Elevated PSA From Screening: What to Do?

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The PSA assay, along with cholesterol and other tests, is a common component of the blood testing that occurs during a man’s annual physical examination. But what should you do if the PSA is outside the normal range on your lab report? If you examine a copy of the written lab report, detailing your tests, you may have encountered some explanatory notes (see below) that are often provided in the report:

“This PSA assay should not be interpreted as absolute evidence for the presence or absence of malignant disease nor should it be used alone as a cancer screening test. Clinical correlation is required.

Elevated PSA concentration can only suggest the presence of prostate cancer until biopsy is performed. PSA concentration can also be elevated in benign prostatic hyperplasia or inflammatory conditions of the prostate. PSA is generally not elevated in healthy men or men with non-prostatic carcinoma.”

Verbiage of this sort suggests that the next step will be a biopsy. In fact, it implies that a biopsy is almost a forgone conclusion. Needle biopsy of the prostate to evaluate men with high PSA has been the gold standard approach for 30 years. Until recently, taking multiple prostate samples for microscopic examination was the only way to detect prostate cancer.

Random Needle Biopsy Procedure

The 12-core random needle biopsy procedure has been fine-tuned into an efficient procedure, and may be performed by a urologist in his office.

 The man is positioned on his side with his legs drawn up toward his chest. Novocain is injected around the prostate and then twelve, large-bore needle cores are extracted with a spring-loaded biopsy gun through the rectum. Antibiotics are routinely administered to prevent infection.

If skillfully performed, the biopsy process takes 10 to 20 minutes.

After the procedure, men usually experience bleeding in the urine and semen for a couple of weeks. Temporary problems with erections can occur. Despite antibiotics, a small number of men (about 2 percent) will develop infections serious enough for hospitalization. The cores removed from the prostate are transported to be analyzed by a specialized doctor called a pathologist. Results are usually available within two to three days.

Interpreting the Pathology Report

The doctor reviewing the biopsy specimen, the pathologist, reports the presence or absence of cancer from the cores removed from the gland. When cancer is present, the pathologist also reports the amount of cancer (number of cores containing cancer) and the cancer’s grade. The cancer’s grade, is one of the most confusing aspects of prostate cancer.

Back in the 1960s, a famous pathologist, Dr. Donald Gleason, reported that the future behavior of prostate cancer could be predicted by cellular patterns seen under the microscope. He developed a grading system ranging from 2 to 10 that foretold how likely it would be for the cancer to spread (metastasize).

Parts of his Gleason scoring system remain in use to this day. Other aspects of the system have evolved over time.

The biggest change has been the discovery that Gleason scores of 6 or less are not malignant. While these “abnormal cells” have some of the appearances of a cancer, scientific studies have now determined that Gleason 6 or less does not metastasize. Abnormal cells that don’t metastasize should classified as benign tumorsnot cancer.

A Medical Industry in Transition

Unfortunately, change occurs slowly in the medical world. When you or a loved one gets a copy of the official pathology report and see the word adenocarcinoma, you will probably find this to be highly alarming. About one-million men undergo biopsy every year. Of these one million men, slightly more than 100,000 of them will be diagnosed with Gleason 6 (or lower) adenocarcinoma.

The prostate cancer industry is finally starting to adjust to the realization that grade 6 cancers are not really cancer. However, in 2015, only about half of the men diagnosed with Grade 6 (50,000 men) were placed on active surveillance monitoring rather than having immediate surgery or radiation. The fact that 50% of the men still underwent radical treatment, risking sexual impotence and loss of urinary control (incontinence) for an essentially harmless condition, strongly suggests that the medical industry needs to improve. How can such aggressive treatment be justified in light of what we now know about grade 6 or less prostate cancer?

Cancer Is a Four-Letter Word

Doctors are starting to alter their mindsets, but it takes time to change. Part of the problem is that cancer is a four letter word. Labels are powerful, even when they are untrue. For example, the word racist provides a good analogy. The word “racist,” whether or not the term is justified, sticks like glue. The more people defend themselves, the guiltier they appear.

Another powerful reality retarding change is that a huge, multi-billion-dollar prostate cancer industry has been built up over the last 40 years. It is difficult for urologists to change their ways and refrain from doing surgery. Spending time in the operating room is part of their ingrained identity. And realistically, until 10 years ago, there were no other options. Aggressive treatment could be easily justified in an era when everyone believed that that all prostate cancer was life threatening. Radical therapy was universal requirement.

The Uncertainties of Monitoring

Another reason that men with low-grade cancer still undergo unnecessary treatment with surgery is that patients and doctors alike still feel that it is the prudent approach. Studies show that the 12-core biopsy fails to detect higher grade cancer (grade 7 through 10) 25 percent of the time! Remember, the cores are inserted into the prostate randomly, without any knowledge of the tumor’s location. Considering this inaccuracy, there is a reasonable fear that higher-grade cancer may be lurking undetected in the prostate. Sometimes men choose to undergo treatment “Just to be safe.”

