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Prostate Cancer

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 one of the most common cancers affecting men. In the United States, the lifetime risk of being 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 is approximately 11%, and the lifetime risk of death is 2.5%. 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 a slow-growing cancer that takes years, or even decades, to develop into advanced disease. Several men 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 are asymptomatic. Late-stage cancer can present with bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, urinary symptoms, and/or weight loss Weight loss Decrease in existing body weight. Bariatric Surgery. Most cases 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 are identified based on diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests to determine prostate-specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (PSA) levels and are confirmed based on image-guided transrectal biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Management 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 depends on age, 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, comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, risk stratification, and preferences of the patient. Management options include active surveillance Surveillance Developmental Milestones and Normal Growth, androgen deprivation therapy, radiotherapy, chemotherapy Chemotherapy Osteosarcoma, and radical prostatectomy Prostatectomy Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). Benign Prostatic Hyperplasia.

Last updated: May 17, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Epidemiology

  • Worldwide:
    • 2nd most common cancer 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
    • The lifetime risk of being 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 is 11%.
    • The 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):

  • 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 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 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)
    • ↓ PSA levels
    • ↑ High-grade 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
  • 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
  • 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 to 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 and contributes to malignancy Malignancy Hemothorax

Related videos

Pathophysiology

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 and zonal anatomy

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:

  • An organ under the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess
  • Primarily composed of glandular tissue that secretes fluid into the ejaculate (which makes up semen, together with sperm and seminal fluid)

Zonal anatomy:

  • Peripheral zone: 
    • Comprises > 70% 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
    • Approximately 70% 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. cancers are in the peripheral zone.
    • Closest to the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy 
  • Central zone: 
    • 15%‒20% 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. cancers are in the central zone. 
    • Surrounds the ejaculatory ducts Ejaculatory Ducts Paired ducts in the human male through which semen is ejaculated into the urethra.
  • Transitional zone Transitional zone Anal Cancer
    • 10%‒15% 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. cancers are in the transitional zone Transitional zone Anal Cancer
    • Surrounds the proximal urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy
    • Key area of concern for benign Benign Fibroadenoma prostatic hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation ( BPH BPH 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)
  • Fibromuscular stroma:
    • Cancer in the fibromuscular stroma is rare.
    • Does not contain glandular tissue
    • Surrounds the apex 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 cancer

Prostate gland and main prostate zones:
peripheral, transitional and central zones in relation to other structures of the male genitourinary system.

Image by Lecturio.

Tumorigenesis

Under the influence of the factors listed below, 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. epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology 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. intraepithelial neoplasia (precursor lesion) → localized adenocarcinoma → metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis and androgen-resistant cancer

  • Adenocarcinoma accounts for > 90% of cases: develops primarily from a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the glandular tissue
  • Development 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 is affected by:
    • Environmental factors
    • Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens
      • 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 cells rely on testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens for growth and survival.
      • Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens dependence is seen with antiandrogen therapy.
      • Mechanisms develop to overcome androgen blockade and eventually lead to androgen resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing.
    • Inherited genetic factors 
      • 2-fold ↑ risk in men with 1st-degree relatives with the disease
      • Germline MYC (oncogene 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) variants
      • Other rare variants include BRCA2 and DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure mismatch repair Mismatch repair A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Exonucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome genes Genes 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. DNA Types and Structure (part of 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).
    • Acquired genetic factors
      • TMPRSS-ETS fusion 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 is the most common 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 alteration 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 (noted in 50% of cases).
      • Silencing of the 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 encoding p27 (a protein controlling cell growth and division)
      • Amplification of MYC and deletion of PTEN: ↑ cell growth and ↑ androgen resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
Pathogenesis of prostate cancer

Pathogenesis of prostate cancer:
Normal prostate gland comprises basal and luminal cells. Majority of prostate cancers arise from the peripheral zone. Under the influence of diet, androgens, and inflammation caused by genetic variants, precursor lesions (prostatic intraepithelial neoplasia) develop. As further genetic or epigenetic alterations occur, the lesions progress to adenocarcinoma. Tumors initially regress with antiandrogen therapy, but eventual androgen resistance occurs.

