30 Jun Active Surveillance Utilization For Prostate Cancer Remains Low
MedicalResearch.com Interview with:
Hui Zhu, MD, ScD
Section Chief, Urology Section
Louis Stokes Cleveland Veterans Affairs Medical Center
and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation
MedicalResearch: Tell me a little bit about the impetus for this study. What gap in knowledge were you trying to fill?
Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause of cancer death in American men, behind only lung cancer. However, for the majority of men, prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer.
In an effort to avoid suffering and death from prostate cancer for those men with the lethal form, the early detection of prostate cancer (before the disease has reached a stage when it is no longer curable) through widespread prostate cancer screening was instituted in the late 1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and most prostate cancers were detected at an early, treatable stage. Screening successfully reduced the risk of death from prostate cancer by 20%.
Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal prostate cancer. As a result, about 800 men must be screened and about 30 men must be diagnosed and treated to avoid one death from the prostate cancer, according to recent results from the largest prostate cancer screening trial.
Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively, leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary treatment, these men are exposed to the potential side effects and complications of treatment, including erectile dysfunction and urinary incontinence.
In response to the harms associated with screening and treatment, the US Preventative Services Task Force issued a statement in 2011 (formalized in 2012) recommending against prostate cancer screening in all men. Unfortunately, while minimizing the risks of overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution eliminates any of the potential benefits of screening for those men with the lethal form of the disease.
As urologists, our solution is different. Rather than throw the baby out with the bathwater, we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing its associated risks. To achieve this, our goal is to better distinguish between those men who have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the lethal form of the disease at an early stage when it is still curable. The dilemma is that our currently available diagnostic tests are unable to accurately differentiate lethal from nonlethal prostate cancer with 100% certainty at the time of initial diagnosis.
The solution, or at least part of the solution, is active surveillance. In men who appear to have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to observe these cancers, at least initially. This is the concept behind active surveillance. Active surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing and reserving the option of treatment for those men with prostate cancers that exhibit lethal characteristics. In this way, active surveillance preserves the benefits of screening while minimizing the harms of overdiagnosis and overtreatment.
Active surveillance was first introduced in the early 2000s, but its efficacy and safety have only been elucidated recently over the last 5 years. Given that active surveillance may be one solution to the screening dilemma, we wanted to evaluate contemporary active surveillance utilization, which is the impetus for our study. Based on the most recent data available to us, we chose the years 2010-2011, which coincide to the time immediately before and during the release of the US Preventative Services Task Force statement against PSA screening.
MedicalResearch: We’re talking about men with low-risk prostate cancer, correct? Can you elaborate about what that means for these men?
Dr. Zhu: Low-risk prostate cancer is a term we use as urologists to describe prostate cancer that has a low-risk of clinical progression, that is, prostate cancer that is unlikely to invade outside the prostate, metastasize to other organs, or become lethal. These prostate cancers are usually small in size and of low grade (e.g., Gleason grade 3). The PSA values of those patients are also relatively low, e.g., less than 10 ng/dL. Unfortunately, our diagnostic means of characterizing localized prostate cancers through the digital rectal exam, PSA, and biopsy results has limited accuracy. For example, about 30% of men who are initially characterized as having low-risk disease may actually have more aggressive occult disease that is not initially detected, according to recent studies.
MedicalResearch: To make sure I understand the statistics: 11-40 percent of the men were eligible to undergo active surveillance. But of ALL the men, only 6-12 percent actually underwent active surveillance.
The rest got one or more kinds of medical, surgical and radiation treatment? Is that correct?
