Posts Tagged ‘prostate specific antigen’

Prostate Cancer Update 2017: A More Nuanced Approach

December 3, 2016

Andrew Siegel MD  12/3/2016

prostate_cancerAttribution of above image: Blaus (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)%5D, via Wikimedia Commons

It was not so long ago that all prostate cancers were lumped together, the thought being that a cancer is a cancer and best served by surgical removal. Consequently, with the best of intentions, some unnecessary surgical procedures were performed that at times resulted in impaired sexual function, poor urinary control, and unhappy patients.

Fortunately, urologists have become wiser, recognizing that individual prostate cancers are unique and that a nuanced approach is the key to proper management. Some prostate cancers are so unaggressive that no cure is necessary, whereas others are so aggressive that no treatment is curative. One thing is for certain—we have vastly improved our ability to predict which prostate cancers need to be actively treated and which can be watched.

The Challenge Of Diagnosing Prostate Cancer

The vast majority of patients who have undiagnosed prostate cancer have NO symptoms—no pain, no bleeding, no urinary issues, no anything. The possible diagnosis of prostate cancer is usually entertained under three circumstances: when there is an elevated PSA (Prostate Specific Antigen) blood test; when there is an accelerated PSA (when the change in PSA compared to the previous year is considered to be too high); and when there is an abnormal prostate DRE (digital rectal exam)—a bump, lump, hardness, asymmetry, etc. The bottom line is that if you don’t actively seek prostate cancer, you’re not going to find it. When prostate cancer does cause symptoms, it is generally a sign of locally advanced or advanced prostate cancer. Therein lies the importance of screening.

The Dilemma Of Screening For Prostate Cancer

The downside of screening is over-detection of low risk prostate cancer that may never prove to be problematic, but may result in unnecessary treatment with adverse consequences. The downside of not screening is the under-detection of aggressive prostate cancer, with adverse consequences from necessary treatment not being given.

How Is The Diagnosis of Prostate Cancer Made?

When the PSA is elevated or accelerated and/or if there is an abnormal prostate DRE in a reasonably healthy man with good longevity prospects, an ultrasound-guided prostate biopsy is in order. Obtaining tissue for an exam by a pathologist is the definitive and conclusive test. The biopsy will reveal if cancer is present and its location, volume and grade (aggressiveness).

If prostate cancer is present, it is useful to determine the risk potential of the prostate cancer (“risk stratify”) by classifying it into categories based upon the following:

T (Tumor) category

T1c: cancer found because of PSA elevation or acceleration with a normal DRE

T2a: palpable (that which can be felt on DRE) cancer of half or less of one side

T2b: palpable cancer of more than half of one side

T2c: palpable cancer of both sides

T3a: cancer outside prostate, but sparing the seminal vesicles (reproductive structures that store semen)

T3b: cancer involving seminal vesicles

T4: regional spread of cancer to sphincter, rectum, bladder or pelvic sidewall

Gleason Score

Dr. Gleason devised a system that grades prostate cancer by observing the cellular architecture of prostate cancer cells under the microscope. He recognized that prostate cancer grade is the most reliable indicator of the potential for cancer growth and spread. His legacy, the grading system that bears his name, provides one of the best guides to prognosis and treatment. The pathologist assigns a separate numerical grade ranging from 3 – 5 to each of the two most predominant patterns of cancer cells. The sum of the two grades is the Gleason score. The Gleason score can predict the aggressiveness and behavior of the cancer, with higher scores having a worse prognosis than lower scores.

Grade Group 1 (Gleason score 3+3=6)

Grade Group 2 (Gleason score 3+4=7)

Grade Group 3 (Gleason score 4+3=7)

Grade Group 4 (Gleason score 4+4=8)

Grade Group 5 (Gleason score 4/5+4/5=9 or 10)

The significance of the Gleason Grade Group can be understood by examining the PSA five years after surgical removal of the prostate, correlating survival with the Grade Group. Ideally, after surgical removal of the prostate gland the PSA should be undetectable. A detectable and rising PSA after surgical removal is a sign of recurrent prostate cancer. The five-year rate of PSA remaining undetectable (biochemical recurrence-free progression) for surgical removal of the prostate in Grade Groups 1-5 is the following: 96%, 88%, 63%, 48%, and 26% respectively, indicating the importance of the grading system with respect to prognosis.

Number cores with cancer

Generally 12 – 14 biopsies are obtained, occasionally more. In general, the more cores that have cancer, the greater the volume of cancer and the greater the risk.

Percent of tumor involvement (PTI)

The percentage of any given biopsy core that has cancer present. In general, the greater the PTI, the greater the risk.

PSA

PSA is an excellent “tumor marker” for men with prostate cancer. In general, the higher the PSA, the greater the risk category.

PSA density

The relationship of PSA level to size of the prostate, determined by dividing the PSA by the volume of the prostate. The volume of the prostate is easily determined by ultrasound or by MRI (magnetic resonance imaging). A PSA density > 0.15 is greater risk.

 

Risk Stratification For Prostate Cancer

Based upon the aforementioned parameters, an individual case of prostate cancer can be assigned to one of five risk categories ranging from very low risk to very high risk. This risk assignment is helpful in predicting the future behavior of the prostate cancer and in the decision-making process regarding treatment.

