ASCO GU: Early Treatment and Active Surveillance of Prostate Cancer Patients

Mack Roach, MD

Hans T. Chung, MD

Ahead of the American Society of Clinical Oncology 2013 Genitourinary Cancers Symposium (ASCO GU), held February 14–16 in Orlando, Florida, we spoke with two symposium committee members, Dr. Mack Roach, of the University of California, San Francisco, and Dr. Hans T. Chung, of the University of Toronto, about early treatment and surveillance of prostate cancer patients.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Dr. Roach, what are the current options for patients who are diagnosed with early-stage prostate cancer? And are there different approaches depending on whether the patient is symptomatic or asymptomatic?

Dr. Roach: I would like to start with the second part of the question-the issue of asymptomatic vs symptomatic. We really don’t want to be diagnosing men because they're symptomatic for prostate cancer. If you diagnose a man when they are symptomatic, then they have locally advanced disease typically and the cure rate is going to be substantially lower, so you don’t want to wait until a patient is symptomatic before you diagnose them with prostate cancer. But the options for patients who have early disease, which of course is not going to be a patient who is symptomatic, include active surveillance if it is very early in the disease, particularly if the patient has comorbidities. These patients can be managed with radical prostatectomy, of course, they can be managed with forms of radiation, either brachytherapy or some form of external-beam radiation including what we call IMRT, intensity-modulated radiation. And some men will chose to have proton-beamed radiation. So those are the major options: active surveillance, and definitive treatment with either surgery or radiation.

Cancer Network: What are the deciding factors for a patient who will get active surveillance vs an active treatment?

Dr. Roach: Well, the major factors should be the patient’s age and the existence of comorbidities. If you have a patient who has hypertension, diabetes, are in their 70s and have some history of congenital heart failure, they probably should not be screened for prostate cancer in the first place. But if they are screened and found to have low-risk prostate cancer, then you have to think seriously how much benefit the patient will get from treatment. If a patient has comorbidities as described, but they have very high-risk prostate cancer, so Gleason score of 9, PSA of 20, and extensive involvement of the prostate, you may still want to treat them, depending on how bad the comorbidities are. But again, with the low-risk patients, the problem is that the benefits of treatment are going to be smaller if the disease is early. So it is really about the comorbidities. Also, there are quality-of-life issues. If you have a patient who is sort of in between, so he doesn’t have severe comorbidities but has some, and they are sexually active and want to retain their quality of life, and they understand that the benefits of treatment may be small, and the side effects of treatment may be big, those people may choose to be followed and treated in a delayed fashion, so only when their disease is found to be more extensive. Some patients can go years without any evidence of progression.

Cancer Network: Dr. Chung, in terms of active surveillance, is there any consensus in terms of the options Dr. Roach talked about, any consensus in North America about which patients should be monitored with active surveillance compared to those that should undergo treatment or surgery? Is there a scoring rubric that is used in decision-making?

Dr. Chung: So there are guidelines from the NCCN, the National Comprehensive Cancer Network and they recommend that active surveillance be considered for patients with very low-risk or low-risk prostate cancer and of course, they take into consideration the expected patient survival. In terms of scoring rubrics used for decision-making, I don’t think there is a national or international consensus per se, but I think most centers are going in the same direction. So triggers for treatment for patients on active surveillance include PSA doubling time, so a change in PSA while on active surveillance; Gleason score progression, so upon repeat biopsy, if there is an upgrade in the Gleason score, which gauges the severity of the disease. Also an increase in core involvement in the biopsy, so if there is now more disease in each of the biopsy needles and digital rectal exam results. So those are the things we look at.

Cancer Network: OK, so then in terms of controversies of active surveillance, is this something that most patients understand or do patients tend to opt for treatment in both of your experiences.

Dr. Chung: So the controversy of active surveillance is that despite all of these triggers we use, the PSA score, the digital rectal exam, the Gleason score, these are not perfect. So we do know that there will be a proportion of these patients that despite close monitoring, they do progress, so their prognosis is not the same as the initial prognosis. So there is currently a lot of work in looking for biomarkers or predictors to try to separate those patients whose cancers are more aggressive vs those who have cancers that are on a more indolent course. These biomarkers may include collections from DNA or even imaging.

