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PLME > Prostate Cancer > Flashcards

Prostate Cancer Flashcards

1
Q

Epidemiology

A
  • median age at diagnosis is 67
  • overall incidence is 163.0/100,000 men/yr
  • overall mortality is 26.7/100,000 men/yr
  • 30k men/yr develop castrate resistant prostate cancer
  • 1 in 6 men will be diagnosed with prostate cancer in their lifetime
  • b/w 1984-1991, 30-40% presented with advanced disease; today only 5-15% have metastatic disease at presentation
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2
Q

prostate cancer risk factors

A 
known:
*age
*ethnicity
*family history
suspected
*diet
unlikely
*fertility
medical myths
*vasectomy 
*benign prostate hyperplasia (BPH)
*bike riding
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3
Q

age is the dominant risk factor. what are the percentages of risk for the different age groups?

A
  • age 50-59: 9%
  • age 60-69 12.5%
  • age 70-79 32%
  • age 80-89 37%
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4
Q

ethnicity

A
  • the highest age adjusted incidence of prostate cancer occurs in African-Americans
  • nearly 2x the incidence that occurs in non-African americans
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5
Q

family history

A
  • 2-3x increased risk in patients with primary relative prostate cancer <70
  • familial clustering identified
  • BRCA2
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6
Q

diet, obesity and physical activity

A
  • 1/3 of cancer deaths in the US are attributed to nutritional factors
  • soon will exceed tobacco as the most significant lifestyle cause of cancer mortality
  • obesity, physical inactivity and excess caloric intake increase risk of several types of cancer
  • obesity related to cancers of breast (postmenopausal), kidney, endometrium, esophagus, prostate and colon (especially in men) and gallbladder (especially in women)
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7
Q

what are the ways of diagnosis prostate cancer?

A
  • PSA
  • digital rectal exam
  • biopsy
  • imagine studies
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8
Q

PSA

A
  • prostate specific antigen is a protein produced by the epithelial cells lining the prostate ducts. Its function is to liquefy the seminal fluid
  • it is prostate tissue-specific not prostate cancer-specific
  • 4-10: 25% chance of having prostate cancer
  • > 10: 67% chance of having prostate cancer
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9
Q

what are some PSA confounders?

A
  • benign prostatic hypertrophy
  • prostatitis
  • age
  • ejaculation
  • digital rectal exam
  • medicines
  • e.g. 5-alpha reductase inhibitors
  • herbal preparations
  • beware of compounds with estrogenic properties that lower androgen levels
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10
Q

what are some ways to improve the diagnostic accuracy of PSA?

A
  • age-specific PS
  • lowering the threshold for abnormal in younger men
  • percent-free PSA
  • PSA occurs in 2 major forms- free and bound
  • the % of free PSA is lower in men with prostate cancer. percent-free of <25% is worrisome for cancer
  • PSA velocity
  • the change of PSA over time. a rate of rise faster than 0.75/yr is worrisome for cancer
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11
Q

digital rectal exam

A
  • good specificity
  • poor sensitivity
  • low cost
  • poor compliance
  • inter-observer variability
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12
Q

What is the staging of prostate cancer?

A
  • PSA
  • digital rectal exam
  • trans rectal ultrasound
  • gleason score
  • bone scan
  • +/- CT scan or MRI
  • biopsy and TNM staging system
  • Tumor, Nodes, Metastases
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13
Q

what is prostate cancer T1 disease?

A
  • cannot be felt
  • T1a- cancer found in =< 5% TURP specimen
  • T1b- cancer found in >= 5% TURP specimen
  • T1c- cancer found as a result of PSA elevation only
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14
Q

what is prostate cancer T2?

A
  • can be felt during DRE
  • T2a- felt on one side of prostate
  • T2b- felt on both sides of prostate
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15
Q

what is prostate cancer T3?

A
  • has spread beyond the prostate
  • T3a- extra capsular extension
  • T3b- tumor invades seminal vesicles(s)
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16
Q

what is prostate cancer T4?

A
  • has invaded local organs
  • bladder invasion
  • invasion into surrounding pelvic side wall
  • may cause pain in joints and back
17
Q

what are some sites of metastasis?

