Prostate Cancer

Question 1

What are risk factors for prostate cancer?

Answer 1

Race (Black)
Ethnicity (US, Scandinavia)
Age (>65)
Family Hx (first degree relative)

Question 2

Why is prostate screening controversial?

Answer 2

There are benefits to screening but also the harm of overdiagnosis
Screening via PSA blood test w digital rectal exam
DO NOT screen past 70 yo! Not necessary!

Question 3

What is the clinical presentation of locally invasive prostate cancer?

Answer 3

Ureteral dysfunction
Increased urinary frequency
Urinary hesitancy
Dribbling
Incomplete bladder emptying

Question 4

What is the clinical presentation of advanced prostate cancer?

Answer 4

Back pain
Spinal cord compression
Leg edema
Pathologic fractures
Anemia
Weight loss

Question 5

What are prognosis factors in prostate cancer?

Answer 5

Prostate-Specific Antigen (PSA)
Tumor SIZE + EXTENT
Histologic grade (Gleason score)

Question 6

What kind of marker is PSA (prostate-specific antigen)?

Answer 6

Specific to the prostate but not for prostate CANCER
- Finasteride/dutasteride may decrease
- BPH may increase
Even WNL PSA people still get cancer
PSA > 10 ng/mL = higher risk of prostate cancer

Question 7

How is prostate cancer staged?

Answer 7

Tumor: based on imaging and digital rectal exam
Node: are regional lymph nodes affected? [NX = not assessed, N1 = yes N0 = no]
Metastasis: M0 = no metastasis, M1 = yes metastasis

Question 8

How does the Gleason Score work in prostate cancer? What score is “low risk” and what is “high risk”?

Answer 8

Defined by how prostate cells look under a microscope
Observes first + second most predominant pattern (sum)
Score 1-5 each, lower is better

LOW risk ≤ 6
HIGH risk ≥8

Question 9

If a prostate cancer patient has VERY LOW recurrence risk with < 10 years expected survival, what treatment should be initiated?

Answer 9

Observation

Question 10

If a prostate cancer patient has VERY LOW recurrence risk with 10-20 years expected survival, what treatment should be initiated?

Answer 10

Active surveillance

Question 11

If a prostate cancer patient has VERY LOW recurrence risk with ≥20 years expected survival, what treatment should be initiated?

Answer 11

Active surveillance (preferred)
RT/brachytherapy
Prostatectomy

Question 12

If a prostate cancer patient has LOW recurrence risk with < 10 years expected survival, what treatment should be initiated?

Answer 12

Observation

Question 13

If a prostate cancer patient has LOW recurrence risk with ≥10 years expected survival, what treatment should be initiated?

Answer 13

Active surveillance (preferred)
RT/brachytherapy
Prostatectomy

Question 14

If a prostate cancer patient has FAVORABLE INTERMEDIATE recurrence risk with 5-10 years expected survival, what treatment should be initiated?

Answer 14

Observation (preferred)
RT/brachytherapy

Question 15

If a prostate cancer patient has FAVORABLE INTERMEDIATE recurrence risk with ≥10 years expected survival, what treatment should be initiated?

Answer 15

Active surveillance
RT/brachytherapy
Protectomy +/- pelvic lymph node dissection

Question 16

If a prostate cancer patient has UNFAVORABLE INTERMEDIATE recurrence risk with 5-10 years expected survival, what treatment should be initiated?

Answer 16

Observation
RT + androgen deprivation therapy
RT + brachytherapy +/- androgen deprivation therapy

Question 17

If a prostate cancer patient has UNFAVORABLE INTERMEDIATE recurrence risk with ≥10 years expected survival, what treatment should be initiated?

Answer 17

Protectomy + pelvic lymph node dissection
RT + androgen deprivation therapy
RT + brachytherapy +/- androgen deprivation therapy

Question 18

If a prostate cancer patient has HIGH or VERY HIGH recurrence risk with ≤ 5 years expected survival AND asymptomatic, what treatment should be initiated?

Answer 18

Observation
Androgen deprivation therapy
RT

Question 19

If a prostate cancer patient has HIGH or VERY HIGH recurrence risk with >5 years expected survival OR symptomatic, what treatment should be initiated?

