Prostate cancer II Flashcards
Man’s lifetime risk of developing PC
1 out of 9
percentage of patients who develop BCR after treatment of localized PC
27–53%
average time of onset of castrate resistance after starting ADT
19 months
abiraterone mechanism
inhibits androgen synthesis
first generation anti-androgens
bicalutamide, milutamide, and flutamide
FDA approved second generation anti-androgens
1) enzalutamide
2) apalutamide
3) **darolutamide
4) abiraterone
Immunogenicity of PC
PC is very good at avoiding the immune system. PCs exhibit evasive strategies to avoid detection and destruction by the immune system. Only approved therapy is sipuleucel T.
how sipuleucel T works
autologous vaccine which triggers activation of antigen-presenting cells, mainly DCs, from signaling by a recombinant fusion protein, comprised of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor. These revamped DCs are then infused back into the patient and the vaccine generates CD4+ and CD8+ T cell responses against PAP, an antigen highly expressed in most PC cells.
PC and PDL1 expression
low levels of PD-L1
conventional chemo drug for metastatic PC
docetaxel with prednisone
rate of bone mets in mCRPC
90%!
Imaging used for PC biopsy
transrectal ultrasound (TRUS)
PARP inhibitors approved for prostate cancer
- 2 PARP inhibitors were recently approved (olaparib (Lynparza) and rucaparib (Rubraca))
- new research suggests 20-30% prevalence of defects in genetic repair mechanisms in PC
why you need to give prednisone with abiraterone
Abiraterone reduces serum cortisol and stimulates a compensatory increase in ACTH. Consequently, prednisone is glucocorticoid replacement therapy
PSA and correlation to tumor volume
Absolute PSA does NOT correlate well to tumor volume, trend in PSA and doubling time correlate better
Taxane based therapies for prostate cancer
Docetaxel
Cabizataxel
what are other things that can elevate PSA?
**BPH
prostatitis, biopsy,
**cystoscopy
***urinary retention
ejaculation, DRE
prostate cancer RF’s
black, positive FH, BRCA mutation
docetaxel cycles for prostate cancer
Continued until intolerable toxicity or disease progression (up to 10 cycles in trials)
degarelix mechanism
GnRH antagonist
Definition of BCR
It is now detectable and rising PSA because the assay’s are more sensitive, no longer 0.2 ng
First step after BCR
Repeat PSA to rule out a PSA bounce
Utility of F-18 NaF PET/CT or PET/MRI in comparison to bone scan
More sensitive but less specific (picks up a lot of inflammatory bone conditions like arthritis)
Management of BCR in general
Repeat PSA, then if candidate for local therapy, image with MRI or Choline PET/CT, then biopsy.
- IF not candidate, bone imaging only.
Most common SE of XRT for localized prostate cancer
erectile dysfunction (confirm)
relugolix mechanism
GnRH antagonist
why should all men with MCRP get germline testing?
5 to 10 percent of patients have germline mutations in DNA mismatch repair genes, and they may be eligible for poly (ADP-ribose) polymerase (PARP) inhibitors
gene panel is looking at what
homologous recombination genes (BRCA, BRCA2, ATM, PALB2)
PARP inhibitor formulation
oral
Other clinical significance of DNA repair defects on germline testing of prostate cancer patients
- predictive for sensitivity to platinum agents
- a recent study also showed that patients
definition of high volume disease
- visceral mets and/or 4 or more bone mets with at least 1 met beyond the pelvis vertebral column
Indications for adjuvant RT after RP in low-risk prostate cancer
- positive margins
- seminal vesicle involvement
- extracapsular extension
- detectable PSA
PARP Inhibitors have most activity in which HRR gene deficiency
BRCA2
of cycles of docetaxel in castrate sensitive and castrate resistant
hormone sensitive – 4 cycles
castrate resistant – up to 10
Definition of high volume disease
presence of visceral metastases and/or ≥4 bone metastases, including at least one outside the vertebral bodies and pelvis, or Gleason score ≥8 disease
Apalutamide SE to know
skin rash
of cycles of docetaxel in high volume castrate sensitive setting
6
Definition of BCR after RP
2 + nadir
when do you typically see PSA bounce? pathophys?
- 12-18 months after lupron
- with return of testosterone, normal prostate cells start producing PSA again
Pathophys for why chemo has been found to be effective frontline
Delays development of resistance to androgen deprivation
when to check testosterone (per Mittal)
1) baseline (rule out hypogonadism)
2) at progression (confirm castrate resistant)
- only real utility otherwise is confirming adherence to ADT
Degarelix, relugolix mechanism
GNRH antagonists
What are the second generation antiandrogens?