Image by Lecturio.

Clinical Presentation

  • The majority of diagnosed patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are identified by screening Screening Preoperative Care 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.
  • Usually asymptomatic in early stages
  • Manifestations in later stages:
    • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (most common site of disseminated 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)
    • Weakness from spinal-cord compression Compression Blunt Chest Trauma
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • Urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
    • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
    • 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
    • Hydronephrosis Hydronephrosis Hydronephrosis is dilation of the renal collecting system as a result of the obstruction of urine outflow. Hydronephrosis can be unilateral or bilateral. Nephrolithiasis is the most common cause of hydronephrosis in young adults, while prostatic hyperplasia and neoplasm are seen in older patients. Hydronephrosis 

Diagnosis

Prostate-specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination

Prostate-specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination levels are determined to detect early cancer.

Background:

  • Protein produced by 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 (but not specific to malignancy Malignancy Hemothorax)
  • A small amount enters the bloodstream in healthy individuals.
  • ↑ Serum PSA level 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 is due to:
    • ↑ Number of cells producing PSA, despite malignant cells synthesizing less PSA
    • 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 ↑ levels of PSA to enter the bloodstream

Interpretation:

  • PSA ≥ 4 ng/mL is considered positive and the most widely accepted standard, which balances 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.
  • Long-term use of 5-alpha-reductase inhibitors:
    • Associated with ↓ PSA levels with long-term medication use
    • Correction factor should be applied for accurate interpretation.
    • If there is an ↑ in PSA level, the patient should be referred to urology.
  • Other urological conditions that can elevate PSA levels:
    • BPH BPH 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
    • Urological procedures (e.g., catheter placement, cystoscopy) 
  • Repeat testing is recommended in the case of ↑ PSA (after addressing factors possibly influencing the elevation)

Clinical variables to interpret PSA levels:

  • General age-adjusted PSA (ng/dL) thresholds are as follows: 
    • 40‒49 years of age: 2.5
    • 50‒59 years of age: 3.5
    • 60‒69 years of age: 4.5
    • 70‒79 years of age: 6.5
  • PSA density:
    • Ratio of PSA 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 using imaging studies)
    • Value ≥ 0.15 ng/mL/g is an indication 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. biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • PSA velocity: 
    • Cancer grows faster and the increase in PSA levels is more rapid.
    • At least 3 measurements should be obtained over a 2-year period.
  • Free and complexed PSA: 
    • 2 forms of PSA: free, and complexed to protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs
    • In cancer: ↑ in PSA complexed to protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs

Digital rectal examination Digital Rectal Examination A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening ( DRE DRE A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening)

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. biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

  • Confirmatory test required for diagnosis
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is performed using an image-guided (transrectal ultrasound or MRI) transrectal approach.
  • Considerations before pursuing biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma:
    • Age and ethnicity of the patient
    • 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 of the patient
    • Comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
    • Immediate and long-term risks of biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, and possible treatment options

Imaging studies

  • Evaluation of the extent 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 volume determination:
    • MRI
    • 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. Imaging Reporting and Data System (PI-RADS) 
      • Used to report the likelihood of cancer in a suspicious area
      • 5-point scale Scale Dermatologic Examination, with 1 representing high unlikeliness and 5 indicating high likeliness of cancer
  • To determine extra-prostatic extension Extension Examination of the Upper Limbs and distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis:
    • CT or MRI of the abdomen and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy
    • PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging: Images may be superimposed with CT and MRI.
    • Bone scan Bone Scan Osteosarcoma
Imaging of a patient with metastatic prostate cancer

Imaging of a patient with metastatic prostate cancer:
(A) Magnetic resonance imaging (MRI) demonstrates the seminal vesicles (SV), the prostate lesion (tumor), and extracapsular extension (ECE).
(B) Bone scan shows solitary L5 vertebral body metastasis.

