Free PSA shows utility for helping detect clinically significant and fatal prostate cancer

In this video, Mark A. Preston, MD, MPH, describes the background and notable findings from the recent Journal of Urology study, “Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial.” Preston is a urologic surgeon at Brigham and Women’s Hospital and an assistant professor of surgery at Harvard Medical School in Boston, Massachussets.

Transcription:

Please describe the background for this study.

Questions remain about the best way to screen for prostate cancer. We have PSA, which has been around for decades. But additional testing to help better risk stratify who needs closer screening, who needs less intense screening, or who needs to go on to a biopsy [is needed]. We also use reflex tests, which is basically an additional test that can be done once the PSA has been done to help decide, is this a PSA value that's suspicious, does it require investigation with MRI and biopsy or not? That was the space that we wanted to investigate and to build on. We thought there could be more that could be done in that space to help clinicians and patients take the next step in care of traditionally elevated PSA level.

What were some of the notable findings? Were any of them surprising to you and your coauthors?

To investigate this question further, we used the PLCO trial. This was one of the largest trials of prostate cancer screening that was done in the United States. It wasn't the best randomized trial because there was a lot of contamination in the control arm, meaning that you had the screening arm that was getting PSA tests, but a significant portion of the control arm also had PSA testing done. And so, it hasn't been able to guide screening practices all that much. However, it's a very rich source of data. And what we realized is that we could use that prospective study design to answer this question. There are almost 7000 men who, at baseline enrollment into that study, in addition to having a total PSA done, also had a free PSA measure. And so, what we looked to do was, within that screening arm of the PLCO trial, look at those men who had that initial PSA, also had a free PSA measure, and then look over the 20 years of follow-up, who developed prostate cancer and more importantly, not just prostate cancer, but who developed clinically significant prostate cancer. This is traditionally prostate cancer that may have a Gleason score of 7 or higher or higher PSA level; basically, cancers that we want to find that may warrant treatment. And in addition to not just clearly significant ones, what about actually fatal prostate cancer? What about men who died of prostate cancer? Those were the outcomes we had as well. So, within this cohort of almost 7000 men, we had about 475 men that had clearly significant cancer and 98 men who had died of prostate cancer that we were using for this analysis. The takeaways that we found are that regardless of age, or even racial background—there was a pretty good distribution of races within the PLCO portion that had free PSA measured—we found that free PSA, when added to total PSA, improved prediction of clinically significant prostate cancer and fatal prostate cancer. This was primarily in men with a PSA above 2, which is in keeping with prior studies that have looked at free PSA. The interesting thing here is free PSA is not a new biomarker. It's been around for decades. There have been studies that have shown that it can improve the diagnosis of overall prostate cancer, but we wanted to go further than that—not just diagnosing prostate cancer, which, if you live long enough, most men will get, or it might be low-grade cancer that we don't necessarily want to find, but we wanted to find those more clinically significant ones. So, this was one of the largest studies that have been done on free PSA, especially with real outcomes of clinically significant fatal prostate cancer over 20 years.

This transcript was edited for clarity.