Those who do choose active surveillance probably have their prostate biopsied every couple of years. They may not be aware, that their doctors try to compensate for the inaccuracy of the random biopsy by repeating it over and over. While this is uncomfortable and slightly risky, long-term studies show that this approach is reasonably safe. Most of the men whose higher grade disease was missed on the initial biopsy have it detected by a subsequent biopsy when the cancer is at an early enough stage for it still to be cured.

Imaging, Targeted Rather Than Random Biopsy

In my practice, rather than making patients go through such an unreliable random biopsy procedure, we refer them to a center-of-excellence for prostate scanning with multi-parametric MRI. In experienced hands using state-of-the-art equipment, high-grade cancer can be ruled out with far greater accuracy than what can be achieved with a 12-core random biopsy. In addition, prostate MRI is relatively blind to the presence of Grade 6 or less cancer. Since lower grade disease is “missed” by prostate MRI, many men are spared the shock of an unnecessary cancer diagnosis.

There are relatively few imaging centers around the country, perhaps 50 to 100, that perform prostate imaging with acceptable accuracy. The essential components for reliable results are: 

  1. State-of-the-art, 3-Tesla Multi-Parametric MRI (mpMRI) scanners.
  2. MRI technicians who are well-trained in how to perform prostate imaging properly
  3. Physicians carefully trained in the interpretation of prostate imaging.  The advances in prostate imaging are occurring so quickly that even some board-certified radiologists remain unaware of what the latest technology can achieve.

Men whose 3T mpMRI imaging shows no suspicious lesions can consider forgoing biopsy altogether and perhaps undergo follow up with additional imaging if their PSA remains elevated. When a suspicious lesion is detected, a targeted biopsy using at most 3 or 4 cores can be directed specifically at the abnormality.

Interpreting the Prostate MRI Report

The doctor who reads the scan summarizes his overall impression of the findings, which fall into three basic categories:

  1. No evidence for high-grade disease (therefore, no need for a biopsy).
  2. A suspicious lesion is detected. (A targeted biopsy is necessary. If high-grade disease is diagnosed, further staging followed by counseling about treatment is needed).
  3. An ambiguous area is detected. (Either a targeted biopsy can be considered or alternative, ongoing monitoring with another scan ins 6 to 12 months can be considered).

When to Biopsy Ambiguous Lesions

Imaging “sees” all sorts of things besides cancer, including scar tissue, areas of active inflammation (prostatitis), and nodular areas of prostatic hypertrophy (BPH). The lesions of greatest concern are the ones that are larger, located in the peripheral zone of the prostate, bulge the capsule, or are associated with increased blood flow or diffusion. An ambiguous lesion may require biopsy if subsequent follow-up scans show progressive enlargement. The decision about whether to biopsy an ambiguous lesion immediately or continue monitoring with periodic scan should be made by having a discussion between the patient and a medical doctor who understands this new technology.

Stop PSA Screening Altogether?

In 2011, due to concerns about over-diagnosis from PSA testing and immediate random biopsy leading to serious side effects from unnecessary treatments, the U.S. Preventative Services Task Force recommended against routine PSA screening. Studies show that many primary doctors took these recommendations to heart and have stopped doing screening altogether. But the Task Force is missing the point. PSA screening is not the problem. The problem is rushing into an immediate random biopsy anytime a PSA elevation occurs. A careful, stepwise approach that begins with prostate imaging and follows up with targeted biopsy when an abnormality is detected can practically eliminate the problem of over-treatment.

Final Thoughts About PSA Screening

The medical world is adapting very slowly to how 12-core random needle biopsy leads to the needless diagnosis of, Gleason-grade 6 cancers. Every year in the United States 100,000 men are diagnosed with these harmless “cancers.” Unfortunately, many of them undergo unnecessary radiation or surgery anyway. The first step toward getting better care for men who undergo PSA screening should be wider-spread use of state-of-the-art imaging, rather than rushing to do a random biopsy.

Sources:

Eggener S, et al. Journal of Urology Vol. 185, P. 869, March 2011.

Klotz L, et al. Journal of Clinical Oncology Vol. 28, P. 126, January 2010.

Sakr W, et al. Journal of Urology Vol. 150, P. 379, 1993.

Thompson I, et al. New England Journal of Medicine Vol. 349, P. 215, July 2003.

US Preventative Task Force. Prostate Cancer: Screening. May 2012. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/prostate-cancer-screening

Wilt T, et al. New England Journal of Medicine Vol. 367, P. 203, July 2012.

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