Dr. Zhu: Yes, approximately 11-40% of men were eligible for active surveillance, depending on the criteria used to define “low-risk” disease. Since we cannot be 100% sure that a low-risk prostate cancer is nonlethal at first glance, we use different criteria (based on Gleason grade, PSA level, clinical stage, and cancer volume) to further stratify low-risk patients. As the inclusion criteria become more stringent, our certainty that the cancer is truly nonlethal increases, but the number of men who meet the criteria decreases. By the least stringent (most inclusive) criteria (e.g., Klotz criteria), 40% of men in the study were eligible for active surveillance. By the most stringent (least inclusive) criteria (e.g., modified Epstein criteria), only 11% of men in the study were eligible. Of men eligible for active surveillance by Klotz criteria, only 6.5% received active surveillance. Of men eligible for active surveillance by modified Epstein criteria, only 12.1% received active surveillance. Therefore, as our certainty in the nonlethal nature of the prostate cancer increased, so did our use of active surveillance. Having said that, the actual utilization was very low. By comparison, in Europe, where active surveillance is more widely accepted (i.e. professionally and culturally accepted), active surveillance rates range from 16-59%. In all fairness, however, it is only recently that long-term data revealing the safety and efficacy of active surveillance has been released. For example, it is now clear that using Klotz criteria to determine a man’s suitability for active surveillance is safe. Based on recently published long-term followup data, 55% of men on active surveillance using Klotz criteria remain untreated on active surveillance at 15 years, while only 2.8% of men develop metastatic disease and only 1.5% of men die from prostate cancer.
MedicalResearch: What’s the take-home message of your report? What should the public take from it?
Dr. Zhu: The diagnosis and management of prostate cancer is dynamic. The use of active surveillance, although low in this study, is an ongoing process that is gaining acceptance among urologists and patients. Urologists and researchers are currently working on ways to better differentiate lethal from nonlethal prostate cancer through the use of systematic needle biopsies, serial PSA levels, tissue biomarkers including genetic markers, and modern MRI imaging techniques. These new strategies have shown promise in helping urologists better identify which patients may benefit from upfront treatment and which may be better served with active surveillance.
MedicalResearch: Do these findings mean that many men are getting treatments that they don’t need and could be harmful? What are your thoughts about that?
Dr. Zhu: Yes, many men are overtreated for prostate cancer, and aside from the risks of unnecessary treatment itself, these men are exposed to the complications associated with treatment, including erectile dysfunction and urinary incontinence. However, at the time of treatment, it is not always clear which men “need” treatment, i.e. which men have lethal vs. nonlethal prostate cancer. This is where active surveillance helps. The initial period of observation and careful monitoring can help tease out which cancers are more likely to become lethal and should be treated from those cancers that are nonlethal and better left untreated.
MedicalResearch: What can we learn from your report about the places that use active surveillance more and less?
Dr. Zhu: During the study period, active surveillance use seemed to be used more heavily at centers of excellence and regionally within the Northeast. These practices likely reflect both provider factors as well as patient preferences. As active surveillance has gained more national exposure and acceptance, its current use may be more widespread.
MedicalResearch: What is the message here for patients and their loved ones/caretakers? What should they take from this? What about physicians?
Dr. Zhu: Prostate cancer is a challenging disease. Early prostate cancer detection through screening has potential risks and benefits. By limiting treatment only to lethal forms of the disease, active surveillance has the potential to mitigate some of these risks while maintaining the possibility of cure for those men with lethal disease. Age-appropriate men should discuss the risks and benefits of screening with their physicians, and men with newly diagnosed localized prostate cancer should ask their physicians whether active surveillance is a good option for them.
MedicalResearch: What else should readers know?
Dr. Zhu: Prostate cancer, even the lethal form, is highly treatable when it is detected at an early stage through the use of screening. Men aged 55 to 69 years who are considering being screened for prostate cancer should have a discussion with their physicians which involves weighing the benefits of preventing death from prostate cancer against the known potential harms associated with screening and treatment.
Maurice MJ, Abouassaly R, Kim SP, Zhu H. Contemporary Nationwide Patterns of Active Surveillance Use for Prostate Cancer. JAMA Intern Med. Published online June 29, 2015. doi:10.1001/jamainternmed.2015.2835.
Hui Zhu, MD, ScD, Section Chief, Urology Section, & Louis Stokes Cleveland Veterans Affairs Medical Center (2015). Active Surveillance Utilization For Prostate Cancer Remains Low