Simon Kim, MD, discusses the advantages and disadvantages of prostate cancer screening.
Dr. Simon’s presentation was part of the UH Focus on Wellness CME program presented by the Primary Care Institute, to view the entire CME program . click here SPEAKER 1: This is a very controversial area. I don't have a clear-cut answer. I wish I did. And I'm a urologist talking about whether we should screen or not screen. There are big policy implications, just not for our patients, but also for the public health and the country as a whole. So just some disclosures, I have no disclosures. I am funded by ASCO for a career development award, and an R1, to actually help improve active surveillance for men who are treated with prostate cancer-- who have been diagnosed with prostate cancer. So some quick epidemiology. Prostate cancer is the most commonly diagnosed [INAUDIBLE] among men in the United States. 3,000 men die of prostate cancer each year. It's the second most common cause of cancer-related mortality in the United States. And why do we screen? So this is from President Nixon. We screen because we hope to detect cancers earlier, such that we could treat them so they're not symptomatic, we have higher and higher cure rates, and provide more effective treatment. And so what are the traditional methods of screening? As we know, it's PSA testing, digital rectal exam. There are new emerging technologies out there-- the MRI, the prostate biomarkers. I would say that the last two, which are not the focus of my talk, are emerging methods of diagnosis. There isn't really great high-level evidence about the last two, so I'll focus on PSA testing mostly. So this is an area of controversy. I don't have the clear-cut answer here, because if you look at a panel of guidelines, there's no consensus about whether we should screen or not. You can go as extreme as the most recent US Preventive Task Force, which issued a Grade D recommendations that we shouldn't screen any man who's at average risk for prostate cancer. And they released this at May of 2012 at the AUA, our national meeting, and created a lot of consternation amongst urologists. And they predicated it based on two things. One, the evidence for screening is not great. And I admit that. And two, as a urologist and someone who treats prostate cancer commonly, we over-treat a lot of prostate cancer. We recognize that, and hopefully we're improving. And the AAFP, the American Association of Family Practice, agreed with them. They said, this is a Grade D recommendation. We are harming patients by screening them. The AUA backed off. We initially recommended screening at age 50-- which was not the best evidenced either-- We backed off in response, saying we should screen patients between ages 55 to 69 years of age, after having a thorough discussion of the risks and benefits and engaging in shared decision makings for patients. And the American Cancer Society, Dr. Otis Brawley, also-- they have not changed their guidelines-- issues a similar recommendation about screening men after having a thorough discussion about the risks and benefits and having shared decision making for patients who have a greater than 10 year life expectancy, starting at the age of 55. So we're at this crossroads. I admit, I don't have the clear-cut answer. When patients come to me asking this question, I don't have the answer, because we're sort of at this fork in the road right now. So there are two ways of looking at prostate cancer screening, in my opinion. One is that you can say, well, we should not screen because these older patients who we treat on the right don't need treatment. We're harming them by exposing them to a biopsy, and the vast majority of patients who are getting treated. The converse of that argument is that if you don't screen, we'll go back to the days of the 1980s, where you have men up here in the top right who have metastatic prostate cancer at presentation. If you are in favor of screening or not in favor of screening, if you screen patients-- We have a lot of great technologies out there to treat patients with-- robotic surgery, proton beam-- and we could cure a lot of patients, possibly. But you could also argue that we're over-treating a third of patients with localized prostate cancer. So I found this article really interesting. It's getting a lot of press. Richard Ablin wrote this very controversial piece saying that the PSA test was the biggest mistake in medicine. And this was particularly relevant because he invented it. He was a PhD scientist at Washington University, wrote this very controversial piece saying that he regretted ever actually discovering the PSA test, because we were over-diagnosing and over-treating a lot of men for prostate cancer. And Gilbert Welch-- [INAUDIBLE] at Dartmouth when I finished my fellowship-- published this very controversial article showing that since the advent and introduction of the PSA test, we have diagnosed 1 million men of prostate cancer. Of those 1 million men, 90% of them in the United States were getting treated. I would argue that a third of these men probably did not treatment. How do we do a PSA-- how do we get to diagnose with prostate cancer? Well, we do a TRUS biopsy and a digital rectal exam. And it's important to note that the TRUS biopsy is not that accurate. 2/3 of men undergo a biopsy and it's negative. 