Prostate Cancer & Benign Prostatic Hypertrophy Flashcards

1
Q

Prostate Cancer

general

A

Common, slow-growing cancer affecting men

Prostate cancer is associated with slow growth and may not be clinically significant during the lifetime of a patient

Epidemiology:
3rd leading cause of cancer in men in the United States
~192,000 cases diagnosed annually
Lifetime risk of being diagnosed with prostate cancer is 11%
Lifetime risk of dying from this condition is 2.5%

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2
Q

prostate cancer

RF

A

Inherent factors (major):
Age
Rare in men < 40 years of age
Peaks in men between 65 and 74 years of age
More common, and earlier onset in African Americans
Family history (1st-degree relatives diagnosed at < 65 years of age)
Family history of other heritable cancers
Breast cancer (BRCA1andBRCA2gene) mutations
Melanoma
Colorectal cancer, Lynch syndrome
Ovarian cancer
Pancreatic cancer

Medical factors:
Obesity
5-alpha-reductase inhibitors (finasteride)
↓ PSA levels
↑ High-grade risk of prostate cancer
Trichomonas vaginalisinfection

Social and environmental factors:
High-fat, low-vegetable diet
Smoking
Exposure to Agent Orange
Herbicide and defoliant chemical used during the Vietnam War between 1965 and 1972

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3
Q

Prostate gland

A

Walnut-sized structure in males that is primarily composed of glandular tissue
Positioned inferior to the bladder and surrounds the superior portion of the urethra
Primary function is to secrete a weakly acidic fluid that nourishes and transports sperm
Semen = sperm + seminal fluid

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4
Q

Prostate specific antigen (PSA)

A

is secreted within the seminal fluid and can pass into the blood

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5
Q

Zonal Anatomy

Anatomical zones

A

Peripheral zone
Comprises >70% of the prostate gland
Approximately 70% of prostate cancers
Closest to the rectum

Central zone
15%‒20% of prostate cancers
Surrounds the ejaculatory ducts

Transitional zone
10%‒15% of prostate cancers are in the transitional zone
Surrounds the proximal urethra
Key area of concern for benign prostatic hyperplasia (BPH)

Fibromuscular zone
Cancer in the fibromuscular stroma is rare
Does not contain glandular tissue
Surrounds the apex of the prostate

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6
Q

Tumorigenesis

TuDevelopment of prostate cancer is affected by

A

Environmental factors
Diet and smoking

Androgens
Prostate cancer cells rely on testosterone for growth and survival

Inherited genetic factors
2-fold ↑ risk in men with 1st-degree relatives with the disease
GermlineMYC(oncogene in prostate cancer) variants
Rare variants includeBRCA2and DNA mismatch repair genes (part of Lynch syndrome)

Acquired genetic factors
TMPRSS-ETSfusion gene is the most common gene alteration in prostate cancer (noted in 50% of cases)
Silencing of the gene encoding p27 (a protein controlling cell growth and division)
Amplification ofMYCand deletion ofPTEN: ↑ cell growth and ↑ androgen resistance

Under the influence of the factors, prostate epithelium → prostate intraepithelial neoplasia (precursor lesion) → localized adenocarcinoma → metastasis and androgen-resistant cancer

Adenocarcinoma accounts for > 90% of cases: develops primarily from a mutation in the glandular tissue

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7
Q
A
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8
Q

prostate cancer

Clin man

A

Majority of diagnosed patients are identified by screening for prostate cancer
Usually asymptomatic in early stages…this is when you want to Dx patients

Manifestations in later stages:
Bone pain (most common site of disseminated prostate cancer – lumbar spine and pelvis)
Weakness from spinal-cord compression
Weight loss
Fatigue
Urinary retention
Hematuria
Erectile dysfunction
Hydronephrosis

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9
Q

Prostate cancer

Labs

A

Prostate-specific antigen (PSA)
Protein produced by prostate cells (NOT specific to malignancy)

A small amount enters the bloodstream in healthy individuals

↑ Serum PSA level in prostate cancer is due to:
↑ Number of cells producing PSA
Disruption in the basement membrane, allowing ↑ levels of PSA to enter the bloodstream

Total PSA ≥ 4 ng/mL is considered positive
Free and total (complexed) levels can be measured
↑ in total PSA level → referral to urology

Note that there are two major forms of PSA found in the blood: percent-free and complexed PSA
Complexed PSA (total) directly measures the amount of PSA that is attached to other proteins (the portion of PSA that is not “free”)
Increase in complexed PSA (complexed to protease inhibitors) in patients with cancer

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10
Q

prostate cancer

Considerations for falsely High or Low PSA

A

Long-term use of 5-alpha-reductase inhibitors (finasteride)
Commonly used medications to treat benign prostatic hypertrophy
Associated with ↓ PSA levels
Correction factor should be applied for accurate interpretation

