Active Surveillance Remains a Critical Approach for Early Prostate Cancer

Brian F. Chapin, MD

No prostate cancers are exactly alike, explains Brian F. Chapin, MD, adding that practicing physicians must individualize patient care based on the information they obtain from risk stratification.

Active surveillance remains an important measurable method for patients with low-risk prostate cancer to avoid overtreatment, he says, but optimizing its use presents many challenges.

“How do you identify those patients?” asks Chapin, who spoke on the topic during the 2017 OncLive^® State of the Science Summit on Genitourinary Malignancies. “How do you avoid missing patients who may have more aggressive disease, either hiding in places so that it was not identified at the initial evaluation, or something that might show up over the course of the patient’s life.”

OncLive: Please provide an overview of your discussion on early-stage prostate cancer.

In an interview during the meeting, Chapin, assistant professor, Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center, discussed the importance of active surveillance in patients with prostate cancer at a low risk of developing metastases. He also highlights the benefits of surgery and radiation as active treatment methods for patients with locally advanced disease.Chapin: I was asked to speak about early diagnosis and treatment for early prostate cancer. Specifically, the focus on the talk was about prostate cancer screening, discussing some of the limitations to what we have toward prostate cancer screening with the use of prostate-specific antigen (PSA) testing and digital rectal exam, and then focusing on the use of transrectal ultrasound biopsy, as well as the MRI-fusion guided biopsies in order to identify prostate cancer.

Once the cancer is identified, we go over the risk stratification for prostate cancer and how we identify patients who we would like to treat with active surveillance versus treatment with radiation or prostatectomy.

How do you decide whether a patient should undergo active surveillance or active treatment?

This talk focused on the low-risk population, trying to identify them, and explaining that we are identifying a group of patients who are likely to have low-risk metastatic potential, and a low chance of having their prostate cancer progress to the point of needing additional treatment for systemic manifestations of the disease. The ways we risk stratify patients into the low-risk category, which is mainly the group that we will put on an active surveillance program, is mostly by Gleason scoring. This is a pathologic assessment of the tumor, and we identify Gleason score 6—which is grade 3 + 3 tumors—as being low risk and having low metastatic potential.

There are other factors that fit in, such as PSA and digital rectal exam, which we use to categorize patients in the low-risk group. Then, at The University of Texas MD Anderson Cancer Center, for example, we primarily use a protocol-based program where we do a confirmatory biopsy within 6 months of the original biopsy, and planned assessments every 6 months with a digital rectal exam and PSA test.

How has the use of active surveillance changed the landscape of prostate cancer?

Every 1 to 2 years, we do a repeat biopsy and/or MRI-scan imaging to help us better assess the patient’s situation and make changes, as there are changes in the patient's disease. There has been a large increase in the number of patients going onto an active surveillance program. We have seen an increase nationally, where it used to only be a small proportion of men. Now, we are seeing that up to 40% of men who are diagnosed with low-risk tumors are going onto an active surveillance program.

How do you have this particular conversation with patients—that they have cancer, but it’s not something that actually needs to be treated?

There has been a shift. People, I think, have a new appreciation for the fact that not all prostate cancers are the same. There are prostate cancers that are indolent and are unlikely to cause significant problems. Patients are becoming more aware of that, so they are seeking out other options and not just going with the original recommendation that may be for active treatment. It’s a difficult conversation, especially because the system that we use to assess the tumors is a little bit confusing. Typically, the lowest grade you can have on a biopsy is a Gleason 6 tumor, but patients automatically assume that theirs is a middle-grade tumor because 1 through 5 happens before 6.

This has been addressed by the International Society of Urological Pathology in 2014; they tried to change the way we approach this and group the Gleason 6 as grade group 1, the 3 + 4 (7) tumor is grade group 2, and so on. You can tell someone they have a grade group 1 tumor and hopefully make them understand that it’s not really as aggressive or concerning.

I also basically explain to patients that, when we look at the clinical outcomes of patients with Gleason score 6 prostate cancer, there are large studies of patients who have had prostatectomy and no dissections. There is limited to no actual evidence of node involvement in those patients. The patients who have a prostatectomy had a Gleason score 6, the mortality is extraordinarily low—like decimal point low.

What impact has the MRI ultrasound-fusion guided biopsy had on the prostate cancer field?

It is not because we are such great surgeons and we’re so good at doing the operation. It’s because the biology of the disease is not one that’s aggressive. Therefore, they’re unlikely to have a significant problem over many years. We have to account for a lot of the things that play into this, like their comorbidities, age, and life expectancy, and make some decisions based on all of the clinical information. It really is an individualized decision that has to be made. In the United States, it’s different than in Europe. In the United States, the MRIs are often something that is not approved by insurance companies unless the patient has a diagnosis of prostate cancer. Even with that, sometimes, they’re unwilling to let the patient undergo an MRI.

Largely, at The University of Texas MD Anderson Cancer Center, we use MRIs in patients who had a previous biopsy that was negative. Patients then have a rising PSA in revaluation; we sometimes get urine-based markers, such as PCA3 in addition to an MRI scan. If the MRI has an abnormal finding, then we usually will address that with a fusion-based biopsy.

We are identifying some of those tumors that are not necessarily picked up by the standard biopsy approach, maybe even in an earlier time point than in the past, where often tumors would not be picked up by a standard biopsy until it got to a size where it could be identified.

There has been buzz surrounding the use of liquid biopsies in other solid tumors. Does it have the same promise in prostate cancer?

In Europe, and possibly the United States, people are starting to consider doing MRIs before doing a biopsy. Again, there are difficulties with insurance payments for that and the cost of an MRI in the United States is quite expensive versus one in the United Kingdom. I don’t know if that is going to change dramatically in the near future but at some point, as imaging improves, that will hopefully become the standard approach. Then, we can avoid some of the unnecessary biopsies that we’re doing. I do think so, but in the setting of metastatic castration-resistant prostate cancer (mCRPC). It is possible in some of the high-risk population, but identifying circulating tumor cells (CTCs) in a lower intermediate- and low-risk prostate population—I don’t know if we’re going to see a lot of that. And, if we do, the number of mutations that occur in those types of tumors are so low that I’m not sure it’s going to direct our decisions for treatment.

What are the main takeaways for community oncologists on this topic?

However, we are seeing that, in high-risk patients, we are able to identify CTCs and we can now do single-cell sequencing. That does provide some information, as well as in the hormone-naïve and mCRPC setting, and that’s where were learning quite a bit about where liquid biopsies might be beneficial. For the discussion on active surveillance, the main point to stress that not all prostate cancers are the same. There is the risk stratification that has to take place and we have to use that information to decide on individualized treatment.

Not all prostate cancers need aggressive therapy but, at the same time, there are cancers that do have lethal potential that we need to address.

From the locally advanced and surgical approach setting, multimodality therapy is the proper answer for the best treatment for high-risk prostate cancer. It’s not, “Does surgery win or does radiation therapy win?” What surgery does provide is the ability to identify the pathologic elements, the prostate and the lymph nodes, and then use that information to determine what sequential therapy do we follow that up with.

At this time, it’s a good starting step for the treatment of prostate cancer, but I do feel that radiation therapy hormones and surgery are both effective means of treatment. It’s just a question of how to sequence those.