Answer 19

RT + androgen deprivation therapy
RT + brachytherapy + 1-3 yrs androgen deprivation therapy
RT + androgen deprivation therapy + ABIRATERONE
Prostectomy + pelvic lymph node dissection

Question 20

If a patient has LOCALLY INVASIVE prostate cancer with ≤ 5 years expected survival AND asymptomatic, what treatment should be initiated?

Answer 20

Observation
Androgen deprivation therapy

Question 21

If a patient has LOCALLY INVASIVE prostate cancer with > 5 years expected survival OR symptomatic, what treatment should be initiated?

Answer 21

RT + androgen deprivation therapy + abiraterone
RT + androgen deprivation therapy
Androgen deprivation therapy +/- abiraterone
Prostectomy + pelvic lymph node dissection

Question 22

If a patient has ADVANCED prostate cancer, is CASTRATE NAÏVE with NO METASTASIS, what treatment should be initiated?

Answer 22

Monitoring
ADT

Question 23

If a patient has ADVANCED prostate cancer, is CASTRATE NAÏVE with METASTASIS, what treatment should be initiated?

Answer 23

ADT:
+ Abiraterone OR Enzalutamide OR Apalutamide
+ Docetaxel x 6 cycles + [Abiraterone or Darolutamide]

Question 24

If a patient has ADVANCED prostate cancer, is CASTRATE RESISTANT with NO METASTASIS, what treatment should be initiated?

Answer 24

ADT plus:
- PSA doubling time > 10 months = MONITOR
- PSA doubling time ≤ 10 months = Apalutamide/Darolutamide/Enzalutamide

Question 25

If a patient has ADVANCED ADENOCARCINOMA prostate cancer, is CASTRATE RESISTANT with METASTASIS, what treatment should be initiated? [WORST]

Answer 25

**Adenocarcinoma** ADT plus: - Abiraterone - Enzalutamide - Docetaxel x 6 cycle - Sipuleucel-T - Radium 223

Question 26

If a patient has ADVANCED SMALL CELL prostate cancer, is CASTRATE RESISTANT with METASTASIS, what treatment should be initiated? [WORST]

Answer 26

Chemotherapy - Cisplatin/etoposide - Carboplatin/etoposide - Docetaxel/carboplatin - Cabazitaxel/carboplatin

Question 27

What is the GOLD STANDARD treatment for prostate cancer?

Answer 27

**Androgen Deprivation Therapy** Surgical (bilateral orchiectomy) OR Medical (LH releasing hormone agonist +/- antiandrogen)

Question 28

What is the goal serum testosterone after one month of ADT in prostate cancer?

Answer 28

Goal: testosterone < 50 ng/dL after one month

Question 29

Name the FOUR LHRH agonists

Answer 29

Goserelin Leuprolide Triptorelin Histrelin (implant) [monthly/multimonthly injections]

Question 30

What are some ACUTE AEs of LHRH agonists?

Answer 30

Tumor flare, hot flashes, erectile dysfunction, edema, gynecomastia, injection site reaction (like menopause for men)

Question 31

What are some LONG-TERM AEs of LHRH agonists?

Answer 31

Osteoporosis, clinical fracture, obesity, insulin resistance, increased risk of diabetes, CV events, hyperlipidemia

Question 32

Why do LHRH agonists have tumor flares when it should be decreasing the tumor?

Answer 32

Initial tumor flare caused by a surge in LH/FSH release

Question 33

What kind of test should be done before starting long-term ADT in prostate cancer?

Answer 33

Baseline bone mineral density test before starting longterm ADT Vitamin D + calcium supplementation

Question 34

Name the 2 LHRH ANTagonists used in prostate cancer. What is the MoA?

Answer 34

Degarelix Relugolix MOA: binds reversibly to receptors in pituitary gland, dramatically reducing LH/FSH

Question 35

What are the three FIRST GEN ANTIANDROGENS? What are some AEs of these drugs? What is monitored?

Answer 35

Bicalutamide Flutamide Nilutamide ADEs = diarrhea, gynecomastia, increased LFTs, hot flashes Monitoring = LFTs monthly, serum testosterone, PSA, pulmonary function (nilutamide)

Question 36

What are the three SECOND GEN antiandrigens? Can these be used in metastasis or not?