Image: “Rationale for stereotactic body radiation therapy in treating patients with oligometastatic hormone-naïve prostate cancer” by O. Bhattasali et al. License: CC BY 3.0

Staging

Parameters

The following elements are crucial determinants of outcome and are used for risk stratification in selecting a treatment approach:

Tumor-nodes-metastases staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

The TNM staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis is based on the 8th-edition staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis guidelines by the American Joint Committee on Cancer. There are 2 categories of staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis:

  1. Clinical staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis: based on physical exam, imaging, and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  2. Pathological staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis: based on findings after prostatectomy Prostatectomy Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic – removal through an incision above the pubis and through the urinary bladder; retropubic – as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). Benign Prostatic Hyperplasia
Table: Tumor Tumor Inflammation staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis
Tumor Tumor Inflammation clinical stage (cT) Description
cTX CTX Paget’s Disease of Bone Primary tumor Tumor Inflammation cannot be assessed.
cT0 No evidence of primary tumor Tumor Inflammation
cT1 No palpable disease on DRE DRE A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening
  • T1a: cancer incidentally found in ≤ 5% of tissue obtained in a surgery for benign Benign Fibroadenoma disease
  • T1b: cancer incidentally found in > 5% of tissue obtained in a surgery for benign Benign Fibroadenoma disease
  • T1c: cancer found during biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma for elevated PSA
cT2 Palpable disease on DRE DRE A physical examination in which the qualified health care worker inserts a lubricated, gloved finger of one hand into the rectum and may use the other hand to press on the lower abdomen or pelvic area to palpate for abnormalities in the lower rectum, and nearby organs or tissues. The method is commonly used to check the lower rectum, the prostate gland in men, and the uterus and ovaries in women. Prostate Cancer Screening, but confined within 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.
  • T2a: ≤ 50% on 1 side 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.
  • T2b: > 50% on 1 side 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.
  • T2c: both sides affected
cT3 Palpable outside 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. laterally, or involving the seminal vesicles Vesicles Female Genitourinary Examination
cT4 Tumor Tumor Inflammation is fixed, or it can invade the adjacent structures (external sphincter, rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy, bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess, levator ani, or pelvic wall).
DRE: digital rectal examination
PSA: prostate-specific antigen
Table: Tumor Tumor Inflammation staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis
Tumor Tumor Inflammation pathological stage (pT)* Description
pT2 Organ confined
pT3 Extra-prostatic extension Extension Examination of the Upper Limbs
pT4 Tumor Tumor Inflammation is fixed or invades other adjacent structures (external sphincter, rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy, bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess, levator ani, or pelvic wall).
*There is no pathological T1 classification.
Table: Lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node (N) staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis
Clinical node stage (cN) Description
cNX Regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy not assessed
cN0 No regional lymph-node involvement
cN1 Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis in regional lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node(s)
Table: Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis (M) staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis
Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis stage Description
M0 No distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis
M1 Distant metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis to:
  • M1a: non-regional lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node(s)
  • M1b: bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types(s)
  • M1c: other sites (with or without bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types disease)

Histological grading Grading Methods which attempt to express in replicable terms the level of cell differentiation in neoplasms as increasing anaplasia correlates with the aggressiveness of the neoplasm. Grading, Staging, and Metastasis

Grade group is based on the Gleason score.

  • Standard measure of differentiation 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
  • 5 patterns graded from 1–5: 
    • 1 being closest to the normal tissue
    • 5 being the most abnormal
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma specimen is examined under low magnification to identify the most common (1st number) and 2nd most common (2nd number) patterns. 
  • The 2 numbers are added to obtain the Gleason score.
  • Gleason score is used to predict clinical behavior and outcome.
    • Lower score and grade group: Cancer is likely to grow and spread slowly.
    • High score and grade group: Cancer is likely to grow and spread rapidly.
    • Order is as important as the total score in predicting prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas (e.g., 3 + 5 = 8 has a more favorable prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas than 5 + 3 = 8).
Table: Grade group based on the Gleason score
Grade group Gleason score Pattern
1 Gleason ≤ 6 Well-differentiated tumors
2 Gleason 3 + 4 = 7 Predominantly well-formed glands with few poorly formed glands
3 Gleason 4 + 3 = 7 Predominantly poorly formed glands with less well-formed glands
4 Gleason 8 Only poorly formed glands or predominantly well-formed glands and a lesser component with a lack of glands 
5 Gleason 9‒10 Advanced; lacks gland formation or exhibits necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage 

Prognostic stage

The TNM stage, PSA, and histological grade group can be used to determine the prognostic stage group.