Very Low Risk: T1c; Gleason score ≤ 6; fewer than 3 cores with cancer; less than 50% of cancer in each core; PSA density < 0.15

Low Risk: T1-T2a; Gleason score ≤ 6; PSA < 10

Intermediate Risk: T2b-T2c or Gleason score 7 or PSA 10-20

High Risk: T3a or Gleason score 8-10 or PSA > 20

Very High Risk: T3b-T4 or Gleason grade 5 as the predominant grade (the first of the two Gleason grades in the Gleason score) or > 4 cores Gleason score 8-10

 

Prostate Cancer Treatment

Prostate cancer treatment is based upon risk category and life expectancy and includes the following:

RALP (robotic-assisted laparoscopic prostatectomy): surgical removal of the prostate gland using robotic assistance

RT (radiation therapy): this can be used as definitive treatment or alternatively for recurrent disease after RALP or immediately following healing from RALP under the circumstance of adverse pathology report

ADT (androgen deprivation therapy): a means of decreasing testosterone level, since the male sex hormone testosterone stimulates prostate growth

AS (active surveillance): actively monitoring the disease with the expectation to intervene with curative therapy if the cancer progresses. This will involve periodic DRE, PSA, MRI, and repeat biopsy.

Observation: monitoring with the expectation of giving palliative therapy (relieving pain and alleviating other problems that may surface without dealing with the underlying cause)  if symptoms develop or a change in exam or PSA suggests that symptoms are imminent.

 

Prostate Cancer Treatment Based Upon Risk Stratification

Very Low Risk

< 10 year life expectancy: observation

10-20 years life expectancy: AS

> 20 years life expectancy: AS or RALP or RT

Low Risk

<10 years life expectancy: observation

>10 years life expectancy: AS or RALP or RT

Intermediate Risk

<10 years life expectancy: observation or RT + ADT 4-6 months

>10 years life expectancy: RALP or RT + ADT 4-6 months

High Risk

RALP or RT + ADT 2-3 years

Very High Risk:

T3b-T4: RT + ADT 2-3 years or RALP (in select patients) or ADT

Lymph node spread: ADT or RT + ADT 2-3 years

Metastatic disease: ADT

Bottom Line: Excluding skin cancer, prostate cancer is the most common cancer type in men, accounting for 26% of newly diagnosed cancers with men having a 1 in 7 lifetime risk. The median age of prostate cancer at diagnosis is the mid 60s and in 2015 there were 221,000 new cases per year, 27,500 deaths (the second most common form of cancer death, after lung cancer) and there are currently about 2.5 million prostate cancer survivors in the USA.  It is important to diagnose prostate cancer as early as possible in order to decide on the most appropriate form of management—whether it is surgery, radiation, or observation/monitoring. Risk stratification can help the decision-making process.

“Appropriate treatment implies that therapy be applied neither to those patients for whom it is unnecessary nor to those for whom it will prove ineffective. Furthermore, the therapy should be that which will most assuredly permit the individual a qualitatively and quantitatively normal life. It need not necessarily involve an effort at cancer cure. Human nature in physicians, be they surgeons, radiotherapists, or medical oncologists, is apt to attribute good results following treatment to such treatment and bad results to the cancer, ignoring what is sometimes the equally plausible possibility that the good results are as much a consequence of the natural history of the tumor as are the bad results.”

Willet Whitmore, M.D.

(Dr. Whitmore served as chief of urology for 33 years at what is now Memorial Sloan-Kettering Cancer Center. He died of prostate cancer at age 78 in 1995.)

Wishing you the best of health,

2014-04-23 20:16:29

http://www.AndrewSiegelMD.com

A new blog is posted every week. To receive the blogs in the in box of your email go to the following link and click on “email subscription”:  www.HealthDoc13.WordPress.com

Author of MALE PELVIC FITNESS: Optimizing Sexual & Urinary Health http://www.MalePelvicFitness.com

Author of THE KEGEL FIX: Recharging Female Pelvic, Sexual and Urinary Health  http://www.TheKegelFix.com

 

 

 

 

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Prostate Cancer Screening: What’s New?

February 28, 2015

Andrew Siegel MD 2/28/15

The Dilemma

The downside of screening is over-detection of low-risk prostate cancer that may never prove to be problematic, but may result in unnecessary treatment with adverse consequences. The downside of not screening is the under-detection of aggressive prostate cancer, with adverse consequences from necessary treatment not being given.

The Buck Stops Here

Prostate biopsy (ultrasound guided) is the definitive and conclusive test for prostate cancer. An elevated PSA (Prostate Specific Antigen) blood test or an abnormal DRE (digital rectal exam) are the findings that typically lead to the recommendation for prostate biopsy.

What’s New In Prostate Cancer Screening?

The following are refinements in the screening process that can help make the decision about whether or not to proceed with a prostate biopsy, potentially sparing some from the need to undergo the biopsy and clearly indicating the need for biopsy in others.

  • Free PSA
  • PSA Velocity
  • PSA Density
  • PCA-3
  • Prostate MRI
  • 4K Score

Free PSA

PSA circulates in the blood in a “free” form, which it is unbound and a “complex” form, in which it is bound to a protein. The free/total PSA can enhance the specificity of PSA testing. The greater the free/total PSA, the greater the chances that benign enlargement of the prostate is the cause of the PSA elevation. In men with a PSA between 4-10, the probability of cancer is less than 10% if the ratio is greater than 25% whereas the probability of cancer is almost 60% if the ratio is less than 10%.

