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