Prostate Cancer pdf - د. سعد

Baghdad College of Medicine / 4

grade

Student’s Name :

Dr. Saad Dakhil
Lec. 2

PROSTATE CANCER

Mon. 28 / 3 / 2016

DONE BY : Ali Kareem

مكتب اشور لالستنساخ

2015 – 2016

Prostate Cancer Dr. Saad Dakhil

28-3-2016

©Ali Kareem 2015-2016

ODULE

8: P

ROSTATE

ANCER

: S

CREENING

& M

ANAGEMENT

KEYWORDS: Prostate cancer, PSA, Screening, Radical Prostatectomy

EARNING

BJECTIVES

At the end of this clerkship, the medical student will be able to:
1. Identify and name the basic anatomic zones of the prostate gland, including

the locations where prostate cancer develops
2. Describe the physiologic role of the prostate

– “what does the prostate do?”

3. Describe the distinctive epidemiological features of prostate cancer
4. Understand the controversy surrounding the use of serum PSA as a screening
tool for prostate cancer.
5. List the signs & symptoms of prostate cancer
6. Describe the natural history and the common patterns of progression of
prostate cancer
7. List the major components in the staging of prostate cancer
8. Briefly describe the treatment options for localized and metastatic prostate
cancer
9. Describe when prostate cancer does NOT need to be treated

NTRODUCTION

The prostate is a male sex accessory gland located within the pelvis below the

bladder and above the urogenital diaphragm. The prostate encircles the urethra like a

doughnut and is derived from the urogenital sinus. The role of the prostate is to

secrete fluid into the ejaculate that accompanies sperm and seminal vesicle fluid to

make up the semen. The contribution of the prostate to the ejaculate includes; acid,

zinc and a serine protease known as PSA (prostate specific antigen) that is an enzyme

responsible for the liquefaction of semen. The prostate continues to grow

(hyperplasia) with age and may cause voiding dysfunction.

Prostate cancer is the most common solid organ cancer in men and is currently the

second leading cause of cancer death in men behind lung cancer

Autopsy studies suggest that this cancer is much more common than observed

clinically and thus any screening strategy must take care not to diagnose cancer in

patients that will not suffer clinically from the disease. The incidence of clinically

Prostate Cancer Dr. Saad Dakhil

28-3-2016

©Ali Kareem 2015-2016

diagnosed prostate cancer and mortality is highest in Blacks, intermediate in

Caucasians and least in Asians. There currently is no effective systemic therapy for

prostate cancer. Being derived from a sex accessory gland, most prostate cancers are

hormone sensitive and respond favorably to androgen hormonal ablation but the

effect is short-lived due to either the development of or selection for hormone

insensitive clones within the malignancy. Thus, the treatment stratagem for prostate

cancer today is early detection whilst the tumor is confined to the prostate or

surrounding tissues and can be cured by either removal or treatments aimed at the

primary. Although there are low response rates to currently available chemotherapies

and a palliative effect of hormonal therapy, there are no cures for metastatic

prostate cancer.

ROSTATE

ANCER

CREENING

Unfortunately, there are no symptoms with early prostate cancer. As such, the AUA

currently recommends that interval prostate cancer screening be offered to all men

beginning at 40 years of age in the form of baseline PSA measurement and digital

rectal exam. The serum PSA test should not be considered a substitute for the digital

rectal exam. Rather, the tests are complimentary and, along with other key variables

including patient ethnicity, age, and family history, should serve as a strategic fund of

knowledge to be used when deciding whether or not to proceed with biopsy.

A flawless and standardized interpretation of elevated PSA values has yet to be

determined. Although it has been well demonstrated that patients with elevated

serum PSA levels are more likely to be harboring aggressive disease, elevated PSA

levels can also be seen in less biologically aggressive prostate cancers. Other potential

causes of elevated PSA values include benign prostatic hypertrophy, prostatitis, and

urogenital tract instrumentation (ie catheter placement). As such, serum PSA

screening interpreted outside the context of important patient-specific variables

carries with it a significant risk of what has been called overdiagnosis: the

identification and treatment of patients who might otherwise have lived out the rest

Prostate Cancer Dr. Saad Dakhil

28-3-2016

©Ali Kareem 2015-2016

of their lives without experiencing any of the terrible symptoms associated with

advanced prostate cancer. Since the treatment of prostate cancer is associated with a

significant level of patient morbidity (including bowel dysfunction, urinary

dysfunction, and impotence), the use of serum PSA as a screening tool has been a

topic of significant controversy.

