Prostate cancer

By: Yazeed Saleem Abdukareem

University ID: 190145
Epidemiology of prostate cancer

• prostate cancer is the most commonly diagnosed male malignancy.

• the second leading cause of male cancer death in the United States
• 99% of all prostate cancers occur in those over the age of 50, but it can be quite
aggressive when it occurs in younger men
• more common in African Americans at more than double the rate in the general
population
• The overall 5-year survival rate is 99% in the United States
Fortunately, most prostate cancers tend to grow
slowly and are low-grade with relatively low
risk and limited aggressiveness
Basic Prostate anatomy

• The prostate: is a gland of the male reproductive system.

• It is located anterior to the rectum
• just below the bladder
• It is about the size of a chestnut and somewhat conical in shape
• consists of a base, an apex, an anterior, a posterior and two lateral surfaces.
• The prostate surrounds the posterior part of the urethra
Histological zones

However, more important clinically is the histological division of the prostate into three zones (according to McNeal):
•Central zone – surrounds the ejaculatory ducts, comprising approximately 25% of normal prostate volume.
• The ducts of the glands from the central zone are obliquely emptying in the prostatic urethra, thus being rather immune to urine
reflux.
•Transitional zone – located centrally and surrounds the urethra, comprising approximately 5-10% of normal prostate volume.
• The glands of the transitional zone are those that typically undergo benign hyperplasia (BPH)
•Peripheral zone – makes up the main body of the gland (approximately 65%) and is located posteriorly.
• The ducts of the glands from the peripheral zone are vertically emptying in the prostatic urethra; that may explain the tendency of
these glands to permit urine reflux.
• That also explains the high incidence of acute and chronic inflammation found in these compartments, a fact that may be linked to
the high incidence of prostate carcinoma at the peripheral zone.
• The peripheral zone is mainly the area felt against the rectum on DRE, which is of irreplaceable value.
The fibromuscular stroma (or fourth zone for some) is situated anteriorly in the gland. It merges with the tissue of the urogenital diaphragm.
function

• The main purpose of the prostate is to produce fluid for 

semen
• 30% to 35% of the semen

• contain zinc, citric acid, calcium, phosphates, and

other enzymes essential for sperm health and motility
• provides alkalinity, which helps maintain a high pH
When ejaculation occurs, sperm is forcefully expelled from the tail of
the epididymis into the deferent duct. Sperm then travels through the
deferent duct through up the spermatic cord into the pelvic cavity, over
the ureter to the prostate behind the bladder. Here, the vas deferens joins
with the seminal vesicle to form the ejaculatory duct, which passes
through the prostate and empties into the urethra
Risk factors

Prostate cancer risk factors include male

gender, older age, positive family history,
increased height, obesity, hypertension, lack of
exercise, persistently elevated testosterone
levels, Agent Orange exposure, and ethnicity
The prostate gland requires androgen
(testosterone) to function optimally

Prostate cancer is most commonly found in the

peripheral zone, primarily that portion of the
prostate that can be palpated via digital rectal
examination (DRE)
Diet

• However, a lard diet (high in unsaturated fats) has been shown in

a mouse model to significantly enhance the progression of
prostate cancer
• Lower vitamin D blood levels may increase the risk of
developing prostate cancer.
• Diets high in saturated fat and milk products seem to increase the
cancer risk
• Fish consumption may lower prostate cancer deaths but does not
affect the occurrence rate
• Overall, a Mediterranean diet (rich in anti-oxidants from olive
oil, tomatoes, etc.) appears to be somewhat helpful in reducing
prostate cancer risk
Chemical Exposure and Medications

• Agent Orange exposure may increase the

risk of prostate cancer recurrence,
particularly following surgery.
• The use of statins, metformin, and NSAIDs,
especially those with anti-COX-2 activity,
may decrease prostate cancer risk
 Infections

Infections with chlamydia, gonorrhea, or syphilis seem to increase the

risk of developing prostate cancer.
 Sexual Activity

Multiple lifetime sexual partners or starting sexual activity early in

life increases the risk of prostate cancer. Frequent ejaculation may
decrease overall prostate cancer risk, but reducing ejaculatory
frequency is not associated with a corresponding increase in the
incidence of advanced disease
Genetics

