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Oncology > 17 - Prostate Cancer > Flashcards

17 - Prostate Cancer Flashcards

1
Q

Most common cause of cancer in American men

A

Prostate Cancer

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2
Q

Second leading cause of cancer deaths in the USA

A

Prostate Cancer

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3
Q

Lifetime risk of men in this country developing prostate cancer

A

16%

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4
Q

Prostate Cancer - Risk Factors

A

Age (65 - 74, mean 66)

Ethnicity (African American men higher risk)

Genetics (Men with ≥1 first degree relative have 2x risk. Men with 2 - 3 first degree relatives have 5 - 11x risk)
BRCA 1 (1.8-fold risk in men
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5
Q

Screening tests for prostate cancer

A 
PSA (prostate specific antigen)
Digital rectal exam
PSA velocity
PSA density
Free to total PSA ratio
PCA3
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6
Q

Prostate Specific Antigen (PSA)

A

Glycoprotein enzyme produced in prostate epithelial cells
Tissue barrier between prostate lumen and blood are disrupted in cancer
Used as screening tool now

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7
Q

PSA Performance

A 
Cut off of 4.0 ng/mL
Sensitivity 21% for any cancer, 51% for high grade
Specificity 91%
Positive predictive value 30%
Negative predictive value 85%

Can be false positives or false negatives

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8
Q

Benign settings for an elevated PSA

A 
Benign Prostatic Hyperplasia (BPH)
Bacterial Prostatitis
Acute urinary retention
Ejaculation
Digital rectal exam
Prostate biopsy
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9
Q

Digital Rectal Exam (DRE)

A 
Can detect tumors in posterior and lateral aspects
Poor inter-observer agreement
Sensitivity 59%
Specificity 94%
PPV 5 - 30%
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10
Q

Prostate Cancer Screening considerations

A

Not all men will die from it
Lifetime risk of prostate cancer 16%
Lifetime risk of dying from prostate cancer

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11
Q

Prostate Cancer Screening Recommendations

A

USPSTF recommends against PSA screening
ASCO says that if you have >10 year life expectancy, discuss risks/benefits of PSA testing
ACS and AUA - Recommendations to discuss PSA testing depend on age, life expectancy and clinical risk

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12
Q

Prostate Cancer - Presentation

A

80% of men are asymptomatic and diagnosed with elevated PSA. THey undergo a prostate biopsy

Symptoms:
Urinary frequency
Urgency
Nocturia
Hesitancy
Hematuria
Hematospermia (uncommon)
Bony pain in metastatic setting
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13
Q

Prostate Cancer - Diagnosis

A

Transrectal Ultrasound Guided Biopsy
Evenly distributed but random samples of the prostate
6 core biopsies previously
Now we do 12

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14
Q

How much does a normal prostate weigh?

A

20 g

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15
Q

Zones of the prostate

A

1 - Peripheral
2 - Central
3 - Transitional
4 - Anterior Fibromuscular Stroma

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16
Q

Site for benign prostatic hyperplasia

A

3 (Transitional zone)

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17
Q

Site for carcinoma

A

1 (Peripheral zone)

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18
Q

Prostate Histo findings you might encounter

A

Inflammation - Prostatitis

Benign nodular enlargement, Benign prostatic hyperplasia

Intraepithelial lesion - High grade prostatic intraepithelial neoplasia

Invasive cancer

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19
Q

Benign Prostatic Hyperplasia

A

Extremely common over the age of 50
20% of men ages 40 have it
70% of men age 60 have it

Hyperplasia is almost EXCLUSIVELY in the transition zone
Forms large nodules in the periurethral region

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20
Q

Benign Prostatic Hyperplasia - Clinical Picture

A 
Partial or complete urethral obstruction
Urinary frequency
Nocturia
Difficulty in starting and stopping urine stream
Overflow dribbling
Dysuria and infections

May lead to:
bladder hypertrophy and distension

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21
Q

Benign Prostatic Hyperplasia - Pathological Exam

A

Prostate weighs 60 - 100g (3 - 5 times as much as before)
Most common specimen - Transurethral resection of prostate (TURP)
Grossly - the nodule of BPH vary from soft yellow pink to tough pale grey, depending on percentage of glands
Microscopically - BPH consists of nodules with variable amount of glandular and stromal component

