Since the prostate specific antigen (PSA) test was introduced in the late 1980s, prostate cancer mortality has dropped by more than 40 percent. However, there has been tremendous controversy over whether the PSA test has caused that decline. In a newly published study, UC Davis researchers suggest that PSA screening likely plays an important role.
To illuminate the issue, researchers at the UC Davis Comprehensive Cancer Center looked at survival for men initially diagnosed with metastatic cancer, hypothesizing that success in treating advanced cancer and improvements in mortality for metastatic disease could be driving observed changes in overall survival, independent of PSA testing. However, the researchers found that over the past 25 years mortality for men with advanced, metastatic prostate cancer has been mostly unchanged. Their study appears online in the journal Cancer.
While the PSA test has clearly improved early detection of prostate cancer, there’s been concern that the diagnostic tool has a limited impact on mortality. The test measures blood levels of PSA, a protein produced by the prostate gland. The higher a man’s PSA level, the more likely it is that he has prostate cancer. But the test does a poor job gauging the acuity of the disease, which has led to unnecessary therapies and associated side effects for men with slow-growing cancers. In 2012, the United States Preventative Services Task Force advised against routine PSA testing.
"Our research found that while the death rate from prostate cancer overall has declined, men whose cancer has spread beyond the prostate are still dying at the same rate as before,” said urologic oncologist and senior study author Marc Dall’Era. “This finding suggests that routine PSA testing, which has dramatically reduced the incidence of metastatic disease, may be effective in reducing mortality from the disease, as well."
To test their hypothesis that improved treatment was responsible for the overall lower mortality rate, the team examined data from the California Cancer Registry. They looked at men 45 or older who first presented with metastatic prostate cancer between 1988 and 2009 and at overall survival for 19,336 men, stratifying the groups by time of diagnosis (including before and after PSA introduction), ethnicity, age, cancer grade and other factors.
The research corroborates previous studies that had shown a 65 percent reduction in those initially diagnosed with metastatic cancer since the PSA’s introduction. This reduction resulted from men being diagnosed at earlier stages after PSA screening. However, the new study shows that for those who were diagnosed with metastatic prostate tumors, survival has not improved.
“The effect we’re seeing on mortality in this group is more that we’ve shifted the stage of diagnosis much earlier,” said Dall’Era. “In other words, because the PSA test detects cancer earlier, fewer men go on to be diagnosed with metastatic disease. However, there has been no survival improvement for men with metastatic disease to account for the overall mortality decline among all men with prostate cancer.”
The research also demonstrates the urgent need to develop better treatments for men with metastatic prostate cancer, said Ralph de Vere White, director of the UC Davis Comprehensive Cancer Center, and a study co-author.
"This is a landmark paper because it highlights, in an indisputable way, the problem we face,” de Vere White said. “Though we can reduce prostate cancer mortality, we have failed to reduce mortality among those with metastatic disease – the advanced prostate cancer that ultimately kills these men.”
Though the study did not find any survival gains for men with advanced cancer, there are nuggets of good news. For example, the survival disparity between African American and Caucasian men has declined over time. The research shows that both groups had similar survival rates following the PSA’s introduction. In fact, the team found that socioeconomic status is much more significant than race in determining survival.
Ultimately, the study failed to identify a potentially significant contributor to the decline in prostate cancer mortality. The authors said additional research is needed to determine what is causing these gains, including a renewed focus on the PSA test’s role in preventing mortality.
“The survival of men with metastatic prostate cancer has not changed dramatically,” said Dall’Era. “At the same time, the number of men presenting with metastatic prostate cancer has dropped precipitously due to PSA screening. Does that mean PSA screening is causing that 40 percent decline in prostate cancer mortality? These data suggest that we should continue to evaluate the benefits of PSA screening before making sweeping policy recommendations against its use.”
Other researchers on the study include Jennifer N. Wu, Kari M. Fish and Christopher P. Evans.
This research was funded by the UC Davis Comprehensive Cancer Center Epidemiology Shared Resource.
UC Davis Comprehensive Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its specialists provide compassionate, comprehensive care for more than 10,000 adults and children every year, and access to more than 150 clinical trials at any given time. Its innovative research program engages more than 280 scientists at UC Davis, Lawrence Livermore National Laboratory and Jackson Laboratory (JAX West), whose scientific partnerships advance discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis collaborates with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer care. Its community-based outreach and education programs address disparities in cancer outcomes across diverse populations. For more information, visit cancer.ucdavis.edu.