The number of men with advanced prostate cancer at the time of first diagnosis would most likely rise without routine PSA screening, according to a new study.

Without routine screening for prostate cancer with the prostate-specific antigen (PSA) test, 17,000 more men in the US every year would discover they had the advanced or metastatic form of the disease, according to a new study by the University of Rochester Medical Center (URMC) that is due to be published in the journal Cancer this week.

Prostate cancer is the second leading cause of cancer death in American men, behind only lung cancer. According to figures from the American Cancer Society 1 man in 36 in the US will die of prostate cancer.

Most prostate cancer-related deaths are due to advanced or metastatic disease, where the cancer has spread from where it first started in the prostate gland to other parts of the body like the lungs, bones, and liver.

The PSA test is a screening tool for early detection of prostate cancer. The test measures the amount of prostate specific antigen (PSA) in a blood sample. PSA is a protein made in the prostate, by both normal and cancer cells: a raised PSA level may indicate a problem with the prostate, but not necessarily cancer.

There has been controversy about whether, when used routinely, the PSA test does more harm than good.

In 2011 the US Preventive Task Force (USPTF) recommended not all men should have routine PSA screening, drawing much criticism from doctors.

The government panel had looked at the scientific evidence for and against the PSA test and concluded it brought little benefit as a screening tool, because the harms of early detection outweighed the benefits.

For example, a major concern that the panel raised was that the PSA test leads to finding and treating non-aggressive tumors that might never spread, causing patients to undergo invasive procedures and experience serious side-effects such as urinary incontinence and erectile dysfunction.

The confusion that ensued from the USPTF recommendation caused the American Society of Clinical Oncology (ASCO) to publish its own opinion in July 2012.

The ASCO decided that general screening was not a good idea for men whose life expectancy was under 10 years, and men expected to live more than that should talk to their doctors about whether the PSA test was right for them.

To see what might happen if routine PSA screening were to be abandoned, Emelian Scosyrev, assistant professor of Urology at URMC, and Edward M. Messing, URMC’s chair of Urology, and president of the Society of Urologic Oncology, analyzed information from the years before PSA testing was routine (1983 to 1985) in the US, and compared it to the current era of widespread screening (2006 to 2008).

The data came from the Surveillance, Epidemiology, and End Results (SEER) database, the largest cancer registry in the US.

Scosyrev and Messing were particularly interested in records of men whose prostate cancer had already spread at the time of diagnosis.

They found that in 2008, about 8,000 cases of prostate cancer were diagnosed when the cancer had already spread.

So they designed a mathematical model to estimate what this figure would have been without routine PSA screening. To do this they used the pre-PSA incidence rates of metastatic prostate cancer.

After adjusting the data to take into account age, race, and geographic variations in the US population, they predicted the number of cases diagnosed with metastatic disease would be about 25,000, which is three times the number actually observed, or 17,000 more cases.

However, the authors emphasize their study is observational, and has limitations.

For instance, it is impossible to know whether the fewer cases of metastatic disease diagnosed in 2008 is purely because of the PSA test and early detection.

Another factor is the potential lead time of screening. For some people, receiving a diagnosis that the cancer is there but has not spread does not necessarily lead to improved survival: for instance, it could be the metastasis was present at time of screening but not detected. This could result in delay of timely treatment.

But despite this, the authors conclude that the huge screening and effort to raise awareness about PSA that took place from the 1990s through to the early 2000s led to a large shift toward earlier-stage disease diagnosis and fewer cases of metastases.

Messing told the press that in the US, over the last 20 years, prostate cancer death rates have fallen by nearly 40%. Treatment methods (surgery and radiation therapy) have not changed much in that time, and other studies suggest more than half of this reduction is due to earlier detection.

“Our findings are very important in light of the recent controversy over PSA testing,” said Messing.

“Yes, there are trade-offs associated with the PSA test and many factors influence the disease outcome. And yet our data are very clear: not doing the PSA test will result in many men presenting with far more advanced prostate cancer. And almost all men with metastasis at diagnosis will die from prostate cancer,” he added.

Written by Catharine Paddock PhD