In May of 2012, the United States Preventative Services Task Force (USPSTF), a

federally appointed group of 16 individuals commissioned to make recommendations

concerning clinical preventative services, issued a Class D recommendation regarding

the use of serum PSA in prostate cancer screening. This means they believe that they

have found

“fair evidence that [PSA screening] is ineffective or that harms outweigh

the benefits.

” They argue that the use of PSA screening and digital rectal exam in

asymptomatic patients will cause more harm in the form of treatment morbidity than

benefit. It should be noted that while the board includes members with both primary

care and nursing backgrounds, none of them are board certified urologists.

The AUA strongly disagrees with the USPSTF

’s recommendation and has taken steps

to better educate both the public and the health profession at large regarding the role

of serum PSA and digital rectal exam in prostate cancer screening. Since the

introduction of PSA as a screening tool in 1986, the number of total prostate cancer

deaths has decreased by approximately 30%. Also, the number of patients suffering

from the dire consequences of advanced prostate cancer (to include severe bone pain

and bulky tumors that obstruct the urinary tract) has decreased, an important victory

that the USPSTF

’s recommendation fails to take into account. The American Cancer

Society and the American Society of Clinical Oncologists agree with the AUA

’s stance.

Consequently, the AUA has worked with other patient and physician advocacy groups

to introduce legislature that will allow for specialist input into the USPSTF

’s

recommendations and prevent the issuing of sweeping mandates that could

potentially confuse patients and compromise care.

Nevertheless, the AUA recognizes that the interpretation of an asymptomatic

patient

’s PSA level is a nuanced exercise that must be tailored to the patient in

question. Therefore, the AUA no longer recommends one single PSA threshold for

biopsy. Although previous thresholds such as 2.5 and 4.0 ng/mL have been used in the

Prostate Cancer Dr. Saad Dakhil

28-3-2016

©Ali Kareem 2015-2016

past, the AUA now recommends that the decision to biopsy should take into account

the patient

’s DRE results, age, ethnicity, comorbidities, and prior biopsy history in

addition to their serum PSA level.

In order to increase the efficacy of serum PSA interpretation, a number of

performance variables are used clinically. These include age-adjusted PSA, density,

velocity, and the free-to-complexed PSA ratio.

a. Age Adjusted PSA: Since PSA normally rises with age, age-adjusted thresholds

have been described. Benign growth of the prostate that normally occurs with

age is the most common cause of PSA elevation. Roughly 70% of patients with

an elevated PSA level between 4 and 10 will have a negative prostate biopsy.

Conversely, there is no level of PSA at which you can guarantee a patient that

they do not have cancer. Moreover, the absolute PSA level does not predict

whether or not prostate cancer is harmful.

b. PSA Density: Another strategy used to improve the results of PSA screening is

the calculation of PSA density by measuring prostate volume and dividing the

absolute PSA level by the prostate volume (in mL). Prostate volume

measurements can be obtained by either transrectal ultrasound or MRI. By these

criteria, a PSA density threshold of 0.15 or greater is an indication for prostate

biopsy.

PSA Velocity. Since prostate cancer presumably grows faster than normal

prostate, PSA velocity (or change in PSA levels over time) is another strategy to

detect prostate

cancers in men with “normal” PSA levels. PSA values fluctuate

significantly over time due to physiological variation, thus PSA velocity is best

determined using at least 3 measurements obtained over a 2-year period. The

threshold value for PSA velocity is dependent on the total PSA. The threshold is

0.35 ng/ml/year for PSA values < 4 ng/ml and 0.75 ng/ml/year for patients with

total PSA values >4 ng/ml,

d. Free-Complexed PSA. PSA exists in the serum in two forms, free and complexed

to protease inhibitors. Patients with prostate cancer tend to have a higher

percentage of PSA complexed to protease inhibitors and thus the percentage of

free PSA within the serum is used to add information to the total PSA in patients

Prostate Cancer Dr. Saad Dakhil

28-3-2016

©Ali Kareem 2015-2016

with PSA levels between 4 and 10 and help determine the degree of suspicion

for biopsy. Although there again is no agreement on the best threshold value for

free PSA, values above 25% reliably predict the absence of clinically significant

prostate cancer.

