Prostate Cancer Flashcards
Medications with survival benefit in metastatic CR prostate cancer
Four
1) Taxanes
2) second generation antiandrogens
3) immunotherapy (sipuleucel-T)
4) radium-223
What are the aggressive variant prostate cancers?
1) *Pure small cell
2) neuroendocrine carcinomas
abiraterone mechanism
- androgen synthase inhibiotr
- irreversibly inhibits the products of the cytochrome P450, family 17 (CYP17) gene (including both 17,20-lyase and 17-alpha-hydroxylase). In doing so, abiraterone blocks the synthesis of androgens in the tumor as well as in the testes and adrenal glands.
only cytotoxic chemotherapy that has been shown to prolong survival in prostate cancer
taxanes
cabizataxel contraindications and SE profile
myelosuppression and may require premedication to minimize the risk of infusion reactions. Contraindications include underlying hepatic dysfunction or compromised bone marrow function.
Indication for radium 223 in prostate cancer
Isolated and symptomatic bone metastases without (no other clinically significant sites of disease (including visceral metastases))
Hereditary cancer syndromes associated with PC
BRCA 1 and 2, HOXB13
Evidence for prophylaxis against prostate cancer?
Some evidence that finasteride decreases risk of developing low-grade prostate cancer
% of adenocarcinoma in PC
95%
Primary vs. secondary Gleason grade
primary = dominant histologic pattern
secondary = next most common histologic pattern
Cutoffs to know for Gleason grade
Less than 6 = not considered to be PC
8-10 = high-risk disease
Term for premalignant lesions for prostate cancer
High-grade prostatic intraepithelial neoplasia (PIN)
Signs/symptoms of advanced prostate cancer
- weight loss, fatigue, DIC, bone pain
Indications for prostate biopsy
1) Rapidly rising PSA
2) Palpable hard nodule on DRE
What to adjust for for PSA
Always age adjusted
Management of palpable hard nodule on DRE
Always biopsy, even if low PSA
How is prostate cancer biopsied — # of cores + scoring
12 cores are generally obtained to ensure adequate sampling, with highest score found in gland used (prostate cancer is multifocal)
Staging of intermediate/high risk PC
Bone scan + CT abdomen/pelvis
Prostate cancers that can be observed
1) Very low-risk
2) low-risk PC w/ life expectancies under 10 years
what active surveillance entails
1) Monitor PSA
2) DRE
3) periodically rebiopsying prostate gland
why is doubling time important to measure
Correlates to mortality
When lymph node dissection is indicated during radical prostatectomy
Patients with regional lymph node involvement and no evidence of distant metastatic disease (confirm)
Complications of radical prostatectomy
- urinary incontinence and leakage
- urinary stricture
- impotence
management of ED after radical prostatectomy
Trial ED meds (may still be helpful)
Complications of radiation
Acute = inflammation of surrounding structures (cystitis, proctitis, enteritis)
Fatigue
Mild cytopenias
Impotence, urethral stricture, cystitis, hematuria
Diarrhea and proctitis
Neoadjuvant treatment prior to RP or radiation?
Not indicated
adjuvant chemo following RP?
Not indicated, adjuvant ADT plays a role in certain circumstances
Role for adjuvant radiation after RP
1) extracapsular extension
2) positive surgical margins
Definition of biochemical recurrence
2 separate serum PSA’s >0.2 ng/mL
Treatment options for castrate sensitive metastatic prostate cancer
ADT +
1) novel second generation antiandrogen (abiraterone/prednisone OR apalatumide or enzalutamide
2) docetaxal
3) ADT alone
Treatment options for castrate resistant metastatic prostate cancer
Continue ADT +
1) Same options as castrate sensitive. Next step depends on what patient has received before.
GnRH agonists + typical formulation
- leuprolide
- buserelin
- goserelin
- triptorelin
*depot formulation to permit less frequent administration
next step when patient has a rising PSA on total androgen blockade
check serum testosterone to ensure patient is truly castrate
Prevalence of castration-resistant prostate cancer
With time, all patients with metastatic PC eventually progress to develop castration-resistant disease
Explain how castration-resistant PC develops
1) Upregulation of androgen receptors
2) Activation of androgen receptor by other steroid hormones
3) Splice variants of the androgen receptors
4) Prostate cancer cells synthesize their own androgens, so the local tumor androgen environment is higher
Treatment options for patients with CRPC
1) secondary hormonal therapy
2) chemo with taxanes
3) vaccines (sipuleucel-T)
4) Radiopharmaceuticals (Radium-223)
5) Clinical trials
What is secondary hormonal therapy?
Blocking other sources of testosterone production in the body (testosterone produced from adrenal glands and the tumor itself) or inhibiting androgen receptor signaling
What are the bone-targeting agents
Denosumab
Bisphosphonates
when radiation is indicated for bone mets
1) painful (most patients get significant palliation of pain when radiation is used)
2) at risk for pathologic fracture
3) lesions concerning for or causing spinal cord compression
how is radiographic progression defined?
2 or more new lesions on a bone scan OR interval growth of visceral OR lymph node disease
Adverse effects of ADT?
