ProstateProstateThe 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 prostateProstateThe 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%. ProstateProstateThe 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 prostateProstateThe 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 boneBoneBone 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 TypespainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways, urinary symptoms, and/or weight lossWeight lossDecrease in existing body weight.Bariatric Surgery. Most cases of prostateProstateThe 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 testsDiagnostic testsDiagnostic 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 antigenAntigenSubstances that are recognized by the immune system and induce an immune reaction.Vaccination (PSA) levels and are confirmed based on image-guided transrectal biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma. Management of prostateProstateThe 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 expectancyLife expectancyBased on known statistical data, the number of years which any person of a given age may reasonably expected to live.Population Pyramids, comorbiditiesComorbiditiesThe 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 surveillanceSurveillanceDevelopmental Milestones and Normal Growth, androgen deprivation therapy, radiotherapy, chemotherapyChemotherapyOsteosarcoma, and radical prostatectomyProstatectomyComplete 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.
The lifetime risk of being diagnosed with prostateProstateThe 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 prostateProstateThe 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 historyFamily HistoryAdult Health Maintenance of prostateProstateThe 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
Breast cancerBreast cancerBreast 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 BRCA2geneGeneA 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
MelanomaMelanomaMelanoma 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 cancerColorectal cancerColorectal 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 syndromeLynch syndromeLynch 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 cancerOvarian cancerOvarian 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:
ObesityObesityObesity 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., finasterideFinasterideAn 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 prostateProstateThe 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
TrichomonasTrichomonasA 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
SmokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases
Exposure to Agent OrangeAgent orangeA 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 estrogenEstrogenCompounds 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: AnatomyreceptorsReceptorsReceptors 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 malignancyMalignancyHemothorax
ProstateProstateThe 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
ProstateProstateThe 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 bladderBladderA 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 prostateProstateThe 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 prostateProstateThe 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 rectumRectumThe 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 prostateProstateThe 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 ductsEjaculatory DuctsPaired ducts in the human male through which semen is ejaculated into the urethra.
10%‒15% of prostateProstateThe 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 zoneTransitional zoneAnal Cancer.
Surrounds the proximal urethraUrethraA 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 benignBenignFibroadenoma prostatic hyperplasiaHyperplasiaAn 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 (BPHBPHBenign 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 prostateProstateThe 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 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, prostateProstateThe 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.epitheliumEpitheliumThe 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 → prostateProstateThe 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 → metastasisMetastasisThe 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 mutationMutationGenetic 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 prostateProstateThe 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
Diet
SmokingSmokingWillful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand.Interstitial Lung Diseases
AndrogensAndrogensAndrogens 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
ProstateProstateThe 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 testosteroneTestosteroneA 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.
TestosteroneTestosteroneA 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 resistanceResistancePhysiologically, 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 prostateProstateThe 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 DNADNAA 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 Structuremismatch repairMismatch repairA 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 syndromegenesGenesA 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 syndromeLynch syndromeLynch 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 geneGeneA 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 geneGeneA 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 prostateProstateThe 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 geneGeneA 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 resistanceResistancePhysiologically, 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: 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.
The majority of diagnosed patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship are identified by screeningScreeningPreoperative Care for prostateProstateThe 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:
BoneBoneBone 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 TypespainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways (most common site of disseminated prostateProstateThe 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)
FatigueFatigueThe 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 retentionUrinary retentionInability to empty the urinary bladder with voiding (urination).Delirium
Erectile dysfunctionErectile DysfunctionErectile 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
HydronephrosisHydronephrosisHydronephrosis 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 antigenAntigenSubstances that are recognized by the immune system and induce an immune reaction.Vaccination
Prostate-specific antigenAntigenSubstances that are recognized by the immune system and induce an immune reaction.Vaccination levels are determined to detect early cancer.
Background:
Protein produced by prostateProstateThe 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 malignancyMalignancyHemothorax)
A small amount enters the bloodstream in healthy individuals.
