Prostate Cancer & Benign Prostatic Hypertrophy Flashcards
Prostate Cancer
general
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%
prostate cancer
RF
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
Prostate gland
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
Prostate specific antigen (PSA)
is secreted within the seminal fluid and can pass into the blood
Zonal Anatomy
Anatomical zones
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
Tumorigenesis
TuDevelopment of prostate cancer is affected by
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
prostate cancer
Clin man
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
Prostate cancer
Labs
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
prostate cancer
Considerations for falsely High or Low PSA
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)
prostate cancer
PSA velocity
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
prostate cancer
Digital rectal examination (DRE)
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
prostate cancer
Prostate biopsy
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
prostate cancer
Imaging studies
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
prostate cancer
Tx considerations
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
prostate cancer
Active surveillance
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
prostate cancer
Tx
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
prostate cancer
Screening Recommendations
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
prostate cancer
Screening Strategy: PSA
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
prostate cancer
Follow up
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
Benign Prostatic Hypertrophy (BPH)
general and symptoms
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
Benign Prostatic Hypertrophy (BPH)
Pathogenesis
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
BPH
Sx
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
BPH
PE
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
BPH
Labs and imaging
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
BPH
lifestyle mods
Non-surgical
Behavioral modifications
Limiting fluid intake/bladder irritants (caffeine, alcohol)
Avoiding constipation
Timed voiding regimens to improve bladder emptying
BPH
Medical therapy
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
BPH
Surgical therapy and indications
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
