Articles on Urological Issues

PSA—Screening Guidelines and Background

The United States Preventive Services Task Force (USPSTF) changed their PSA screening guidelines from “PSA screening is of no value” (2012) to “PSA screening is of value” (May 8, 2018). This review of PSA screening guidelines is intended to provide insight and clarification.

These guidelines are from the USPSTF and the American Urology Association.

CURRENT PSA SCREENING GUIDELINES

  1. 2018 Men aged 55 to 69 at average risk of developing prostate cancer
  2. Men over age 70 who are expected to live 10 years and have an increased risk of developing prostate cancer
  3. Men aged 45 who have an increased risk of developing prostate cancer: African Americans and those men with one first degree relative with prostate cancer OR who have first degree relatives who have died of cancer of the breast, ovary or pancreas
  4. Men aged 40 with 2 or more first degree relatives with prostate cancer—the highest risk group

RISK FACTORS FOR DEVELOPING PROSTATE CANCER

  1. African Americans: twice the risk of developing prostate cancer.
  2. Men with one first degree relative (father or brother) with prostate cancer: twice the risk of developing prostate cancer. The risk increases with 1 or more family members who died of prostate cancer.
  3. Men who have a first degree relative who died from cancer of the breast, ovary, or pancreas: increased risk of developing prostate cancer.
  4. Men with multiple first degree relatives with prostate cancer—these men are in the highest risk group.

NOTES

  1. The most reliable indicator of prostate cancer is PSA Velocity. The PSA should increase by ~ 0.1 per year. An increase of 0.5 per year is a “Risk Count”. Each time this occurs the risk of developing prostate cancer increases 50%.
  2. Screening intervals can be every two years, especially if the PSA is less than 1.0. “Interval cancers” (cancers detected between screening events) are rare.

BACKGROUND

The first article to prove that PSA was of value in detecting early prostate cancer was published in 1991. This article and FDA approval resulted in PSA screening being widely used in the detection of prostate cancers that would not otherwise be found and detection of prostate cancer at earlier stages.

The effect:

  1. A decrease in the mortality rate from prostate cancer
  2. Detection of prostate cancers at a much earlier stage—when curable
  3. Detection of some prostate cancers that did not need to be treated due to low volume and low grade

DEVELOPMENTS IN PSA SCREENING RECOMMENDATIONS

In 2012 the USPSTF stated that PSA screening was of no value in the early detection of prostate cancer and was associated with significant harms. They recommended all PSA screening be abandoned.

In 2013 an American Urology Association distinguished panel stated:

  • PSA screening is most beneficial in men age 55 to 70 All men for whom
  • PSA screening is recommended should be counseled about the benefits and the potential risks

In the years between 2012 and 2018 the 20-year decline in prostate cancer mortality plateaued. In addition, there has been a significant increase in men presenting with high volume and metastatic prostate cancer who cannot be cured.

In May 2018 the USPSTF reversed their 2012 recommendation and stated that “PSA screening is of value in the age group 55 to 69”

PSA SCREENING—SHARED DECISION MAKING

Men who are appropriate candidates for PSA screening are informed that PSA screening has potential benefits: an increased cure rate due to earlier detection.

  • An elevated PSA can lead to the recommendation to obtain a prostate biopsy. A prostate biopsy takes about ~ 30 minutes to perform and intravenous sedation is commonly used so that there is no discomfort.

Prostate biopsies have risks that are relatively minor:

  • Infection—The risk of infection has been reduced. The nation-wide risk of infection is approximately 4%. With the use of two antibiotics Roper urologists have decreased this risk to approximately 2%. Currently a study is being done that has shown that the risk of infection can be reduced to 0.03%, a reduction from 2 in 100 biopsies to 1 in 300 biopsies.
  • Bleeding in the urine or in the stool is a risk that is minor and generally resolves in 1-2 days

CAUSES OF AN ELEVATED PSA

PSA can be elevated for several reasons:

  • Prostate cancer
  • Inflammation of the prostate (prostatitis)
  • Prostate size: the PSA level depends on the size of the prostate. Men with larger prostates have PSA levels that are higher than men with smaller prostates

WHAT IS THE RISK OF DEVELOPING PROSTATE CANCER

Prostate cancer is the most common cancer in men (after skin cancer) and the second most common cause of cancer death in US men.

