Study of Baseline PSA Screening of Men (45 years old) - Peter Albers

December 30, 2019

Peter Albers discusses his study of baseline PSA screening of young men across the nation of Germany. The study consists of 45-year-old men who are randomized in two cohorts, one group gets a PSA immediately and the other cohort has a delay of five years. The initial PSA value determines the patient’s risk-adapted strategy and dictates the schedule of further testing. Dr. Albers states that the trial is essentially testing whether to screen at 45 or at 50 with the endpoint being prostate cancer metastasis after 15 years.

Biographies:


Peter Albers, MD, Professor of Urology, Düsseldorf University

Charles J. Ryan, MD is the B.J. Kennedy Chair in Clinical Medical Oncology at the University of Minnesota and Director of the Division of Hematology, Oncology, and Transplantation.

 

Read the Full Video Transcript

Charles Ryan: Hello, we're at EAU in Barcelona where I'm delighted to be sitting down with Peter Albers, who's Professor of Urology and Chairman of the Department of Urology at the Düsseldorf University Hospital in Germany. Thank you for joining us today, Professor Albers. You're head of a very large PSA screening trial across the nation of Germany. Tell us a little bit about this study. 

Peter Albers: Yeah, the study was set up in order to prove the hypothesis of a baseline screening in young men. So we started five years ago to accrue 45-year-old men and they are randomized in two cohorts. The one cohort's getting a PSA right away and the other way, the other cohort, has a delay of five years. In all patients, we have blood sampling and then we are actually testing a risk-adapted strategy. So this means a PSA value of 1.5 and below would mean that the next PSA values taken five years later. This is true for about 90% of the program. Then another 8% is in the intermediate risk group between 1.5 and three. And they will have a repeat scan, repeat PSA, in two years. And then we are aiming to select out high-risk group with a PSA of above three. And those programs are in 45-year-old men. We recommend diagnosis, including MRI.

Charles Ryan: So the study's really looking at screen at 45 or screen at 50, more or less, is the study question.

Peter Albers: Exactly. The endpoint is metastasis, prostate cancer metastasis after 15 years. We rely on the data from MALMO published by Andrew Vickers and Hans Lilja. We are in close contact with both, that helped us with the statistics. And then we are aiming in showing that screening at 50 may be sufficient and non-superior, non-inferior, to the earlier screening. But superior in terms of obviously avoiding side effects of screening.

Charles Ryan: So you're addressing the issue of, essentially, over aggressive screening in younger men and trying to eliminate that if you will. Is that-

Peter Albers: Exactly. Is more or less you can also say it's an anti-screening trial. 

Charles Ryan: Right, it's an anti-screening screening trial. Yeah. 

Peter Albers: So we try to figure out how safe is 90% group in delaying or less frequency of PSA screening.

Charles Ryan: So if the study is positive, what it will show, it would be essentially that screening at 50 is acceptable in terms of metastasis. But would you still recommend that patients or subjects have a baseline PSA at 45 or not? Are you basically-

Peter Albers: No. If it's positive then we would shift the baseline PSA value from 45 to 50. 

Charles Ryan: Okay. 

Peter Albers: And we obviously have to select out risk groups.

Charles Ryan: Right. 

Peter Albers: So we're having a national cohort study in Germany as well with 200,000 men. And we have the same baseline questionnaire for, for example, family history assault. So perhaps there are some risk groups where you may recommend still an earlier screening.

Charles Ryan: Right. 

Peter Albers: But aiming, the aim of the study is to shift it from 45 to 50.

Charles Ryan: Okay. And what are the assumptions, if I can ask, about the 50-year-old population on the rate of metastasis after 15 years? It must be a very small number of patients. 

Peter Albers: Yeah. 0.3.

Charles Ryan: 0.3%. Okay. 

Peter Albers: And but it's statistically sufficient- 

Charles Ryan: Sure. 

Peter Albers: To be calculated with 50,000 men. 

Charles Ryan: Yeah. 

Peter Albers: To reduce it with screening to about 0.15, 0.18 and so the statistics is very valid. And in spite of having a very rare event.

Charles Ryan: Yeah. 

Peter Albers: We are able to generate some assumptions at 15 years and not waiting for death of disease. 

Charles Ryan: Sure. Of course. Okay. So it's 0.3% for the 50-year-old patient who is otherwise healthy who is having a screening PSA. 

Peter Albers: Yep. 

Charles Ryan: So three-tenths of one percent of them will have metastatic prostate cancer after 15 years. 

Peter Albers: Yeah. 

Charles Ryan: And the reduction that you're looking at is by adding screening and risk-adapted therapy.

Peter Albers: A 30% reduction.

Charles Ryan: A 30% reduction.

Peter Albers: Yeah. 

Charles Ryan: Now does your study mandate or dictate the therapy that would be administered should the what happens after the screening is performed?

Peter Albers: There's no mandate or we don't dictate it. We have up to now 80 cancers and most of them underwent radical prostatectomy. Interestingly enough, the majority of those cancers are not low-risk cancers, so they are at Gleason 7 and higher. So this was also astonishing for us that this is not a low-risk cancer group. So if a patient at this early age has cancer, he has the same chance to have an aggressive cancer as diagnosed with 60. 

And another interesting early result is that we need the confirmatory PSA value. So in this study, we have a confirmed PSA up to four weeks and only 55% of those men have a confirmed PSA above three.

Charles Ryan: Interesting.

Peter Albers: So and this is very interesting because all the other screening trials, like PLCO, ERSPC, relied on one PSA value. And we have discovered that a lot of infections are taking place in these young men.

