Click here to read more Quest articles. print | Print this page
From the Winter 2019 Quest
Research continues to review details of PSA testing. Understanding the historical context, and the impact of screening, helps determine the best ways to use the test in a modern clinical setting. ©Dan Oldfield
In 1992 - before the advent of PSA screening for the early detection of prostate cancer - mortality rates for men in the U.S. with the disease were on the rise. Only 60% of men received their diagnosis when their cancer was still localized in the prostate. In addition, 19% of men diagnosed with the disease had distant metastases, i.e., the disease had spread beyond the pelvis, and 14% had cancer that had spread regionally outside the prostate to the lymph nodes or surrounding tissue. It is much more difficult to cure prostate cancer once it has spread beyond the prostate. Hence in 1992, the 5-year survival rate for men diagnosed with advanced disease was only 29%.

Thankfully, these statistics are no longer the case. The advent of PSA screening for the early detection of prostate cancer changed the landscape of care for men in the U.S. In 1991, Dr. Catalona published his landmark trial in the New England Journal of Medicine that showed the PSA test was useful as a screening test. The test was adopted into clinical practice.

In 2019, nearly 80% of men diagnosed with prostate cancer have had the disease detected while it is still localized in the prostate and easier to manage. Rates of regional metastases are down to 10-15%, and distant metastases rates have dropped to approximately 5% at diagnosis. During the PSA screening era from 1992-2015, there has been a 53% decrease in the U.S. prostate cancer mortality rate. However, in men having metastases at the time of diagnosis, the 5-year survival remains at about 30%. Thus, PSA screening for the early detection of prostate cancer has saved the lives of many men.

High quality, long-term scientific research in Europe supports this claim. In the Goteborg, Sweden trial, the risk for prostate cancer mortality was 35% lower for men who underwent PSA screening. The greater mortality benefit was for men who started screening at ages 55-59 years old, with a 53% lower risk of dying from the disease. Similarly, in the European Randomized Study of Screening for Prostate Cancer (ERSPC), men who underwent PSA screening had a 21% lower risk of dying from prostate cancer.

The PLCO Trial

In 2009, a study conflicting with the ERSPC published results in the New England Journal of Medicine. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial found a 0% decrease in prostate cancer deaths for patients who had undergone PSA screening. The results were widely reported in the media and caused a significant controversy over the use of PSA testing for the early detection of prostate cancer.

However, several years later the New England Journal of Medicine published a scientific letter to the editor with a reevaluation of the PLCO data. In reality, there had been a greater than 90% contamination rate in the "control" arm of the study, meaning that the majority of men who were not supposed to have PSA screening actually had the tests. This incorrectly skewed the results against PSA screening. A new analysis of the PLCO data published in the Annals of Internal Medicine in 2017 revealed there was a 27-32% lower prostate cancer death risk with prostate cancer screening, similar to the rates reported in the ERSPC trial.

The USPSTF guidelines controversy

While this debate was ongoing, the U.S. Preventive Services Task Force (USPSTF) began revising its national guidelines. The USPSTF is a panel of experts in disease prevention and evidence-based medicine that makes national recommendations about clinical preventive services.

In 2008, the USPSTF panel recommended against screening men older than 75 years old. In 2012, the USPSTF issued a problematic grade "D" recommendation against PSA screening for all men, concluding that the harms outweighed the benefits. Unfortunately, at that time the panel heavily weighed the data from the PLCO trial. The panel also did not include any urologists, radiation oncologists, or medical oncologists.

In the three years after the 2012 USPSTF recommendation, the PSA screening rates and rates of interventions for prostate cancer diagnosis and treatment declined substantially. Fewer men were being diagnosed and treated for the disease, and the proportion of men diagnosed with metastatic cancer increased. This suggests that due to the decline in screening, more men were being diagnosed with prostate cancer after the disease had already spread out of the prostate. The prostate cancer mortality rate also began to climb upwards.

Expected impacts of discontinued PSA screening

National statistics networks have projected the effect of stopping PSA screening in the U.S. population. The U.S. National Cancer Institute Intervention and Surveillance Modeling Network (CISNET) data predicted that stopping screening would result in twice as many metastatic cases, returning to pre-PSA era levels and a 13-20% increase in preventable prostate cancer deaths by 2025. Discontinuing screening for men older than 70 years would fail to prevent 35-39% of avoidable prostate cancer deaths. The CISNET similarly projected that if screening were phased out in 2012, the number of cases of distant stage disease would return to the pre- PSA screening era levels by 2025. Data from the Goteberg trial supports these predictions: for men in the trial who stopped PSA screening, after nine years the incidence of potentially lethal prostate cancers was the same as it was for men in the group without any screening at all.

Updated USPSTF guidelines

In 2018, the USPSTF reviewed the new scientific evidence regarding PSA screening for prostate cancer and revised its recommendations. Currently, for men ages 55-69 years old, the panel recommends that clinicians and patients practice shared decision making and discuss the benefits and harms of screening for the early detection of prostate cancer. For men age 70 or older, unfortunately, the panel still advises against PSA-based screening.

While the revised guidelines are a step in the right direction, they are missing some key strategies that could not only save lives, but also reduce suffering from prostate cancer. Prevention of metastatic disease is also important, as advanced cancer can cause substantial suffering and require difficult treatments.

This article is adapted from Dr. Catalona's presentation at the International Cancer Conference, which was held September 7-9, 2019 at Trinity College Dublin.