In 2018 approximately 170,000 men will be diagnosed with prostate cancer and approximately 30,000 men will die from prostate cancer. The average risk is 17% in US men or 1 in 6.

These are guidelines. PSA screening remains inexpensive and can be useful in evaluation prostate problems. With the patient’s agreement and after a review of the potential benefits and minor risks, physicians will hopefully be more comfortable be more comfortable discussing PSA screening with their patients.

Prostate Cancer Treatment: A Rebuttal of the Associated Press Article of September 15, 2016

On Thursday, September 15, the Post and Courier published an article from the Associated Press (AP) on a study of prostate cancer treatment options. “10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer” was published in the New England Journal of Medicine (NEJM).

The NEJM article reported on a study of 1,643 men who participated in a clinical trial. The study included three groups of approximately 500 men, each assigned either to monitoring (no treatment), surgery to remove the prostate, or radiation therapy to the prostate. The conclusion was that at 10 years prostate cancer mortality was equal regardless of the treatment, with no significant difference among the three treatment options.

The AP article did note that “More men being monitored and not treated saw their cancers worsen”.

A quote from the lead author was “There’s been no evidence that treating the disease early on makes a difference”.

The final quote in the AP article was from another of the authors, Dr. Malcolm Mason who noted, “We need something to allow us to identify men with aggressive disease earlier”.

What was not mentioned in the AP article but was noted in the NEJM article was that in the non-treated group 3 times as many men developed spread of their prostate cancer to the bones as compared to men treated with surgery and men treated with radiation therapy.

Also not mentioned by the AP was in the men monitored 25% required treatment (surgery or radiation) due to prostate cancer progression within 3 years of beginning monitoring and a total of 54.8% required treatment prior to the 10-year end of study date.

Lowcountry Urology Clinics contacted Dr. Malcolm Mason regarding what we perceived were significant deficiencies in the study.

Our points:

  1. The study was only a 10-year study. This may seem like a long time but with prostate cancer it is not. SEER (Surveillance, Epidemiology and End Results) data from the US indicate that most men with prostate cancer not treated will live 10 years. What is not mentioned in the AP article or the NEJM article is the quality of life in the final 3-4 years of life with prostate cancer that has progressed: spread of the cancer to bones, inability to urinate, bleeding from the prostate and obstruction of the kidneys.
  2. The study showed a 3 times higher incidence of spread of prostate cancer to the bones in the monitored group compared to the two groups who were treated.
  3. In the group of men monitored, over 50% had experienced progression of disease and required treatment prior to the end of the study.

Dr. Mason’s Response: (shortened for space consideration)

  1. “These are 10-year results in a population in which we really need 15 and 20-year followup. This has to be one of the caveats around the results at this stage – including the relatively low mortality rate of prostate cancer”.
  2. “We have certainly gained tremendously in understanding as you say…we need to discuss the data on disease progression and metastasis rates with our patients”.
  3. “I guess that for men with high risk, localized disease the discussion is somewhat different…yes, the threshold for treatment is lower”.

The Bottom Line:

  1. A 10-year study of treatment options for prostate cancer is not sufficient. At least 15 years and preferably 20 years of follow up is needed in order to make valid conclusions.
  2. In all patients with prostate cancer the grade and extent of the cancer as well as the patient’s age and associated medical conditions need to be considered before the patient and the urologist reach a decision regarding the best treatment.
  3. Many men with untreated prostate cancer will live 10 years. However, this does not consider the significantly impaired quality of life during the last 3-4 years of life in those patients with prostate cancer progression.
  4. Every patient and every prostate cancer is different. There is no “one size fits all” option for treating this complex disease.

The Take-away:

Consult your Lowcountry Urology Clinics Urologist prior to making a decision about the treatment of YOUR prostate cancer.

