Prostate cancer II Flashcards by Ned Jones

Man’s lifetime risk of developing PC

1 out of 9

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percentage of patients who develop BCR after treatment of localized PC

27–53%

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average time of onset of castrate resistance after starting ADT

19 months

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abiraterone mechanism

inhibits androgen synthesis

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first generation anti-androgens

bicalutamide, milutamide, and flutamide

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FDA approved second generation anti-androgens

1) enzalutamide
2) apalutamide
3) **darolutamide
4) abiraterone

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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.

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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.

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PC and PDL1 expression

low levels of PD-L1

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conventional chemo drug for metastatic PC

docetaxel with prednisone

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rate of bone mets in mCRPC

90%!

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Imaging used for PC biopsy

transrectal ultrasound (TRUS)

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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

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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

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PSA and correlation to tumor volume

Absolute PSA does NOT correlate well to tumor volume, trend in PSA and doubling time correlate better

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Taxane based therapies for prostate cancer

Docetaxel
Cabizataxel

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what are other things that can elevate PSA?

**BPH
prostatitis, biopsy,
**cystoscopy
***urinary retention
ejaculation, DRE

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prostate cancer RF’s

black, positive FH, BRCA mutation

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docetaxel cycles for prostate cancer

Continued until intolerable toxicity or disease progression (up to 10 cycles in trials)

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degarelix mechanism

GnRH antagonist

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Definition of BCR

It is now detectable and rising PSA because the assay’s are more sensitive, no longer 0.2 ng

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First step after BCR

Repeat PSA to rule out a PSA bounce

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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)

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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.

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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

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