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22
Q

High Grade Prostatic Intraepithelial Neoplasia (HGPIN)

A

Preserved normal architecture
Basal cell layer present
Luminal cells: Multilayered, nuclear enlargement and prominent nucleoli

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23
Q

HGPIN

A

Putative precursor lesion

Unclear whether HGPIN inevitably progresses into prostate cancer

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24
Q

Prostate cancer

A

Most common - Adenocarcinoma

Other cancers in prostate: Sarcoma, lymphoma

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25
Q

Prostate adenocarcinomas

A

Arise in the peripheral zone

Needle core biopsy transrectally
If it’s negative for carcinoma:
Is there inflammation? (acute/chronic)
Are there precursor lesions? (HGPIN)

If it’s positive for carcinoma:
It’s cancer

26
Q

Prostate Adenocarcinoma - Histologic features

A

Small, crowded and infiltrative glands

Only one layer of cells (basal cell layer absent)

Nuclei are large with prominent nucleoli

27
Q

Gleason Score

A

Grades:
1 - Not used in clinical practice
2 - Not used in clinical practice
3 - You can draw an outline around each individual gland
4 - You can see some lumens, but the glands have begun to fuse, so you can’t outline each gland anymore
5 - No more glands, only infiltrating cells

If there are two scores present in different parts, you add them up. (4 & 3 = 7)

If there is only one score uniformly all around, you just double it (3 & 3 = 6)

28
Q

Extent of cancer

A

of core biopsies involved
Percentage of sampled tissue
Perineural invasion present

29
Q

Interpreting Gleason Scores

A

4 is the most common Gleason grade
3 is the second most frequent Gleason grade

6 is the score with the best prognosis
7 has an intermediate prognosis
8 - 10 are the worst prognoses

30
Q

New Grading System

A

Grade Group 1 - Gleason score of 6
Grade Group 2 - Gleason score of 7 (3 + 4), with predominantly 3 (not many fused glands)
Grade Group 3 - Gleason score of 7 (4 + 3), with predominantly 4 (mostly fused glands)
Grade Group 4 - Gleason score of 8
Grade Group 5 - All else

31
Q

Prostatic Adenocarcinoma - Immunohistochemistry

A

Markers for basal cell layer
PIN4 immunostain
P63 and HMWCK basal cell markers

32
Q

Prostatic Adenocarcinoma - Resection specimens

A

Margins: Positive or Negative
Spread to periprostatic soft tissue, seminal vesicles, bladder neck
Perineural invasion
Metastases

33
Q

Prostatic Adenocarcinoma - Metastasis

A

First spreads via lymphatics to obturator nodes
Then spreads to para-aortic nodes
Hematogenous spread is mainly to bones
Osteoblastic lesions in the lumbar spine, proximal femur, pelvis, thoracic spine, ribs

34
Q

Prostate Cancer - Stage I/II

A

T1 - Tumor not palpable/detectable (detected by PSA)

T2 - Palpable, confined to prostate

35
Q

Prostate cancer - Stage III/IV

A

T3 - Through prostate capsule or involving seminal vesicles
N0 - Negative nodes
M0 - No distant metastases

T4 - Invading other structures
N1 - Positive nodes
M1 - Distant metastases

36
Q

Prostate Cancer - Stage at Presentation

A

81% - Localized (confined to primary site) [100% 5 year survival]
12% - Regional (Regional lymph nodes involved) [100% 5 year survival]
4% - Distant (Cancer has metastasized)
3% - Unknown (Unstaged)

37
Q

Prostate Cancer - Local Treatment

A

Surgery
Radiation (External beam or Brachytherapy)
Observation (Active surveillance)

38
Q

Surgery - Prostatectomy

A

Retropubic or perineal approach
Open or minimally invasive
Nerve sparing approach - Preservation of autonomic cavernous nerves in neurovascular bundle

Advantages:
Pathologic staging, pelvic nodes accessible

Risks:
Impotence 59% at 2 months, 43% at 2 years
Incontinence 52% at 2 months, 15% at 2 years
Surgical risks

