Prostate Cancer Flashcards
Epidemiology
- Most ___ malignancy in men in US
- 2nd most common cause of cancer related ___ in men
- Estimated that ~16% of men will be diagnosed with prostate cancer during their lifetime (1 in ___ men from birth to death)
- common
- death
- 8
Etiology/Pathogenesis
Hormonal
- ___ is a growth signal to the prostate
- Most risk factors associated with prostate cancer are related to increased exposure to testosterone
Alterations in ___ receptor
- testosterone
- androgen
Risk Factors
Age
- increased lifetime exposure to ___
Race
- More common in ___, less common in Asians
Family History
- testosterone
- African-Americans
Pathology
Grading: ___ score (2 - 10)
- Scores of 2 to 4 are ___ , well differentiated
- Scores of 8 – 10 are ___ , poorly differentiated
- slow growing
- aggressive
Prostate Specific Antigen (PSA)
Liquefies seminal secretions and
increases with disorders of the prostate
* Normal range is ___ - ___ ng/mL
* > 4 ng/mL requires evaluation
* > ___ ng/mL highly suspicious for malignancy
* PSA velocity: > ___ ng/mL rise per year suspicious for malignancy
- 0-4
- 10
- 0.75
Definitions
- m1 = Metastatic (found
on scans) - m 0 = Non-metastatic ( ___ only)
- HSPC = ___ sensitive prostate
cancer - CRPC = ___ resistant prostate
cancer
- PSA
- hormone
- castration
Treatment: Localized
Observation
- Involves monitoring the course of disease with the expectation to deliver palliative therapy for the development of ___
- PSA and DRE every 6 months
- Advantage: Avoids immediate morbidity associated with treatment
- Disadvantage: Risk of disease complications such as urinary retention or fractures
Active surveillance:
- Based on premise that prostate cancer is a benign and indolent disease
- Involves active monitoring of disease. If cancer noted to progress, will initiate potentially ___ therapy
- Advantage: QOL less affected
- Disadvantage: 1/3 of patients require treatment, follow ups/biopsies
- symptoms
- curative
Treatment Overview: Localized
Radiation therapy
- External beam vs. brachytherapy
- Reasonable alternative to patients who are not ___ candidates
- Can add adjuvant ___ if intermediate or poor risk
- start prior to radiation therapy
and then continue on for 1-3 years
- surgical
- ADT
androgen deprivation therapy
Treatment: Localized
Radical prostatectomy + PLND
- Definitive ___ therapy
- survival with surgery: ~ 85% at 10 years
curative
PLND = Pelvic lymph node dissection
Androgen Deprivation Therapy
Goal is to induce ___ levels of testosterone
- Goal level = < __ ng/dL after 1 month of therapy
Androgen deprivation therapy (ADT)
- ___ agonist ± ___ or orchiectomy
castrate
50
LHRH, anti-androgen
Antiandrogens
- Blocks androgen receptors and inhibits androgen uptake and binding in target tissues
examples:
- Bicalutamide, Nilutamide, Flutamide, ___ , ___
- In the metastatic setting, not generally given as monotherapy
- Will give in combination with androgen ablation therapy such as LHRH agonist in the metastatic setting
Abiraterone, Enzalutamide
lutamides
Androgen Deprivation Therapy
LHRH agonists
- ___ and is as effective as orchiectomy
examples
- leuprolide, goserelin, triptorelin, histerelin
Toxicities:
– Acute: Tumor ___ (in the metastatic setting), ___, hot flashes, erectile dysfunction, edema, injection site reaction
- Long term: ___ , fracture, obesity, insulin resistance, changes in ___ , increased risk of both ___
and cardiovascular events
- reversible
- flare, gynecomastia
- osteoporosis, lipids, diabetes
Relugolix - Compared to LHRH agonists, had less cardiovascular events
Metastatic Disease
Goal of therapy – ___ of disease
- Need to determine whether this is a PSA recurrence or overt metastatic disease
- Determine PSA ___ time
- palliation
- doubling
Metastatic Disease: m0 HSPC
If only PSA recurrence, may delay start of ___
If the patient experiences a rapid PSA
velocity or ___ PSA doubling time and has a long-life expectancy: Consider ___
* If PSA doubling time ___ 6 months: Can give ADT
* If PSA doubling time ___6 months: can observe
Orchiectomy
- ADT
- short, ADT
- <
- >
Intermittent ADT: m 0 HSPC
Can start on LHRH agonist alone or with oral ADT
- When the PSA level has returned to a pre-specified baseline (i.e., 4 ng/dL), androgen suppression is ___
- restarted if PSA increases (10-20 ng/dL)
- d/c
Intermittent ADT
- Men with ___ failure only, could consider intermittent therapy