ROSTATE

ANCER

TAGING AND

REATMENT

Prostatic anatomy is described in zones. The main arterial blood supply to the

prostate is the inferior vesical artery. The central and transition zone surround the

urethra and are the site of benign prostatic hyperplasia. Prostate cancer most often

occurs in the peripheral zone which is closest to the rectum. Prostate cancer is

diagnosed by prostate biopsy, as described above, in patients with either an abnormal

DRE and/or abnormal PSA. The vast majority of patients who are diagnosed today

were identified by prostate cancer screening and have early potentially curable

disease. The TNM staging is used for prostate cancer. The clinical stage is based upon

how it was detected and the digital rectal exam.

T1 disease is based upon whether it was discovered inadvertently in the tissue

obtained during surgery for benign disease (T1a involving < 5% and T1b is >5%) or

whether the cause of the biopsy was an elevated PSA (T1c). T2 disease is based upon

the palpation of cancer in the prostate on digital rectal exam (a: less than half of one

side, b: more than half of one side, and c: both sides of the prostate). Patients have

T3 disease when cancer is palpable outside the prostate either laterally or involving

the seminal vesicles. Besides clinical stage, the histology of the cancer has a

significant impact upon prognosis. The Gleason score (or sum) is the standard measure

of the differentiation of prostate cancer. There are five patterns (1

– 5) with 5 being

the worst. The biopsy material is examined under low power magnification the most

common and second most common patterns are identified. These two numbers are

added up to obtain the final Gleason score. The individual numbers and order are just

as important in predicting prognosis as the total score since a patient with a Gleason

score of 3 + 5 = 8 has a better prognosis as a patient with 5 + 3 = 8.

The treatment of localized prostate cancer includes radiation therapy, surgery, and

Prostate Cancer Dr. Saad Dakhil

28-3-2016

©Ali Kareem 2015-2016

expectant management (watchful waiting). The decision on how to manage prostate

cancer in a newly diagnosed patient is quite complex and filled with controversy. The

age (life expectancy) and health of the patient in addition to the characteristics of

the cancer are taken into account. A frequent concern today is whether or not the

cancer that is diagnosed is clinically significant. Expectant management is offered to

patients who have very low grade (no Gleason pattern 4 or higher) and low volume

disease (< 3 biopsy cores involved) or <10-year life expectancy due to medical illness

or age and a reasonable expectation that they will be compliant to the observation

protocol. Younger and healthier men or men with more aggressive cancers should

undergo therapy with either radiation or surgery. Alternative therapies such as

cryosurgery, high intensity focused ultrasound, and herbal therapy have not been fully

assessed for the management of clinically localized prostate cancer.

Radiation therapy may be administered by external beam, brachytherapy or a

combination of the two. The major side effects of radiation therapy are erectile

dysfunction, in approximately 40%, and radiation proctitis. Stress urinary incontinence

does not often occur after radiation therapy, but severe voiding symptoms due to

bladder irritation occurs in approximately 15% of patients with significant voiding

symptoms (AUA symptom score of > 15 out of 35) who undergo brachytherapy.

Moreover, brachytherapy cannot be performed in patients with large prostate glands.

Surgical removal of the prostate can be performed either by open surgery, radical

retropubic or perineal, or by laparoscopic surgery with out without robotic assistance.

There is no clear evidence to suggest that one approach is significantly better than

another and the decision is often left to the treating physician and patient. The major

risks of surgery are erectile dysfunction and stress urinary incontinence. The results

vary based upon patient age, experience of the surgeon and whether or not the

patient is a candidate for

“nerve-sparing.”

