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Prostate Cancer

Davis A Romney, MD

Ironwood Cancer and Research Centers

Feb 18, 2014

Overview

• Start with the basics: Definition of cancer• Most common cancers in men

• Prostate, lung, and colon cancers• Cancer statistics• Prostate cancer screening

• US Preventative Services Task Force and PSA screening• Prostate cancer workup• Technological advances in prostate cancer treatment• Q&A session

What is Cancer?

• A group of over 100 diseases characterized by uncontrolled abnormal cell growth• Benign – growth is limited to the surrounding environment without

the ability to metastasize• Malignant – cancerous cells have the ability not only to invade

locally but also to metastasize to distant sites in the body via the blood stream or lymphatic channels

• Cancer is named based on its site of origin (eg. prostate cancer or lung cancer)

• When cancer metastasizes to another organ it is still named based on its site of origin (eg. breast cancer that has spread to the lung is not called lung cancer but rather metastatic breast cancer to the lung.)

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Where does cancer come from?

• Cells in our bodies are constantly dividing

• Errors in DNA sequences can lead to genetic mutations

• Mutations in genes that regulate cellular replication can lead to uncontrolled cell growth: oncogenes vs tumor suppressor genes

What causes DNA mutations?

• Random errors in DNA replication

• Mutagens such as carcinogens found in cigarettes, industrial chemicals, etc.

• Radiation from the natural environment (eg. Radon gas)

• Viruses that integrate themselves into our DNA

• Chronic inflammation• Hereditary causes “bad

genes”

What is Cancer?

• Once a mutation occurs in a cell that regulates replication, a cascade effect tends to occur

• Because of the de-regulation in growth, DNA replication becomes less efficient and more errors are introduced

• Over time more and more mutations accumulate until the cells no longer resemble their native tissue and may become malignant

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Loss of Cell Cycle Regulation

Cancer Progression

Common Cancer Sites

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Estimated New Cancer Cases in the US in 2013

Estimated Cancer Deaths in the US in 2013

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Cancer Death Rates Among Men, US, 1930-2009

Cancer Deaths Averted from 1991-2009 in Men

Lifetime Probability of Developing Cancer for Men 2007-2009

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Prostate Anatomy and Function

Prostate Anatomy and Function

• Tubuloalveolar exocrine gland of the male reproductive system

• Secretes a slightly alkaline fluid, milky or white in appearance, that usually constitutes 50–75% of the volume of the semen

• The alkalinity of semen helps neutralize the acidity of the vaginal tract, prolonging the lifespan of sperm

Prostate Cancer Screening

• Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), is a glycoprotein enzyme

• PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely

• It is also believed to be instrumental in dissolving cervical mucus

• PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders

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Prostate Cancer Screening

• Prior to 2009, routine prostate cancer screening included and annual digital rectal exam (DRE), and screening serum PSA from age 50-75

• In 2011 the US Preventative Services Task Force (USPSTF) published a recommendation to suspend all routine PSA screening

Prostate Cancer Screening

• USPSTF reason for decision• Most cases of prostate cancer have a good prognosis, even without treatment,

but some are aggressive; the lifetime risk of dying of prostate cancer is 2.8%

• Seventy percent of deaths due to prostate cancer occur after age 75 years

• Estimates from the 2 largest trials suggest overdiagnosis rates of 17% to 50% for prostate cancer screening

• There is a high propensity for physicians and patients to elect to treat most cases of screen-detected cancer, given our current inability to distinguish tumors that will remain indolent from those destined to be lethal

• 1 man in 1,000 – at most – avoids death from prostate cancer because of screening

• 30 to 40 men will develop erectile dysfunction or urinary incontinence due to treatment

• 1 man in 3000 will die due to complications from surgical treatment

Prostate Cancer Screening

• Why all the controversy?• The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer

Screening Trial was the primary source for the recommendation

• Nearly two-thirds of men randomized in the study underwent PSA screening prior to entry into the study, a factor that undoubtedly eliminated high-risk cancers before the study even began.

• Only 31 percent of men with an abnormal digital rectal examination and a PSA of more than 4 ng/mL underwent prostate biopsy

• The USPSTF had no urologists as part of its council.

• A large European trial published after the recommendation was made found the men who underwent screening had 20% less of a chance of dying from prostate cancer over an 11 year period.

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Prostate Cancer Screening – AUA recommendations

• PSA screening in men under age 40 years is not recommended.

• Routine screening in men between ages 40 to 54 years at average risk is not recommended.

• For men ages 55 to 69 years, the decision to undergo PSA screening involves weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, shared decision-making is recommended for men age 55 to 69 years that are considering PSA screening, and proceeding based on patients’ values and preferences.

