THE "NEW" PROSTATE CANCER INFOLINK

As we have already, albeit briefly, reported, two “major” papers were published in the New England Journal of Medicine today, and they both were designed to address the appropriateness of mass screening for prostate cancer — among men over the age of 55 years in the USA and over 50 years in Europe respectively.

We wish to state two things immediately:

• These papers have only (perhaps) resolved one of the many issues that have driven the screening controversy for the past 20 years.
• What you have or will read in or hear from the mass media almost certainly will be (or already has been) a vast over-simplification of the complexities inherent in these two papers.

We want to begin by clearly stating that mass screening of all men over a certain age for risk of prostate cancer is not at all the same thing as individual testing for prostate cancer risk. Statistics do not apply to individuals, and decisions about health care are extremely personal, as they most certainly should be. Even if both of the studies published today had categorically proven that, on average, mass screening for prostate cancer was associated with absolutely no survival benefit whatsoever, this would still not have meant that testing of individuals was necessarily inappropriate.

Second, we wish to make it very clear that the issue of whether screening for prostate cancer is appropriate needs to be very carefully separated from the issue of whether the potential harms of prostate cancer treatment are worth the risk of screening. These are two different if closely related discussions — but they are all too often addressed as if they were one issue.

Third, we recommend to every reader of this article that (if at all possible) you watch all of the videotaped discussion between Dr. Philip Kantoff (a member of the Scientific Advisory Board of The “New” Prostate Cancer InfoLink) and Dr. Mary McNaughton-Collins, which appears on the web site of the New England Journal of Medicine. This is a thoughtful and helpful discussion of the two papers, and although the discussants take two different approaches in thinking about these studies, they come to very similar conclusions about the implications of the data — as does Dr. Michael Barry in his editorial on these two papers, where he states that:

… a shared decision-making approach to PSA screening [between the individual patient and his physician], as recommended by most guidelines, seems more appropriate than ever.

So, with all of this said, let’s see what we have actually been taught by these two studies.

The first article, by Andriole et al., is the initial report of prostate cancer data from the so-called PCLO trial. Between 1993 and 2001, this study enrolled 76,693 men at 10 study centers in the USA into its prostate cancer component. These men were randomly assigned to one or other of two groups: an annual screening group of 38,343 men and a “usual care” group of 38,350 control patients.

The men in the annual screening group were offered a PSA test every year for 6 years and a physical examination (a DRE) every year for 4 years. All PSA tests were performed at a single laboratory. The men in the screening group and their health care providers were given the results of these tests and decided together on any necessary follow-up evaluations. It is very important to understand that men in the “usual care” group also received PSA and DRE tests according to the recommendations of certain professional organizations. The distinction is that these men were not being screening rigorously according to the specific guidelines used for the screening group. All patients were followed  for 7 to 10 years and all cancers, deaths, and causes of death were identified and recorded.

The results of this US trial are as follows:

• There was an 86 percent compliance rate for annual PSA testing in the screening group, and an 86 percent compliance with DRE testing.
• Rates of PSA testing in the usual care group ranged from 40 percent in the first year to 52 percent in the sixth year and for DRE testing in these men they ranged from 41 percent in the first year to 46 percent in the fourth year; in other words, approximately half of the men in the control group were being regularly tested for risk of prostate cancer!
• At 7 years of follow-up, the incidence of prostate cancer in the screening group was 116/10,000  person-years (2,820 cancers diagnosed) and the incidence of prostate cancer in the control group was 95/10,000 person-years (2,322 cancers diagnosed).
• The incidence of prostate cancer-specific death was 2.0/10,000 person-years (50 deaths) in the screening group and 1.7/10,000 person-years (44 deaths) in the control group.

The authors of the study conclude only that, “After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups.”