•No single gene is responsible for prostate cancer, although many

genes have now been implicated
•Mutations in BRCA1 and particularly BRCA2 
•Men with a first-degree relative (father or brother) with prostate
cancer have twice the risk of the general population.[29]
•Risk increases with an affected brother more than with an affected
father
•Men with two first-degree relatives affected have a five-fold greater
risk.
•P53 mutations in localized prostate cancer are relatively rare and
are more frequently seen in metastatic disease
Ethnicity

Mortality:

•2.0: Blacks
•20.1: General Population
•19.4: American Indians
•18.7: Whites (Caucasians)
•16.5: Hispanics
•8.8: Asians
pathophysiology
• The prostate gland requires androgen (testosterone) to function
optimally
• Cancer begins with a mutation in normal prostate glandular cells,
usually beginning with the peripheral basal cells.
• Prostate cancer is most commonly found in the peripheral zone,
primarily that portion of the prostate that can be palpated via
digital rectal examination
• Prostate cancer is an adenocarcinoma as it develops primarily from
the glandular part of the organ and shows typical glandular
patterns on microscopic examination.
• The cancer cells grow and begin to multiply, initially spreading to
the immediately surrounding prostate tissue forming a tumor
nodule
• may remain localized within the prostate for decades.
•Prostate cancer commonly metastasizes to the bones and lymph
 Grading system

The Gleason prostate cancer score has been shown, over time, to be
the most reliable and predictive histological grading system available.
has been universally adopted for all prostate cancer pathological
descriptions

The samples of tissue from the biopsy are studied in a laboratory. If cancerous cells
are found, they can be studied further to see how quickly the cancer will spread.
This measure is known as the Gleason score

The lower the score, the less likely the cancer will spread:
•Grade Group 1 (Gleason Score less than or equal to 6): Only individual
discrete well-formed glands
•Grade Group 2 (Gleason Score 3+4=7): Predominantly well-formed
glands with a lesser component of poorly-formed, fused, or cribriform
glands
•Grade Group 3 (Gleason Score 4+3=7): Predominantly poorly-formed,
fused, or cribriform glands with a lesser component of well-formed
glands
•Grade Group 4 (Gleason Score 8): Only poorly-formed/fused/cribriform
glands; or predominantly well-formed glands with a lesser component
lacking glands; or predominantly lacking glands with a lesser component
of well-formed glands
•Grade Group 5 (Gleason Scores 9 or 10): Lacks gland formation (or with
necrosis) with or without poorly formed, fused, or cribriform glands
In clinical practice, Grade Group 1 is histologically considered "low
grade," Grade Group 2 is "intermediate grade," and Grade Group 3 or
higher is "high grade" disease.
 staging
The Key Distinction in Prostate Cancer Staging is Whether or Not the
Cancer is Confined to the Prostate and is Therefore Potentially
Curable
•T1 and T2 cancers are limited to just the prostate and are considered
"localized."
•T3 cancer has spread outside the prostatic capsule but has not reached the
rectum or bladder. Cancer may also have spread to the seminal vesicles
(stage T3c), which tends to be an ominous sign.
•T4 cancers have spread outside the prostate to adjacent regional structures
such as the bladder. They may also metastasize to the lungs, lymph nodes,
or liver which would be identified by their N (nodes) or M (metastasis)
scores. Stage T4 prostate cancers with distant metastases have an
overall 5-year survival rate of only 29%.
History and physical exam
history

Signs and symptoms

Early prostate cancer is usually asymptomatic. However, it may

sometimes cause symptoms similar to benign prostatic
hyperplasia, including frequent urination, nocturia, difficulty
starting and maintaining a steady stream, hematuria, and dysuria

