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Understanding Prostate Cancer Types

Perhaps the most important thing that I have learned in researching this topic:  We need to think that there are TWO types of prostate cancer

  • The type that never causes harm (the vast majority)

  • The kind that is aggressive and can cause metastases and death

This distinction is important because, simply put, we don’t have to treat the first kind.  We don’t even have to look for it.  The problem; it’s hard to tell which is which. 

The Role of PSA Screening

PSA vs. Rectal Exam and Ultrasound

Advantages of PSA Screening

Prevalence of Asymptomatic Prostate Cancer

The Impact of Race

Screening Recommendations

The Benefits of Screening

The Harms of Screening

Treatment Options

Final Thoughts

The research that truly launched Prostate Specific Antigen (PSA) as a screening tool came in a landmark study from 1991.  (though it was approved by the FDA in 1986)

 

1,653 healthy men 50 years of age or greater.   Each of them had their PSA's checked.


They wanted to compare how well this helped detect cancer versus doing Ultrasounds OR Digital Rectal Exams (in simple terms that we all know--the finger up the butt)

Group A:  Those with PSA's between 4.0 and 9.9,  a total of 107 men or 6.5%
Group B:  Those with PSA's greater than 10.0,  a total of 30 men or 1.8%
Group C:  Just to note, 92% of men had PSA's that were 'normal' or  < 4.0

Once over the threshold of 4.0, these men were then given ultrasound guided prostate biopsies.

Group A men 19 out of 85 (22%) had prostate cancer found with these biopsies
Group B men 18 out of 27 (67%) had prostate cancer found with these biopsies.  
  (A total of 37 men;  19 + 18 were found to have prostate cancer out of the 1,653 that were screened.  Approx. 2%)

Compared to RECTAL EXAM ALONE
Group A and B before biopsy results all had digital rectal exams.  The examiner was able to identify 25 out of the 37 cancers (32% of the cancers 12/37 were missed) Meaning, PSA caught 32% more cancers.  

Compared to ULTRASOUND
Group A and B before biopsy results all had ultrasounds.  Ultrasound detected 21 out of the 37 cancers (43% of the cancers 16/37 were missed)  Meaning, PSA caught 43% more cancers than ultrasound alone.

Aside from the improved detection numbers with PSA compared to Ultrasound and Digital Rectal Exam, it offers two other important factors:

  • It is objective, quantitative and obtainable independently of the examiner's skill.

  • It is more acceptable to patients

Caveat--In this paper, they made the following statement which I think is very fascinating.  "There is concern about whether screening tests will detect the so-called latent prostatic cancers that exist in approximately 30 percent of men over the age of 50.  Most of these tumors cause neither morbidity nor mortality."

 


We are SCREENING men for Prostate Cancer with the PSA test and Rectal exam.

 

But...are we FINDING it?


The simple answer seems to be NO.  


A fascinating study was done in 2015 which pooled multiple studies to see how many men had prostate cancer and never knew.  They took 19 different studies, a total of 6,024 men who died of something other than prostate cancer.  Say you got hit by a bus, they would check your prostate and see if you had cancer.  What they found was shocking.  Asymptomatic prostate cancer is very prevalent.   Please see table below which illustrates this point.

 

AND Race really does matter

These numbers were remarkable to me when I read them.  It's hard to believe there is that much prostate cancer out there that is not diagnosed and...didn't affect these men at all. Recall, these are men that died from some other cause and randomly had their prostates checked.


Age             Asian        Caucasian        African American
20-29        1.8%         3.7%                    6.7%
30-39        0.9%         15.5%                 30.4%
40-49        2.8%         23.2%                 35.4%
50-59        7.9%         22.1%                 45.9%
60-69        14.5%      29.0%                 46.9%
70-79        21.3%      47.4%                 50.5%

The high prevalence of asymptomatic and unsuspected prostate cancer, as demonstrated by these autopsy and biopsy studies, underlies the potential for widespread diagnosis of cases of prostate cancer that would have caused no clinical harm had they remained undetected.


Which means that most men who are treated experience no direct clinical benefit. It has been estimated that 42-66% of diagnosed prostate cancer would have caused no clinical harm had they remained undetected.