Dr. Roach: I think the key thing is making sure you don’t underestimate how much disease these patients have. The issue is that just because a patient has low-risk disease, if they only had six biopsies taken, and they were random biopsies, compared to patients who have had more extensive evaluation-we frequently rebiopsy patients with low-risk disease here at UCSF because sometimes if you do an ultrasound-guided biopsy where you actually see something on an ultrasound, you can make a more educated biopsy and find disease that was missed. There are also controversies as to how many positive cores represent higher risk patients-so how much of the core should represent disease? Those guidelines exist but they are soft. There are also some people who believe that imaging, like endorectal MRI with spectroscopy and diffusion-weighted imaging and contrast enhancement might be useful for selecting those patients who would be ideal candidates for active surveillance. If I had a low-risk prostate cancer that was diagnosed, and I was trying to decide if I wanted to be actively surveyed or treated, I would want to make sure that a higher grade component disease was not missed on the biopsy, so I might want to undergo one of these imaging studies. But, it is not standard of care. But the fact is, there is evidence that you can sometimes pick up a high-grade component of the disease that was missed by biopsy.

Cancer Network: Are there any new tests or imaging modalities either to detect or for surveillance of prostate cancer patients that are in development or have been recently implemented?

Dr. Roach: I think that with endorectal MRI technology, and there are other imaging technologies that exist, the question is what is their role, should they be used? Some insurance companies pay for them, some don’t. When should they be used and for which patients? We have the ability to combine the biopsy with an MRI. One problem is if you do an MRI study, and you see something suspicious, how do you make sure that you actually get a sample of that suspicious part of the gland that looked suspicious by MRI. The ideal way to do it is to do the biopsy under imaging. That kind of technology is not routinely available. The question is if we prove that that technology is useful, maybe we need to make it routinely available.

Dr. Chung: We have two MRI studies ongoing at Sunnybrook, one is called UroNav and one is called the ASIST trial. Both are trying to determine the role of multi-parametric 3T MRIs. The UroNav study was recently presented at the RSNA conference, and they compared MRI-guided biopsies vs plain random biopsies and found that the MRI-guided biopsies could detect more clinically significant cancer (ie, those of Gleason score of 7 or above) with less trauma, so less core biopsies and more accuracy.

Cancer Network: Lastly, as far as new approaches to early-stage treatment, are there any updates or changes in the last few years or any new results that we can look forward to at ASCO GU meeting this year?

Dr. Chung: I am very excited about hypofractionated radiotherapy, that is looking at compressing our standard fractionation radiation. So the standard would be 8 weeks of radiation and trying to compress that to 2, 3, or 4 weeks to see if there are equivalent long-term outcomes and toxicity. That is the big question right now, but early data seem to suggest that this approach is just as good as the standard, so that would be exciting. The second would be dose-painted radiotherapy which means you give a higher dose to a known area of cancer within the prostate. So rather than just treating the whole prostate with the same dose which we do currently, you would treat the prostate with the same dose, but if you see a nodule within the prostate, you would give that area a higher dose.

Cancer Network: Can we expect results for any of these modalities at the ASCO GU meeting or are these trials still ongoing?

Dr. Chung: There have been many studies with hypofractionated radiotherapy; it’s just long-term outcomes that are still to come. Punctate dose radiation I think we will hear more and more about it. I think it will likely be mentioned at this conference.

Cancer Network: Dr. Roach, do you have any studies or results to highlight?

Dr. Roach: I don’t think that at this meeting, there will be something that is profoundly transformative with respect to treating men with low-risk prostate cancer. I do think that there is an interesting study that Dr. Chung and I did a few years ago, a prospective study looking at a 5-alpha reductase inhibitor to see whether or not a drug that did not cause castration, and the side effects of castration, could be used to suppress the progression of men with low-risk disease. So I talked about the standard treatments for low-risk prostate cancer, radical surgery, observation, and forms of radiation. I think that there is potential that drug therapy could be developed that would be relatively nontoxic, that could slow the progression of disease to a point that if you had a 70-year-old man you could give him a pill to take once a day that slowed progression of the disease. So instead of the disease reaching a T3 lesion, a locally advanced lesion, in 5 to 10 years, it could be 10 to 15 years. Our study was a proof of principle that maybe with sophisticated imaging and a series of patients with low-risk disease, you could document the responses or at least enroll patients on such a study. So in the future, investigations into the use of less toxic drugs to manage patients with low-risk disease is also another option that is not a standard treatment now.

Cancer Network: Thank you both so much for joining us today.

Dr. Chung: Thank you.

Dr. Roach: OK, thanks.