Prostate cancer may also be associated with problems involving

sexual function and performance, such as difficulty achieving an
erection or painful ejaculation
• Metastatic prostate cancer can cause severe bone pain, often in
the back (vertebrae), pelvis, hips, or ribs. Spread into the
femur is usually to the proximal part of the bon
• Prostate cancer can result in spinal cord compression, causing
tingling, leg weakness, pain, paralysis, and urinary and fecal
incontinence. (metastatic spinal cord compression
(MSCC))
 family history 

• history of positive germline mutations, such

as BRCA1 or BRCA2,
• family history of early breast cancer in
female family members or close relatives
•  family history of colon cancer might
suggest Lynch syndrome, which is
associated with both prostate cancer and
urothelial malignancies
• African American ethnicity also increases
the risk.
Physical exam

• most common positive physical finding of prostate cancer is a firm or

hard nodule on digital rectal examination.
• There might also be some asymmetry or general firmness on the exam
• A rock-hard prostate would be very suggestive of at least locally advanced
disease
diagnosis
DRE
•

gfvd wer, 59dd241ba9@inboxmail.life

© www.lecturio.com | This document is protected by copyright.
PSA is a serine protease enzyme produced by the columnar
epithelial cells of the prostatic ducts and acini. causes the semen
to become less viscous over time and improves sperm function
and fertility

The highest levels are found in the semen, with some PSA
leaking from the prostate into the lymphatic and vascular
systems. Both benign and malignant cells produce prostate-
specific antigen, with cancer cells leaking more PSA into the
surrounding extracellular fluid which eventually increases levels
in the serum. 
 There are multiple causes for an elevated PSA which have nothing to
do with cancer, including prostate disease, trauma, inflammation,
prostatitis, urogenital procedures, biopsies, prostatic enlargement, etc

Some physicians will recommend a two to six-week course of prostate-

specific antibiotics (usually a quinolone, doxycycline, or
sulfamethoxazole/trimethoprim) to attempt to lower the PSA if due to
prostatitis or low-grade inflammation and avoid further investigations
for possible prostate cancer; however, this practice is controversial and
not generally recommended as a number of studies have failed to show a
significant benefit to this approach.
Elevated Prostate-Specific Antigen (total PSA) levels (usually
greater than 4 ng/ml) in the blood are how 80% of prostate
cancers initially present, even though elevated PSA levels
alone correctly identify prostate cancer only about 25% to
30% of the time.
•If the free PSA percentage is more than 25%, the cancer risk is
less than 10%.
•If the free PSA percentage is less than 10%, the cancer risk is
about 50%
At least two abnormal PSA levels or the presence of a palpable
nodule on a digital rectal examination (DRE) are required to
justify further investigation or a biopsy

Patients with a PSA level greater than 10 ng/ml

 Prostate imaging

Ultrasound and MRI are the primary imaging modalities used for
initial prostate cancer detection and diagnosis.
•Prostate MRI has much better soft tissue resolution than ultrasound and can
identify areas in the gland that are genuinely "suspicious" with a high degree of
accuracy and reliability (positive predictive value greater than 90%).
•In Europe, a positive MRI finding is sometimes sufficient to diagnose prostate
cancer without necessarily requiring histological confirmation.

•negative predictive value (NPV) has been reported as low as 72% to 76%,
meaning that a negative MRI report will miss about one in four high-grade
prostate cancers
 biopsy
The Only Test that can Dependably and Conclusively Confirm a
Cancer Diagnosis is Still a Histologically Positive Prostate Biopsy,
Which Remains the Recommended Standard of Care.

 This is almost always done with transrectal ultrasound guidance to

make sure that all areas of the prostate are adequately sampled

The most commonly used pattern is to take two specimens from

each of three areas (base, mid-gland, and apex) on both sides. This
is called a 12-core sextant biopsy. The purpose is to better identify
the extent and exact location of the tumor

The transperineal biopsy approach reduces the risk of infection from

about 1% to almost zero. ( gaining popularity, especially in Europe)
Up to 1/3 of men experience substantial
side effects after biopsy

gfvd wer, 59dd241ba9@inboxmail.life

© www.lecturio.com | This document is protected by copyright.
Prostate cancer screening

serum levels of PSA were used as a prostate cancer screening tool
because serum PSA levels start to increase significantly about seven
to nine years before the clinical diagnosis of malignancy

