Prostate Cancer Screening

Overview

Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer

• Cancer of the prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. gland
• Adenocarcinoma accounts for > 90% of cases.

Epidemiology

• Worldwide:
  • 2nd most common cancer diagnosis in men
  • > 1.3 million cases diagnosed annually
• In the United States:
  • 3rd leading cause of cancer in men
  • Approximately 192,000 cases diagnosed annually
  • Lifetime risk of a prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer diagnosis is 11%.
  • Lifetime risk of dying from prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer is 2.5%.
• 5-year survival after diagnosis:
  • Localized disease or regional spread: nearly 100%
  • Distant metastatic disease: 31%

Risk factors

Inherent factors (major factors):

• Age
  • Rare before 40 years of age
  • Peaks between 65 and 74 years of age
• More common, and earlier onset, in African Americans
• Family history Family History Adult Health Maintenance of prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer, particularly in 1st-degree relatives who were diagnosed at < 65 years of age
• Family history Family History Adult Health Maintenance of other heritable cancers
  • Breast cancer Breast cancer Breast cancer is a disease characterized by malignant transformation of the epithelial cells of the breast. Breast cancer is the most common form of cancer and 2nd most common cause of cancer-related death among women. Breast Cancer, BRCA1 and BRCA2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations
  • Melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma
  • Colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer, Lynch syndrome Lynch syndrome Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome
  • Ovarian cancer Ovarian cancer Ovarian cancer is a malignant tumor arising from the ovarian tissue and is classified according to the type of tissue from which it originates. The 3 major types of ovarian cancer are epithelial ovarian carcinomas (EOCs), ovarian germ cell tumors (OGCTs), and sex cord-stromal tumors (SCSTs). Ovarian Cancer
  • Pancreatic cancer

Medical factors:

• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
• 5-alpha reductase inhibitors (e.g., finasteride Finasteride An orally active 3-oxo-5-alpha-steroid 4-dehydrogenase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. Androgens and Antiandrogens)
  • ↓ prostate-specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination ( PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer) levels
  • ↑ high-grade prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer risk
• Trichomonas Trichomonas A genus of parasitic flagellate eukaryotes distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. Nitroimidazoles vaginalis infection

Social and environmental factors:

• High-fat, low-vegetable diet
• Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
• Exposure to Agent Orange Agent orange A herbicide that contains equal parts of 2, 4-dichlorophenoxyacetic acid (2, 4-d) and 2, 4, 5-trichlorophenoxyacetic acid (2, 4, 5-t), as well as traces of the contaminant 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. Herbicide Poisoning
  • Herbicide and defoliant chemical used during the Vietnam War between 1965 and 1972
  • Associated with more aggressive cancer
• Exposure to chlordecone 
  • Insecticide used between 1973 and 2003 in the Caribbean
  • Binds estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, which may contribute to malignancy Malignancy Hemothorax development

Screening Rationale

Individualized screening Screening Preoperative Care

• Screening Screening Preoperative Care offers a small potential benefit in reducing the chance of death from prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer. 
• The potential benefit will take many years, even decades, while the harms take place soon after screening Screening Preoperative Care starts.
• Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer often has a slow growth rate, in which:
  • Half of cases do not present clinically.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship frequently die from other medical conditions.
• Each patient is encouraged to decide on the potential benefits and harms discussed based on his own values.

Benefits of screening Screening Preoperative Care

• Goals:
  • Identify high-risk, localized prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer that can be successfully treated 
  • Prevent prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer-related morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status, including advanced or metastatic disease
• Benefits of PSA-based screening Screening Preoperative Care:
  • In men aged 55–69 years, screening Screening Preoperative Care may prevent 1.3 deaths from prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer per 1,000 men screened over 13 years.
  • Screening Screening Preoperative Care may prevent 3 cases of metastatic prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer per 1,000 men.
  • However, trials have not shown a reduction in all-cause mortality Mortality All deaths reported in a given population. Measures of Health Status.

