Expert Stresses Importance of PSA-Based Screening in Early-Stage Prostate Cancer

Scott Eggener, MD

While the United States Preventative Services Task Force (USPSTF) has taken a stand against routine prostate-specific antigen (PSA) screening for prostate cancer, updated findings from the landmark Prostate, Lung, Colorectal, and Ovary (PLCO) screening trial could flip opinions, explains Scott Eggener, MD.

In the study, results showed that 80% of the control group reported at least 1 PSA test during the trial. Additionally, more than half had PSA assessments within the year prior to enrollment, and 70% reported having a PSA test in the 2 years prior to joining the control group of the trial. A high rate of PSA testing in the control arm suggests that meaningful comparisons with the intervention group could be impossible, according to the new analysis of the PLCO data, which was reported at the 2016 American Urological Association Annual Meeting.

Controversy has surrounded PSA screening—although it has been linked to a significant decrease in mortality rates, it is also associated with overdiagnosis and overtreatment. Eggener discussed these issues in early-stage prostate cancer during the 2016 State of the Science Summit on GU and Prostate Cancer.

OncLive: What do oncologists need to know regarding the current landscape of early prostate cancer?

In an interview with OncLive during the meeting, Eggener, associate professor of Surgery, Urologic Oncology, at the University of Chicago Medicine, discusses the implications of the PLCO trial update, and shares his views on PSA-based screening and how to appropriately use it for patients with early-stage prostate cancer.Eggener: Smart PSA-based screening can absolutely save lives. We have a problem with overdetection and overtreatment of men who are unlikely to benefit from it, so the gist of it is to identify men who have a reasonable life expectancy, are well informed, are interested in PSA screening, and can be biopsied appropriately.

However, many low-risk prostate cancers absolutely do not require treatment, and active surveillance has excellent long-term outcomes. Nevertheless, if they have an intermediate- or high-risk cancer and a reasonable life expectancy, treatment can save lives and is completely appropriate.

Can you shed light on some of those biomarkers?

There were some interesting findings recently presented on the PLCO trial. It seems to go against what the USPSTF was pushing for this whole time. Can you discuss that study and the findings?

In addition to that, there are many novel screening biomarkers—tissue-based biomarkers with good science and data behind them, and there are advances. The upcoming—and current—challenge is how to integrate them appropriately into the standard care pathways, particularly given their typically excessive cost.In the screening setting, there are a lot of very strong data showing [the efficacy of] the 4Kscore, the Prostate Health Index, and the MiPS score. There’s a SelectMDx score that recently presented some data. After the diagnosis—once someone has a biopsy showing cancer—there are tissue-based biomarkers such as Prolaris, Oncotype DX, and GenomeDX.It was really an ambitious, important, and landmark trial where the intent was terrific. It was in the United States. It took a large population of men and randomized them—where half of them got PSA screening, and half of them did not—and saw if screening for prostate cancer saves lives.

When the data were originally presented many years ago, it did not [indicate that screening] saves lives and everyone was taken aback. It has informed policy here and elsewhere really going against PSA screening. Well, it turns out—which has been known for a while but not to the extent as the recent data shows—90% of men in the control arm, meaning the men who were never supposed to get a PSA, either got a PSA before the trial or during the trial.

What do you think are going to be the implications of these findings?

In that trial’s control arm, where 90% of patients did get a PSA, what was the reasoning they did so?

Why does this gap exist, where PSA was believed to have this opposite effect?

Then, the complete paradox is in the 2 arms. The control arm collectively had more PSAs drawn during the trial than the other arm, which is the one that was supposed to be screened with PSA. Therefore, it is, unfortunately, a completely garbage trial—a colossal waste of money and effort—and, hopefully, public policy reflects that going forward.There is a lot that goes into the final USPSTF recommendations, and we do not have enough time to dive into it. However, simply based on data, it is clear that PSA screening, in an appropriate population, saves lives. European data suggest it can save anywhere from 20% to 40% of deaths from prostate cancer. However, in the big picture, we need to be smart about who to screen, who not to screen, who to treat, and who not to treat. I am absolutely confident that we can save people from dying of prostate cancer, but also minimize morbidity. Not every man automatically needs treatment.Presumably, they entered into the trial; they were asked or told not to get a PSA. However, these men see many physicians inside or outside of the trial. PSA screening was so pervasive in the United States that these guys either ended up requesting a PSA, their doctor asked them to get it, or their doctor just ordered it without them knowing about it.It was really known before the results of the trial came out. There were people writing in the literature; we can pull it up where it basically says, “This is a flawed trial.” Too many people in the control arm were contaminated and were getting PSAs.

As an expert in the field, what kind of advice can you give to community oncologists in terms of whom they should and should not screen, and/or whom they should and should not treat?

Then, the data came out. In a sort of middle-of-the-road journal, there was a paper that said that there were really high rates of contamination. Just recently, they looked back at it and found out that the high rate of contamination was only when they asked people in the past year. If they look throughout the duration of the entire trial, it was the 90%—so that was really mind-boggling, and disturbingly so. That is why it got such press and why it was in The New England Journal of Medicine.There is a lot of nuance to it. What I would say is, if a guy has a reasonable life expectancy, estimated to be 8 to 10 years, and he understands the possible pros and cons of PSA screening, I think it is perfectly sensible to get a PSA test.

If the PSA is higher than it should be for a man his age, then always, always repeat it. Incumbent in that is if it is higher than it should be and he is considering a biopsy, I prep men before a biopsy that, even if we find cancer, not all cancers necessarily need to be treated immediately. Many of them can be safely observed, but the only purpose of a biopsy is to find out whether there is a high-grade or high-volume cancer that could eventually cause some problems.

Separate from that is that there are higher-risk groups that have a family history of prostate cancer and/or are of African-American descent. There are all of these other tests that are above and beyond PSA in their operating characteristics and really do a better job. The unfortunate part is they happen to be fairly expensive, so I do not routinely order them but, for select patients, it is helpful.