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Urology In-Service/Board Review > Prostate Cancer > Flashcards

Prostate Cancer Flashcards

1
Q

MOA:
Leuprolide
Goserelin

A

GnRH agonist

Increase LH release

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2
Q

MOA:
Degarelix
Abarelix

A

GnRH Antagonist

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3
Q

MOA:
Abiraterone
Ketoconazole

A

Androgen Synthesis Inhibitors (Adrenal)

Ketoconazole: CYP 17, 11B hydroxylase
Abiraterone: CYP 17

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4
Q

MOA:
Bicalutamide
Flutamide
Nilutamide

A

1st Gen Anti-Androgen

decreases binding at AR

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5
Q

MOA:
Enzalutamide
Apalutamide
Darolutamide

A

2nd Gen Anti-Androgen

decreases binding at AR, decreases nuclear translocation and transcription

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6
Q

MOA:
Docetaxel
Cabazitaxel

A

Chemotherapy

microtubule disruption

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7
Q

MOA:

Mitoxantrone

A

Chemotherapy

Topoisomerase II inhibition

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8
Q

MOA:
Olaparib
Rucaparib

A

PARP inhibitor

BRCA 1/2 mutations, other HRR mutations

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9
Q

MOA:

Sipuleucel-T

A

Immunotherapy

Target cells displaying PAP-GMCSF

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10
Q

MOA:

Pembrolizumab

A

Immunotherapy

Anti-PD1

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11
Q

PLCO Trial

A
  • RCT - Screening trial
  • Prostate, lung, colorectal, ovarian screening = PLCO
  • No difference in prostate cancer specific mortality with yearly PSA screening vs. no screening
  • Criticism = contamination (there was a LOT of screening and even previous biopsy in the control arm as well)
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12
Q

MOA:
Denosumab
Zoledronic acid

A

Bone Protecting Agents

Decrease osteoclast activity

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13
Q

MOA:

Radium-223

A

Alpha particle creating double strand breaks in DNA

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14
Q

Treatment options:

Low Risk Prostate Cancer

A 
AS
Cryo
(HIFU)
RP (no LND)
XRT (prostate +/- SV)
Brachy monotherapy
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15
Q

Treatment options:

Favorable Intermediate Risk Prostate Cancer

A 
AS
Cryo
(HIFU)
RP (no LND)
XRT (prostate +/- SV +/- LN) +/- 4-6 months ADT
Brachy +/- XRT
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16
Q

Treatment options:

Unfavorable Intermediate Risk Prostate Cancer

A

(AS)
RP + LND
XRT (prostate + SV + LN) + 4-6m ADT
Brachy + XRT +/- 4-6m ADT

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17
Q

Treatment options:

High Risk Prostate Cancer

A

RP + LND
XRT (prostate + SV + LN) + 2-3y ADT
Brachy + XRT + 1-3y ADT

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18
Q

Treatment Options:

N1M0 Prostate Cancer

A 
WW
ADT immediately (alone; intermittent or continuous)
RP + LND + XRT + long term ADT
XRT (prostate + SV+ LN) + long term ADT
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19
Q

Definition:

Low Volume Metastatic Burden in Prostate Cancer

A

No visceral mets
Any # nodal mets
Bone mets confined to vertebral bodies/pelvis

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20
Q

Definition:

High Volume Metastatic Burden in Prostate Cancer

A

At least 1 visceral (non-nodal) met

>= 4 bone mets with at least one bone met outside of vertebral column/pelvis

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21
Q

ERSPC Trial

A

ERSPC = European Randomized Study for the Screening of Prostate Cancer

  • RCT, 162k men age 55-69, PSA checked every 4 years
  • Primary outcome = prostate cancer specific mortality (1 death fewer per every 1,000 men screened)
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22
Q

Urine Biomarkers

A

PCA3
Select MDx
MiPS

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23
Q

Tissue Biomarkers

A

OncotypeDx
ConfirmMDx
Prolaris
Decipher

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24
Q

Serum Biomarkers

A

PHI

4K score

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25
Q

CAP/ProtecT trial

A
  • 415k men randomized to one single PSA vs no PSA at 50-69 years
  • 10 years follow up
    1. More cancer in intervention arm
    2. No difference in cancer mortality
    3. No difference in survival
  • -> Single PSA test not recommended for population screening
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26
Q

Important AEs

Abiraterone

A

Glucocorticoid deficiency, increased mineralocorticoid production
Give with steroids

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27
Q

Important AEs:

Enzalutamide

A

Seizures, falls, HTN, hallucination, CV, mental

28
Q

AUA Guideline Statement for screening in men >70 in excellent health

A
  • Higher threshold for biopsy (>10 ng/mL)

- Stop screening if PSA <3ng/mL

29
Q

Important AEs:

Apalutamide

A

rash, hypothryoidism, falls/fractures, seizures, CV

30
Q

Important AEs:

Ketoconazole

A

Decreased androgen, glucocorticoid and mineralocorticoid synthesis
Hepatotoxicity, N/V

31
Q

Important AEs:

Docetaxel, Cabazitaxel

A

BM suppression, neutropenia

32
Q

How do tumor look on multiparametric MRI?
T1/T2?
DWI?
DCE?

