Conservative Management Is on the Rise in Intermediate-Risk Prostate Cancer

Michael S. Leapman,

MD, MHS

Associate Professor of Urology,

Yale School of Medicine

Clinical Program Leader, Prostate & Urologic Cancers Program

Yale Cancer Center

New Haven, CT

PATIENTS DIAGNOSED WITH intermediate-risk prostate cancer are increasingly likely to be managed with active surveillance or watchful waiting rather than immediate treatment, based on a recent analysis published in JAMA. In this patient population, the decision to treat or observe patients is challenging and can vary widely across the United States.

In low-risk prostate cancer, nontreatment approaches are recommended by the NCCN and other guidelines, but in intermediate-risk disease, it can often fall to the judgment of the treating physician and patient. Researchers from Yale Cancer Center analyzed the Surveillance, Epidemiology, and End Results (SEER) database and found that 12.3% of patients in 2020 opted for active surveillance/ watchful waiting compared with only 5.0% in 2010.¹ They looked deeper into risk factors that affected their risk stratification such as prostate-specific antigen (PSA) level, Gleason grade, and disease stage. The trend toward more conservative management over a decade was especially clear in patients with less aggressive disease, pointing toward an emphasis on personalized care in prostate cancer.

Michael S. Leapman, MD, MHS, senior author and associate professor at Yale School of Medicine, discussed his takeaways from the study results and possible explanations for this trend in an interview with Peers & Perspectives in Oncology.

Peers & Perspectives in Oncology: Could you describe your study on active surveillance or watchful waiting in patients with intermediate-risk prostate cancer?

MICHAEL S. LEAPMAN, MD, MHS: The study was a review of people diagnosed with prostate cancer in the United States, drawing from the SEER registry, and we found a significant increase in the use of active surveillance or watchful waiting in patients with intermediate-risk prostate cancer. That is a group where, historically, the majority have been treated, and what we found is that the majority still are treated, but the rates of active surveillance have gone up considerably in that group.

What is the rationale for using active surveillance in this patient population?

Even though patients have intermediate-risk prostate cancer, that’s a very broad category. The majority of people who are diagnosed with localized prostate cancer fall in this big umbrella category. There are some patients who have truly aggressive prostate cancer who are in the intermediate-risk category, but on the other end of the spectrum, some cancers that meet that definition are edge cases—a PSA level that’s a little bit high or a little bit of a higher-grade cancer.

We know the risk of death from intermediate-risk prostate cancer, especially in certain subsets, is quite low. Treatment of prostate cancer has potential harm to patients, including adverse events [AEs] that result from surgery, radiation, or hormone therapy. These can include urinary incontinence, sexual dysfunction, bowel or rectal toxicity, as well as AEs from androgen deprivation, which can include hot flashes, loss of bone mineral density, fatigue, and cardiovascular effects. It’s a question of the risk [vs] benefit of treating these patients.

Why is there variation in how physicians are approaching this decision?

The most important factor by which it varies is probably the provider…. Rates of active surveillance or conservative management are historically higher in academic vs community hospital settings, but the numbers are leveling off. Some of the drivers may be physician comfort and expertise in prostate cancer management because the concept of doing surveillance is a newer concept. The dogma has been: If you see cancer, you treat it. There may be a generational conflict, which may underlie some of it. There are also financial motivations to treat prostate cancer vs watch it.

Ultimately, physicians are trying to do the best thing for patients, and this is an area where there is some uncertainty in the data. There are concerns about long-term impacts of surveillance. It’s also difficult to tell a patient who wants to be treated that they shouldn’t be treated…. It requires some nuance and subtlety in explaining why treatment might not be right for everyone. It doesn’t mean that no one should be treated, but… it is a fairly nuanced decision, and there are pros and cons on both sides.

How much is the decision driven by the patient vs the physician?

It’s probably both. It starts with the physician and how they discuss it with the patient. But in my own practice, more and more patients do research after they see the diagnosis. In the NCCN guidelines and the clinical practice guidelines, active surveillance is the recommended preferred approach for low-risk prostate cancer. For low risk, the case is somewhat closed, even though uptake hasn’t fully reached the point where it should. Intermediate risk is difficult because the guidelines suggest that surveillance could be done, but it’s an area where there’s still equipoise in terms of what the best initial approach [is].