39
Q

Prostate Cancer Treatment - Radiation

A

External beam radiation:
In combination with hormonal therapy, depending on risk
No direct comparison to surgery, but outcomes thought to be equivalent
Side effects: Radiation proctitis, enteritis, cystitis, sexual dysfunction, low risk for urinary incontinence

Brachytherapy:
Radioactive seed implants
Can be given with external beam radiation with higher risk prostate cancer
Side effects: Urinary retention, proctitis, sexual dysfunction

40
Q

Prostate Cancer Treatment - Active Surveillance

A

Observation rather than immediate treatment for patients with low risk prostate cancer

PSA

41
Q

Prostate Cancer Treatment - Metastatic

A

Androgen Deprivation Therapy

Old school: Surgical Orchiectomy
Quick, cost-effective, no compliance issues

More modern: Medical orchiectomy
GnRH agonists (overstimulation downregulates GnRH receptors, decreasing LH & FSH levels)
Add antiandrogen threapy (Bicalutamide) to counter “flare”

42
Q

GnRH agonists

A

Goserelin
Leuprolide
Buserelin
Triptorelin

All injectible
Goal: Testosterone level down to 50

43
Q

GnRH antagonist

A

Degarelix

Blocks GnRH receptors

44
Q

Hormone Sensitive vs Castrate Resistant

A

Hormone sensitive prostate cancer develops resistance to hormonal therapy after about 2 years

This is called “Castrate Resistant Prostate Cancer” (CRPC)

Metastatic CRPC is lethal

45
Q

Castrate Resistant Prostate Cancer - Treatment

A

Chemotherapy (Docetaxel, Cabazitaxel)
Secondary hormonal manipulation (Abiraterone, Enzalutamide)
Immune therapy
Radium 223

46
Q

Chemotherapy - Docetaxel - Mechanism of action

A

Taxane - Inhibits depolymerization of tubulin, stabilizes microtubules

IV every 3 weeks

Hepatic metabolism

47
Q

Chemotherapy - Docetaxel - Side effects

A 
Cytopenias
Peripheral neuropathy
Alopecia
Darkening of skin and nails
Nausea/Vomiting
Taste alteration
Edema
48
Q

Chemotherapy - Cabazitaxel - Mechanism of action

A

Taxane - Inhibits depolymerization of tubulin, stabilizes microtubules

IV every 3 weeks

Works for metastatic CRPC after docetaxel treatment has failed to halt the progression

49
Q

Chemotherapy - Cabazitaxel - Side effects

A

Cytopenias
Diarrhea
Nausea/Vomiting
Fatigue

50
Q

Abiraterone

A

CYP-17 Hydroxylase Inhibitor

Reduces the production of testosterone even further. Can reach undetectable levels or

51
Q

Abiraterone - Effects

A

4 extra months overall survival
Improves pain
Improves quality of life
Improves time before needing chemo

52
Q

Abiraterone -Side Effects

A

Blocking androgen formation leads to upstream metabolites to pile up. One of those is aldosterone.

Mineralicorticoid excess:
Hypertension
Hypernatremia
Hypokalemia
Fluid retention
53
Q

Enzalutamide

A

Novel anti-androgen

Can block every step of the process from androgen’s extracellular binding to DNA transcription regulation

Taken PO

54
Q

Enzalutamide - Effects

A

Improves overall survival
Improves quality of life
Improves pain
Improves time to needing chemo

55
Q

Enzalutamide - Side Effects

A

Fatigue
Hypertension
Decreased appetite

56
Q

Sipuleucel-T

A

Immune Therapy
Patients get leukocytes pheresed from their blood
Monocytes isolated
Monocytes exposed to growth factor and prostate cancer proteins
Monocytes re-infused as APCs that present the cancer proteins

57
Q

Sipuleucel-T - Effects

A

Improves overall survival

Does not affect PSA or radiographic imaging

58
Q

Sipuleucel-T - Side Effects

A

Infusion-related reactions (chills, fatigue, fever, nausea, headache)

59
Q

Radium 223

A

Hones to osteoblastic regions, since it’s in the same family as calcium

Given IV monthly for 6 months
Improves overall survival
Improves time to symptomatic skeletal event

60
Q

Radium 223 - Side effects

A

Low rates of myelosuppression

Minimal toxicities

Oncology (23 decks)

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