PSA Velocity

It is extremely useful to compare the PSA values from year to year. Under normal circumstances, PSA increases by only a small increment, reflecting age-related benign prostate growth. PSA acceleration at a rate greater than anticipated is a red flag that may be indicative of prostate cancer and is one of the most common prompts for undergoing biopsy.

PSA Density

There is a direct relationship between prostate size and PSA, with larger prostates producing higher PSA levels. PSA density (PSA/prostate volume) is the relationship of the PSA level to the size of the prostate. PSA density > 0.15 is a red flag that may be indicative of prostate cancer.

PCA-3 (Prostate Cancer Antigen-3)

PCA-3 is a specific type of RNA (Ribonucleic Acid) that is released in high levels by prostate cancer cells. Its expression is 60-100x greater in prostate cancer cells than benign prostate cells, which makes this test much more specific for prostate cancer than PSA.  PCA-3 is a urine test. The prostate is gently “massaged” via DRE to “milk” prostate fluid into the urethra. The first ounce of urine voided immediately after massage is rich in prostatic fluid and cells and is collected and tested for the quantity of PCA-3 genetic material present. Urinary levels of PCA-3 are not affected by prostate enlargement or inflammation, as opposed to PSA levels. PCA-3 > 25 is suspicious for prostate cancer.

Prostate MRI (Magnetic Resonance Imaging)

MRI is a high-resolution imaging test that does not require the use of radiation and is capable of showing the prostate and surrounding tissues in multiple planes of view, identifying suspicious areas. MRI uses a powerful Tesla magnet and sophisticated software that performs image-analysis, assisting radiologists in interpreting and scoring MRI results. A validated scoring system known as PI-RADS (Prostate Imaging Reporting and Data System) is used. This scoring system helps urologists make decisions about whether to biopsy the prostate and if so, how to optimize the biopsy.

PI-RADS classification Definition
I Most probably benign
II Probably benign
III Indeterminate
IV Probable cancer
V Most probably cancer

4Kscore Test

The 4Kscore Test measures the blood content of four different prostate-derived proteins: Total PSA, Free PSA, Intact PSA and Human Kallikrein 2. Levels of these biomarkers are combined with a patient’s age, DRE status (abnormal DRE vs. normal DRE), and history of prior biopsy status (prior prostate biopsy vs. no prior prostate biopsy). These factors are processed using an algorithm to calculate the risk of finding a Gleason score 7 or higher (aggressive) prostate cancer if a prostate biopsy were to be performed. The test can increase the accuracy of prostate cancer diagnosis, particularly in its most aggressive forms.

(It cannot be used if a patient has received a DRE in the previous 4 days, nor can it be used if one has been on Avodart or Proscar within the previous six months. Additionally, it cannot be used in patients that have within the previous six months undergone any procedure to treat symptomatic prostate enlargement or any invasive urologic procedure that may be associated with a PSA elevation.)

As of now, the test is not covered by insurance and costs $395 from the lab that performs it.

Bottom Line: Excluding skin cancer, prostate cancer is the most common cancer in men (accounting for 26% of newly diagnosed cancers with men having a 1 in 7 lifetime risk). The median age of prostate cancer at diagnosis is the mid 60’s and there are 221,000 new cases per year, 27,500 deaths (the second most common form of cancer death, after lung cancer) and there are currently about 2.5 million prostate cancer survivors in the USA.  It is important to diagnose prostate cancer as early as possible in order to decide on the most appropriate form of management–surgery, radiation, or observation/monitoring (the most common treatment pathways, although there are other options as well).  These refinements in the screening process can help urologists make the decision about whether or not to proceed with a prostate biopsy.  

 

Wishing you the best in health,

2014-04-23 20:16:29

http://www.AndrewSiegelMD.com

A new blog is posted every week. To receive the blogs in the inbox of your email go to the following link and click on “email subscription”: www.HealthDoc13.WordPress.com

Author of Male Pelvic Fitness: Optimizing Sexual and Urinary Health:available in e-book (Amazon Kindle, Apple iBooks, B & N Nook, Kobo) and paperback: http://www.MalePelvicFitness.com

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PSA Absurdity

January 31, 2015

Andrew Siegel MD   1/31/15

Women_Against_Prostate_Cancer_logo

(Image designed  by Abby Cycotte for WAPC)

Prostate cancer is the most commonly diagnosed cancer in males (excluding skin cancers)—paralleling breast cancer in females in many ways—with an estimated 233,000 new cases diagnosed in 2014. Over the latest 5-year period for which data is available, the death rate for prostate cancer decreased based upon improved early detection and treatment. There are 3 million prostate cancer survivors in the USA. The vast majority of prostate cancers are diagnosed by Prostate Specific Antigen (PSA) screening, a simple blood test.

Prostate cancer screening with PSA has been the subject of intense controversy and debate, a controversy that I—as a practicing urologist—don’t quite get. A major backlash against screening occurred in 2012. It started with the United States Preventive Services Task Force (USPSTF) grade “D” recommendation against PSA screening and their call for total abandonment of the test. Of note, there was not a single urologist on the committee. The same organization had previously advised that women in their 40’s should not undergo routine mammography, setting off another blaze of controversy. As a busy clinical urologist for almost three decades, I was deeply disturbed by their recommendation.