Screening options include a digital rectal exam and a prostate-

specific antigen (PSA) blood test. Such screenings may lead to a
biopsy with some associated risks

Routine PSA screenings are not recommended in men 75 years or over,

based on the conclusion that definitive treatment of localized cancers for
most older men has minimal effect on overall survival while adding
significant treatment side effects and morbidities to many. It is also not
recommended in men who realistically have <10 years of life
expectancy. 
While it unquestionably increases prostate cancer detection rates,
the value of PSA testing is less clear in avoiding overtreatment,
improving quality of life, and lengthening overall survival, which
is why routine PSA screening for prostate cancer remains
quite controversial.

The current controversy is whether PSA screening provides sufficient

benefits to offset the complications and side effects of "unnecessary"
biopsies and curative therapies since most men with prostate cancer will
have slow-growing, low-grade cancers for whom definitive, curative
therapy often causes considerable harm with little or no survival benefit.
Against screening

•There was no real change in overall survival for most patients

for at least the first ten years after the initial diagnosis.
•Many patients (about three-quarters) are getting negative
biopsies or show only low-risk disease, which is often
overtreated.
•"Unnecessary" biopsies contribute to patient anxiety, are
uncomfortable, add cost, and may have complications like
infections and bleeding.
•Several recent large studies show little or no survival benefit to
large-scale screenings.
In Favor of PSA Screenings

•Many of the larger studies suggesting a lack of survival benefit to large-

scale PSA screenings have been shown to be poorly done,
significantly biased, severely contaminated, and full of major statistical
errors.

•The prostate cancer death rate in Sweden, where PSA testing is minimal, is higher
than lung cancer and more than double the mortality rate for prostate cancer in the
United States.
•We are constantly improving diagnostic testing and treatment options to lower
costs and minimize side effects while increasing survival and improving quality
of life, but without early PSA screening, these new minimally invasive
technologies cannot be used.
•

gfvd wer, 59dd241ba9@inboxmail.life

© www.lecturio.com | This document is protected by copyright.
•

gfvd wer, 59dd241ba9@inboxmail.life

© www.lecturio.com | This document is protected by copyright.
Routine PSA screenings are not recommended
in men 75 years or over,
treatment
•

gfvd wer, 59dd241ba9@inboxmail.life

© www.lecturio.com | This document is protected by copyright.
•

gfvd wer, 59dd241ba9@inboxmail.life

© www.lecturio.com | This document is protected by copyright.
treatment

There is no clear evidence that either radical prostate surgery

or radiation therapy has a significant survival advantage over
the other, so treatment selection has relatively little effect on
life expectancy
Management
 Prostate cancer

Stages of Prostate Cancer

Stage A—nonpalpable, confined to prostate
Stage B—palpable nodule, but confined to prostate
Stage C—extends beyond capsule without metastasis
Stage D—metastatic disease
Histological type of cancer cells

Acinar adenocarcinoma in 90% - 95 % .

Non acinar cancer :

Sarcomatoid Ductal Adenosquamous

carcinoma adenocarcinoma Carcinoma

Urothelial Squamous cell

neuroendocrine
carcinoma carcinoma
Symptoms : :

1.Most commonly Asymtomatic in early stage . (cancers begin in the periphery of the gland and move centrally .
Most patients presenting with prostate cancer do so with screen-detected cancer and are asymptomatic. Local symptoms
associated with prostate cancer can include:
Lower urinary tract symptoms (LUTS)
Hematuria
Hematospermia
Erectile dysfunction
Urinary retention
However, those symptoms are generally not caused by prostate cancer. Physical examination alone cannot reliably differentiate benign prostatic disease from
cancer.
Findings in patients with advanced disease may include the following:
Cancer cachexia
Bony tenderness
Lower-extremity lymphedema or deep venous thrombosis
Adenopathy
Overdistended bladder due to outlet obstruction
Neuropathy

Locally advanced symptoms