• To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision-making and decided on screening. As compared to annual screening, it is expected that screening intervals of two years preserve the majority of the benefits and reduce over diagnosis and false positives.

• Routine PSA screening is not recommended in men over age 70 or any man with less than a 10-15 year life expectancy.

Prostate Cancer Screening

• Summary• Routine screening is not recommended for men under

age 54 or over age 70

• Patients should be informed about the risks and benefits of screening

• Patient with urinary symptoms or a positive DRE, should have a PSA as part of their routine work up

• High risk patients (family history, African Americans) should strongly consider routine screening

Prostate Cancer Diagnosis

• Men with a positive DRE or elevated PSA should be considered for prostate biopsy

• This is typically performed with a rectal U/S probe and needle guide

• 6 zones of the prostate are sampled, usually with two cores from each zone

• Risks of the procedure include: pain, bleeding, infection, and temporary worsening of urinary symptoms

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Prostate Cancer Pathology –Gleason Score

1. Small uniform cells, tightly packed

2. Varied cell sizes and shapes, loosely packed

3. Increased cell size and shape irregularity, less distinction between cells

4. Large, irregular, fused cells

5. Irregular, fused cells that have invaded surrounding tissue

Prostate Cancer Pathology –Gleason Score

• Based on the sum of two numbers: the first number is the score of the most common tumor pattern, the second number is the score of the second most common pattern

• For example, if the most common tumor pattern was grade 3, but some cells were found to be grade 4, the Gleason Score would be 3+4 = 7

Prostate Cancer Staging

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Prostate Cancer Staging

Prostate Cancer Risk Assessment

Low Risk

• PSA <10• Gleason < 6• T1 – T2a

Intermediate Risk

• PSA 10-20• Gleason 7• T2b

High Risk

• PSA >20• Gleason 8-10• T2c or higher

Treatment Options

• Treatment Dependent on Stage and Risk

• Active Surveillance

• Prostatectomy

• External Beam Radiation

• Brachytherpay

• Proton Therapy

• Cryotherapy

• SBRT

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Active Surveillance

• DRE and PSA q3 months for 1 year then q6 months assuming stable PSA

• Repeat biopsy in 1 year or if PSA doubles or rises to >10

• Proceed to treatment for any patient who upstages risk factor; Gleason 7, PSA>10

Prostatectomy

• Pros

• Pathologic staging

• Convenience

• Higher BFS than EBRT and Brachytherapy

• Cons

• Risk of ED, incontinence

• Penile Shortening

• Risk of pain, bleeding, infection

• Overall Survival same

External Beam Radiation - IMRT

• Pros

• Non-invasive

• BFS 85%+

• Same Overall Survival as other treatments

• Cons

• Less convenient 40-45 daily treamtents (~8wks)

• Higher risk of rectal side effects

• Very expensive

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Brachytherapy

• Pros

• Convenience

• Less invasive than surgery

• Higher BFS than EBRT

• Lower risk of ED than surgery or EBRT

• Cons

• Higher risk of irritative voiding symptoms

• Lower BFS than surgery

• Not everyone a candidate

Proton Therapy

• Pros

• Lower integral dose than IMRT

• Higher radiobiologic effect

• Cons

• Limited treatment centers

• VERY expensive

• Limited long term follow up

• Possible higher rectal toxicity

Cryotherapy

• Pros

• Convenient (single treatment)

• Less invasive than surgery

• Lower risk of incontinence than surgery

• Cons

• Limited long term follow up data

• 100% incidence of erectile dysfunction in early studies

• Acute urinary symptoms

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SBRT – Stereotactic Body Radiation Therapy

• Pros

• 3-5 Treatments

• Non-invasive

• Higher radiobiologic effect

• Cons

• Very limited long term f/u

• Not approved by CMS,

• Should be part of a clinical trial

Androgen Depravation Therapy

• Bilateral Orchiectomy

• Medical Castration

• GnRH agonist (Lupron)

• GnRH antagonist (Degarelix)

• Androgen blockade (Casodex)

• Select Intermediate Risk and High Risk Patients

Low Risk Treatment

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Low Risk Treatment Results – Prostate Cancer Results Study Group

Overall Survival

Intermediate Risk Treatment

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High Risk Treatment

Prostate Cancer

• Most common cancer in men in the US, and second most common cause of cancer death.

• Routine screening is controversial, and risk and benefits should be discussed with patients

• Low risk patients should strongly consider active surveillance

• Overall survival rates for low risk prostate cancer patients are similar for all treatments

• Prostate cancer treatment has evolved significantly, and risks associated with treatment have improved

Q and A

• Thank you