I wouldn’t fault a physician or a patient for wanting to be treated or not. We don’t have strong evidence to suggest that one is better than the other for the intermediate-risk group. Some of it is substratifying and saying, “What are the features that are the most concerning that should drive treatment or not drive treatment?”

Is the type of provider involved in treating localized disease a factor?

Active surveillance is almost exclusively done by the urologist. There are some studies showing that if you see a radiation oncologist, you’re more likely to be treated, but that doesn’t necessarily tell us cause and effect. Maybe they saw that person because their intention was to be treated. We still think that this initial decision-making is very much in the court of the urologist. That’s where a lot of the efforts are being put forward to educate and to figure out the best way to navigate that first decision.

What were the most interesting findings you observed?

Even though we looked at the intermediate-risk definition, you can get there in lots of ways. The broadest definition is someone who has a PSA level between 10 and 20 ng/mL, a Gleason score of 7, or a higher-stage cancer on examination. Any 1 of those 3 will constitute an intermediate-risk definition. When we broke it down by where surveillance is growing, it’s primarily in patients with a higher PSA level. The grade of cancer is still a big driver of treatment, even though there’s been a big growth in those with PSAs in the range of 10 to 20 ng/mL but a more modest growth in those who have an intermediate-grade cancer.

What questions remain from your study, and what are your next steps?

We have a very active program studying prostate cancer active surveillance to understand what the drivers and motivators are for treatment, to help understand some of the national variation, and to begin to think about ways to motivate evidence-based practice, particularly in the low-risk setting where the evidence is stronger that we shouldn’t treat most patients who have nonaggressive cancer in the beginning. We’re very interested in understanding the factors that can help promote good evidence-based care vs ones that detract from it….

Another wrinkle of this, which is not covered in our paper, is that there are a host of adjunctive tools, such as imaging and biomarkers, that help tell us about the cancer’s aggressiveness. I’ve been very interested in understanding how well those tools work. Are they helping us give a better prognostic estimate to a patient? Does precision medicine help tell people [whether] they should be treated…and with what intensity?

Could the use of these tools contribute to the trend toward active surveillance?

We’ve done some studies where we’ve tried to look at that, and we have seen a correlation between areas that have [more] use of those tests and more use of conservative management.

I don’t know that we can conclude firmly that they are causing it; they may just go hand in hand. It’s possible that doctors and patients who are choosing to do monitoring want the tests more rather than the tests causing a change in the management. That’s a fundamental question that we’re trying to answer because we’re doing a lot of the testing, and whether it is causing us to do different things in our management remains to be determined.

One of the big barriers to doing surveillance is the need to do follow-up testing. Some patients reasonably don’t want to go through additional biopsies, imaging, or invasive diagnostic testing. We’re very interested in ways to identify changes in cancer risk that would motivate treatment sooner to make monitoring less invasive.

What else stands out about your study approach?

It comes from the SEER registry, which is a national cancer registry. What’s unique about it is that it’s been difficult to determine who got surveillance and who didn’t, because sometimes the definitions are unclear. This is a database that was specifically made by SEER with the purpose of identifying conservative management: active surveillance or watchful waiting.

Active surveillance and watchful waiting are really 2 separate categories in the database; they don’t distinguish. We know that those patients aren’t being treated, but active surveillance refers to a more intensive form of monitoring with the intent to treat in the future if there’s a change, whereas watchful waiting is probably more reserved for people who are in poor health, in whom we’re not going to check as intensively, and we’re not going to offer more treatment unless they really are symptomatic. It’s an umbrella term, and we don’t know the breakdown between the two.

REFERENCE

1. Ajjawi I, Loeb S, Cooperberg MR, et al. Active surveillance or watchful waiting for intermediate-risk prostate cancer, 2010-2020. JAMA. Published online November 20, 2024. doi:10.1001/jama.2024.20580