The primary concept this article brings up is that there may be two types of cancers. The vast majority that really don't cause any harm at all and the rare lethal variant. The problem is how to tell them apart.


There are some risk factors for more likely to be lethal such as smoking and being taller (no reason given for this one).  Interestingly, drinking coffee lowers risk.  But, the bottom line, there is no easy way to tell at this time.

  • United States Preventative Services Task Force (USPSTF)—They give a Grade C recommendation to screening men between ages 55 to 69. Grade C means “Clinicians should not screen men who do not express a preference for screening.” Ages >70 they give a grade D.  They recommend against PSA-based screening.

  • American Academy of Family Practice:  Recommends against screening altogether.  

  • Canadian Task force:  Recommends against screening altogether.

  • American Urological Association:  Recommends screening between ages 55 and 69 with PSA every 2 years if patient has a life expectancy > 10-15 years.

  • American College of Physicians:  Similar to the AUA except between ages 50 and 69. 

  • American Cancer Society:  Shared decision making > 50; earlier if family history is strong or African American.

The Digital Rectal Exam (DRE) is not recommended for screening.  Lack of evidence.  
 

 

I’ll start with the problem. The more deadly the disease, the greater benefit to screening.  For prostate cancer the survival rates are very high—whether you treat or don’t treat.


After 5 years, 99% are alive
After 10 years, 98% are alive
After 15 years, 93% are alive

 

In a study from 2016,1,500 men were randomized to treatment versus surveillance.  The 10-year survival in both groups was 99%.   Which means, if you screen or don’t screen.  Treat or don’t treat, 99% are alive after ten years.

 

This is why the numbers from a 7 country European trial (ERSPC) below seem so abysmal

If you screen 1,000 men between ages 55 and 69 you prevent 1 death

If you screen 1,000 men between ages 55 and 69 you prevent 3 cases of metastatic disease
If you screen 1,000 men > 70 there is NO benefit
 

Aside from the false positives, for which there are many.  According to a study out of the European Journal of Cancer in 2011, “Over a 10 year period, 15% had one false positive.”  (This means a PSA value that is concerning but ultrasound and biopsies that do not show cancer), there is still the problem that most cancers would have caused no morbidity.

 

The harms of testing are felt to be the following:

  • Anxiety from being told you might have cancer

  • An unpleasant ultrasound (a rectal probe)

  • A very unpleasant transrectal biopsy which can lead to blood in the semen, pain, infection.  In fact, 4% of biopsies result in hospitalization.

  • Overtreatment with surgery, anti-androgen therapy or radiation therapy (it’s felt to be overtreatment if you would have died from something else)

 

 

For those with cancer localized to the prostate (it hasn’t metastasized) there are basically three choices:

  • Surgery (radical prostatectomy).  Just remove the gland

  • Radiation (external beam, proton beam, brachytherapy)

  • Surveillance

Adverse Outcomes with surgery

 

3/1,000 deaths from surgery
50/1,000 serious surgical complications
200/ 1,000 urinary incontinence requiring pads
667/1,000 erectile dysfunction

 

Adverse outcomes with radiation


165/1,000 with bowel symptoms
>500/1,000 with erectile dysfunction

 

Recall in looking at these numbers that the number of lives saved is 1/ 1,000 over 13 years of follow up.  
 


I’ll end with a question of politics.   In 2012, the United States Preventative Services Task Force (USPSTF) recommend NO SCREENING in all men based upon the evidence…If you screened 1,000 men with PSA, you saved only 1.07 lives after 10 years of follow up.

In 2017, they changed to current recommendation to screen men between ages 55 and 69 because…they extended the study 3 more years.  At that point, they found that you saved 1.28 lives after 13 years of follow up.  


A frustration I have is the lack of evidence for men at the highest risk.  Refer back to table up above with African Americans being at significantly greater risk.   Should there not be different recommendations based upon race?  A problem is that in the American study there were only 4% African Americans and in the European trial it was well under 1%.

If it were up to me, I would do the following:

  • Screen African American men between ages 50 and 69

  • Screen men with one or more close family members with prostate cancer before age 70

  • I would NOT screen Asian men period

  • For Caucasian men without a family history, I would tend to not screen unless specifically asked.

Reference Cited

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