A
  • T1 + T2: Water content – tumors are water poor/dark on T2
  • Diffusion‐weighted images (DWI): Water diffusion – tumors are dense/dark
  • Dynamic contrast enhanced images (DCE): Contrast flow – vascularity, tumors are bright
33
Q

Important AEs:

Zoledronic Acid, Denosumab

A

Osteonecrosis of the jaw

34
Q

PROMIS Trial

A
  • 576 Men
    • MRI, TRUS‐bx and Saturation transperineal bx
    • Avoid 27% of the biopsies if negative MRI
    • MRI guidance ‐ found 18% more cases of significant cancers
35
Q

Important AEs:

Olaparib

A

Anemia, fatigue, anorexia, diarrhea, cough, dyspnea, thrombocytopenia, AKI

36
Q

Definition:

Castration

A

Bilateral Orchiectomy
LHRH Agonist
GnRH Antagonist

Goal Testosterone <50 ng/dL

37
Q

Definition:

Biochemical Recurrence after RP

A

Undetectable PSA after surgery –> 2+ increases above threshold 0.2 ng/dL

38
Q

PRECISION trial

A
  • 500 men randomized to MRI vs. standard biopsy

Clinically Significant Cancer (GS ≥ 3+4): More found in MRI targeted group

Clinically Indolent Cancer: More found in standard biopsy group

28% in MRI group could avoid a biopsy

39
Q

Definition:

Biochemical Recurrence after RT

A

PSA increase by >= 2ng/mL above nadir

40
Q

Treatment Options:

M1 CSPC

A 
ADT + 
Abiraterone/prednisone
Docetaxel (high volume)
Apalutamide
Enzalutamide
EBRT (low volume)
41
Q

Treatment Options:

M1 CRPC

A 
ADT+
Abiraterone/prednisone
Docetaxel
Enzalutamide
Radium 223
Mitoxantrone
Sipuleucel T
Pembrolizumab
42
Q

Treatment Options:

M0 CRPC

A

Ensure castrate levels of testosterone
If PSADT >10m (long): may be able to monitor
If PSADT <10m (short): Enzalutamide, apalutamide, darolutamide

43
Q

AUA vs. NCCN Risk Stratification Table

A
44
Q

Prostate Cancer Staging

A
45
Q

SPCG-4 Trial

A
  • Swedish trial, mostly healthy younger patients with intermediate or higher risk disease, followed for 23 years
  • Surgery (RP) vs. watchful waiting
  • Improved overall and disease specific survival in RP group compared to observation
46
Q

PIVOT Trial

A
  • Mixed risk disease, older sicker VA patients
  • Underpowered*
  • Surgery (RP) vs. watchful waiting
  • No survival advantage in surgery group
  • BUT surgery reduced the risk of metastases (p=0.0001) among men with Gleason score ≥ 7 tumors
47
Q

CHAARTED Trial

A

M1 CSPC

ADT + Docetaxel

  • 790 men with mHSPC randomized to ADT +/‐ docetaxel
  • Improved OS (57.6 mo vs 44 mo)
  • Improved PFS and rate of PSA <0.2
  • Significant improvement in high‐volume disease
  • At long term follow up, even greater OS benefit, especially in high volume disease
48
Q

STAMPEDE Trial

A

M1 CSPC

ADT + Docetaxel

  • Long term follow up
  • Improved OS (43.1 mo vs 59.1 mo)
  • No difference in low vs high volume disease

ADT + Abiraterone
-37% relative improvement in survival (HR 0.63) at 40 month follow up

ADT + Prostate EBRT

  • 2061 men randomized to ADT v ADT plus EBRT to primary tumor
  • Median OS 48m (EBRT) vs 46m (control)
  • In all pts: HR 0.92, p 0.266
  • In low met burden: HR 0.68, p 0.007
49
Q

PROTECT Trial

A
  • Mostly low risk disease
  • Surgery (RP) vs. Radiation (RT) vs. Active Surveillance (AS)
  • No differences in overall or disease specific survival between groups
    ‐ RP and RT were better than AS for Clinical progression (p<0.001) and Metastatic disease (p=0.004)
50
Q