Answer 36

Apalutamide (non-metastatic) Enzalutamide (non-metastatic AND metastatic) Darolutamide (non-metastatic)

Question 37

What is the MOA and some AEs of antiandrogen APALUTAMIDE for advanced prostate cancer? What did the SPARTAN trial find about this drug?

Answer 37

MOA: Nonsteroidal androgen receptor inhibitor AEs: Fatigue, HTN, rash, diarrhea, nausea, arthralgias, fracture risk, peripheral edema SPARTAN trial = increased **falls and fractures**, with a small number of people developing **seizures!**

Question 38

What is the MOA of antiandrogen DAROLUTAMIDE for advanced prostate cancer? What are some AEs? Should it be taken with or without food? Do any dose adjustments need to be made? What did the ARAMIS trials find?

Answer 38

MOA: Competitive androgen receptor inhibitor AEs: fatigue, HTN, rash WITH FOOD Dose adjust for renal impairment ARAMIS trial = NO increase in seizures!

Question 39

What is the MOA of antiandrogen ENZALUTAMIDE for advanced prostate cancer? What are some AEs? Do any dose adjustments need to be made? What did the AFFIRM trial find?

Answer 39

MOA: pure androgen receptor signaling inhibitor AEs: diarrhea, fatigue, headache, myalgias, edema Dose adjustment for CYP2C8 inhibitors/CYP3A4 inducers AFFIRM trial showed increase risk of **seizures!**

Question 40

If a patient with metastatic prostate cancer has NOT had prior docetaxel and NO prior hormone therapy, what treatments are preferred?

Answer 40

Abiraterone Docetaxel Enzalutamide (Consider: radium-223, olaparib/niraparib, Sipuleucel-T)

Question 41

If a patient with metastatic prostate cancer has NOT had prior docetaxel and HAS prior hormone therapy, what treatments are preferred?

Answer 41

Docetaxel Olaparib/Rucaparib

Question 42

If a patient with metastatic prostate cancer has HAD prior docetaxel and NO prior hormone therapy, what treatments are preferred?

Answer 42

Abiraterone Cabazitaxel (docetaxel alternative) Enzalutamide

Question 43

If a patient with metastatic prostate cancer has HAD prior docetaxel and HAD prior hormone therapy, what treatments are preferred?

Answer 43

Cabazitaxel (docetaxel alternative) Docetaxel rechallenge

Question 44

In what cases may RADIUM-223 be considered in prostate cancer?

Answer 44

Symptomatic bone metastasis from prostate cancer

Question 45

In what cases may SIPULEUCEL-T be considered in prostate cancer?

Answer 45

Asymptomatic but METASTATIC (not to liver) with life expectancy > 6 months and good performance status

Question 46

What drug must be taken adjunctively with docetaxel? What are some AEs of docetaxel? *in what organ dysfunction should we use caution?*

Answer 46

Adjunctive PREDNISONE AEs: myelosuppression, alopecia, edema, peripheral neuropathy Caution in **hepatic impairment**

Question 47

What is the MOA of abiraterone?

Answer 47

Irreversibly inhibits CYP17 (enzyme for androgen synthesis) Inhibits formation of testosterone precursors

Question 48

What are some AEs of abiraterone? What drug should be used adjunctively? What should we monitor?

Answer 48

AEs: diarrhea, edema, increase K+, HTN, hepatotoxicity, increased triglycerides Adjunctive STEROIDS (prednisone or MPS) Monitor: LFTs, K+ & phosphate, BP monthly

Question 49

What is olaparib in prostate cancer?

Answer 49

Selectively inhibits poly (ADP-ribose) polymerase (PARP) enzymes, which aid in DNA repair [by stopping DNA repair, allows other agents to effectively destroy cells]

Question 50

Why is cabazitaxel second line to docetaxel in prostate cancer treatment?

Answer 50

Cabazitaxel has poor afinity for multidrug resistant proteins and therefore does not work in all tumor types Also has severe ADEs (febrile neutropenia, mucositis)

Question 51

In what VERY specific type of prostate cancer could we use Lu-177–PSMA-617 (Pluvicto)?

Answer 51

PSMA-positive metastatic castration-resistant prostate cancer

Question 52

Bone metastasis is fairly common in prostate cancer. How would you supportively treat this?

Answer 52

Zoledronic acid Denosumab