In 2013 the American Urological Association (AUA) issued guidelines recommending against PSA testing before age 55, with testing every other year between ages 55-69 and then only after “informed decision making,” a discussion between physician and patient weighing benefits and harms.

AUA Guideline Statements:

  1. Do not screen men under age 40.
  2. Do not screen men age 40-54, unless high risk (family history or African American), in which case decision should be individualized.
  3. Screen men 55-69 after informed decision making.
  4. Screening interval of “two years or more” may be preferred to annual screening to reduce harms of screening.
  5. Do not screen men older than 70 or any man with life expectancy less than 10-15 years, although some men in excellent health may benefit from screening.

When these guidelines came out, I was in disbelief and shock. Why did the AUA—whose mission statement is “to promote the highest standards of urological clinical care through education, research and in the formulation of health care policy”—kowtow on this vital issue?

Further fueling the controversy and confusion is the lack of consensus among professional groups including the European Association of Urology, the National Comprehensive Cancer Network and the Prostate Cancer World Congress. Uncertainty in the lay press has prompted both patients and physicians to question PSA testing and recommendations for prostate biopsy.

Is there really any harm in screening? Screening provides information and there are no side effects aside from whatever complications may ensue from drawing a small amount of blood. There are potential side effects from prostate biopsy (although they are few and far between) and certainly there are potential side effects with treatment; however, it seems that both the USPSTF and the AUA have confused screening with treatment. The potential side effects of active treatment should not influence the diagnosis of prostate cancer by the proper means. “Treatment or non-treatment decisions can be made once the cancer is found, but not knowing about it in the first place surely burns bridges.”—Dr. Jay Smith

I ardently disagree with the assertions of the task force and the AUA. Urologists, radiation oncologists, and medical oncologists (those physicians who are in the “trenches” and take care of prostate cancer on a daily basis) understand how devastating prostate cancer can be and the importance of early detection.

So what has been the upshot of this controversy? What has happened is that instead of proceeding directly to prostate biopsy, many more men with an elevated or accelerated PSA are having repeat PSA testing (often fractionated to determine free PSA/total PSA), the PCA-3 urine test and a prostate MRI. If the regulatory agencies had cost savings on their agenda, they have failed miserably as more testing (that incurs a significant expense) is being done than ever before.

Busy urologists are seeing more and more indecision and equivocation among primary care physicians who are confronted with patients who want screening, but guidelines that suggest that it is not necessary. Despite the USPSTF recommendations and AUA guidelines, urologists are actually seeing more referrals for elevated PSA than ever before.

Hard Facts:

  1. PSA screening has resulted in downward stage migration—detecting prostate cancer in an early and curable stage, before it spreads and becomes incurable. If these guidelines are adhered to, we will most certainly give back the gains we have made and experience a reverse stage migration and a return to the pre-PSA era when up to 20% of men presented with advanced disease.
  2. PSA testing unequivocally reduces metastatic prostate cancer (cancer that has spread) and death from prostate cancer: USA death rates from prostate cancer have fallen 4% annually since 1992, five years after introduction of PSA testing.
  3. Rigid guidelines unfortunately do not allow for a nuanced and individualized approach to early prostate cancer detection. PSA has many shortcomings, but used intelligently and appropriately will continue to save lives.
  4. Baseline PSA testing for men in their 40’s is useful for predicting the future of prostate cancer.
  5. Not permitting men age 40-55 the opportunity for screening denies them the potential to diagnosis a disease that is potentially lethal; this population has a long life expectancy and therefore the greatest need for early diagnosis and curative treatment.
  6. Older men in good health with over a 10-year life expectancy should not be denied PSA testing simply on the basis of their age.
  7. 95% of male urologists and 80% of primary care physicians have annual PSA screening—clearly, those in the know feel that screening is beneficial.
  8. Death from prostate cancer is unpleasant, often involving painful metastases to the spine and pelvis and not uncommonly, kidney and bladder outlet obstruction; our charge as urologists is to try to not let this scenario come to fruition.

When interpreted appropriately, the PSA test provides important information in the diagnosis, pre-treatment staging, risk assessment and monitoring of prostate cancer patients. Marginalizing this important test does a great disservice to those who may benefit from early prostate cancer detection.

I have practiced urology in both the pre-PSA era and the post-PSA era. In my early years of training, it was not uncommon be called to the emergency room to treat men who could not urinate, who on digital rectal exam were found to have rock-hard prostate glands and imaging studies that showed diffuse spread of prostate cancer to their bones—metastatic prostate cancer with a grim prognosis. In the post-PSA era, that scenario—fortunately—occurs on an extremely infrequent basis thanks to PSA screening. The vast majority of men who present that way these days are those who have opted NOT to obtain a screening PSA as part of their annual physical exams.

Bottom Line: The downside of screening is over-detecting low-risk prostate cancer that may never prove to be problematic, but may result in unnecessary treatment with adverse consequences. The downside of not screening is under-detecting aggressive prostate cancer, with adverse consequences from necessary treatment not being given. We need to separate screening from treatment and screen smarter.”—Dr. Judd Moul

The major challenge for those of us who treat prostate cancer is to distinguish between clinically significant and clinically insignificant disease and to decide the best means of eradicating clinically significant disease to maintain quantity and quality of life. Not all prostate cancers require active treatment and not all prostate cancers are life threatening. The decision to proceed to active treatment is one that men should discuss in detail with their urologists to determine whether active treatment is necessary, or whether surveillance may be an option, appropriate in selected men with low-risk prostate cancer (low PSA; minimum number of biopsies showing cancer; low-grade cancer as determined by the pathologist). Those at greater risk can be managed appropriately (surgery or radiation) and many cured, avoiding the potential for progression of cancer and painful metastases and death.