3% of men will have hemospermia, hematuria, and rectal bleeding, and that's relatively minor in my opinion. But the one more alarming thing is that 1.5% of men who had been admitted for urosepsis-- that number's actually increased from 0.4% to 1.5% recently based on SEER-Medicare data because of the ubiquitous use of antibiotics. The other thing, too, is that the US Preventive Task Force really called into question the benefit of PSA testing, because the vast majority of patients in the United States are getting treated. 90% of men who diagnose with prostate cancer are either going to undergo surgery or radiation. My specialty and what I specialize in, there is no single treatment I could say is superior. There's no clinical trial comparing surgery to radiation. And that trial never happened because of the large number of patients that would need to be recruited. And moreover, patients simply will not do it. We tried that in the 1990s and recruited horribly. And the last thing too is, if you're very honest, surgery and radiation are associated with significant quality of life implications. And so this is a busy graph, and I don't want to get into the specifics of it. But Matt Resnick's a friend of mine at Vanderbilt-- he published this paper in "The New England Journal of Medicine." And it was sobering. The two messages I want to say is that a patient undergoes surgery or radiation, at least a third of patients had significant urine incontinence at 15 years. And the bottom graph here is even more sobering. At 15 years, the vast majority of patients will have issues with erectile dysfunction following surgery or radiation. And Bruce Jacobs is a friend of mine. He published this paper-- and this is why my specialty in urology and radiation oncology has sort of become the target of CMS-- because we are over-treating patients. So Bruce Jacobs looked at this data-- using SEER-Medicare data-- for low-risk prostate cancer. I would argue active surveillance should be a integral part of the discussion. And as you see here on the left, at least 40% of patients United States who have low-risk prostate cancer are getting treatment. The other thing about prostate cancer is the indolent disease process. I measure outcomes at 10 years. If patients have less than a 10-year survival, I would argue they shouldn't be treated, irrespective of their stage, irrespective of their risk stratification. In the United States, 50% of patients who have a less than 10-year life expectancy are receiving treatment. Another reason why PSA testing causes harm is because we're biased-- urologist and radiation oncologists in particular. And I was funded previous to this national survey. And the take-home message here is that if you ask a urologist, what is the best treatment? Surgery. You ask a radiation oncologist, what is the best treatment? Radiation therapy. And the small minority of specialists said active surveillance is the best. And that's on the far right. Well, AUA really endorses PSA testing and prostate cancer screening. And if you're in the camp saying, well, look, it's beneficial, you could say that since the 1980s, when we introduced PSA testing, there has been this huge migration from locally advanced disease to organ-combined disease. And second, there's been a reduction in prostate cancer specific mortality. So this paper actually shows that. 1987 to '89 on the far left-- 80% of patients had disease outside the prostate. 1996, that went down to 50% due to PSA testing. And Otis Brawley-- who is the President of the ACS, American Cancer Society-- who is not a big fan of PSA testing, published this paper saying that, if you look at the bottom, since the introduction of PSA testing, the mortality of prostate cancer has gone down over time. So I just want to look at this Grade D recommendation for the US Preventive Task Force. It's based on two clinical trials. I think to be informed about the discussion, I think we should thoroughly look at the evidence. And so Virginia [INAUDIBLE] published this result saying that we should not screen people based on these two trials. If you look at the meta analysis here, you can clearly see there's only really one group, or subgroup, in Sweden where a few randomized patients for PSA testing improved prostate cancer survival. But if you look at the evidence more carefully, I would argue that some of these trials were a little bit flawed. So the PLCO trial led by Gerald Andriole at Wash U. randomized about 76,000 patients from 10 academic centers from 1993 to 2010-- randomized usual care, or screening with a PSA or DRE. Indications for biopsy were a PSA of greater than four, or abnormal DRE. And as you see in this trial on the top graph here, if you got screened, you're going to get diagnosed. I mean, that makes sense. But the more telling thing, the more sobering thing for urologists and primary care providers, is that for those who were screened and not screened, there was no difference in prostate cancer survival. So their conclusion was, there was no evidence that prostate cancer improved survival from this malignancy. I would argue, though-- and even Gerald Andriole, who's the urologist who ran the trial, said this was a flawed study for this following reason-- 2/3 of men who were randomized underwent screening prior to the trial. So it was not a pristine trial. Furthermore, 50% of men who were in the intervention arm were not compliant with the protocol. If you look at the European trial, seven countries randomized 55 to 74 to either control arm, or screen with a PSA and a DRE for four years. And here, as you can see in this trial, screening actually did improve prostate cancer survival. And their conclusion-- that screening's associated with an absolute reduction of 0.71 possible cancer deaths per 