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Textbook reading

Prostate Cancer
Sumber :Campbell-Walsh Urology, Eleventh Edition

Dr. Ferdi Stefiyan


NIM : 0412771822003
Departemen Bedah RSMH/FK Unsri
Epidemiology
• Incidence
– the most common noncutaneous malignancy in
U.S. men since 1984, now accounting for 27% of
all such cancers (Siegel et al, 2014)
– 1 in 7 (15.3%) among men alive will be diagnosed
with prostate cancer
– 1 in 38 (2.6%) will die from this disease (Brawley
et al, 2012a)
– The second most common cancer and the sixth
leading cause of cancer deaths worldwide
Epidemiology
• Age at Diagnosis
– Rarely diagnosed in less than 50 years of age,
only 2% of all cases (Jani et al, 2008).
– the proportion of men diagnosed with prostate
cancer by age is
• <55 years = 10.1%,
• 55 to 64 years = 30.7%,
• 65 to 74 years = 35.3%,
• 75 to 84 years = 19.9%,
• > 84 years = 4.4% (Brawley et al, 2012a).
Sign and symptoms
Symptoms of local disease Symptoms of advanced
disease
Urinary complaints or retention Weight loss and loss of appetite
Back pain Anemia
Hematuria Bone pain, with or without
pathologic fracture
Neurologic deficits from spinal
cord compression
Lower extremity pain and
edema due to obstruction of
venous and lymphatic
tributaries by nodal metastasis
Diagnosis
• Elevated prostate-specific antigen (PSA)
– Risk of disease 8% with PSA level ≤1,0 ng/mL
– 25% with PSA levels of 4-10 ng/mL
– Over 50% for levels >10 ng/mL
• Abnormal digital rectal examination (DRE)
findings
– DRE is examiner-dependent
– Most patients diagnosed with prostate cancer
have normal DRE result
Differential Diagnoses
• Acute Bacterial Prostatitis and Prostatic
Abscess
• Bacterial Prostatitis
• BPH
• Nonbacterial prostatitis
• Tuberculosis of Genitourinary System
RISK FACTORS
• Familial and Germline Genetic Influences
– Genetics and environment are important in the origin
and evolution of prostate cancer.
– GWAS (genome-wide association study) have
identified multiple chromosomal loci and specific
variant alleles in germline DNA that confer risk of
getting prostate cancer.
– HOXB13 and BRCA are two genes that substantially
increase individual risk. BRCA-related tumors present
with more aggressive clinical features
RISK FACTORS
• Inflammation and Infection
– Chronic inflammation leading to cellular
hyperproliferation to replace damaged tissue
contributes to the development of prostate cancer.
– Compromised cellular defenses against inflammatory
oxidants are important in prostate cancer initiation
and promotion.
– Inflammation may be triggered by diet, infection,
estrogens, or other environmental agents.
– history of sexually transmitted infection or prostatitis
is associated with a higher risk of prostate cancer.
RISK FACTORS
• MOLECULAR EPIDEMIOLOGY
– Androgen exposure of the prostate plays an important
but incompletely defined role in prostate
carcinogenesis.
– Estrogen is also important in prostate cancer
development, Intraprostatic estrogen production may
also be important in prostate cancer development.
– The IGF (Insulin-like Growth factor) axis is important in
prostate cancer risk and progression.
– Vitamin D and its interaction with its receptor
modulate risk and disease aggressiveness.
RISK FACTORS
• OTHER INFLUENCES
– Smoking increases the risk of disease recurrence
and death resulting from prostate cancer.
– Obesity is associated with :
• lower serum prostate specific antigen (PSA),
• increases the risk of getting high-grade prostate cancer,
• associated with higher treatment failure rates and
disease-specific mortality.
ETIOLOGY AND MOLECULAR GENETICS
• Insufficient exposure of the prostate to DHT
appears to protect against the development of
prostate cancer.
• Epigenetic regulation of gene expression by
promoter methylation, hypomethylation, and
chromatin remodeling is important in prostate
cancer development and progression.
• miRNA (microRNA) and lncRNA are also
important epigenetic mechanisms of modulating
tumor growth and progression
ETIOLOGY AND MOLECULAR GENETICS
• The AR plays a central role in prostate cancer development
and progression.
• Gene fusions, especially those involving androgen-sensitive
promoters such as TMPRSS2 and the ETS family of
oncogenic transcription factors, are fundamental drivers of
prostate cancer initiation and progression.
• Somatic mutations in a variety of genes with diverse
biologic functions have been implicated in prostate cancer
development and progression.
• Mutations, amplification, and ligand promiscuity of the AR
are important determinants of progressive castrate-
resistant prostate cancer.
Prostate Cancer Tumor Markers
• Today, most prostate cancer arises as clinically
nonpalpable (stage T1c) disease with PSA between 2.5
and 10 ng/mL.
• Although PSA is widely accepted as a prostate cancer
tumor marker, it is organ specific and not disease
specific.
• In serum, PSA circulates in both bound and unbound
forms. Three proteins that are known to bind to PSA in
blood are ACT, A2M, and API.
• Finasteride (5 mg) and other 5α-reductase inhibitors
