DR. HOFFMAN: Dr. Penson, as a urologist, what do you think about the potential biases in ERSPC in that screened patients were more likely to be treated at university centers? Is that a real concern?
DR. PENSON: I think that’s a very fair criticism of the study. One of the problems that you have with the European study—and to some degree, even the American study—is that there was really no protocol for treatment once a diagnosis was made. There are treatment differences not only in the European study but also in the American study. For example, we know for a fact that there are differences in the quality of surgical interventions between high-volume and low-volume hospitals. I suspect that the same differences exist for radiation therapy. Therefore, I think there are differences with regard to who underwent treatment and where the patients were treated in the European study.
People wish to compare the European study to the American study, but as stated earlier, the European study is a meta-analysis with a number of different screening protocols, and the patients involved in those screening protocols aren’t necessarily a representative population of the United States. So, my take-home message is that we should not generalize the results of either study to all patients. Results of each study can only be applied to patients that reflect those enrolled in that particular study.
DR. HOFFMAN: Over the last 2 decades, professional organizations have issued a number of screening guidelines. Initially, the AUA and ACS were very pro-screening. However, over time, they have acknowledged the fact that screening decisions are complicated, involving tradeoffs between benefits and harms, and that we need to help men make informed decisions. The USPSTF argued for years that there was insufficient evidence either for or against screening.
After the long-awaited publication of the randomized screening trial results, the AUA revised their guidelines. Dr. Penson, can you tell us about these guidelines?
DR. PENSON: As a urologist, I am affiliated with the AUA, which is the primary specialty organization for urology. The AUA’s guidelines are more of best practice statements than guidelines, per se, because they were released immediately after the randomized clinical trials were completed; thus, these trials didn’t have a prominent role in the document as they should have. So, now, AUA is revising the guidelines again, as they do every few years.
DR. HOFFMAN: Dr. Wolf, you were the lead author on the recently revised ACS guidelines. Can you highlight your recommendations and talk about how they contrasted with the AUA guidelines?
DR. WOLF: The ACS guideline, similar to that of the AUA, calls for informed decision making as the centerpiece of the guideline. I think the exact wording was, “Men should have an opportunity to make an informed decision with their healthcare provider about whether to be screened for prostate cancer.” It really does highlight the importance of informed decision making. In fact, in the guideline, it specifically states, “Prostate cancer screening should not occur without an informed decision-making process.”
One difference is the age at which that informed discussion begins. The ACS recommends that the discussion between doctor and patient about whether to screen begin at the age of 50 years. We also recommend that men whose life expectancy is below 10 years not be engaged in that discussion. In other words, the ACS determined that if the patient does not have a 10-year life expectancy, he would not benefit from early detection. In contrast, the AUA guideline, which was just published in 2013, recommends initiating the informed decision-making process at the age of 55 years in average-risk men.20 For men who choose to be screened, they recommend screening until the age of 69 years, rather than following the 10-year life expectancy guideline. In general, the AUA appears to be adhering more strictly to the protocol of the ERSPC.
Other elements of the ACS guideline are also risk-based in the sense that for men whose initial PSA level is below 2.5 ng/mL, the recommendation is now to conduct screening every 2 years rather than annually. If a man’s PSA level is between 2.5 and 4.0 ng/mL, the ACS still calls for annual screening. The AUA guideline, again adhering closely to the European trial protocol, calls for screening every 2 to 4 years.
The ACS guideline also indicates that community-based screening should be discouraged, unless thorough informed decision making can be done at the time of the screening. If that cannot be established, then community-based screening should not be offered. By community-based, I mean in public settings or hospital-based settings where there is a significant chance that decision making would not occur. Such screening should be discouraged.
The ACS guideline includes a delineation of the core elements that should be included in the discussion to assure that informed decision making occurs. These include the potential benefits; for example, prostate cancer can be found earlier with screening than without screening, and early detection may reduce the chance of dying from prostate cancer. However, we also included the disadvantages of screening, including the significant risk of overdiagnosis and overtreatment; the risk of false-positive and false-negative results; the risks of prostate biopsy; and the significant risk of sexual dysfunction, urinary incontinence, and bowel injury that are associated with treatment of screen-detected cancer: these are the key elements.
