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Oncology > 17 - Prostate Cancer > Flashcards

17 - Prostate Cancer Flashcards

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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
Prostate adenocarcinomas
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
Prostate Adenocarcinoma - Histologic features
Small, crowded and infiltrative glands Only one layer of cells (basal cell layer absent) Nuclei are large with prominent nucleoli
27
Gleason Score
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
Extent of cancer
of core biopsies involved Percentage of sampled tissue Perineural invasion present
29
Interpreting Gleason Scores
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
New Grading System
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
Prostatic Adenocarcinoma - Immunohistochemistry
Markers for basal cell layer PIN4 immunostain P63 and HMWCK basal cell markers
32
Prostatic Adenocarcinoma - Resection specimens
Margins: Positive or Negative Spread to periprostatic soft tissue, seminal vesicles, bladder neck Perineural invasion Metastases
33
Prostatic Adenocarcinoma - Metastasis
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
Prostate Cancer - Stage I/II
T1 - Tumor not palpable/detectable (detected by PSA) | T2 - Palpable, confined to prostate
35
Prostate cancer - Stage III/IV
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
Prostate Cancer - Stage at Presentation
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
Prostate Cancer - Local Treatment
Surgery Radiation (External beam or Brachytherapy) Observation (Active surveillance)
38
Surgery - Prostatectomy
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
Prostate Cancer Treatment - Radiation
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
Prostate Cancer Treatment - Active Surveillance
Observation rather than immediate treatment for patients with low risk prostate cancer PSA
41
Prostate Cancer Treatment - Metastatic
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
GnRH agonists
Goserelin Leuprolide Buserelin Triptorelin All injectible Goal: Testosterone level down to 50
43
GnRH antagonist
Degarelix | Blocks GnRH receptors
44
Hormone Sensitive vs Castrate Resistant
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
Castrate Resistant Prostate Cancer - Treatment
Chemotherapy (Docetaxel, Cabazitaxel) Secondary hormonal manipulation (Abiraterone, Enzalutamide) Immune therapy Radium 223
46
Chemotherapy - Docetaxel - Mechanism of action
Taxane - Inhibits depolymerization of tubulin, stabilizes microtubules IV every 3 weeks Hepatic metabolism
47
Chemotherapy - Docetaxel - Side effects
``` Cytopenias Peripheral neuropathy Alopecia Darkening of skin and nails Nausea/Vomiting Taste alteration Edema ```
48
Chemotherapy - Cabazitaxel - Mechanism of action
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
Chemotherapy - Cabazitaxel - Side effects
Cytopenias Diarrhea Nausea/Vomiting Fatigue
50
Abiraterone
CYP-17 Hydroxylase Inhibitor | Reduces the production of testosterone even further. Can reach undetectable levels or
51
Abiraterone - Effects
4 extra months overall survival Improves pain Improves quality of life Improves time before needing chemo
52
Abiraterone -Side Effects
Blocking androgen formation leads to upstream metabolites to pile up. One of those is aldosterone. ``` Mineralicorticoid excess: Hypertension Hypernatremia Hypokalemia Fluid retention ```
53
Enzalutamide
Novel anti-androgen Can block every step of the process from androgen's extracellular binding to DNA transcription regulation Taken PO
54
Enzalutamide - Effects
Improves overall survival Improves quality of life Improves pain Improves time to needing chemo
55
Enzalutamide - Side Effects
Fatigue Hypertension Decreased appetite
56
Sipuleucel-T
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
Sipuleucel-T - Effects
Improves overall survival | Does not affect PSA or radiographic imaging
58
Sipuleucel-T - Side Effects
Infusion-related reactions (chills, fatigue, fever, nausea, headache)
59
Radium 223
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
Radium 223 - Side effects
Low rates of myelosuppression | Minimal toxicities

Oncology (23 decks)

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