Urological conditions that can elevate PSA levels:
Benign Prostatic Hypertrophy (BPH)
Prostatitis
UTI/Urinary retention
Urological procedures (catheter placement, cystoscopy)

Repeat testing is recommended in the case of ↑ PSA (after addressing factors possibly influencing the elevation)

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11
Q

prostate cancer

PSA velocity

A

Cancer grows faster and the ↑ in PSA levels is more rapid
A minimum of 3 measurements over a 2-year period

General age-adjusted PSA thresholds are as follows:
40‒49 years of age: 2.5 ng/dL
50‒59 years of age: 3.5 ng/dL
60‒69 years of age: 4.5 ng/dL
70‒79 years of age: 6.5 ng/dL

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12
Q

prostate cancer

Digital rectal examination (DRE)

A

No longer recommended for asymptomatic patients
Low sensitivity and specificity

If an abnormality (hard nodule, asymmetry) is detected on rectal exam, further evaluation should be conducted

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13
Q

prostate cancer

Prostate biopsy

A

Confirmatory test required for diagnosis

Biopsy is performed using an image-guided (transrectal ultrasound or MRI) transrectal approach
Considerations before pursuing biopsy
Age and ethnicity of the patient
Life expectancy of the patient
Comorbidities
Immediate and long-term risks of biopsy, and possible treatment options

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14
Q

prostate cancer

Imaging studies

A

Evaluation of the extent of prostate cancer and volume determination:
MRI
Prostate Imaging Reporting and Data System (PI-RADS)
Used to report the likelihood of cancer in asuspicious area
5-point scale, with 1 representing high unlikeliness and 5 indicating high likeliness of cancer
To determine extra-prostatic extension and distant metastasis:
CT or MRI of the abdomen and pelvis
PET: images may be superimposed with CT and MRI
Bone scan

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15
Q

prostate cancer

Tx considerations

A

Definitive treatments are associated with substantial side effects that impact the quality of life

Multiple factors are considered in treatment:
Age and life expectancy:
Overall health and comorbidities
Characteristics of the cancer and risk stratification
Patient preferences

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16
Q

prostate cancer

Active surveillance

A

Deferred treatment with monitoring
Serial PSA and DREs over regular intervals
Repeat biopsies
MRI
Intention to treat for disease progression or change in patient preference
Preferred in patients with very low- or low-risk cancer

17
Q

prostate cancer

Tx

A

Radiation therapy (RT)
External beam RT (EBRT): can cause erectile dysfunction and radiation proctitis
Brachytherapy:
Radioactive seed implants
Can cause bladder irritation

Surgery (radical prostatectomy)
Options:
Open surgery
Laparoscopy with or without robotic assistance
Removal of the prostate gland, seminal vesicles, and pelvic lymph nodes, followed by reconstruction (reconnecting the bladder neck and the urethra)
Can cause erectile dysfunction and stress urinary incontinence

18
Q

prostate cancer

Screening Recommendations

A

American Cancer Society

Screening should not take place without a discussion about the harms and benefits

  • 50 years of age for men with an average risk of prostate cancer and life expectancy ≥ 10 years
  • 45 years of age for men with a high risk of prostate cancer (African Americans and those with a 1st-degree relative diagnosed with prostate cancer at < 65 years)
  • 40 years of age for men with a higher risk (> 11st-degree relative who had prostate cancer at < 65 years)
  • Men ≥70 years
    Benefits do not outweigh the expected harms
    Should NOT be routinely screened for prostate cancer

Men who do not express a preference for screening should not be screened

19
Q

prostate cancer

Screening Strategy: PSA

A

Prostate-specific antigen is currently the only recommended screening method for prostate cancer

There is no perfect PSA cut-off value that avoids all false positives or all false negatives

False-positive rate: ~70%
Benign causes of elevated PSA levels (contributing to false-positive rate)
Benign prostatic hyperplasia
Prostatitis
Urinary retention
Urologic procedures (cystoscopy, transurethral resection of the prostate)

False-negative rate: ~15%

Positive: Total PSA ≥ 4 ng/mL
Most widely accepted standard
Different cutoff levels for decision-making: age-specific reference ranges sincePSAlevels tend to increase with age
For patients on a 5-alpha reductase inhibitor (ARI)
Correction factor (2.5) must be applied for accurate interpretation since ARIs lower PSA values
If there is an increase in PSA level, the patient should be referred to urology

Negative: Total PSA < 4 ng/mL
Apply the correction factor for patients on a 5-alpha reductase inhibitor
Continue routine screening if the patient prefers