- Improved QOL and no difference in OS between intermittent therapy and continuous ADT
biochemical
m0CRPC
If PSA is still increasing and not responding to ADT and no distant metastasis found on scans, consider m0CRPC
- Continue ___ (usually an LHRH agonist)
– Add in one of the following agents: ___ , Apalutamide, Darolutamide
___ does not have indication in M0 setting
ADT
- Enzalutamide
- Abiraterone
Enzalutamide (Xtandi)
- Blocks androgen binding and translocation of the androgen receptor
- Drug interactions: Avoid CYP ___ inhibitors, can ↓ concentrations that are substrates for CYP3A4, 2C9, 2C19
- Decreases serum concentrations of ___
- Caution use in patients with ___ history
- Don’t have to take prednisone with it (unlike ___ )
- CYP2C8
- warfarin
- seizure
- abiraterone
Apalutamide
- ___ androgen receptor inhibitor
- Results in decreased proliferation of tumor cells and increased apoptosis
- Drug interactions: Many listed, Primarily metabolized via CYP ___ and CYP ___
- Use caution in patients with a history of ___, QT prolongation, falls, and thyroid dysfunction
- Non-steroidal
- CYP3A, CYP2C8
- seizure
Darolutamide
- Structurally ___ androgen receptor antagonist
- Offers potentially less toxicities and less severe toxicities (Less fractures, falls, seizures, weight loss)
- Drug interactions: Mainly metabolized through CYP ___
- Toxicities: Fatigue, back pain/arthralgias, rash, diarrhea,
hypertension, anemia, nausea
- unique
- CYP3A4
m 1 HSPC
Patient now has visceral metastases (seen on scans)
- Hormone sensitive disease
- Determine therapy based on the volume of disease
* Low volume
* High volume
If not previously performed:
* Tumor testing for ___ or dMMR
* Germline testing for gene mutation
- MSI-H
MSI-H = Microsatellite instability-high
Low volume m1HSPC
- ADT: LHRH agonists
- Continue ADT and add any of the following:
* Abiraterone + ___
* Enzalutamide
* Apalutamide
- Prednisone
High Volume m 1 HSPC
Could do any of the previously mentioned therapies:
– ADT
– ADT + Abiraterone + Prednisone
– ADT + Enzalutamide
– ADT + Apalutamide
Now ___ becomes an option
chemo
m1HSPC = Chemo + ADT
___ + ADT for 1st line treatment
(CHAARTED Trial)
docetaxel
category 1 recommendations for
1st line, M1 disease high volume
Use all for high-volume, castrate sensitive, metastatic disease
– ADT + Docetaxel + ___ or ___
- Abiraterone
- Darolutamide
Metastatic Castrate Recurrent Prostate Cancer
(CRPC)
- All patients will become ___ refractory
- Median survival of 6 months
- PSA ↓ used as a surrogate marker of response
- Continue ADT and maintain castrate testosterone concentrations
hormone
m1CRPC
In addition to continuing ___ therapy, the patient could do any of the following:
- ADT
___ -Second line therapy
- Taxane derivative (Microtubule inhibitor)
- Unlike other taxanes. Poor affinity for ___ proteins, therefore conferring activity in resistant tumors
- Toxicities: More severe ___, more
___ , more febrile neutropenia
Cabazitaxel
- neutropenia
- diarrhea
Bone Metastases
___ dichloride:
- Alpha particle-emitting isotope: Emits high energy, short-range alpha particles targeting bone metastases
- Approved for CRPC, symptomatic bone metastases, and no known visceral metastatic disease
Radium 223
dMMR/MSI-H
Pembrolizumab
- As with other solid tumors, pembrolizumab
received agonistic FDA approval for those cancers which express ___ or ___ characteristics
dMMR, MSI-H
Theranostic Radiopharmaceuticals
THERApeutics + diagNOSTICS
- the combination of using one radioactive drug to identify (diagnose) and a second radioactive drug to
deliver therapy to targeted tissue
- Lu-177 PSMA ( ___ ) - approved for PSMA-positive ___
Key Side effects:
– Myelosuppression
– Renal toxicity
– Dry mouth
– GI toxicity
- Pluvicto
- mCRPC
Prostate Cancer Prevention
Several large prevention trials sponsored by the NCI are ongoing
- Finasteride – (PCPT trial)
- Demonstrated that finasteride decreased the rate of acute urinary retention, need for surgery for symptomatic BPH, and decreased risk of progression of BPH
– 30% decrease in prostate cancer prevalence during the study period
Non-significant increase in higher grade tumors
ASCO and the American Urological Association suggested a discussion regarding the use of 5-α-reductase
inhibitors for 7 years as chemo prevention should occur in high-risk men
Treatment Summary