LATITUDE Trial

A

M1 CSPC

  • 1199 patients receive ADT +/‐ abiraterone acetate + prednisone
    • 50% symptomatic at baseline
  • Needed 2of 3 high risk features (Gleason >=8, >=3 bone lesions, visceral mets)
  • Improved OS and radiographic PFS
51
Q

ENZAMET Trial

A

M1 CSPC

ADT + Enzalutamide

  • Compared ADT + enzalutamide with standard of care (ADT+ bicalutamide, nilutamide, flutamide, docetaxel)
  • Improved OS (HR 0.67)
  • More AEs in enzalutamide group
52
Q

TITAN Trial

A

M1 CSPC

ADT + Apalutamide
-HR 0.67

53
Q

Adjuvant vs. salvage XRT after RP

A 
Adjuvant
• pT3 pathology
• Positive margin
• No BCR
• Consider genomic testing

Salvage
• PSA recurrence
• Low pretreatment PSA and long PSADT better
• Give with ADT

54
Q

Trials: Salvage RT + ADT

A 
GETUG 16
• 743 Patients with PSA failure after RP
– PSA between 0.2 and 2 ng/mL
• RT vs RT plus 6 months ADT 
• Improved progression free survival

RTOG 9601
• 760 Men with PSA failure after RP
• RT vs RT plus bicalutamide
• Improved overall survival

55
Q

Biochemical Recurrence after Prostatectomy

A
  • Undetectable PSA after surgery with a subsequent increases on
    2 or more determinations above threshold of 0.2 ng/mL
56
Q

Biochemical Recurrence after RT Treatment

A

– RTOG‐ASTRO Phoenix Consensus: PSA increase by > 2 ng/mL
above the nadir
– Consider earlier evaluation in candidates for salvage local
therapy (young, healthy)

57
Q

Definition: CRPC

A

Testosterone <50 ng/dL AND

New radiographic or clinical mets on ADT OR
PSA greater than 2ng/mL and rising

58
Q

SPARTAN Trial

A

M0 CRPC
PSADT <= 10m

ADT + Apalutamide (vs. ADT + placebo)
-Improved MFS (40.5 mo vs 16.2 mo)

59
Q

PROSPER Trial

A

M0 CRPC
PSADT <= 10 mo

ADT + Enzalutamide (vs ADT + placebo)
-Improved MFS (36.6 mo vs 14.7 mo)

60
Q

M1 CRPC ADT + Abiraterone Trials

A

• COU‐AA‐301 – ADT + Abiraterone
– Prior docetaxel

• COU‐AA‐302 – ADT + Abiraterone
– No prior docetaxel/chemotherapy naive

Addition of abiraterone: time to PSA progression and progression free survival both better in Abiraterone groups

61
Q

M1 CRPC ADT + Enzalutamide Trials

A

AFFIRM – ADT + Enzalutamide
– Prior docetaxel

• PREVAIL – ADT + Enzalutamide
– No prior docetaxel/chemotherapy naive

Addition of enzalutamide better for overall survival

62
Q

Chemotherapy Drugs for M1 CRPC

A
  • Docetaxel (TAX 327, SWOG 9916): OS improved
  • Cabazitaxel (TROPIC, FIRSTANA) - FDA approved after Docetaxel, OS improved

• Mitoxantrone (CALGB 9182)
– Currently limited role in mCRPC

63
Q

ARAMIS Trial

A

M0 CRPC
PSADT <= 10 mo

ADT + Darolutamide (vs ADT + placebo)
-Improved MFS (40.4 mo vs 18.4 mo)

64
Q

IMPACT Trial

A

M1 CRPC Immunotherapy with Sipuleucel-T

  • Improved OS
  • No difference in PFS
  • No PSA decline
65
Q

PROFOUND Trial

A

PARP Inhibitor: Olaparib
mCRPC
– Patient who progressed on enzalutamide or abiraterone
– >/= 1 homologous recomb. repair gene mutated

Improved PFS and OS

SE: anemia, fatigue, anorexia, diarrhea, cough, dyspnea, thrombocytopenia, AKI

66
Q

TRITON2 Trial

A

PARP Inhibitor: Rucaparib

Phase 2 trial, mCRPC
>/=1 somatic or germline mutation
– Progressed on prior AR‐therapy and taxane

Most notable response rates (ORR/PSA) for BRCA1/BRCA2 mutations
• Accelerated FDA approval

Urology In-Service/Board Review (12 decks)

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