↑ Serum PSA level in prostateProstateThe 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 membraneBasement membraneA 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 specificitySensitivity and SpecificityBinary 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:
BPHBPHBenign 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
ProstatitisProstatitisProstatitis 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 retentionUrinary retentionInability to empty the urinary bladder with voiding (urination).Delirium
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 prostateProstateThe 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 prostateProstateThe 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.biopsyBiopsyRemoval 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 inhibitorsProtease InhibitorsCompounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases).Anti-HIV Drugs
In cancer: ↑ in PSA complexed to protease inhibitorsProtease InhibitorsCompounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases).Anti-HIV Drugs
Digital rectal examinationDigital Rectal ExaminationA 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 (DREDREA 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)
No longer recommended for asymptomatic patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship
Low sensitivity and specificitySensitivity and SpecificityBinary 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
ProstateProstateThe 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.biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma
Confirmatory test required for diagnosis
BiopsyBiopsyRemoval 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 biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma:
Age and ethnicity of the patient
Life expectancyLife expectancyBased 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
ComorbiditiesComorbiditiesThe 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 biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma, and possible treatment options
Diagnosis of prostate cancer: Image-guided transrectal approach is used to confirm the presence of carcinoma in the prostate gland.
Image: “Diagnosis of Prostate Cancer” by Tonry, C., Finn, S., Armstrong, J. et al. License: CC BY 4.0, edited by Lecturio.
Imaging studies
Evaluation of the extent of prostateProstateThe 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
ProstateProstateThe 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 scaleScaleDermatologic Examination, with 1 representing high unlikeliness and 5 indicating high likeliness of cancer
CT or MRI of the abdomen and pelvisPelvisThe 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
PETPETAn 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.
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:
Histological grade group (based on the Gleason score)
Tumor-nodes-metastases stagingStagingMethods which attempt to express in replicable terms the extent of the neoplasm in the patient.Grading, Staging, and Metastasis
The TNM stagingStagingMethods 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 stagingStagingMethods 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 stagingStagingMethods which attempt to express in replicable terms the extent of the neoplasm in the patient.Grading, Staging, and Metastasis:
Clinical stagingStagingMethods 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 biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma
Pathological stagingStagingMethods which attempt to express in replicable terms the extent of the neoplasm in the patient.Grading, Staging, and Metastasis: based on findings after prostatectomyProstatectomyComplete 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
No palpable disease on DREDREA 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 benignBenignFibroadenoma disease
T1b: cancer incidentally found in > 5% of tissue obtained in a
surgery for benignBenignFibroadenoma disease
T1c: cancer found during biopsyBiopsyRemoval and pathologic examination of specimens from the living body.Ewing Sarcoma for elevated PSA
cT2
Palpable disease on DREDREA 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 prostateProstateThe 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 prostateProstateThe 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 prostateProstateThe 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 prostateProstateThe 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 vesiclesVesiclesFemale Genitourinary Examination
T3a: extra-prostatic extensionExtensionExamination of the Upper Limbs (through the capsuleCapsuleAn envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides.Bacteroides)
TumorTumorInflammation is fixed, or it can invade the adjacent structures (external sphincter, rectumRectumThe 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, bladderBladderA 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
TumorTumorInflammation is fixed or invades other adjacent structures (external sphincter, rectumRectumThe 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, bladderBladderA 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).
M1b:boneBoneBone 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 boneBoneBone 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 gradingGradingMethods 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 prostateProstateThe 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
BiopsyBiopsyRemoval 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 prognosisPrognosisA 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 prognosisPrognosisA 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 necrosisNecrosisThe death of cells in an organ or tissue due to disease, injury or failure of the blood supply.Ischemic Cell Damage
Micrograph of prostate cancer with Gleason score 6 (3 + 3): In this image, generally well-differentiated glands are seen.
Image: “Micrograph of prostate cancer with Gleason score 6 (3 + 3)” by Jennifer Gordetsky and Jonathan Epstein. License: CC BY 4.0
Micrograph of prostate cancer with Gleason score 10: In this image, the architecture is very different from normal prostatic tissue, with solid sheets of cells instead of well-defined glands.
Image: “Micrograph of prostate cancer with Gleason score 10 (5 + 5) with solid sheets of cells” by Jennifer Gordetsky and Jonathan Epstein. License: CC BY 4.0
Prognostic stage
The TNM stage, PSA, and histological grade group can be used to determine the prognostic stage group.