“PSA is the best screening test we have for prostate cancer, and until there is a replacement for PSA, it would be unconscionable to stop it. Contrary to the USPSTF report, compelling evidence shows that PSA screening reduces prostate cancer deaths. This evidence needs to be shared with the public.”
–Dr. William Catalona

The Samadi Challenge For Prostate Cancer

Dr. David Samadi, Chief of Prostate Robotic Surgery at Lenox Hill Hospital, has created a challenge to women, since they are the proactive gender in terms of understanding the importance of health risks, screening and routine checkups and are often the driving force in men’s health.  Men are much more reluctant to engage with the health care system than women—particularly preventive health care—and Dr. Samadi sees women playing a pivotal role in encouraging men to focus on prostate health. On a larger scale, he sees women as ideal advocates and champions to help raise global awareness for prostate cancer. The Samadi Challenge involves women learning the risk factors for prostate cancer, improving the lifestyles of the men in their lives, encouraging men to have annual screening and in the case of being diagnosed with prostate cancer, urging men to seek appropriate treatment. Dr. Samadi launched a FaceBook page: “Women for Prostate Health,” a means to help women initiate a conversation about prostate health.

Wishing you the best of health,

2014-04-23 20:16:29

http://www.AndrewSiegelMD.com

A new blog is posted every week. To receive the blogs in the in box of your email go to the following link and click on “email subscription”: www.HealthDoc13.WordPress.com

Author of Male Pelvic Fitness: Optimizing Sexual and Urinary Health: available in e-book (Kindle, iBooks, Nook, Kobo) and paperback: http://www.MalePelvicFitness.com

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Must My Prostate Cancer Be Treated?

January 4, 2014

Blog # 135

“To do nothing, that’s something.”

Samuel Shem, The House of God

Prostate cancer needs to be accorded respect as there are 240,000 new cases diagnosed annually and it accounts for 30,000 deaths per year, being the second leading cause of cancer death in men, only behind lung cancer.

Unlike many other malignancies, prostate cancer is often not a lethal disease and may never need to be treated. Shocking, right…a cancer that does not necessarily need to be cut out or managed in any way! Patients with slow-growing, early stage cancer as well as older men with other health issues may be put on surveillance, aka watchful waiting, as opposed to traditional treatment with surgery or radiation.

The problem is that not all prostate cancers are slow-growing and early stage, and the challenge is how to predict the future behavior of the cancer so as to treat it appropriately—offering cure to those with aggressive cancer, but sparing the side effects of treatment in those who have non-aggressive cancer. The goal of active surveillance is to allow men with low risk prostate cancer to avoid radical treatment with its associated morbidity and/or delay definitive treatment until signs of progression occur. This involves two things—vigilant monitoring and a compliant patient who is compulsive about follow-up.

The ratio of 7:1 of the lifetime likelihood of diagnosis of prostate cancer (about 1 in 6 men) to death from prostate cancer (about 1 in 40 men) points out that many men with prostate cancer have an indolent (i.e., slow growing) cancer. Because of this fact, an alternative strategy to aggressive management of all men with prostate cancer is active surveillance, a structured means of careful follow-up with rigorous monitoring and immediate intervention should signs of progression develop. Being a candidate for this approach is based upon the results of the PSA blood test, findings on the digital rectal exam, and the details of the biopsy, which usually involves obtaining one dozen samples of prostate tissue.

General eligibility criteria for active surveillance include all of the following (Note that these are basic guidelines and need to be modified in accordance with patient age and general health— certainly if one has a life expectancy < 10 years, he would be a good candidate for active surveillance, regardless of the following):

  • PSA (Prostate Specific Antigen) less or equal to 10 (PSA is the blood test that when elevated or accelerated indicates the possibility of a problem with the prostate and is often followed by a prostate ultrasound/biopsy)
  • Gleason score 6 or less (possible score 2-10, more about this below)
  • Stage T1c-T2a

 (T1c = picked up by PSA with normal prostate on rectal exam; T2a = picked up by abnormal prostate on rectal exam, involving only one side of the prostate)
  • Less then 3 of 12 biopsy cores involved with cancer
  • Less then 50% of any one core involved with cancer

Prostate cancer grade is often the most reliable indicator of the potential for growth and spread. The Gleason score provides one of the best guides to the prognosis and treatment of prostate cancer and is based on a pathologist’s microscopic examination of prostate tissue. To determine a Gleason score, a pathologist assigns a separate numerical grade to the two most predominant architectural patterns of the cancer cells. The numbers range from 1 (the cells look nearly normal) to 5 (the cells have the most cancerous appearance). The sum of the two grades is the Gleason score. The lowest possible score is 2, which rarely occurs; the highest is 10. The Gleason score can predict the aggressiveness and behavior of the cancer. High scores tend to suggest a worse prognosis than lower scores because the more deranged and mutated cells usually grow faster than the more normal-appearing ones.