20
Q

prostate cancer

Follow up

A

Retesting should be performed every 1–2 years if the level is < 4 ng/mL

Interval recommendations vary between organizations

Can be individualized based on PSA level and the patient’s risk factors

Consider repeat testing in 6–8 weeks if the level is between 4 and 7 ng/mL to rule out benign causes

If the PSA is still elevated, or > 7 ng/mL on the initial screen, refer to urology

Further urologic workup will be needed:
Free:total (f/t) PSA ratio (f/t PSA < 10%–15% suggests cancer)
PSA density (ratio of PSA level to prostate volume measured on transrectal ultrasound)
Magnetic resonance imaging (MRI) of the prostate
Prostate biopsy

21
Q

Benign Prostatic Hypertrophy (BPH)

general and symptoms

A

Also referred to as Benign Prostatic Hyperplasia
Histologic diagnosis with an increase in the total number of stromal and epithelial cells within the transition zone of the prostate gland

Growth is NOT premalignant and presents low levels of clinical risk
Common condition (40-50%) of men > 50 years
Incidence increases with age

Symptoms include bladder outlet obstruction (BOO), leading to lower urinary tract symptoms (LUTS)
↑ frequency of urination
Slowness or dribbling of the urinary stream

22
Q

Benign Prostatic Hypertrophy (BPH)

Pathogenesis

Normal prostate (left image) and an enlarged prostate or BPH (right image), which is associated with bladder outlet obstruction
A

Androgens, testosterone, and DHT (the more potent androgen) play a key role in BPH
↑ Prostate cell proliferation
Inhibit cell death

BPH directly leads to
Urethral compression
BOO

Incomplete voiding and/or increased storage of urine
Increased bladder smooth muscle tone and pressure lead to decreased compliance

BPH with BOO results in secondary detrusor instability or overactive bladder

DHT – dihydrotestosterone
Detrusor muscle: muscle which forms a layer of the wall of the bladder

23
Q

BPH

Sx

A

Lower Urinary Tract Symptoms
Voiding
Difficulty with starting/stopping urination
Weak stream/dribbling
Straining
Storage
Sudden urgency and frequency
Incomplete emptying of the bladder
Incontinence
Nocturia

24
Q

BPH

PE

A

History: voiding patterns, fluid intake, diet, pertinent medical history, current medications

Physical exam:
Abdominal: search for suprapubic tenderness, distended/palpable bladder, hernias, prior surgical scars
Pelvis: motor/sensory function, inguinal hernias

Genitourinary:
Basic genital exam
Digital rectal exam (DRE):
Assesses size of the prostate gland (normally about the size of a walnut)
Smooth enlargement
Post-void residual bladder scan to assess how well the patient empties

25
Q

BPH

Labs and imaging

A

Laboratory tests
Urinalysis: identifies hematuria, proteinuria, bacteriuria
Serum creatinine: establishes baseline renal function
Prostate-specific antigen (PSA)

Diagnostic procedures/imaging
Cystoscopy
Office procedure to view the prostate, bladder, urethra with a camera
Assists in operative planning for BPH and to rule out other anatomic causes

Transrectal ultrasound
Not necessary for diagnosis of BPH, but helps with accurately estimating prostate volume

26
Q

BPH

lifestyle mods

A

Non-surgical
Behavioral modifications
Limiting fluid intake/bladder irritants (caffeine, alcohol)
Avoiding constipation
Timed voiding regimens to improve bladder emptying

27
Q

BPH

Medical therapy

A

Anticholinergics (oxybutynin):
Muscarinic receptor blockers to treat irritative overactive bladder symptoms
Side effects: dry mouth, constipation, confusion, dry eyes, blurry vision, sedation, urinary retention
Critical to obtain post-void residual bladder scan to ensure patient is not retaining a large amount of urine prior to use

Alpha-adrenergic receptor blockers (tamsulosin):
Alpha-1 adrenergic receptors are located on prostatic smooth muscle
Blocking signals leads to relaxing the smooth muscle of the bladder neck and prostatic urethra
Side effects: dizziness, low blood pressure, rhinitis, retrograde ejaculation

5-alpha-reductase inhibitors (finasteride):
Block steroidal conversion of testosterone to DHT
Overall effect of shrinking the prostate gland over a period of 6+ months
Side effects: gynecomastia, decreased libido, retrograde ejaculation

28
Q

BPH

Surgical therapy and indications

A

Indications
Acute urinary retention
Chronic renal insufficiency secondary to BOO
Recurrent hematuria
LUTS refractory to medical treatment

Transurethral resection of the prostate (TURP)
Minimally invasive technique under cystoscopic guidance resection with a loop wire electrode
Goal is to remove adenomatous tissue in the transition zone of the prostate and relieve obstruction

Simple prostatectomy
Invasive open or robotic procedure
Reserved for patients with prostate glands > 80 g

29
Q
A