The History Of Prostate Cancer Diagnosis

Prostate cancer is the most common cancer in the United States for men, and the second most common cause of cancer death in men. In 2016 over 230,000 men will be diagnosed with prostate cancer and over 35,000 men will die of prostate cancer. 

Over the past 25 years the diagnosis of prostate cancer has progressed through 3 stages. The first method of diagnosing prostate cancer dates to the beginning of the last century. Diagnosis of prostate cancer required detection of an abnormal area in the prostate noted by prostate examination and the finding of a hard area within the prostate. 

The second method of diagnosing prostate cancer began in the early 1990s with the discovery of PSA (Prostate Specific Antigen), an indication or marker for the possible existence of prostate cancer. Urologists began evaluating the prostate for the existence of prostate cancer with prostate ultrasound-guided biopsy. In this procedure, urologists use an ultrasound scanner to view the prostate on a monitor in real time. With ultrasound guidance, a needle is guided into the prostate to remove a “core” or small sliver of prostate tissue that can be examined. We use a map or “template” to sample key areas in the prostate where prostate cancers are usually found. In most cases, 10 to 12 cores of tissue are removed and sent to a pathology lab to be analyzed for the presence or absence of cancer. This technique was a major advancement in the early detection of prostate cancer. Currently over one million prostate biopsies are performed annually in the United States using ultrasound guidance. It is a common procedure and our group performs over 500 prostate biopsies per year. 

Although ultrasound-guided prostate biopsy was a major advance in our detection of prostate cancer, ultrasound imaging has limitations. A standard first-time biopsy will miss up to 35% of prostate cancers. 

Urologists have known for many years that prostate cancers can be visualized utilizing MRI (Magnetic Resonance Imaging). With research and evaluation, MRI reliability has significantly improved. The current technology allows sharp and detailed images of the prostate. The combination of imaging techniques is known as Multi-Parametric MRI. This is best performed utilizing powerful MRI imaging. Most MRIs are 1.5T. “T” means Tesla or the strength of the magnet. A 3T magnet increases the ability to visualize the abnormalities that need to be identified in order to find a prostate cancer. 

We needed a 3T magnet due to the imaging advantage over the 1.5T magnets in Charleston. The only group with a 3T MRI in the area that agreed to help us bring this technology to South Carolina was Imaging Specialists. They provided significant intellectual support and also made the financial commitment to purchase the software that will enable this procedure to be performed in Charleston. As a result, Lowcountry Urology now offers Prostate Cancer Diagnosis using MRI Fusion Targeted Biopsy using the UroNav ssytem by Invivo.

OMEGA 3 FISH OIL AND PROSTATE CANCER

Fact or Fiction

The popular press has distributed several articles stating that Omega 3 fish oil consumption was related to an increase in the incidence of prostate cancer and that the prostate cancers were more aggressive. The two articles most frequently referenced are the May 9, 2013 issue of The New England Journal and the July 12, 2013 Journal of the National Cancer Institute. A critical review and analysis of these two articles follows.

THE NEW ENGLAND JOURNAL OF MEDICINE ARTICLE

This study enrolled 12,513 patients with 6,244 patients randomly assigned to n-3 fatty acids and 6,269 to placebo. The initial plan for endpoint of the study was the “rate of death, nonfatal heart attack and nonfatal stroke”. At one year the primary end point was revised to “time of death from cardiovascular causes or admission to the hospital for cardiovascular causes”.

At a follow up of 5 years the primary endpoint occurred in 1,478 patients of whom 733 (11.7%) had received n-3 fatty acids and 745 (11.9%) had received placebo (no statistical difference).

The conclusion was that “In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity”

There were 490 cases of cancer (the type of cancer was not specified) among patients who received n-3 fatty acids (7.9% of patients) versus 453 cases of cancer in the placebo arm (7.2%). The difference was not statistically significant.

STUDY DESIGN PROBLEMS

  • The placebo was olive oil. But olive oil may have a positive effect on mortality and morbidity (cardiovascular events).
  • The type of cancer was not specified and the difference in the two groups was not significant.