The second article, by Schröder et al., is the initial report of data from the European Randomized Study of Screening for Prostate Cancer (the ERPC study). Because this study involved patients from 7 different European countries, and there were differences in the study protocol from country to country, this is an extremely difficult study from which to interpret results with a high degree of confidence. However …

The investigators identified 182,000 men aged between 50 and 74 years of age from 7 different European countries starting in “the early 1990s”. (The precise dates that different countries started to enroll patients into this trial varied.) As in the PCLO trial, these men were randomly assigned to a screening group or to a control group. However, there the comparison ends. In the ERPC study, men in the screening group received a PSA test at an average of once every 4 years and the men in the control group supposedly did not receive PSA tests at all. The 162,243 men included in this particular analysis had a predefined core age of between 55 and 69 years. The primary outcome of the study was the rate of death from prostate cancer, and the mortality follow-up was the same for both groups of patients, ending on the last day of December 2006.

The results of the ERPC study are as follows:

• 82 percent of men assigned to the screening group accepted at least one offer of screening.
• The cumulative incidence of prostate cancer in the screening group was 8.2 percent at a median follow-up of 9 years.
• The cumulative incidence of prostate cancer in the control group was 4.8 percent over the same median time frame.
• The rate of death in the screening group as compared to the control group was 0.80 (i.e., 20 percent lower).
• The absolute difference in risk of death in the screening group as compared to the control group was 0.71.
• These data imply that, to prevent a single death from prostate cancer, 1,410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated relative to the men in the unscreened population.
• Looking only at those men who were tested during the first round of screening, the rate of death in the screening group as compared to the control group was 0.73.

In this study the authors concluded as follows: “PSA-based screening reduced the rate of death from prostate cancer by 20 percent but was associated with a high degree of overdiagnosis.”

So what can we say that we have learned?

Well in the first place, it is very clear that the vast majority of men diagnosed with prostate cancer do not die of their disease within 10 years — whether they are screened or not. Every qualified commentator on these papers whose opinions we have either heard or read so far makes this point. Whether we like it or not, this information does support the recent statement of the USPHS Task Force that mass screening of men over 75 years of age is not appropriate. However, it does not negate the Iowa Consensus guidance that every man of 75 or over should have a discussion with this doctor about whether continued PSA and DRE testing is appropriate and necessary! If there is one thing that can be absolutely concluded from these two studies, we believe it is the wisdom of the Iowa Prostate Cancer Consensus guidelines.

The second conclusion that can clearly be drawn from these studies is that a 10-year follow-up is insufficient to determine whether prostate cancer screening has an overall mortality benefit. The 20 percent benefit demonstrated by the ERPC study at 9 years is only border-line significant (P = 0.04). It is our understanding that follow-up of subjects in the PCLO study will be continued, but follow-up of men in the ERPC study has (perhaps unfortunately) been terminated.

The only third conclusion that we are able to draw from these studies is that the debate has not been resolved. From this point on — until better data is available — The “New” Prostate InfoLink’s general statement about prostate cancer screening will read as follows:

The only two large, randomized studies of prostate cancer screening, involving men between 50 and 74 years of age, have not been able to offer a definitive recommendation regarding the value of prostate cancer screening that can be generally applied to most men.

At this time we believe every man should have an individual discussion with his doctor about the benefits and risks of PSA testing and physical examination as a guide toward the possible need for prostate biopsy. The timing of that discussion and the subsequent actions of the patient and his doctor can only be determined on the basis of individual risk and personal perspective.

We recognize that some of our readers will not, perhaps, agree with this viewpoint.

The “New” Prostate Cancer InfoLink has long been of the opinion that this debate will never be resolved unless and until some other test is available that can better differentiate between the probable presence of  high, intermediate, and low risk forms of prostate cancer without the need for prostate biopsy. The studies published today have further confirmed this opinion, and should offer a strong stimulus to the urologic oncology research community to focus greater attention on this issue and less on the esoterica of PSA-based screening.

Filed under: Diagnosis, Risk | Tagged: DRE, PSA, randomized trial, screening |