Charles Ryan: Yeah. 

Peter Albers: So the baseline screening in young men probably is affected by infections and so it's important to confirm the PSA value and the scope.

Charles Ryan: As far as the treatment of prostate cancer in Germany presently, for low and intermediate risk patients, is there a wide variety in the patients of the treatment center being administered in terms of radical prostatectomy, brachytherapy, active surveillance? How does Germany compare to the rest of Europe and maybe the North American population in terms of the types of therapies that people are receiving?

Peter Albers: I think compared to other countries in Europe, the rate of active surveillance patients is higher in Germany. It has increased over the last 10 years. I was responsible for the German Prostate Cancer Centers in the last 10 years and so I know exactly the data and the longitudinal shifts from beginning of 10% now with more than 40% of patients.

Charles Ryan: More than 40%. 

Peter Albers: Treated with active surveillance. 

Charles Ryan: I just got done speaking with Matt Cooperberg from San Francisco and we were talking about active surveillance in North America. And we were, of course, talking about how his goal is to have it reach 50%. Then the conversation was well why are the other 50% being treated? I guess I could ask you the same question. Is it being driven by the economics of healthcare delivery in Germany? Is it being driven family history? Is it being driven by young age? In other words, who are the patients with low-risk prostate cancer who are being treated?

Peter Albers: I think family history is only a small proportion. Young age certainly is a problem. So not all urologists are comfortable to recommend active surveillance in a 50-year-old. However, with the MRI as an additional tool of managing the diagnosis and be more sure about the disease volume. In our institution, we can convince most of the patients to undergo active surveillance even being young. But I have to admit, I think this is true for all healthcare systems, that the economical problem is still there. 

Charles Ryan: Yeah. 

Peter Albers: So active surveillance is time-consuming, doesn't pay off a lot, and so I think this plays certainly a role. But with accumulating data, PROTECT study and others, people are really convinced that active surveillance has a major over low risk. 

Charles Ryan: Do you think with your PSA screening trial that one of the potential complications is that you may end up increasing the number of people who are essentially put on active surveillance? Or is this type of a calculation figuring into what you think will be the outcomes of the PSA screening trial?

Peter Albers: I think in the future it may well be that the diagnosis of prostate cancer can be restricted to a small group of high-risk patients. 

Charles Ryan: Yeah. 

Peter Albers: If they are detected then we have better tools to detect aggressive versus nonaggressive disease. And so I don't think that we really will shift it to the active surveillance cohort because as I said, a whole bunch of those diagnosed patients have aggressive cancer.

Charles Ryan: Right. 

Peter Albers: And we know from Gleason 7, 8, for example, in active surveillance cohorts. We did also study in Germany that after two years more than half of patients have to undergo treatment. So I think the pure Gleason 6 cancers certainly will be managed with active surveillance, but in this high-risk group of the PROBASE study, we have only 30% of Gleason six cancers. 

Charles Ryan: Right. And these aren't going to be the patients who are going to contribute to the metastasis risk at 15 years, most likely, because they would be much lower, at much lower risk I would anticipate.

Peter Albers: Yeah. Yeah, that's right. 

Charles Ryan: Okay. All right. And so in terms of the time, finally in terms of the timeline of your study, it's fully accrued.

Peter Albers: Not yet, we have 42,000 at the moment and we'll finish the study hopefully in October, November this year with 50,000 accrued. 

Charles Ryan: Okay. 

Peter Albers: And then currently we are starting to see the second cohort, so after five years we will have now next year the first 10,000 PSA data for the group that had delay screening. So we have more ... We can publish about the incidence rates and the amount of the high risk versus intermediate risk group. We have next year, probably, data how many will be shifting from the intermediate into the high risk within the next two years. So this is currently about 20%. So we probably have in the high-risk group about 1% of patients. And this would mean that this is still really risk-adapted approach, telling most of the patients you have no risk to develop prostate cancer, hopefully in the next 10 years. But obviously, we have to show-

Charles Ryan: Important to know. Yeah, I mean this is a fascinating topic and a fascinating study because I'm thinking of all the other potential confounding variables, which I'm sure you spent a lot of time thinking about, such as patients their earlier use of hormonal therapies and other things that may confound the presence of metastasis at 15 years. 

Peter Albers: Of course. On the other hand, this will happen in both groups in the same way. So the main message of the study whether to start with 50 or 45 will be answered. And five year no screening is a lot of money and it a lot saving burdens for the patients. 

Charles Ryan: Right. 

Peter Albers: In addition, we have MRIs for those high risks patients and this is an astonishing result at the moment. We have real trouble to evaluate the MRI in those patients.

Charles Ryan: I see.

Peter Albers: Because the infections in the 45-year-old lead to strange pictures. So the disagreement within the four centers of the study is very high and these are excellent centers. Some of them, like Heidelberg or Düsseldorf we have developed the MRI 10 years ago in Germany. And we are in disagreement in the interpretation of PI-RADS 4 and 5 variations, for example. So this is another interesting research object. We have just invited people with artificial intelligence to help us.

Charles Ryan: Interesting. 

Peter Albers: Because this is real problems. MRIs with 45 is completely different from an MRI with 60.

Charles Ryan: Yeah. Well fascinating area and a significant body of work that we'll be learning about. Learning from, I should say, for more than a decade to come. So I want to congratulate you on nearing the completion of your accrual of this important study and we'll look forward to future conversations.

Peter Albers: Okay, thank you so much. 

Charles Ryan: Thank you, Professor Albers for joining us.

Peter Albers: Okay. Thanks.