Enzalutamide, apalutamide, darolutamide
Unrelated but why are PORTs typically required?
For any vesicant, it is preferred
When is intermittent ADT reasonable?
life expectancy less than 10 years + intolerant of ADT
Features that classify pts as having high risk disease with localized PC
- extraprostatic extension (T3a)
- seminal vesicle invasion (cT3b)
- PSA greater than 20
- grade group 4 or 5
What is cyberknife?
SRS for prostate cancer, hypofractionated, appears comparable to EBRT
Castrate level of testosterone
Less than 50
How is biopsy performed with TRUS?
6 cores from each side
Low risk localized per NCCN
T score of T1-T2a and grade group 1, as well PSA level less than 10 ng/mL
High risk per NCCN
T score of T3a or grade group 4 or 5, or PSA level greater than 20 ng/mL in the absence of very high risk features
Favorable intermediate risk per NCCN
no high or very high risk features and no more than one intermediate risk factor such as T2b or T2c, or grade group 2 or 3, PSA level of 10 to 20 ng/mL and grade group 1 or 2, and percentage of positive core biopsy less than 50%
Other major genetic syndrome associated with PC
Lynch syndrome
When is prostate radiation in the metastatic setting appropriate?
Low volume disease
Docetaxel trial
CHAARTED
Abi trials
LATITUDE, STAMPEDE, PEACE-1
Enzalutamide trial
ARCHES, ENZAMET
Apalutamide trial
TITAN
Terminology for tumors with ATM, BRCA, etc.
DDR or HRD (homologous recombination deficiency)
mechanism of abiraterone causing HTN + hypokalemia
It blocks androgen biosynthesis and cortisol production, leading to a compensatory adrenocorticotrophic hormone (ACTH) production, which can lead to increased mineralocorticoid production, leading to hypokalemia and fluid retention, and hypertension. Concurrent administration of prednisone is recommended to prevent compensatory ACTH production
What is T3b disease?
Seminal vesicle involvement
What is high-grade in prostate cancer?
Gleason 8 or higher
Diagnostic modality that T staging is based on?
MRI (not DRE)
What is the first nonregional lymph node involvement?
common illiac
docetaxel dosing
75 mg/m2
What does ARPI typically refer to?
Enzalutamide, apalutamide, abiraterone
What did PROpel look at? Results?
1) Addition of PARP + abiraterone for biomarker unselected mCRPC
2) Positive rPFS
When is bone scan and cross sectional imaging indicated in localized prostate cancer?
Unfavorable intermediate risk or higher
FH indications for germline testing
(>1 first, second, or third-degree relatives with known Fhx of cancer risk mutation (especially BRCA1/2, ATM, PALB2, CHEK2, MLH1, MSH2/6, PMS2, EPCAM)) (Level 2a)
>1 first, second, or third degree relatives with breast cancer <50y, male breast cancer, ovarian cancer, exocrine pancreatic cancer, metastatic, regional, high-risk, or very-high-risk PCa at any age
>= 1 first degree relative with PCa at age =< 60
>2 first, second, or third degree relatives with breast cancer or prostate cancer at any age
>= 3 first or second degree relatives with Lynch syndrome related cancers
Indications for germline testing
- FH indications
- Ashkenazi
- male BC hx
- metastatic disease
- node+
- high/very high risk localized
High risk criteria per STAMPEDE for intensification of therapy
node positive on conventional scan OR 2 of following: T3b or T4, grade group 4 to 5, PSA ≥40 ng/mL)
Is pelvic lymph node dissection routinely done with RP?
this approach can add morbidity to the surgery and is usually limited to those patients at ***high risk for lymph node involvement based on the local extent of disease, serum PSA, and histologic grade group (generally for those with intermediate- or high-risk disease)
Relation of Gleason score to grade groups in prostate cancer
3=3 = grade group 1, 3+4 = grade group 2, 4+3 = grade group 3, gleason 8 = grade group 4, gleason 9-10 = grade group 5
What is the definition of biochemical recurrence?
PSA only, so fewer patients are defined as biochemically recurrent
How is need for lymph node dissection typically determined?
Nomograms but oncologic benefit of node dissection hasn’t really been shown
SBRT vs EBRT in terms of efficacy in prostate cancer
SBRT has less risk, EBRT has higher chance of cure (ablative dose)
recurrence risk outcome in localized prostate cacner
biochemical failure free survival
