (AFFIRM trial)
docetaxel MOA
- promote assembly of microtubules and inhibit depolymeraization of tubulin
- stabilize microtubules in cell
- inhibition of DNA, RNA, protein synthesis
cabazitaxel: similar MOA but has activity in docetaxel-resistant tumors
docetaxel ADR
- myelosuppression
- alopecia
- edema
- peripheral neuropathy
- hypersensitivyt reaction
caution in hepatic impairment
abiraterone MOA
inhibit CYP17 (required for biosynthesis)
abiraterone ADR
- diarrhea
- edema
- hypoK
- HTN
- hepatotox
- hyperTG
- mineralocorticoid exess: give with prednisone
monitor: K, phosphate, BP, LFTs Qmo
olaparib MOA
inhibit ADP-ribose and PARP (aid in DNA repair)
olaparib ADR
- N/V/D
- fatigue
- anemia
- neutro and leukopenia
- abdominal pain
- URI
- increased risk of developing secondary cancer (myelodysplastic syndrome and AML)
monitor blood counts, SCr, s/s of pneumonitis
Radium 223 MOA
- alpha particle release
- dsDNA breakdwonn
- antitumor effect on bone metases
Radium 223 ADR
- peripheral edema
- nuasea
- myelosuppression
Sipuleucel-T MOA
- dentritic cell vaccine
- enahnces T cell response to prostate acid phosphatase (PAP)
Sipuleucel-T admin
Q2W for 3 doses
Sipuleucel-T ADR
- infusion reaction
- chills, fever
- faiuge
- HA
Sipuleucel-T use
only in castrate resistant metastatic (but NOT liver metastases) who are asymp
cabazitaxel ADR
- febrile neutropeni
- hypersensitivity reaction
- mucositis
- edema
lutetium 177 usage
only in PMSA (+) M1 castrate resistant prostate cancer as a second line agent
lutetium 177 admin
IV Q6W for 6 doses
lutetium 177 ADR
- fatigue
- dry mouth
- nausea
- myelosuppression