1,000 men and a mean [INAUDIBLE] of 8.8 years. To prevent one prostate cancer death, you need to invite 1,000 men to be screened, and you need 37 men to be treated now. You could argue-- and I don't have the right answer-- but is the number needed to treat worthwhile? It's a very controversial thing, because a lot of men need to be screened. A lot of men need to be treated to save one life. So the other thing about the US Preventive Task Force is that they hinged their Grade D recommendation-- recognized the fact that 90% of men in the United States are getting treated for prostate cancer. I would argue a third of them do not. And the NCCN recently talked about active surveillance and encouraged it. And if you look at their guidelines-- low-risk prostate cancer, no nodule on DRE, PSA less than 10, a Gleason score of less than six-- even those who had a greater than 10-year life expectancy should be talked to about active surveillance, because the risk of prostate cancer death is 1%. Now, I certainly could do surgery and offer this patient radiation to make that zero. But based on the previous slides for all the quality of life implications, that is a discussion that should be had with the patient. And active surveillance should be now an integral part of the discussion for low-risk prostate cancer patients. And I just point to this great trial by [INAUDIBLE]. I actually know him. He's a very nice guy. He's a urologist in Toronto. And I remember in 1990, he got up in front of a room of urologists, said, for low-risk prostate cancer, I don't know if we should be treating these patients. They have low-risk disease. I cannot tell you the amount of name-calling he was called, because he's a urologist. He's a surgeon. It's cancer. We should get it out. And he did this trial to prove people wrong, and he ultimately was right. He enrolled 819 men with low-risk prostate cancer in Toronto. He said, I don't know what the right evidence is, but let's just watch you and see what happens. Over a period of 10 years, about half these men ended up getting treated because their PSA went up, the Gleason went from six to seven, or their DRE exam worsened. The most telling thing though, the thing that got the press, is that only 1.5% of men died-- 1.5%. And he proved urologists who were very in favor treatment wrong, and rightfully so. And-- Dr [INAUDIBLE] mentioned this earlier. I found this very interesting. I was preparing this talk-- and I'm a urologist, and I do [INAUDIBLE] internal medicine-- but I saw this as it came across my desk. I'm like, wow, this is interesting. They're talking about high-value care and advice for cancer screening. And in the study of the US Preventive Task Force, I found their discussion very interesting, because ultimately-- if you look here at the bottom for prostate cancer-- this mirrors the AUA guidelines. For patients who are 55 to 69, we should have informed discussions about the risks and benefits of screening. And if a patient wants to pursue screening, it's a worthwhile thing to do. So, to screen, or not to screen. I don't have the right answer. There is not a lot of great evidence out there. I would point out one thing which I didn't include in this graph. There are two cancers in the Cuyahoga County which we do worse on from a survival perspective compared to the national average, and that's prostate cancer and cervical cancer. We are by far the worst. I was on faculty at Yale about a year ago, and I was commenting to my friend how many patients I've been seeing with locally advanced disease. I don't know what the reason is, but the prostate cancer outcomes in this county are worse than the national average. And so what I would recommend is that for patients between the ages 50 to 69 with a greater than 10-year life expectancy, we should offer PSA screening after a thorough discussion about the risks and benefits. The screening should include a DRE and a PSA. It should not occur in men who are greater than 70 years old, who have a less than 10-year life expectancy, or for patients who simply say, look, I've viewed the risks and benefits. I simply do not want to be screened. Who should get a biopsy? I would argue there's a lot of good evidence-- we have better technology, in particular the MRI-- for patients who have a PSA greater than four, they should be referred to a urologist for a biopsy or an [INAUDIBLE] DRE. I would encourage you to refer to a urologist who will work with primary care doctors by discussing the role of a biopsy, and then also the role of treatment. I've been here for about 10 months now, and I was in Connecticut for two years prior to this. There are a lot of misaligned incentives when it comes to prostate cancer and treatment decisions-- in particular, the use of the robot IMRT, and now the proton beam. I think it's important that whoever you ultimately refer to, make sure you refer to a urologist who will discuss the risks and benefits of treatment. And also, highlight the importance of active surveillance, because the US Preventive Task Force did have one thing wrong, because they hinged a lot of their discussion based on over-treatment. I was recently at the last AUA and-- I don't have the slides because the papers have been published-- urologists are responding. We are not treating as much low-risk prostate cancer in the nation as before. So I really encourage you to find that urologist who will work with you to make sure that patients are fully informed about the implications of both screening, biopsy, and treatment. Thank you very much. I really appreciate it.