T3T3A 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‒T4T4The 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 tumorTumorInflammation 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 boneBoneBone 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 patientsPatientsIndividuals 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
ProstateProstateThe 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 qualityQualityActivities 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 expectancyLife expectancyBased 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 comorbiditiesComorbiditiesThe 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
Serial PSA and DREs over regularRegularInsulin intervals
Repeat biopsies
MRI
Intention to treat for disease progression or change in patient preference
Preferred in patientsPatientsIndividuals 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
RadiationRadiationEmission 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 dysfunctionErectile DysfunctionErectile 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 radiationRadiationEmission 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).OsteosarcomaproctitisProctitisInflammation of the mucous membrane of the rectum, the distal end of the large intestine.Chronic Granulomatous Disease
Brachytherapy:
Radioactive seed implants
Can cause bladderBladderA 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 prostatectomyProstatectomyComplete 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
LaparoscopyLaparoscopyLaparoscopy 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 prostateProstateThe 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 vesiclesVesiclesFemale Genitourinary Examination, and pelvic lymph nodesLymph NodesThey 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 bladderBladderA 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 AbscessneckNeckThe part of a human or animal body connecting the head to the rest of the body.Peritonsillar Abscess and the urethraUrethraA 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 dysfunctionErectile DysfunctionErectile 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 incontinenceUrinary incontinenceUrinary 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
LeuprolideLeuprolideA 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 releaseReleaseRelease 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 LHLHA 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 ↓ pituitaryPituitaryA 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 TypesLHLHA 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 → ↓ testosteroneTestosteroneA 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
↓ PituitaryPituitaryA 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 LHLHA 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 → ↓ testosteroneTestosteroneA 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
AntiandrogensAntiandrogensAntiandrogenic 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:
Androgen receptorReceptorReceptors 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 antagonists: flutamideFlutamideAn antiandrogen with about the same potency as cyproterone in rodent and canine species.Androgens and Antiandrogens, bicalutamideBicalutamideAndrogens and Antiandrogens, apalutamide, and enzalutamide
Androgen synthesisSynthesisPolymerase Chain Reaction (PCR) inhibitors: abiraterone, ketoconazoleKetoconazoleBroad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Azoles, and aminoglutethimide
Surgical castration with simple orchiectomy (removal of the testiclesTesticlesThe 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): ↓ testosteroneTestosteroneA 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
GynecomastiaGynecomastiaGynecomastia 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
DocetaxelDocetaxelA semisynthetic analog of paclitaxel used in the treatment of locally advanced or metastatic breast neoplasms and non-small cell lung cancer.Microtubule and Topoisomerase Inhibitors
Sipuleucel-TSipuleucel-TAn 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 (ProvengeProvengeAn 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)
VaccineVaccineSuspensions 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 prostateProstateThe 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 prostateProstateThe 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
Programmed cell deathCell deathInjurious 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 patientsPatientsIndividuals 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 instabilityMicrosatellite instabilityThe 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 therapyTargeted TherapyTargeted 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 patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with germline or somatic DNADNAA 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 mutationMutationGenetic 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 radiationRadiationEmission 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 boneBoneBone 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 TypesmetastasisMetastasisThe 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:
RT or surgery: considered in patientsPatientsIndividuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures.Clinician–Patient Relationship with a high probabilityProbabilityProbability 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
Symptomatic boneBoneBone 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 TypesmetastasisMetastasisThe transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Grading, Staging, and Metastasis without visceral disease: radium-223
Differential Diagnosis
BPHBPHBenign 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 prostateProstateThe 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. PatientsPatientsIndividuals 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 bladderBladderA 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. BenignBenignFibroadenoma prostatic hyperplasiaHyperplasiaAn 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.
ProstatitisProstatitisProstatitis 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 prostateProstateThe 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. PatientsPatientsIndividuals 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 painPainAn 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 feverFeverFever 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 urinalysisUrinalysisExamination 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 antigenAntigenSubstances that are recognized by the immune system and induce an immune reaction.Vaccination levels may be elevated. To differentiate prostatitisProstatitisProstatitis 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 prostateProstateThe 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 prostatitisProstatitisProstatitis 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 dysfunctionErectile DysfunctionErectile 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 erectionErectionThe 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 dysfunctionErectile DysfunctionErectile 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 diabetesDiabetesDiabetes 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 prostateProstateThe 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, prostatectomyProstatectomyComplete 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 inhibitorsPhosphodiesterase-5 InhibitorsPulmonary Hypertension Drugs and vacuum-assisted erectionErectionThe 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 incontinenceUrinary incontinenceUrinary 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 prostatectomyProstatectomyComplete 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 exercisesKegel ExercisesPelvic Organ Prolapse), medical therapy, and surgical procedures are options in managing post-surgical UI.
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.
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/
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/
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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