Another new aspect of the ACS guideline included our recommendation that the DRE be included only as an optional component of screening. This is just based on the lack of data to suggest that it’s an effective screening tool at the population level. The European study did not include the DRE as a part of the screening in most countries, and this study showed a mortality benefit. The PLCO Cancer Screening Trial included the DRE, and it was a negative study. Therefore, on the basis of the randomized trial evidence and other evidence, the ACS elected to make the DRE an optional element of the screening process.
DR. HOFFMAN: To lead the discussion into the last guideline from the USPSTF, I’d like to turn to Dr. Volk, who’s written a number of very thoughtful commentaries on this topic. Dr. Volk, can you summarize the USPSTF recommendation and explain why you question it?
DR. VOLK: First, I’d like to spend a moment describing the Task Force. I think the USPSTF is often misunderstood with respect to their composition, function, etc. The USPSTF was authorized by Congress in 1984 to make evidence-based recommendations about clinical preventive services, including, but not limited to, cancer screening. Members of the USPSTF belong to fields of preventive medicine and primary care, and they volunteer their time to serve on the Task Force. They make these recommendations based on a careful assessment of evidence regarding the benefits and harms of a particular preventive health service.
In 2010, the Affordable Care Act legislation authorized the Agency for Healthcare Research and Quality (AHRQ) to provide administrative, research, and communications support to the USPSTF. The current prostate cancer-screening recommendation from the Task Force is a result of a careful comparative effectiveness review that was commissioned by the AHRQ.
The USPSTF functions autonomously from other government agencies. Their guidelines are not vetted by the AHRQ or any other entity with the Department of Health and Human Services. They have independent authority to make recommendations.
A couple of things to keep in mind: The recommendations are evidence-based, and the Task Force is looking at the same evidence that the other organizations are considering. The USPSTF does function autonomously, as I mentioned earlier, and an interesting aspect of their work is that they consider the cost of an intervention only because that cost relates to people’s ability to partake in the intervention.
In July 2012, the USPSTF issued its recommendation about screening for prostate cancer, and we did have a heads up about the update. The USPSTF has implemented a new process in which they post drafts of their recommendations and have a comment period where people can indicate their reactions to an upcoming recommendation. Therefore, we knew that this guideline was going to be released.
This is a “D” level recommendation from the Task Force, and it reads, “The Task Force recommends against PSA-based screening for prostate cancer. This recommendation applies to all men in the general US population, regardless of age.”
They go on to talk about the guidelines not addressing issues such as using PSA for surveillance.
In summary, what the USPSTF has done is review the evidence largely from the 2 screening trials that have been mentioned previously. They have concluded that the harms of screening, which are well known and well documented, exceed the potential benefit of screening; in effect, they recommend against prostate cancer screening.
This is different from their recommendation of 2008 where the USPSTF issued an “I” recommendation, arguing that the evidence was insufficient to recommend for or against screening. Therefore, the USPSTF is a bit of an outlier when considering the recommendations of other groups.
This is a controversial recommendation, and there have been quite a few comments and criticisms about it. We’ve talked about the concerns regarding the PLCO Cancer Screening Trial, and perhaps, the USPSTF gave too much importance to the PLCO Cancer Screening Trial findings, especially considering the high (>50%) contamination rate among the control men.
Additionally, there have been concerns about the USPSTF not giving enough importance to the European trial. In particular, the trial from Goteborg21 showed a significant benefit in terms of prostate cancer mortality and a much lower number needed to be screened as compared to the overall trial.
Then again, they released a “D” level recommendation. People would have been much more comfortable with the recommendation if it had been a “C.” A “C” recommendation would recommend against routine screening, which would be very much in line with the recommendation of other groups that endorse an informed or a shared decision-making process.
DR. HOFFMAN: Dr. Wolf, regarding the informed decision-making process, ACS has consistently supported this concept. Can you define informed decision making and explain its importance?
DR. WOLF: In general, whenever there is an intervention or a diagnostic tool where the balance between the benefits and potential harms is too close to call, it is really incumbent on physicians to engage patients in an informed decision as to whether they wish to proceed.