Risks of screening Screening Preoperative Care

• Harms of screening Screening Preoperative Care: 
  • Frequent false-positive results
  • Leads to over-diagnosis (cancer diagnosed in men who otherwise would not have symptomatic cancer in their lifetime)
• Potential harms of diagnostic biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Infection
  • Rectal bleeding
  • Urinary obstruction
  • Psychological harm
• Potential harms of cancer management:
  • Erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction (up to 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
  • Urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence
  • Bowel dysfunction
  • Psychological harm 

Screening Recommendations

United States Preventive Service Task Force (USPSTF)

• Men aged 55–69 years should: 
  • Discuss potential benefits and harms with their clinician Clinician A physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients. Clinician–Patient Relationship
  • Consider age, family history Family History Adult Health Maintenance, race/ethnicity, comorbid conditions, and life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids
  • Make an individual decision about screening Screening Preoperative Care
• Men ≥ 70 years: 
  • Benefits do not outweigh the expected harms.
  • Should not be routinely screened for prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer
• Men who do not express a preference for screening Screening Preoperative Care should not be screened.

American Cancer Society

• Screening Screening Preoperative Care should not take place without a discussion about the harms and benefits. 
• This discussion should occur at:
  • 50 years of age for men with an average risk of prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer and life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids ≥ 10 years
  • 45 years of age for men with a high risk of prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer (African Americans and those with a 1st-degree relative diagnosed with prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer at < 65 years)
  • 40 years of age for men with a higher risk (> 1 1st-degree relative who had prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer at < 65 years)

Screening Strategy: PSA

Prostate-specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination is currently the only recommended screening Screening Preoperative Care method for prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer.

Background

• A protein produced by normal and neoplastic prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cells
• In healthy individuals, a small proportion will enter the bloodstream.

Causes of elevated serum PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer in prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer

• An increased number of cells producing PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer, despite the fact that malignant cells generally make less PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer
• Disruption in the normal architecture and basement membrane Basement membrane A darkly stained mat-like extracellular matrix (ecm) that separates cell layers, such as epithelium from endothelium or a layer of connective tissue. The ecm layer that supports an overlying epithelium or endothelium is called basal lamina. Basement membrane (bm) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. Bm, composed mainly of type IV collagen; glycoprotein laminin; and proteoglycan, provides barriers as well as channels between interacting cell layers. Thin Basement Membrane Nephropathy (TBMN), allowing a higher proportion of PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer to enter the bloodstream

Interpretation of results

• There is no perfect PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer cut-off value that avoids all false positives or all false negatives.
  • False-positive rate: approximately 70%
    • Benign Benign Fibroadenoma causes of elevated PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer levels (contributing to false-positive rate)
      • Benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. Benign Prostatic Hyperplasia
      • Prostatitis Prostatitis Prostatitis is inflammation or an irritative condition of the prostate that presents as different syndromes: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain, and asymptomatic. Bacterial prostatitis is easier to identify clinically and the management (antibiotics) is better established. Prostatitis 
      • Urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
      • Urologic procedures (cystoscopy, transurethral resection of the prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. )
  • False-negative rate: approximately 15%
• Positive: PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer ≥ 4 ng/mL
  • Most widely accepted standard, which tries to balance the trade-offs between sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests
  • Test characteristics at this cut-off level:
    • For detection of any prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer: sensitivity = 21%; specificity = 91% 
    • For detection of high-grade cancer: sensitivity = 51%
  • Different cut-off levels for decision-making: age-specific reference ranges since PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer levels tend to increase with age
• Negative: PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer < 4 ng/mL
  • Follow-up is needed
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on a 5-alpha reductase inhibitor ( ARI ARI Measures of Risk):
    • Correction factor must be applied for accurate interpretation since ARIs lower PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer values.
    • If there is an increase in PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer level, they should be referred to urology.

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 PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer 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 Benign Fibroadenoma causes.
  • If the PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer is still elevated, or > 7 ng/mL on the initial screen, refer to urology. 
  • Further urologic workup can include:
    • Free:total (f/t) PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer ratio (f/t PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer < 10%–15% suggests cancer)
    • PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer density (ratio of PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer level to prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. volume measured on transrectal ultrasound)
    • Molecular and genomic analysis
    • Magnetic resonance imaging (MRI) of the prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid.
    • Prostate biopsy Prostate Biopsy Prostate Cancer

Screening Strategy: Digital Rectal Examination

• No longer recommended for asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• Low sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests
• Does not provide additional information to a PSA PSA A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. Prostate Cancer test