New Approaches to Early Prostate Cancer

Men today diagnosed with early prostate cancer, Gleason Stage 7 or less, have the option of a new arm of care called watchful waiting. With periodic PSA blood tests, prostate biopsies and imaging studies; urologists and oncologists can follow the patient with disease felt to be not aggressive rather than radiate the lesion or surgically remove it as was done in the past. In some cases, they can watch it even closer with an approach called Active Surveillance. This week a new research treatment was made public.

MedPage Today published work by Steve Raman, M.D., of the UCLA Medical Center on his TULSA-PRO ablation clinical trial. One hundred-fifteen men with localized and low, or intermediate, risk prostate cancer underwent ultrasound blasting of the cancer using the MRI imaging equipment to direct the therapy. In his study, prostate volume decreased from 39 cubic centimeters before treatment down to 3.8 cubic centimeters after a year. Clinically significant cancer was eliminated in 80% of the study participants and 65% had no evidence of cancer after biopsy at one year. PSA blood levels decreased by 95%. The side effects were minimal with low rates of incontinence and impotence and few bowel complications.

The study leader noted that if prostate cancer reoccurred then the modalities of repeat ultrasound treatment, surgery or radiation were still possible. In August 2019, the FDA approved the TULSA-PRO Device for use. The procedure involves placing a rod-shaped device into the urethra. The device has ten ultrasound probes which are controlled by a computer program while the patient is observed in an MRI machine. The probes shoot out sound waves that heat and destroy the tissue the sound is directed at. The procedure is an outpatient procedure which can also be used to shrink a non-cancerous enlarged prostate from benign prostatic hypertrophy.

Prostate Cancer, Digital Rectal Exams, PSA and Screening

The PSA blood test, to detect prostate cancer, clearly has saved lives according to numerous studies. The United States Preventive Task Force (USPTF) recognizes this but has decided that screening for prostate cancer is not a great idea in men aged 55-69. They point out the PSA can be elevated from an enlarged prostate, an inflamed or infected prostate, a recent orgasm while having sex and other causes.

Elevated PSAs led to trans-rectal ultrasound views of the prostate and biopsies of the prostate. These biopsies were uncomfortable, even painful, and often followed by inflammation and infection of the prostate. Many times the prostate biopsy was benign with no cancer detected. The USPTF felt the cost, worry, and potential side effects were a risk far outweighing the benefits of screening. They consequently came out against screening men in this age group.  Naturally this position produced a tidal wave of criticism from urologists and other.

So, the USPTF has produced new recommendations calling for patient education and making a shared decision whether or not to obtain a PSA measurement before you send it out. This is a bit confusing because we always discuss the pros and cons of a PSA before we draw it. Adult men are entitled to hear the pros and cons so they can make their own informed decision.

To complicate matters, a study out of McMaster University in Canada reveals physicians are poorly trained in performing a digital rectal exam. They cite the lack of experience coming out of school and going into training and cite numerous research studies showing a rectal exam is a low yield way to detect prostate cancer. They do not recommend performing digital rectal exams for prostate cancer screening.

This received much media hype and the blur between the efficiency of detecting prostate cancer via a rectal exam and the use of the rectal exam to detect rectal and colon disease has been lost. We perform digital rectal exams to detect prostate cancer and look at the perirectal area for disease. We test the strength and performance of the anal sphincter muscle. We feel for rectal polyps and growths and, in certain situations, test the stool for the presence of blood.

During my internal medicine training my teachers always required a digital rectal exam, stool blood test and slide of the stool as part of the exam. As trainees, we realized the invasiveness of the exam and did our best to be polite, gentle and caring. I always asked for permission first, and still do. How can you tell if something is abnormal if you haven’t performed normal exams?

Last but not least, Finesteride, a medicine used to shrink an enlarged prostate by inhibiting male hormones, has finally been shown to be protective against developing prostate cancer. A study published in the journal of the National Cancer Institute found that men taking it for 16 years had a 21 % lower incidence of prostate cancer.

Omega 3 Fatty Acid Levels and the Risk of Prostate Cancer

A recent well publicized research study known as “The SELECT Trail” showed that Vitamin E supplementation increased the risk of Prostate Cancer compared with placebo (NEJM JW Gen Med Oct 25 2011)  Researchers have now used data from that study analyzed separately now claims that individuals with a higher level of omega 3 fatty acids are at a higher risk of developing high grade prostate cancer. The results were published in the Am J Epidemiol 2011; 173:1429.