Table: Criteria for prognostic stage group
Stage Tumor Tumor Inflammation (T) Node (N) Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis (M) PSA (ng/mL) Grade group
I cT1a‒c, cT2a, pT2 N0 M0 < 10 1
II IIA cT1a‒c, cT2a, pT2 N0 M0 ≥ 10, < 20 1
cT2b–c < 20
IIB T1‒T2 N0 M0 < 20 2
IIC T1‒T2 N0 M0 < 20 3‒4
III IIIA T1‒T2 N0 M0 ≥ 20  1‒4
IIIB T3 T3 A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3. Thyroid Hormones T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones N0 M0 Any 1‒4
IIIC Any N0 M0 Any 5
IV IVA Any N1 M0 Any Any
IVB Any Any M1 Any Any
PSA: prostate-specific antigen

Risk stratification

Information regarding tumor Tumor Inflammation stage, grade group, Gleason score, and PSA level is used to determine clinical-risk categories.

  • Risk may be assessed as:
    • Very low
    • Low
    • Intermediate
    • High
    • Very high 
  • Use of risk-evaluation guides:
    • Appropriateness in ordering imaging studies (e.g., do not obtain CT or bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types scans in very low-/low-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship)
    • Treatment options

Management

Principles of treatment

  • 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 associated with slow growth and may not be clinically significant during the lifetime of a patient.
  • Definitive treatments are associated with substantial side effects that impact the quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life.
  • Multiple factors are considered in treatment:
    • Age 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
    • Overall health and comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus
    • Characteristics of the cancer and risk stratification
    • Patient preferences

Management options

Active surveillance Surveillance Developmental Milestones and Normal Growth:

  • Deferred treatment with monitoring:
    • Serial PSA and DREs over regular Regular Insulin intervals
    • Repeat biopsies
    • MRI
  • Intention to treat for disease progression or change in patient preference
  • Preferred in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with very low- or low-risk cancer

Radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma therapy (RT):

  • External beam RT (EBRT): can cause 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 and radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease
  • Brachytherapy:
    • Radioactive seed implants 
    • Can cause bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess irritation

Surgery (radical prostatectomy Prostatectomy Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic – removal through an incision above the pubis and through the urinary bladder; retropubic – as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). Benign Prostatic Hyperplasia):

  • Options:
    • Open surgery 
    • Laparoscopy Laparoscopy Laparoscopy is surgical exploration and interventions performed through small incisions with a camera and long instruments. Laparotomy and Laparoscopy with or without robotic assistance
  • Removal 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, seminal vesicles Vesicles Female Genitourinary Examination, and pelvic lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, followed by reconstruction (reconnecting the bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and the urethra Urethra A tube that transports urine from the urinary bladder to the outside of the body in both the sexes. It also has a reproductive function in the male by providing a passage for sperm. Urinary Tract: Anatomy)
  • Can cause 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 and stress 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 

Androgen deprivation therapy (ADT):

  • Luteinizing hormone-releasing hormone (LHRH) agonists:
    • Leuprolide Leuprolide A potent synthetic long-acting agonist of gonadotropin-releasing hormone that regulates the synthesis and release of pituitary gonadotropins, luteinizing hormone and follicle stimulating hormone. Antiestrogens acetate, goserelin, triptorelin, and histrelin
    • Initial release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology/surge of LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, then ↓ pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↓ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
  • LHRH antagonists:
    • Degarelix, relugolix
    • Pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types drive without an initial surge in LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle → ↓ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
  • Antiandrogens Antiandrogens Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5-alpha-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism. Androgens and Antiandrogens:
  • Surgical castration with simple orchiectomy (removal of the testicles Testicles The testicles, also known as the testes or the male gonads, are a pair of egg-shaped glands suspended within the scrotum. The testicles have multiple layers: an outer tunica vaginalis, an intermediate tunica albuginea, and an innermost tunica vasculosa. The testicles are composed of testicular lobules and seminiferous tubules. Testicles: Anatomy): ↓ testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens levels
  • General side effects:
    • Reduced sexual desire
    • Impotence
    • Hot flashes
    • Gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia and breast tenderness
    • Depression