1) hot flashes
2) fatigue
3) loss of libido, decline in sexual function
4) increased risk for DM (ADT reduces insulin sensitivity)
5) increased cardiovascular disease risk (ADT can augment LDL, HDL, and triglyceride
6) osteoporosis
7) small but increased risk of alzheimer’s disease
Management of painful gynecomastia
Refer to plastics for breast reduction
How to optimize bone health in men on chronic ADT
1) Baseline bone density test prior to starting ADT
2) Repeat bone density test every 2 years while on ADT
3) calcium + vitamin D daily
4) lift weights + stop smoking
management options for localized, intermediate risk PC
RT + ADT
OR
Radical prostatectomy
term for genetic syndrome associated with BRCA
hereditary breast and ovarian cancer syndrome
what risk stratification is based on
T stage
Gleason Grade
PSA
management options for localized, high risk PC
IF limited life expectancy → external beam RT with or without brachytherapy + long term ADT OR ADT alone
IF longer life expectancy → radical prostatectomy
ADT options + gist of ADT
- GnRH agonists are most commonly used (eligard) except when concern for flare phenomenon OR immediate rapid decrease in testosterone level is required
Eligard typical formulation
long acting 6 month
Use of bisphosphonates in management of bone mets in castration sensitive PC
Not used. only indicated in CRPC.
class of medications used to treat bone mets in CRPC
osteoclast inhibitors
When to stage prostate cancer
Intermediate or higher risk (assuming 10 year life expectancy)
*NOT low risk or favorable intermediate risk if less than 10 year life expectancy
Gleason score range + connotation of higher number
2 (well differentiated) - 10 (poorly differentiated)
Categories defining low risk PC
1) Stage T1c, T2a
2) PSA less than 10
3) Low gleason score (less than 6
why prostate cancer with low PSA is often more aggressive
- these are often the aggressive variant prostate cancers (neuroendocrine)
Eligard generic name
Leuprorelin
Eligard mechanism
- GnRH analogue
- GnRH agonism initially results in stimulation of LH and FSH but HPG axis is depedent on pulsatile hypothalamic GnRH secretion so continuous agonism leads to desensitization of GnRH receptors and downregulation
Indication for germline testing in prostate cancer
1) Positive family history of prostate cancer
2) High or very high risk prostate cancer
3) Metastatic disease
What is a castrate serum level of testosterone?
less than 50 ng/dL
when you never want to give GnRH agonists
- metastatic disease at diagnosis (GnRH agonism initially causes a flare of LH and FSH, which is termed “flare phenomenon”, this can be of particular concern with impending epidural cord compression or urinary tract outflow obstruction)
what are the GnRH antagonists?
Degarelix
Relugolix
Utility of axium scan
No longer used in PSMA era
Indication for sipuleucel
slowly progressive PC
Novel androgen therapy typically referred to as
hormonal therapy
Sipuleucel-T indication
asymptomatic or mild slowly progressive disease AND no visceral mets
visceral mets refers to what?
- liver, lung, adrenal, peritoneal, and brain mets (soft tissue or nodal mets not considered visceral)
definition of biochemical failure after RT
- rise in PSA of 2 above nadir
Indications for observation in PC
- very low risk disease with less than 10 years of survival
- low risk disease with less than 10 years of survival
- favorable or unfavorable intermediate disease with less than 10 year survial
basic process for sipuleucel
WBCs are extracted during leukapheresis, blood product is sent to a production facility and incubated with a fusion protein, activated blood product is returned and reinfused
response assessment with sipuleucel
NOT PSA. You don’t normally see a PSA drop with sipuleucel.
what is xofigo
Ra-223
Relative contraindications to enzalutamide and apalutamide
Seizure history
Mitoxantrone SE’s
- cardiomyopathy
- blue discoloration of fingernails, sclera, and urine
significance of N1 disease in prostate cancer
- metastatic (stage IVA disease)
Clinical features of small cell cancer of the prostate
- extensive local disease, visceral crises,
- low PSA
Unique management of small cell cancer of the prostate
- normally don’t benefit much from ADT
Management of small cell cancer of the prostate + regimens you can use
(platinum based chemo)
cisplatin-etoposide
carbo-etoposide
carbo-docetaxel
abiraterone SE’s
HTN + hypokalemia + AF + CHF + liver dysfunction
what to tell patients about abiraterone
- must be taken on an empty stomach (food will increase absorption). Can’t eat 2 hours before or 1 hour after.
denosumab mechanism
RANKL inhibitor
denosumab vs zometa in terms of SRE’s
- there is phase III data that densoumab prevents SREs about 20% better than zometa
pred dosing with abi in castrate sensitive and resistant
5 mg daily for castrate sensitive
5 mg po BID for castrate resistant
why steroids are given with abiraterone
- decrease risk of mineralocorticoid excess, which can lead to fluid retention, HTN, and hypokalemia
- also cortisol rescue
OS benefit of ADT in early-stage prostate cancer
- no effect on OS
Indications for RT after RP and caveat
- positive margins
- seminal vesicle invasion
- extracapsular extension
- detectable PSA
*but many argue RT should be reserved for salvage setting
Evidence for RT after RP when high risk features are present
PFS benefit but OS benefit hasn’t been shown
FDA indications for Ga 68 PSMA
1) patients with suspected mets who are potentially curable by surgery or RT
2) BCR