For non-localized prostate cancer, hormonal therapy is also used. Prostate cancer was

the first malignancy to be shown to be hormone dependent and for this discovery, a

Nobel Prize was awarded in the mid twentieth century. Hormone therapy involves

depriving the prostate cancer of male sex hormones (androgens) to control cancer

activity. Hormonal manipulation to decrease androgens in the blood stream by either

Prostate Cancer Dr. Saad Dakhil

28-3-2016

surgical castration or the use of long acting drugs to suppress pituitary function is

used to suppress cancer activity. Forms of androgen deprivation include luteinizing

hormone-releasing hormone (LH-RH) agonists (leuprolide acetate and goserelin) that

reduce pituitary drive to the testis to make testosterone; antiandrogens (flutamide,

bicalutamide, and nilutamide) that block the action of testosterone on end organs;

simple orchiectomy to remove the testicles and reduce natural testosterone levels;

and adrenal gland testosterone blockers (ketoconazole and aminoglutethimide) that

block the remaining 5% of testosterone that is made by the adrenal gland. When

hormonal treatments are combined to bring testosterone levels as low as possible,

this is known as total androgen blockade. Studies have not shown whether total

androgen blockade is more effective than orchiectomy or an LH-RH agonist alone.

Hormone therapy is most commonly used to control cancer growth after it has

metastasized. Since hormone therapy is only palliative and not curative, most

prostate cancers will become hormone refractory and grow in the absence of

testosterone. Side effects from hormonal therapy include impotence, hot flashes, loss

of sexual desire, and osteopenia. Bone densitometry should be used periodically to

assess bone strength. Antiandrogens can cause nausea, diarrhea, or breast growth or

tenderness, skin rashes and rarely, liver problems

There is no clear

“right” answer for the typical patient diagnosed with prostate

cancer today. Surgical therapy is generally preferred method of management for the

younger patient with a 30-year life expectancy who has localized cancer. Radiation or

expectant management is generally recommended for the patient over 70 years of

age with localized cancer. The prognosis for most patients with early stage disease is

quite good but some patients have metastases at the time of diagnosis. The

management of metastatic disease today is palliative with hormonal manipulation in

the absence of a cure.

NTERACTIVE

ASES IN

ROLOGY

Prostate Cancer 1 - The Case of Mr. Powers' Prostatic Nodule

http://www.auanet.org/eforms/casestudies/index.cfm?slnm=Prostatic%20Nodule

Prostate Cancer Dr. Saad Dakhil

28-3-2016

Prostate Cancer 2 - The Case of Mr. Powers' Prostate Cancer Recurrence

http://www.auanet.org/eforms/casestudies/index.cfm?slnm=Prostate%20Cancer%20R

ecurrence

PSA Screening 1

– Mr. Herman’s Prostate – Coming Soon

PSA Screening 2 - A Troop of Small Cases

– Coming Soon

EADING

IST

AUA Guidelines for prostate cancer screening:

http://www.auanet.org/content/guidelines- and-quality-care/clinicalguidelines/

main-reports/psa09.pdf

AUA Guidelines for the management of clinically localized prostate cancer: 2007

update.

http://www.auanet.org/content/guidelines-and-quality-care/clinicalguidelines.

cfm?sub=pc

Bostwick DG, Burke HB, Djakiew D et al: Human prostate cancer risk factors. Cancer

2004;101:2371-2490

Partin AW, Kattan MW, Subong EN et al: Combination of prostate specific antigen,

clinical stage, and Gleason score to predict pathological stage of localized prostate

cancer. A multi-institutional update. JAMA 1997;277:1445.

Allaf ME, Carter HB: Update on watchful waiting for prostate cancer. Curr Opin Urol

2004;14:171-175.

Sharifi N, Gulley JL, Dahut WL: Androgen deprivation therapy for prostate cancer.

JAMA 2005;294:238-244.

AUA Speaks Out Against USPSTF Recommendations

http://www.auanet.org/content/health-policy/government-relations-andadvocacy/

in-the-news/uspstf-psa-recommendations.cfm?WT.mc_id=EML6621MKT

END OF THIS LECTURE …