Prostate cancers can be “triaged” into one of three groupings based upon Gleason score. Scores of 2-4 are considered low grade; 5-7, intermediate grade; 8-10, high grade.

The active surveillance monitoring schedule is typically:

  • PSA and DRE every 3-6 months for several years, then annually
  • Prostate biopsies: one year after initial diagnosis, then periodically until age 80 or so (once again, a judgment call)

As long as the cancer remains low-risk, the surveillance protocol may be continued, sparing the patient the potential side effects of surgery or radiation.

Another meaningful way of predicting the behavior of prostate cancer is by using the PSA Doubling Time (PSADT)—defined as the amount of time it takes for the PSA to double. A short PSA doubling time is indicative of an aggressive, rapidly growing tumor, whereas a long PSA doubling time is indicative of an indolent, slow growing tumor. A PSADT of less than 3 years is clearly associated with the potential for progression of prostate cancer.

A change in plan from active surveillance to more active intervention needs to be instituted if any of the following occurs:

  • PSA doubling time is noted to be less then 3 years
  • Biopsy reveals grade progression to Gleason 7 or higher
  • Biopsy reveals increased prostate cancer volume

Approximately half of men on active surveillance remain free of progression at ten years, and definitive treatment is most often effective in those with progression. The absence of cancer on repeated prostate biopsy (because the cancer is of such low volume) identifies men who are unlikely to have progressive prostate cancer.

Bottom Line: Active surveillance is an effective means of minimizing over-treatment of indolent prostate cancer and avoiding the side effects of immediate treatment. Its disadvantages are the need for frequent and repeated testing and biopsy, the anxiety of living with untreated prostate cancer, and the possibility that delayed treatment may not be curative, although that is not usually the case.

Andrew Siegel, M.D.

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Screening For Prostate Cancer Revisited

December 14, 2013

Blog # 132

The ignoramuses at the United States Preventive Services Task Force (USPSTF) gave Prostate Specific Antigen (PSA) testing a grade “D” recommendation and called for the complete abandonment of the test for prostate cancer screening.

Having lived and worked deep within the trenches of urology for over 25 years, I almost stroked when I read their recommendation. I previously crafted video responses: http://www.youtube.com/watch?v=d8fpxszVMTQ

and gave a “horse’s ass” award to the USPSTF in another video: http://www.youtube.com/watch?v=cIIZjk9lrlM

The Prostate Cancer World Congress took place in Melbourne Australia in August of 2013, where experts proposed a consensus view on the early detection of prostate cancer.  This material was published in the British Journal of Urology International.

The consensus was engendered by the great confusion generated after the USPSTF called for the total abandonment of PSA testing. The international experts who wrote the consensus statement included 14 international experts on prostate cancer, unlike the USPSTF, where there was not a single urologist on the committee.

The experts at the Prostate Cancer World Congress adopted the following five statements:   

  1. For men age 50–69, evidence demonstrates that PSA testing reduces death from prostate cancer by 21% and the incidence of metastatic prostate cancer by 30%.
  2. Prostate cancer diagnosis must be uncoupled from prostate cancer intervention.  In other words, not everyone with prostate cancer will need to be actively treated and the potential side effects of active treatment should not influence the diagnosis of prostate cancer by the proper means.
  3. PSA testing should not be considered on its own, but rather as part of a multivariable approach to early prostate cancer detection.  The experts proposed the use of prostate examination, family history, ethnic background, prostate volume, as well as a variety of risk models based upon PSA.
  4. Baseline PSA testing for men in their 40s is useful for predicting the future of prostate cancer. Men with baseline values that are high need further PSA testing.
  5. Older men in good health with over a 10-year life expectancy should not be denied PSA testing on the basis of their age.   This population of older men may certainly benefit from the early diagnosis of aggressive prostate cancers. This does not pertain to men with numerous other significant medical problems, but a healthy man in his mid-70s should not be denied PSA testing that might identify a cancer that has the potential to destroy his quantity and quality of life.  (In particular, the older man who comes to the office accompanied by his father should certainly not be denied!)

The consensus was that we should maintain the gains that have been made over the years since PSA was introduced—in terms of decreasing the number of men diagnosed with prostate cancer metastases (cancer that has spread) and reducing prostate cancer deaths—while minimizing the potential harms of over-diagnosis and overtreatment by increasing the use of active surveillance protocols in those men with low-risk prostate cancer.   Abandoning PSA testing as recommended by the USPSTF would lead to a reversal of all gains made over the course of the past 30 years.  Well-informed men should be offered the opportunity for early diagnosis of prostate cancer. To quote Dr. Jay Smith:  “Treatment or non-treatment decisions can be made once the cancer is found, but not knowing about it in the first place surely burns bridges.”

My take on the subject of screening for prostate cancer:

I like to keep things simple…I believe in two rules that are appropriate for medicine as well as just about everything in life.

Rule # 1: Do no harm.

Rule # 2: Do good.

To apply these rules to the game of golf, for example, “do no harm” means staying out of trouble as much as possible, keeping the ball out of the woods, bunkers and water hazards.  “Do good” by hitting the ball accurately in terms of distance and direction and setting up the next shot.

Screening for prostate cancer involves taking a medical history, doing a rectal exam to check the contour and consistency of the prostate, and a simple PSA blood test. “Do no harm” is satisfied because these tests are in no way harmful to the patient and provide information that is helpful, particularly when done on a serial basis, noting changes over time.