Chemotherapy Chemotherapy Osteosarcoma:

Immunotherapy:

  • Sipuleucel-T Sipuleucel-T An approved vaccine-based therapy for advanced (castration-resistant hormone-refractory) prostate cancer. First, there is an autologous dendritic cell preparation targeting prostatic acid phosphatase (PAP). Blood mononuclear cells are obtained via leukapheresis. Antigen-presenting cells are isolated and then activated in vitro by PAP fused to granulocyte macrophage colony-stimulating factor (GM-CSF). The reinfusion of the product produces T-cell activity against tumors expressing PAP. Cancer Immunotherapy ( Provenge Provenge An approved vaccine-based therapy for advanced (castration-resistant hormone-refractory) prostate cancer. First, there is an autologous dendritic cell preparation targeting prostatic acid phosphatase (PAP). Blood mononuclear cells are obtained via leukapheresis. Antigen-presenting cells are isolated and then activated in vitro by PAP fused to granulocyte macrophage colony-stimulating factor (GM-CSF). The reinfusion of the product produces T-cell activity against tumors expressing PAP. Cancer Immunotherapy
    • Vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination
    • Made from autologous mononuclear cells
    • Induces immunity against 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 
    • For metastatic ADT-resistant 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
  • Pembrolizumab Pembrolizumab Squamous Cell Carcinoma (SCC):
    • Programmed cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death receptor-1 ligand (PD-L1) inhibitor
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship lacking the mismatch-repair (dMMR) mechanism, and for individuals with high levels of microsatellite instability Microsatellite instability The occurrence of highly polymorphic mono- and dinucleotide microsatellite repeats in somatic cells. It is a form of genome instability associated with defects in DNA mismatch repair. Colorectal Cancer (MSI-H)

Other therapies:

  • Targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted and Other Nontraditional Antineoplastic Therapy 
    • Poly-ADP-ribose polymerase (PARP) inhibitors
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with germline or somatic DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure repair mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations (BRCA)
  • Radium-223
    • Emits alpha radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
    • Prevents complications due to bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis

Management

The following management options are based on prognostic stage, and should be guided by the age, health, and preferences of the patient:

  • Stage I:
    • Active surveillance Surveillance Developmental Milestones and Normal Growth (preferred)
    • RT or surgery: considered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a high probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of progression
  • Stage II:
  • Stage III:
    • Recurrence after treatment is more likely.
    • EBRT plus ADT: Brachytherapy may be added.
    • Surgery followed by RT and/or ADT
  • Stage IV:
    •  Lymph-node involvement:
      • RT plus ADT
      • In young individuals with minimal regional lymph-node spread, surgery followed by ADT with or without RT can be considered.
    • Metastatic disease: ADT plus chemotherapy Chemotherapy Osteosarcoma

