Daniel A. Barocas, MD, discusses a study that compared differences in quality of life among patients who have undergone radical prostatectomy, external beam radiotherapy, brachytherapy or active surveillance for low-risk prostate cancer.
Daniel A. Barocas, MD
Daniel A. Barocas, MD
Patients with low-risk prostate cancer should consider active surveillance, as opposed to surgery or radiation, which may be unnecessary, suggests Daniel A. Barocas, MD, lead author of a recently published study in theJournal of the American Medical Association,which compared differences in quality of life among patients who have undergone radical prostatectomy, external beam radiotherapy, brachytherapy or active surveillance for low-risk prostate cancer.
To ease patients into the idea of active surveillance, he recommends that physicians counsel patients on their options before biopsy, as to alleviate any fear or stress that comes with a cancer diagnosis, especially when the suggested treatment option is essentially “no treatment.”
“There is some acceptance of risk on the part of the patient, but typically that risk of disease progression is small compared to the risk of side effects from treatment that they may not need,” said Barocas.
In an interview withTargeted Oncology, Barocas, associate professor, Vanderbilt-Ingram Cancer Center, discusses the study and the benefits of active surveillance in patients with low-risk prostate cancer.
TARGETED ONCOLOGY:What was the intent of this study?
For the patients that have low-risk prostate cancer, doctors are recommending active surveillance. We wanted to compare new treatments and active surveillance and the results are pretty nuanced. I think what is new here is that we are talking about the more contemporary, modern treatments. Side effects of other treatments have been studied previously, but they have not been studied systematically in the more contemporary treatments. Meaning, robotic surgery and the advanced radiation techniques of intensity modulated radiation therapy and sort of modern active surveillance as opposed to the older-style "watchful waiting."
One thing we can say fairly definitively is that these treatments have some side effects, and they are worth discussing with your doctor and ask if you need treatment at all, and if so, what the right treatment is.
TARGETED ONCOLOGY:What were the significant findings?
At face value, the findings show that surgery has a larger impact on sexual function than radiation treatment, and it also has a bigger impact on urinary incontinence. If you get a little bit more into the details, with sexual function for example, that difference was really only large enough to be clinically meaningful in patients that started out with great function. About 45% of men did not have good erections at the time of diagnosis, so there really is only a subset of patients for whom that difference might be important.
Furthermore, some of the radiation patients get hormone therapy with their radiation treatment, which is appropriate particularly in the high-risk patients. In those patients, hormone therapy completely takes away the libido for the period of time the patient is on it. Some men are on it up to 2 or 3 years; for those men, the difference between surgery and radiation might not be significant. Men who had radiation had some side effects on bowel function, and side effects from the hormone therapy that occur in about 45% of men. Those side effects usually dissipated after a year. So, by the 3-year time point, they looked pretty similar to the active surveillance group.
Another small finding was that men who had surgery to remove the prostate actually did better than men who were on active surveillance in terms of those bothersome symptoms of an enlarged prostate. That is intuitiveif you remove the prostate you do not have to deal with the symptoms.
Those are the main findings that we saw, but we also looked at global quality-of-life measures, things like physical functionability to do daily activities, emotional function, and a domain called "energy" or fatigue. There were no differences between groups in those domains. And what that tells us is that men seem to deal with the side effects of treatment without infringing on their general quality of life. Obviously, the domains of sexual function, urinary function, and bowel function are important to people, but in large part they did not seem to have a great impact on the emotional wellbeing or ability to perform their daily activities.
TARGETED ONCOLOGY:In your practice, have you seen an increase of patients opting for active surveillance?
That is a very important question, and is one that transcends the practice level. The short answer is, yes, definitelyand it is something that is happening nationwide. There is no doubt that urologists are recommending active surveillance increasingly for men with low-risk disease and/or men with a limited life expectancy. That is demonstrated daily in our practice but has also been shown in several different studies that both we and others have published. There is a trend toward increasing the utilization of active surveillance in the appropriate settings. I think too often we were overtreating, and I think treatment is decided more sensibly and judiciously these days.