used for treatment of BPH have been shown to lower
PSA levels by an average of 50%.
Prostate Cancer Tumor Markers
• The role for %fPSA (free-to-total PSA ratio) is
more applicable to PSA levels less than 10 ng/mL
• There are four main domains in which clinically
localized prostate cancer biomarkers are needed:
– (1) screening,
– (2) elevated PSA with prior negative biopsy,
– (3) pretreatment in men with a new diagnosis,
– (4) postprostatectomy.
• PSA originates as a 17–amino acid chain
(preproPSA) that is cleaved to yield an inactive
precursor form termed proPSA.
Prostate Cancer Tumor Markers
• PHI (prostate health index) has been FDA-approved for men
50 years and older with total PSA 4-10 ng/mL and negative
DRE.
• Immunohistochemical studies reveal different tissue
expression patterns for hK2 and PSA. In benign epithelium,
PSA is intensely expressed compared with the minimal
immunoreactivity of hK2. In contrast, in cancerous tissue
hK2 is expressed more intensely.
• The 4Kscore is is a diagnostic test intended for use in men
with an elevated PSA considering prostate biopsy.
• PCA3 is a long noncoding RNA that is detectable in the
urine and serves as a diagnostic prostate cancer marker.
Prostate Cancer Tumor Markers
• Key hypermethylated genes that may have a
role in prostate cancer include GSTP1, APC,
RARβ2, and RASSF1A. Hypermethylation
changes are frequently detectable in normal
tissue adjacent to tumors. •
• Circulating tumor cells are being used as novel
tools to correlate with response to therapy, as
well as provide valuable resources with which
to study metastatic disease.
Prostate Biopsy: Techniques and
Imaging
• GRAY-SCALE TRANSRECTAL ULTRASONOGRAPHY
– TRUS technology has become a mainstay of many
imageguided prostate interventions, including
prostate biopsy, brachytherapy, cryotherapy, and high-
intensity focused US.
– Hypoechoic foci seen on gray-scale TRUS should be
considered suggestive of adenocarcinoma of the
prostate and included in the biopsy specimen.
– However, up to 39% of cancers are not visible on
routine gray-scale US imaging.
PROSTATE BIOPSY
• TRUS and/or MRI alone cannot diagnose
prostate cancer without a tissue biopsy.
• Local prostate anesthesia is commonplace and
most useful when using extended-core biopsy
schemes.
• Patients undergoing TRUS-guided prostate
biopsy require oral antibiotic prophylaxis for
up to 24 hours perioperatively.
Diagnosis and Staging of Prostate
Cancer
• The combination PSA level, DRE, and other clinical
factors (e.g., age, race, family history) can be used in
combination to predict the risk that prostate cancer.
• Pathologic criteria that predict prognosis after radical
prostatectomy are :
– tumor grade, (TNM classification)
– surgical margin status,
– presence of extracapsular disease,
– seminal vesicle invasion, and
– pelvic lymph node involvement
• The Gleason grading system is the most commonly
used classification scheme for the histologic grading
Management of Localized Prostate
Cancer
• CONSERVATIVE MANAGEMENT
– Active Surveillance or Watchful Waiting
• monitoring the patient until he develops metastases
that require palliative treatment.
• In most studies of active surveillance, approximately
25% to 50% of patients develop objective evidence of
tumor progression within 5 years
Management of Localized Prostate
Cancer
• RADICAL PROSTATECTOMY
– Radical prostatectomy was the first treatment used for
prostate cancer, and it still remains the gold standard.
– An ideal candidate for radical prostatectomy is a
healthy man with a life expectancy of at least 10
years.
– The most common late complications of radical
prostatectomy are erectile dysfunction, urinary
incontinence, hernia, and urethral stricture.
– The long-term outcome of cancer control is better
documented for open prostatectomy
RADICAL PROSTATECTOMY

• involves complete removal of the prostate


gland and seminal vesicles and usually
includes a modified pelvic lymph node
dissection as well
• radical retropubic prostatectomy
• salvage radical prostatectomy
• radical perineal prostatectomy
RADIOTHERAPY
• External beam radiotherapy uses gamma
radiation beams directed at the prostate and
surrounding tissues.
• Patients with a high PSA level, high Gleason
score, or large volume tumor benefit from ADT
(androgen deprivation therapy) in conjunction
with radiotherapy
• the most frequently used definition to determine
treatment success after radiation therapy is the
Phoenix definition
RADIOTHERAPY
• Brachytherapy is used primarily for the
treatment of patients with clinically localized
prostate cancer
PRIMARY HORMONE THERAPY
• Primary ADT is no longer regarded as appropriate
definitive therapy for men with clinically localized
prostate cancer.
• Neoadjuvant preoperative ADT reduces the rate
of positive surgical margins but does not
significantly affect disease progression
• ADT therapy is never curative; nevertheless,
many patients experience long-term remissions.
• Antiandrogens produce less sexual dysfunction
and osteoporosis but have a greater risk for
adverse cardiovascular complications.