This was a case – control study in which researchers looked at the plasma omega 3 fatty acid levels in stored blood collected at the beginning of the SELECT trial. They compared the levels in 834 men with prostate cancer and 1393 controls without the disease.  The design of the study does not allow one to conclude that if you ingest omega 3 fatty acid supplements you will develop prostate cancer. The study just noted that individuals with prostate cancer as compared to men without had higher plasma levels of omega 3 fatty acids in their blood.

This particular study raised a great deal of media attention and concern especially with the American College of Cardiology advocating supplementation with fish oils for cardiac protection in recent years. This recommendation came despite two recent studies that indicated just the opposite ( NEJM JW Gen Med May 8 2013, and JAMA 2012; 308: 1024).   It is clear from this controversy that the exact role of omega 3 fatty acids, fish oils, omega 6 fatty acids and vegetable oils is still up for debate. I will advise my patients to eat fish in moderation consuming 1-2 fish meals per week if they enjoy fish.  Eating in moderation and allowing our bodies to use the nutrients they need seems to be the wisest course until more is known.

Prostate Cancer Risk Can Be Predicted With a Single PSA Test

The highly acclaimed Institute of Medicine and now the U.S. Preventive Task Force have recommended against routine screening of asymptomatic men for prostate cancer. Now, a study presented by Christopher Weight, MD from the Mayo Clinic Department of Urology adds more information and confusion to the fire. Dr. Weight presented his data at a recent meeting of the American Urologic Association.

The Mayo Clinic followed men younger than 50 years old for 16.8 years.  They concluded that men at age 40 with a PSA value of less than 1ng/ml had a less than 1% chance of having prostate cancer at age 55. They had less than a 3% chance of having prostate cancer at age 60.  They concluded that men with a baseline PSA < 1% in their 40s appear to be able to safely avoid annual screening until age 55.  “Men with a baseline PSA greater than or equal to 1 have a substantial risk of subsequent biopsy and cancer diagnosis and should be followed annually.”

This is one of the first research studies to quantify the actual relationship of screening young asymptomatic individuals and the subsequent risk of developing the disease.  It is the type of research needed to help guide us to make safe and sane recommendations about the type of screening for prostate cancer and frequency of screening using blood tests, ultrasound and of course digital rectal examination to palpate the prostate. All the patients in the Mayo study received a PSA assessment, digital rectal exam and transurethral ultrasound of the prostate at study entry and biennially thereafter.

This study affirms the recommendation for performing a screening digital rectal exam on all men at age forty and subsequently. It begins to answer the question of who needs follow-up PSA testing and when.  However, more research is clearly needed.

Prostate Cancer: Progress in Detection and Treatment

Until recently, prostate cancer was considered by many to be a disease of “old men” only.  As a result, science for the detection and treatment of prostate cancer was lagging decades behind that of breast cancer.  In fact, it was commonly believed that if doctors performed a biopsy on the prostate of all men eighty years old or older, at the time of their death from non-prostate related issues, we could expect to find evidence of undetected prostate cancer in close to 100% of those patients.

The discovery and use of the PSA (Prostate Specific Antigen) led to detection of prostate cancer in younger men. The PSA test was fairly inexact and could become elevated as a result of any of several non-cancerous conditions. It led to numerous biopsies in men who had no clinical findings consistent with prostate cancer but who turned out to have the disease. These young men were treated aggressively, and at times the treatment was as bad if not worse than the disease. The problem was that when we found a prostate cancer we had no idea if it was destined to be aggressive or whether it was going to lie quietly and be indolent for decades.

Different treatment strategies emerged in Europe and the United States.  In Europe the PCA3 test was employed to detect genetic markers of men with elevated PSA’s and normal prostate gland examination who should be biopsied. This test is now gaining acceptance in the USA.

In a February 2011 article published in Nature magazine, researchers announced that they had found a genetic test for prostate cancer  samples that predicted whether the disease would be aggressive (and spread) or not. This new test, coupled with the existing Gleason scoring system, accurately predicted who needed to be treated aggressively and who could be watched instead. A commercial version of this genetic test should be available within two years.  At the same time, another article showed that in patients with minimal prostate cancerous disease, it is safe to observe them rather than aggressively operate on them immediately.

Health experts recommend all men 40 and over have a digital rectal exam on an annual basis. The decision to obtain a PSA is based on history, family history of prostate disease and clinical exam of the prostate. There are no current recommendations by the US Public Health Task Force on Preventive care for screening for prostate cancer with a PSA level. Despite this, I generally obtain a PSA annually on men over 50 after explaining to them the pros and cons of following the current guidelines.

If the new genetic test to predict prostate cancer aggressiveness turns out to be as accurate as suspected, we are finally on the road to being able to treat those who need aggressive treatment and spare others who don’t.