In the state of Michigan, there is a urology collaborative called MUSIC, and they are showing utilization of active surveillance in about 50% among me with low-risk disease. We did a study in the SEER-Medicare Linked Database showing the rising trend of the use of active surveillance in low-risk patients. We did another study using this CEASAR cohort and comparing it to an older cohort that was accrued in a similar fashion, through the SEER registry. I am very encouraged by these studies on long-term oncologic outcomes of active surveillance, which have been very favorablevery few people die of prostate cancer using that strategy and if we can safely keep men away from the side effects of treatment, we are doing them a favor.
Our study did not show any difference in survivalbut it wasn’t intended to show that. For that, you would need to look at much longer follow-up and there are not many good studies that have done that. One randomized trial followed men after 10 years—most of them had low-risk disease and so you wouldn’t expect to see differences in survival because it is relatively low follow-up and mortality events are very uncommon in men with low-risk disease. The other studies we have are not randomized, they are old observational studies using older techniques. Those make surgery look better and I am not sure if that is a fair comparison or not, and I'm not sure if it is still true today with more modern radiation techniques—we usually think of them as neutral, as equally effective. The point that I am making is that some folks believe that surgery may be a more effective or definitive treatment than radiation, and some men might find those side effects acceptable or tolerable if they have more aggressive disease.
TARGETED ONCOLOGY:What message do you think community oncologists need to know about active surveillance?
I think it is a safe alternative for men with favorable disease characteristics. There are pretty specific criteria that we use to recommend active surveillance in terms of having low-risk disease features. It is a nuisance for the patient in the term of repeat testing and biopsies, and there is a potential for patients having some uncertainty or anxiety about living with a cancer that is being observed. But again, the evidence shows that this is a safe strategy. Patients have to accept the possibility of disease progression while they are on active surveillance; although the likelihood of that happening is very low, it is not zero. There is some acceptance of risk on the part of the patient, but typically that risk of disease progression is small compared to the risk of side effects from treatment that they may not need. So, when it is presented to patients in the right way, they seem to understand and accept it.
One additional thoughtand this is anecdotal—is that I find patients accept active surveillance more readily if they have been counseled before biopsy. If they have been counseled before the biopsy, the biopsy could come out 1 of 3 different ways: it could be negative; positive for a clinically significant cancer that we need to treat; or it could come out in this middle ground—a low-grade cancer that can probably be safely observed, which are the cancers that most men will develop over their lifetime and usually do not spread or effect lifespan. If they hear that before the biopsy, then they are less surprised when you talk to them about active surveillance afterward.
The patients that we work with on our research team talk about that sense of fear and failure to understand what comes after the sentence "Sir, you have cancer." It can be very hard to focus and make good decisions when you are scared for your life. And if you had heard beforehand that there are cancers that we find that do not affect lifespan and do not spread, then diagnosis does not trigger that fear response that much and they can make a rational decision about observation.
If you follow people long enough, there is an attrition rate on active surveillance. If you watch people at the 5-year mark, about 30% come off of surveillance and choose treatments. When you look at the figures in our study, you will see that sexual function seems to decline, even in the active surveillance cohort, and some of that is just age-related and some of it is because several of those patients came off of surveillance to go onto surgery or radiation.
TARGETED ONCOLOGY:Is there anything you would like to add?
I'll say 2 things. One is that MRI and some of the newer biomarkers may help us select patients for active surveillance better and may help our patients feel more secure that we are accurately identifying low-risk candidates for active surveillance. And so, there is some good stuff that is in use nowMRIs, like I said, some of the tissue markers, as well as some good things coming down the pike.
The other thing is just a point of interestone of the things that distinguishes our study is having had patient engagement in the design and execution of the study, which really helped us focus on what the patients find important, so that was a valuable experience for us. One of the most gratifying things is seeing the study in the newspaper where it is understandable for lay people. I think that in some respects, it is more gratifying than just being published in a medical journal because it could be potentially useful to a patient.
Barocas DA, Alvarez J, Resnick MJ, et al. Association between radiation therapy, surgery, or observation for localized prostate cancer and patient-reported outcomes after 3 years.JAMA. 2017;317(11):1126-1140. doi: 10.1001/jama.2017.1704.