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