SUMMARY

Without a true placebo the conclusions of the authors are questioned.

The incidence of increased cancer risk in this group has a value that is not statistically significant, regardless of the site of the primary cancer.

The use of olive oil in the placebo arm has the potential of favorably affecting the incidence of cardiovascular events. The benefits of the Mediterranean diet are well known. Thus, the claims from the popular press are significantly flawed.

RECOMMENDATION

Do not be concerned about this studies’ recommendation about the lack of efficacy of Omega 3 fish oil. The American Heart Association and American College of Cardiology recommendations about the benefits of Omega 3 fish oil are on record. Talk to your internist or cardiologist if you have any questions.

Do not be concerned about Omega 3 and cancer risk. This article has no valid data to support discontinuation of Omega 3 due to an alleged increased risk of cancer.

 

 

THE JOURNAL OF THE NATIONAL CANCER INSTITUTE ARTICLE

This study was part of the SELECT trial (Selenium & Vitamin E Cancer Prevention Trial). An observation that vitamin E and selenium may decrease the incidence of prostate cancer led to this trial. In this study 35,534 patients were enrolled and randomized to take vitamin E or selenium alone, a combination of vitamin E and selenium, or a placebo. The initial data from this trial reported in 2008 showed that Vitamin E and selenium taken alone or together did not prevent or decrease the risk of developing prostate cancer. The 2011 update showed that there was a 17% increase in prostate cancer in those patients taking Vitamin E compared to placebo. The study is closed but follow up continues.

After publication of initial and updated results, another study looked at this population with regard to the incidence of prostate cancer and omega 3. Their conclusion was that there was an increased incidence of prostate cancer in those patients who had the highest level of omega 3 in their blood samples.

STUDY DESIGN PROBLEMS

First, this was a “post hoc” study which means that after the study to evaluate the effect of vitamin E on the incidence of prostate cancer was completed, the patient group was evaluated for another potential relationship or conclusion—the study was NOT designed to look at this post hoc potential effect. In this case the group was studied for a potential relationship between omega 3 levels (NOT OMEGA 3 INTAKE) and prostate cancer.

The study which evaluated omega 3 levels found that there was a significantly higher incidence of prostate cancer in the group of men with the highest levels of omega 3 in their blood samples. Note again that this second study looked at the original population which was not chosen or evaluated for dietary or supplement intake.

SUMMARY

“This was a large, well designed study...However, it cannot show that fish oil supplements cause prostate cancer and it is possible that other factors affected men’s risk (although the researchers tried to take these into account)”.

- Quote from an article in the Journal of the American Medical Association

“The research did not look at the participants’ diets or whether they took omega 3 supplements. They based their conclusions on omega 3 blood levels”.

- Quote from an article in the Journal of the American Medical Association

“Don’t stop taking omega-3 fatty acid fish oils for fear of increasing the risk of prostate cancer. The JNCI article was flawed, and other research suggests that omega-3 fatty acid fish oils may actually play a protective role in prostate cancer prevention”.

- Quote from a Time Magazine synopsis quoting the Journal of the National Cancer Institute:

THE BOTTOM LINE

  • There is no reliable study to date that proves that omega 3 supplements will increase the incidence or aggressiveness of prostate cancer.
  • There is a lot of research and information indicating that inflammation is a cause of cancer and cardio-vascular events. The non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to decrease the incidence of colon, breast and prostate cancer. Since omega-3 fatty acids do have an anti-inflammatory effect there is the possibility that omega-3 fatty acids could actually decrease the incidence of cancer. But at this point there are no studies suggesting taking NSAIDs to decrease the probability of developing prostate cancer.
  • The studies on the effectiveness of omega 3 supplements in preventing cardio-vascular events vary from research indicating that this supplement is effective to research that indicates no effect in preventing cardio-vascular events such as heart attacks and strokes.
  • You should consult your internist or cardiologist about their understanding of the research and take their advice.