If exam shows an irregularity of the prostate, if the PSA is elevated, or if the PSA has accelerated significantly over the course of one year in a reasonably healthy man who has at least a ten-year life expectancy, doing a prostate ultrasound and biopsy is indicated. This test does entail a small risk of bleeding and infection, but the potential benefits far outweigh the risks.  “Doing good” is satisfied by the knowledge provided by the biopsy—the reassurance that comes from a biopsy report that shows no cancer and the potential for cure if the biopsy shows cancer.  Furthermore, the specific biopsy results along with other factors can predict which cancers are low-risk, which are medium-risk, and which are high-risk, important considerations in terms of active treatment versus active surveillance.

Many men who are found to have low-risk prostate cancer (low PSA; minimum number of biopsies showing cancer; low-grade cancer as determined by the pathologist) can be followed without active treatment (active surveillance) and those at greater risk can be managed appropriately (surgery or radiation), and many cured, avoiding the potential for progression of cancer and painful metastases and death—all while weighing the benefits of intervention against the risks.  Death from prostate cancer is unpleasant to say the least, often involving painful metastases to the spine and pelvis and not uncommonly, kidney and bladder obstruction, and our charge as urologists is to try to not let this scenario ever come to fruition.

One of our fundamental goals as urologists is to screen for prostate cancer—

the most common cancer in men present in 17% of the population—and if present, to provide appropriate guidance to best maintain both quality and quantity of life.  Anyone who reads the obituaries knows that prostate cancer is a cancer that is lethal, and if you don’t read the obituaries, I can promise you that prostate cancer kills in unkind ways. Even though only 3% of the male population dies from prostate cancer, that amounts to many thousands of men annually… and you do not want to be one of them.  I have my own PSA and prostate exam done every year and PSA screening was responsible for making an early diagnosis of my father’s prostate cancer in 1997, which was cured by surgery, resulting in a healthy and thriving, cancer-free 82 year-old man who will never die from prostate cancer.

BOTTOM LINE: PSA remains an invaluable screening tool for the detection of prostate cancer and ALL men ages 50 and over (40 if there is a family history) should be tested…IT JUST MAY SAVE YOUR LIFE!

Andrew Siegel, M.D.

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Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food: www.promiscuouseating.com

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Until Apple Invents The iFinger, PSA Is The Next Best Thing

October 8, 2011

‘”Don’t let the noise of others’ opinions drown out

your own inner voice.  Have the courage to

follow your heart and intuition.”

Steve Jobs

My blog last week was on prostate cancer vis-à-vis diet and lifestyle.  The lead article on the front page of yesterday’s New York Times reported on new United States Preventive Services Task Force (USPSTF) recommendations with respect to PSA testing (Prostate Specific Antigen).  The bottom line is that this organization is counseling against the use of PSA testing in healthy men.  They posit that the test does not save lives and leads to more tests and treatments that needlessly cause pain, incontinence and erectile dysfunction.

Two years ago, the same organization advised that women in their 40’s should no longer undergo routine mammography, setting off a blaze of controversy.  Their proposals were met with great resistance by many cancer organizations, women, and their physicians, many of whom continue to ignore them.

It should be well noted that the chairwoman of the USPSTF is a pediatrician!  It is obvious that prostate cancer is not a pediatric issue and should not be evaluated and managed by pediatricians.  I, along with other members of the American Urological Association, ardently disagree with the assertions of the task force that prostate cancer testing with the PSA test provides no clear benefits.  Urologists, radiation oncologists, and medical oncologists (those physicians in the know who are in the “trenches” and take care of prostate cancer on an everyday basis) understand how devastating prostate cancer can be, and the quintessential importance of early detection.

Confidently and unequivocally, I can state that when interpreted appropriately, the PSA test provides important information in the diagnosis, pre-treatment staging, risk assessment and monitoring of prostate cancer patients. Marginalizing this important test does a great disservice to those who may benefit from early prostate cancer detection; the recommendations of the task force will ultimately do more harm than good to the many men at risk for prostate cancer.

I have practiced urology for 23 years, in addition to 7 years of residency and fellowship training before entering practice.  I am old enough to have served as a physician in both the pre-PSA era and the post-PSA era.  In my early years of training at the University of Pennsylvania School of Medicine, it was not uncommon to treat men in the emergency room who could not urinate and on exam were found to have a rock-hard prostate and diffuse spread of prostate cancer to their bones…metastatic prostate cancer with a grim prognosis.  In the post-PSA era, that scenario—fortunately—occurs on an extremely infrequent basis thanks to PSA screening.  Essentially, annual screening with PSA and rectal exams has resulted in downward stage migration—picking up cases of prostate cancer in an early, curable stage before they spread and become incurable.  I have little doubt that PSA testing saved my own father’s life, who underwent prostate surgery for cancer 15 years ago and is now a healthy, thriving and active 80-year-old…in ALL respects!

Importantly, prostate cancer is a remarkably heterogeneous disease with every single case being unique—literally as different as snowflakes—thus, the management of prostate cancer must be individualized. The major challenge for those of us who treat prostate cancer is to distinguish between clinically significant and clinically insignificant disease and to decide the best means of eradicating clinically significant disease to maintain both quantity and quality of life.  Not all prostate cancers require active treatment and not all prostate cancers are life threatening. The decision to proceed to active treatment is one that men should discuss in detail with their urologists to determine whether active treatment is necessary, or whether surveillance may be an option for their prostate cancer.

