PSA or No PSA
Because prostate cancer can exist for many years, grow and spread before a man develops symptoms it has been called a “silent killer” of men. It is very important to discover this cancer when it is within the prostate, organ confined and low in stage. The first test in the detection pathway is a PSA test. An elevated PSA blood test does not mean cancer in every man. There are several benign conditions that can cause PSA elevation. But a PSA elevation should lead to a discussion with your doctor about further testing and whether you need to proceed to an MRI and biopsy. This will depend on many factors including your age, health status, race, family history and risk tolerance. All of this is discussed in the book.
Since the FDA approval of PSA in 1986, more than one billion PSA tests have been done. In 2015 the American Association for Cancer Research cited PSA as one of the "Landmark Scientific Discoveries of the 20th Century." T. Ming Chu, PhD, DSc, Chair Emeritus of Diagnostic Immunology Research and Professor Emeritus of Urologic Oncology, led the research in the 1970s that resulted in the discovery of PSA, a diagnostic test that would be used around the world. A patent was issued in 1984 to the state of New York and Roswell Park Cancer Institute. The technology was transferred to the biomedical industry for preparing testing kits. The PSA test received FDA approval in 1986 as a monitor for prostate cancer treatment response and disease recurrence, and in 1994, as a screening test for diagnosis. Every year, 20 million American men, and a similar number worldwide,receive a PSA test, the centerpiece of the early warning system for prostate cancer.
1 in 7 men will be diagnosed with prostate cancer during his lifetime, but only 1 in 35 will die from it.
These odds weren’t always that good. When James L. Mohler, MD, Chair, Department of Urologic Oncology, Roswell Park Cancer Institute was in residency training about 25 years ago, a diagnosis of prostate cancer was the equivalent of a death sentence. "Back then, only 4% of prostate cancers diagnosed were curable. Now, with PSA, the survival rate is between 80 and 90%," says Mohler in a Roswell Park Cancer Institute NEWS release.
Since the advent of PSA screening since 1990, there has been a 53% reduction in prostate cancer mortality in the United States, a greater decline than for any other cancer; PSA screening is estimated to account for 45% to 70% of this. Ref
In the 70s and 80s before PSA was used widely many men were diagnosed with prostate cancer that was high stage. Prior to the emergence of PSA testing, only 68 percent of newly diagnosed men had cancer localized to the prostate and 21 percent had metastatic disease. Today, more than 90 percent of these men have cancer confined to the prostate and only 4 percent have cancer that has spread to other areas of the body. While the PSA test may be limited because it does not indicate whether a cancer is aggressive, the test provides important information in the diagnosis, pre-treatment staging, risk assessment, and monitoring of prostate cancer patients. It has allowed millions of men to make informed treatment decisions that may have saved their lives. The only way to diagnose prostate cancer before PSA was with a rectal exam. By the time the cancer was felt by rectal exam as a hard nodule, it had spread outside the prostate in over half of men. Most of the the cancers were stage T2 or higher, and side effects from treatment were significant. Because the cancers were larger more extensive surgery or radiation had to be done and this caused urinary leakage, impotence and other side effects. The cures were also less in number.
Another group of patients who were diagnosed prior to PSA testing included patients with metastatic cancer who had symptoms such as bone pain from spread of cancer outside the prostate. Both of these groups did not do well with treatment and five year survival rate was under 60%.
Prostate-specific antigen testing has had a dramatic effect on the stage at which the patient gets treated for prostate cancer. Within 15 years of widespread PSA use, the stage at which prostate cancer was detected had shifted and majority of men who are diagnosed in the last 10 years have small, organ confined cancers that are stage T1. FIFTY to 70% of these cancers are low grade and low risk and can be managed by careful monitoring and only the rest will need treatment.
Welch HG, Albertsen PC (2009) Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986-2005. J Natl Cancer Inst 101: 1325-1329.
The PSA Controversy
Over the last few years patients are receiving mixed messages about prostate cancer screening from physicians as well as professional organizations.The major reasons for this has been over-diagnosis and over-treatment of prostate cancer with escalating side effects and costs.
There has always been controversies about the role of PSA in prostate cancer.This is because PSA is an imperfect screening test. A good screening test has high specificity in that it will be positive in most men with prostate cancer and it should also be highly sensitive by excluding most men with prostate cancer if the test is negative. PSA is not specific for prostate cancer and several benign conditions can cause elevated PSA. It is also not very sensitive because the cut off levels for determining lack of prostate cancer is variable based on age, race and presence of benign conditions such as prostate enlargement
Until recently this has led to many repeat PSA tests, serial PSA tests (to determine PSA doubling time and PSA velocity) and unnecessary biopsies that causes anxiety and loss of time from work for patients. Additionally there are costs involved.
The controversies about use of PSA in prostate cancer resurfaced after 2012 when the USPSTF recommended against screening with PSA for all men. The USPSTF decision was based in part on a randomized trial comparing the role of PSA in preventing prostate cancer deaths in screened versus unscreened men. This study called the PLCO trial has been broadly determined by the scientific community to be drastically flawed with regards to its conclusions about the lack of efficacy of PSA in saving lives. The USPSTF did not have all the facts at the time of their decision and it is likely they will eventually reverse their recommendation as the dangers of not using PSA become clinically manifest. Most urologists who are seeing patients every day understand all too well that there are many patients whose lives are saved because of PSA screening. These physicians continue to use PSA for early detection. Having said that, most urologists realize that PSA is an imperfect test and over-diagnosis and overtreatment are real issues that need to be addressed. The diagnosis and treatment of prostate cancer is complex with controversies at many levels. The decision to perform a PSA is only the first of several controversies which include decisions on whom to biopsy and whom to treat and with what modality.
Urologists also need protect themselves from lawsuits alleging delay in diagnosis which may not be defensible if the patient develops metastasis. One of the hotly debated topics at the AUA 2016 was about a patient who progressed and developed metastatic disease even though he was thought to have low risk cancer and monitored for a year based on protocols recommended by reputable academic centers. The lawyer for the patient was not sympathetic because the doctor wanted to spare the patient unnecessary biopsy and side effects of treatment. In the US a doctor will not be penalized for defensive practice of medicine or over-treatment but he may be penalized if the patient he is monitoring ends up with a bad outcome such as bone metastases.
Many urologists in the US will not recommend active surveillance of prostate cancer except in men with limited life expectancy. This is not because the urologist make a living by performing prostate surgeries. Of more importance is the need for the urologist not to miss lethal disease for which he may be held liable. At present no test can determine that a patient has non lethal disease. If there was such a test then patients would not need active surveillance or monitoring with repeat biopsy. Men would be told they have non lethal disease and do not need treatment. However 36 to 57% of patients on monitoring end up with higher grade disease which can become lethal if not treated. Therefore even men with low grade cancers need continuous monitoring all their life. There are psychologic burdens and anxiety issues associated with active surveillance.
Therefore it is only the patient who can ultimately decide his own pathway between monitoring versus immediate treatment based on education about prostate cancer and after discussion with his doctor.
A Baseline PSA is always the First Step
Elevated PSA (prostate specific antigen) is the single most important test that can lead a man to discover if he has prostate cancer. PSA is a protein secreted by prostate cells. A small amount of PSA is normally present in the blood of all men. When prostate cells become cancerous, they divide and grow rapidly. There is some cell breakdown, and more of the PSA gets into the bloodstream. An elevated blood level of PSA suggests that the patient may have cancer and needs to be investigated further. Studies have estimated that PSA elevations can precede symptomatic prostate cancer by 5 to 10 years [16,17] or even longer .