Differential Diagnosis

  • BPH BPH 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: a condition caused by an increase in the number of stromal and epithelial cells within 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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are usually > 50 years of age and present with symptoms of bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess obstruction and/or bladder-storage problems. Benign Benign Fibroadenoma prostatic hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation can lead to an increase in PSA levels. Diagnosis is based on history and invasive testing (cystoscopy, urodynamics, transrectal ultrasound imaging). Management is with medications and/or surgery.
  • 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: a group of inflammatory conditions 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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic or present with urinary symptoms, such as perineal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, increased urinary frequency and urgency, urinary obstruction, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. The diagnosis is generally clinical and supported by urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children and culture data. Management depends on the etiology, but can include antibiotics in cases of infection. Prostate-specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination levels may be elevated. To differentiate 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 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, PSA levels are remeasured after the treatment of 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.
  • 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 (ED): the consistent inability to acquire or maintain an erection Erection The state of the penis when the erectile tissue becomes filled or swollen (tumid) with blood and causes the penis to become rigid and elevated. It is a complex process involving central nervous system; peripheral nervous systems; hormones; smooth muscles; and vascular functions. Penis: Anatomy. 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 is associated with diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus, heart disease, and certain drugs (e.g., antidepressants). Treatments 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 (RT, prostatectomy Prostatectomy Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic – removal through an incision above the pubis and through the urinary bladder; retropubic – as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). Benign Prostatic Hyperplasia) can also result in ED. Management is with phosphodiesterase-5 inhibitors Phosphodiesterase-5 Inhibitors Pulmonary Hypertension Drugs and vacuum-assisted erection Erection The state of the penis when the erectile tissue becomes filled or swollen (tumid) with blood and causes the penis to become rigid and elevated. It is a complex process involving central nervous system; peripheral nervous systems; hormones; smooth muscles; and vascular functions. Penis: Anatomy devices.
  • 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 (UI): the involuntary leakage of urine. There are many types of incontinence, including stress, urge, and mixed type. Radical prostatectomy Prostatectomy Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic – removal through an incision above the pubis and through the urinary bladder; retropubic – as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). Benign Prostatic Hyperplasia can result in stress UI, which presents as urine leakage with exertion or as gravitational incontinence. Lifestyle intervention ( Kegel exercises Kegel Exercises Pelvic Organ Prolapse), medical therapy, and surgical procedures are options in managing post-surgical UI.

References

  1. American Urological Association. (2017). Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. https://www.auanet.org/guidelines/prostate-cancer-clinically-localized-guideline#x6911
  2. American Urological Association. (2020). Medical student curriculum: Prostate cancer screening and management. https://www.auanet.org/education/auauniversity/for-medical-students/medical-students-curriculum/medical-student-curriculum/prostate-cancer/psa
  3. Kantoff, P., Taplin, M., Smith, J. (2020). Clinical presentation and diagnosis of prostate cancer. UpToDate. Retrieved Jan 21, 2021, from https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-prostate-cancer
  4. Kantoff, P., Taplin, M., Smith, J. (2020). Initial staging and evaluation of men with newly diagnosed prostate cancer. UpToDate. Retrieved Jan 23, 2021, from https://www.uptodate.com/contents/initial-staging-and-evaluation-of-men-with-newly-diagnosed-prostate-cancer
  5. Klein, E. (2021). Prostate cancer: Risk stratification and choice of initial treatment. UpToDate. Retrieved Jan 23, 2021, from https://www.uptodate.com/contents/prostate-cancer-risk-stratification-and-choice-of-initial-treatment
  6. Netto, G., Amin, M. (2020). The Lower Urinary Tract and Male Genital System. Kumar, V., Abbas, A., Aster, J., Robbins, S. Robbins and Cotran (Eds.) Pathologic Basis of Disease (10th ed., pp 977–983). Elsevier, Inc. 
  7. Posielski, M., Richards, K. (2020). Prostate cancer staging. Medscape. https://emedicine.medscape.com/article/2007051-overview
  8. Mark, J.R. (2019). Prostate cancer. [Online] MSD Manual Professional Version. https://www.msdmanuals.com/professional/genitourinary-disorders/genitourinary-cancer/prostate-cancer
  9. American Cancer Society (2019). Prostate cancer stages and other ways to assess risk. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/staging.html
  10. American Cancer Society (2019). Initial treatment of prostate cancer, by stage. https://www.cancer.org/cancer/prostate-cancer/treating/by-stage.html
  11. Madan, R.A., Antonarakis, E.S., et al. (2020). Putting the pieces together: Completing the mechanism of action jigsaw for Sipuleucel-T. Journal of the National Cancer Institute, 112(6), 562–573. https://pubmed.ncbi.nlm.nih.gov/32145020/
  12. Antonarakis, E.S., Piulats, J.M., et al. (2020). Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: Multicohort, open-label phase II KEYNOTE-199 study. Journal of Clinical Oncology, 38(5), 395–405. https://pubmed.ncbi.nlm.nih.gov/31774688/
  13. Sandhu, S.K., Omlin, A., et al. (2013). Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Annals of Oncology, 24(5), 1416–1418. https://pubmed.ncbi.nlm.nih.gov/23524863/

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