What exactly is the PSA test?  It’s just a simple blood test that is sent out to a laboratory with results available in a few days.  Prostate-specific antigen (PSA) is a protein produced by the cells of the prostate gland. More specifically, it is an enzyme known as a protease that functions to liquefy semen following ejaculation. The PSA test measures the level of PSA in the blood and is the best tool currently available for detecting prostate cancer in its earliest— and most curable—stages. Although PSA is widely accepted as a tumor marker, it is prostate organ-specific but not cancer-specific. In other words, PSA can be elevated due to the presence of prostate cancer; however, not all elevated PSA tests mean that prostate cancer is present—benign prostate conditions can elevate it as well; the most common of these are prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH, an enlargement of the prostate gland).

Prostate cancer cells do not make more PSA, but rather less PSA than normal prostate cells. The elevated PSA that is detected in the blood associated with prostate cancer occurs because of a disruption of the cellular architecture of the prostate cells, the loss of this barrier of which permits the leakage of PSA into the circulation.

The PSA test is extremely helpful to monitor patients with a history of prostate cancer to check the status of the cancer. If the PSA level begins to rise, it may be the first sign of recurrence. Such a biochemical relapse typically precedes clinical relapse by months or years. Refinements in PSA testing include the following:

PSA velocity: It is very useful to compare the PSA values from year to year. Generally, the PSA will increase by only a small increment, reflecting benign prostate growth. If the PSA accelerates at a greater rate than anticipated—a condition known as accelerated PSA velocity—an ultrasound/biopsy is indicated.

PSA density: PSA density (level of PSA divided by the volume of the prostate) considers the relationship of the PSA level to the size of the prostate. In other words, an elevated PSA might not arouse suspicion if you have a very enlarged prostate.

Age-adjusted PSA: Age is an important factor with respect to PSA levels. It is now recognized that PSA will increase with the aging process in accordance with the increasing size of the prostate gland that occurs with growing older. For this reason, age-adjusted PSA levels can be useful to determine when further diagnostic tests are needed.

Free/Total PSA: Essentially, PSA circulates in the blood in two forms: a “free” form in which the PSA is unbound to any other structures, and a “complex” PSA in which the PSA is bound to a protein. The free PSA/total PSA ratio can offer a predictive value, in similar fashion to the way the HDL cholesterol/total cholesterol can be helpful in a man with an elevated cholesterol level.

In 2009, there were two studies published in the New England Journal of Medicine with respect to screening for prostate cancer. The results were summarized on the front pages of many newspapers, resulting in confusion for many patients. Dr. Andriole, in the United States, reported no mortality benefit from combined digital rectal exam and PSA screening after 7-10 years. Schroeder et al in Europe reported that PSA screening alone (without rectal exams) resulted in a 20% decrease in the death rate at a median follow up of 9 years. It is the consensus of many urologists that these studies were published prematurely, with ambiguous results.

The hard facts:

• 95% of male urologists and 80% of primary care physicians older than 50 have PSA screening—clearly those in the know feel that screening is beneficial.

• USA death rates from prostate cancer have fallen 4% annually since 1992, five years after introduction of PSA testing.

• Generally, urologists do not screen or treat men who have a life expectancy less than 10 years for the very reason that prostate cancer rarely causes mortality in the first decade after diagnosis and that other competing medical issues will cause death before the prostate cancer has a chance to.

• Prostate cancer is a slow-growing process and early detection and treatment is directed at extending life well beyond the decade following diagnosis!

• The aforementioned studies will not prove meaningful until carried out for 15, 20, 25 years and beyond—the time reference in which we expect treatment to make a meaningful difference.

Another controversial subject is at what age to stop screening for prostate cancer. According to the United States Preventative Services Task Force update, the “harms of screening outweigh the benefits in men 75 years old or older.” Studies have shown that at age 75 if you have a PSA less than 3, the chances of later developing high-risk prostate cancer are minimal. My opinion is that all 75-year-olds are not the same, functional age trumps chronological age, and that an individual’s preference regarding screening is of great importance.

I end with an important quote from Dr. Willet Whitmore, M.D., from way back in 1973, but still so relevant (Dr. Whitmore served as chief of urology at what is now Memorial Sloan-Kettering Cancer Center and died in 1995 of prostate cancer.)

Appropriate treatment implies that therapy be applied neither to those patients for whom it is unnecessary nor to those for whom it will prove ineffective. Furthermore, the therapy should be that which would most assuredly permit the individual a qualitatively and quantitatively normal life. It need not necessarily involve an effort at cancer cure. Human nature in physicians, be they surgeons, radiotherapists, or medical oncologists, is apt to attribute good results following treatment to such treatment and bad results to the cancer, ignoring what is sometimes the equally plausible possibility that the good results are as much a consequence of the natural history of the tumor as are the bad results.”

For more information:

www.BergenUrological.com

click on “patient education” and then on “Prostate Cancer: Second Opinion” to read my monograph.

To watch my video on PSA screening:

http://www.youtube.com/incontinencedoc#p/u/5/v3vHbh9gLnw

Andrew Siegel, M.D.

http://www.PromiscuousEating.com