Expert Weighs In: Active Surveillance in Prostate Cancer

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When it comes to active surveillance and prostate-specific antigen (PSA) screening for localized prostate cancer, the paradigm has been shifting and the debate over which is correct has been raging on in recent years, says Andrew Stephenson, M.D.

When it comes to active surveillance and prostate-specific antigen (PSA) screening for localized prostate cancer, the paradigm has been shifting and the debate over which is correct has been raging on in recent years, says Andrew Stephenson, M.D.

Active surveillance is a resource being increasingly used in clinical practice for patients with low-risk disease, Stephenson said, adding that it should continue to be used as long as it is done appropriately.

Moreover, the use of routine PSA screening is being seen in a different light following evolving recommendations from the US Preventative Services Task Force (USPSTF). In April 2017, the USPSTF released a draft guideline stating that, for men aged 55 to 69, the decision to undergo screening should be on an individualized basis. The USPSTF also said physicians should inform their patients of the risks and benefits associated with screening, and they should decide on the best course of action together.

Can you provide an overview of active surveillance in prostate cancer?

In an interview with CURE, Stephenson, who is director of Urologic Oncology at Cleveland Clinic, shared some of the past and current data demonstrating the benefits of active surveillance for patients with localized prostate cancer and the evolving opinions on PSA screening.There has been an important paradigm shift in the management of this disease. We appreciate that there are important impacts on quality of life among the treatments that we would typically offer to patients who have localized prostate cancer—that being surgery and radiation therapy. Although there have been important developments involving the techniques of these treatments, the impact on urinary, bowel, and sexual function continues to be experienced by a substantial number of patients treated with these modalities, even when they are performed by clinicians with substantial expertise.

We also appreciate that the aggressiveness of prostate cancer has changed substantially, in part because of the early diagnostic strategies we have embraced over the last several decades. Stage for stage and grade for grade, the lethality of these cancers that we are currently diagnosing, in some cases, may be somewhat limited. Therefore, by subjecting all patients to treatment for prostate cancer, we may be subjecting them to harm without any real clear benefit.

There have been certain investigators and centers around the country that have embraced active surveillance early on, for which now we have data about the safety and efficacy about this approach. Certainly, it’s clear that for patients who have gone on active surveillance and been followed appropriately, the risk of progression to metastatic disease or prostate cancer mortality is extremely low.

What we have tried to do both here at Cleveland Clinic and at other centers of excellence around the country is to find the appropriate patient for active surveillance. What are the tools we should use to identify candidates for active surveillance? How should these patients be monitored? When should intervention be considered?

Two important developments in this area have been the development of magnetic resonance (MR) and MR-guided biopsy to help identify important cancers and to accurately characterize cancer aggressiveness. Likewise, there has been elegant work looking at genomics and the utility of genomic biomarkers to identify the aggressiveness of prostate cancer to better select patients for treatment.

What was the rationale on active surveillance in previous years versus how it was used today?

Those are two important developments that will play a large part in determining who are our appropriate candidates for active surveillance, and then we can intensify or scale back the intensity of treatment, diagnostic tests, and surveillance tests that these patients undergo.I presented some data suggesting the lethality of cancers among patients who do not receive an aggressive therapy approach. This is largely data from the pre-PSA era—so, several decades ago—suggesting that in the absence of aggressive local therapy, these patients are destined to die of prostate cancer in a very large percentage of cases. This data may not be applicable to contemporary patients because we are diagnosing cancers in a much earlier stage. Although PSA screening has reduced the mortality from prostate cancer, it also identifies a lot of cancers that may not be biologically important. Therefore, stage for stage and grade for grade, the cancers that we are currently diagnosing have a much lower probability of progressing to

Anecdotally, what impact have you seen active surveillance have on the field?

metastatic disease and lethal disease than cancers we treated several decades ago. There has been a substantial paradigm shift where, a decade ago, active surveillance was seldom performed for patients with long life expectancy because we were concerned about not treating a potentially aggressive cancer and the downstream consequences of that.

How do patients normally handle the conversation of "You have cancer, but you don't require treatment?

However, importantly, patients are becoming increasingly aware of some of the side effects of treatment. Likewise, we as clinicians who treat this cancer understand that, in many cases, these patients are not destined to suffer from their cancer diagnosis in every way. A recent survey suggests that upwards of 40 percent of lower-risk patients are now being considered for active surveillance. Historically, these rates, nationwide, have been typically 5 percent to 10 percent or less. There have been important changes in how frequently surveillance is being recommended to patients. Historically, rates of active surveillance in the United States have been substantially lower than in other countries, particularly Europe even in Canada. The thought was that American patients are more risk-adverse and are not willing to accept the potential risks of having progressive cancer, say, relative to patients in Europe or Canada.

That is not really the case. It is all about the message that we deliver to patients. If we are very data driven in how we explain the various treatment options, patients are actually relieved if they are informed appropriately that they have a low-risk cancer. This cancer may pose a minimal threat to their wellbeing and longevity over the next 10 years and, in many cases, that is very clear.

The USPSTF recently changed their views on PSA screening. Can you comment?

They are relieved; oftentimes, patients are being diagnosed with cancer and it’s the first major health crisis that they are faced with. There is all of the anxiety and uncertainty that goes with having a cancer diagnosis. However, when you explain the risks and the appropriate context and discuss the role of surveillance, patients are certainly relieved that they’re not required to, in many cases, embark on an aggressive treatment strategy upfront. Patients, in my experience and in my practice, are very receptive to the concept of active surveillance. There has been no topic in medicine that has generated greater controversy over the last three decades than whether PSA screening should be routinely practiced among men over the age of 45 or 50. There have been several randomized trials which reported conflicting results about the benefits and harms of PSA screening.

The USPSTF, which is charged with identifying the utility and the safety of things such as cancer screening, gave PSA screening a grade D recommendation several years ago. That was largely on the basis of not so much as a lack of a benefit of screening, but an indictment of how the prostate cancer community in the United States was treating patients with PSA-detected over the last several decades. It was in the sense that everyone who had a diagnosis of prostate cancer got treatment, regardless of their age, life expectancy and the aggressiveness of their cancers.

What has happened since the USPSTF released their grade D recommendation — where they did not recommend screening — is that there have been emerging data showing that, in many cases nowadays, patients are not getting aggressive treatment approaches, active surveillance is increasingly being embraced, and the limitations of some of the trials were nicely highlighted in several studies.

In fact, the USPSTF has reconsidered the role of PSA screening. They now recommend shared decision making between patents and their clinicians about the relative harms and benefits of screening. That has always been my approach when I see patients about PSA screening. It is far more balanced than their initial recommendations a few years ago.