A 
bone
lymph nodes
lung
lier
CNS
18
Q

pathology

A
  • adenocarcinoma (gland-like) accounts for 95% of prostate cancers
  • variant cancers account for the remaining 5%:
  • neuroendocrine cancer
  • sarcomatoid cancers
  • lymphoma
  • transitional cell (urothelial) cancer
19
Q

prostate cancer grade

A
  • the gleason system is based on the glandular pattern of the adenocarcinoma as identified at relatively low magnification
  • both the primary and secondary architectural patterns are assigned a grade from 1 (most differentiated) to 5 (least differentiated).
20
Q

gleason grade distribution

A

6 low grade
7 intermediate grade
8-10 high grade

21
Q

primary therapy early stage disease

A
  • prostatectomy
  • open
  • robot-assisted laparascopic
  • external beam radiation
  • brachytherapy
  • cryosurgery
  • active surveillance
22
Q

primary therapy

A
  • surgery is reserved form men less than 70-75 years old, with a life expectancy of 15 years, and likely organ confined disease:
    1. PSA at diagnosis
    2. clinical stage
    3. gleason score
23
Q

external beam radiation

A
  • better option than prostatectomy if:
  • higher risk to have extra-prostatic disease
  • older patients (>70-75)
  • patients with concurrent medical illnesses that diminish candidacy for surgery
  • often given concurrently with short term hormonal therapy which enhances radiation activity
24
Q

active surveillance

A
  • appropriate option for low risk patients:
  • PSA<10mg/dl
  • T1c or T2a disease
  • gleason 6
  • no more than 3 biopsy cores positive
  • no more than 50% of anyone core positive
  • patients undergo semi-annual-clinical evaluations and annual repeat biopsies to exclude disease progression or upstaging with sampling
25
Q

what are the prostate cancer molecular features?

A
  • the role of the androgen receptor in cell signaling and proliferation of prostate cancer cells
  • understanding mechanisms for castrate resistant disease (CRPC)
  • treatment options for CRPC
26
Q

AR-Testosterone Pathway General Principles

A
  • the testis are stimulated by the hypothalamus-pituitary axis and produces 90% of a man’s androgens. remaining 10%:
  • adrenal glands
  • prostate cancer cells
  • AR is a cytoplasmic receptor. it needs to undergo binding to androgens and multiple configurations to enter the nucleus
  • once within the nucleus AR binds to DNA with the help of co-activators and elicits biologic response. in prostate cancer these include:
  • cell proliferation
  • lack of apoptosis
  • PSA production
27
Q

AR biologic pathway

A
  • key
  • SHBG= sex hormone binding globulin
  • DHT= dihydrotestosterone
  • HSP= heat shock protein
  • AR= androgen receptor
  • ARA70= androgen receptor agonist 70
  • GTA= general transcription apparatus
28
Q

Treatment Options Androgen Deprivation Therapy

A
  • bilateral orchiectomies
  • lutenizing hormone releasing hormone (LHRH) antagonist therapy
  • degeralex
  • LHRH agonist therapy
  • leuprolide…
  • often combined with an androgen receptor antagonist (flutamide, bicalutamide…)
29
Q

Biology of Castrate Resistant Prostate Ca

A

*activation of AR at low levels of T/DHT
-changes in the PCA cell that allows for phosphorylation of the AR
-enhances the binding of the AR to T/DHT
*AR mutations
-mutations in the ligand binding domain affect the ligand binding pocket and liberalize the spectrum of AR agonists to a wider range of steroid hormones and pharmaceutical antiandrogens
*indirect mechanisms of AR activation
-deregulation of apoptotic genes
-neuroendocrine differentiation of prostatic cells
-decreased expression of coexpressors
+change in CoA:CoR alters AR activity in the setting of low levels DHT
*increased levels of AR protein without mutations
*incomplete blockade of AR-ligand production
-medical or surgical castration does not result in undetectable androgen levels
+adrenals androgens
+intracrine mechanism

30
Q

what are the treatment options for CRPC advanced disease?

A
  • alternative endocrine manipulations
  • chemotherapy
  • immunotherapy
  • skeletal protective therapy

PLME (5 decks)

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