Innovations Redefining Prostate Cancer Care

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a Medical Oncologist and Co-Director of the Sarcoma Program at Cleveland Clinic. Today I'm happy to be joined by Dr. Alberto Pieretti an Urologic Oncologist at Cleveland Clinic Weston Hospital. He's here today to talk about advances in prostate cancer. So, welcome.

Alberto Pieretti, MD: Well, thanks for the invitation. It's a pleasure to be with you and to discuss what are we doing in prostate cancer and where are we going, and how are we helping our patients with this disease.

Dale Shepard, MD, PhD: Sure. So give us a little bit of an idea of what you do here at Cleveland Clinic.

Alberto Pieretti, MD: Yeah, so I'm an urologic oncologist. I train, I do urology at Mass General Hospital in Harbor. I did oncology at MD Anderson in Texas. I have been with Cleveland Clinic for the last three years, and my role here is diagnosis of different types of GU cancer. In those patients who have localized disease, surgery is an option for a lot of them. So I perform those surgeries. There are patients who have locally advanced disease that we do multidisciplinary care between medical oncology, radiation oncology, and surgery. So from that perspective, we work as a team to provide the best cancer care. And then other patients that have advanced disease that I partner with my colleagues from medical oncology and radiation oncology so we could offer the best options for them.

Dale Shepard, MD, PhD: And I guess maybe before we dive too much into this, since prostate cancer is a multidisciplinary disease in many cases, how do you guys work to ensure good multidisciplinary care for patients at all stages? When do you get the other disciplines involved, even with localized disease?

Alberto Pieretti, MD: Yeah, so I try to get involved medical oncology and radiation oncology in the majority of my patients that I feel like they need treatment, because the only option is not surgery. There are patients that, one, could have surveillance. Some patients want to talk with medical oncology and radiation oncology about this option. But then in those patients that we feel that they need treatment, one option could be radiation, radiation with androgen deprivation therapy or surgery, and it's a shared decision-making between the patient and the physicians. I think it's fair for the patients that they hear all the side of the stories. So I try to involve medical oncology and radiation oncology so the patients could listen to all the options, and based on the risk and benefits of each approach, we could take a decision about what is the best for the patient.

Dale Shepard, MD, PhD: So I guess when you think about management of prostate cancer, two questions come to mind early. First would be, what do you think are the most significant recent advances in diagnosis and most recent advances treatment that you think is really changing what we do?

Alberto Pieretti, MD: Yeah, that is a tough question because there has been a lot of changes in the management of prostate cancer, going from diagnosis, the use of MRIs and biomarkers to minimize the number of unnecessary biopsies. Not every patient with an elevated PSA needs a prostate biopsy. Actually, if we do biopsies to the majority of these patients, the majority of them are not going to have prostate cancer or they will have low-risk prostate cancer where the diagnosis create more stress and anxiety than the harm that could create the disease itself. So with the MRI, we could minimize the number of biopsies by 30% to 40%. And then the biopsies could be more precise because we guide the biopsies to the areas of interest, so allow us to understand better the disease itself and we could do appropriate consult.

Other advances in localized disease are the PET scan. Now we have molecular images that are way more precise than a bone scan or a CT scan. It allows to stage the disease better. Also, when we talk about treatment now we in advanced disease, in low-volume metastatic disease, the use of targeted radiation therapy has been shown to be a benefit. If you have an image modality that allows you to be more precise, then our treatments could be more precise and we could understand who are the patients who may benefit more from this radiation than it was 10 or 15 years ago.

Dale Shepard, MD, PhD: So let's walk through each of those. You talked about even diagnosis and biopsies. Where are we currently with ability to use things like biomarkers to determine who really needs to get a biopsy, minimizing even at the biopsy stage?

Alberto Pieretti, MD: Yeah, so there are several biomarkers. Some of them actually have been pushed through Cleveland Clinic, like IsoPSA. We have IsoPSA, we have four care four case, so there are multiple of them that allows... The goal of each of them could be a little bit different, but the majority of them is for the detection of clinical significant prostate cancer. And the rationale for the biomarkers is that PSA is not specific for prostate cancer, so we try to use different tools to make the diagnosis of this. Biomarker is a good way to start to screening and which patient do we need to escalate further either images or biopsies for the diagnosis? So the benefit of this is, again, to minimize over-diagnosis of non-significant prostate cancer and then to minimize the harm that could have a prostate biopsy.

Dale Shepard, MD, PhD: Have those become fairly widely adopted in practice, the biomarker-guided biopsy decisions?

Alberto Pieretti, MD: Yeah, depending on the guidelines that you're reading, some people use PSA, a biomarker, and then an MRI. Some people just go up straight to an MRI. Some of these biomarkers don't have prospective or randomized data, so we don't have a strong level one evidence in a lot of them, which is the case for prostate MRI. In MRIs, we actually have fantastic level one evidence. So the data is extremely strong about MRI. So I think in general in the academic world, everyone uses an MRI before a biopsy. In the community, we get a lot of referrals where patients don't necessarily get an MRI. And that creates a lot of problems because, is this a truly patient that is a candidate for active surveillance? Or if this is a low-risk prostate cancer, was this patient had an adequate biopsy where we could say that we could monitor this patient? So at an academic level, I think we're doing pretty good, and on a community level, I think there is a lot of levels of improvement. And I think it's a lot about how well we're guidelines are reading and how the information has been passed.

Dale Shepard, MD, PhD: And then once the decision has been made to biopsy, we had a previous podcast episode, we talked about perineal biopsy, what does the world look like now in terms of biopsy technique?

Alberto Pieretti, MD: Yeah, so at least in my practice, I only do transperineal biopsies. We have one recent randomized trial that was done in the UK that the question was, is the detection of clinical significant prostate cancer different? From that perspective, the transperineal shows an improvement in the detection of clinical significant prostate cancer by 6%. And then when we look for complications, kind of the biggest complications that we could have with a prostate biopsy is sepsis. And it's admission to the hospital, potential ICU, with all the associated side effects of that. So we look for infections. Then the transperineal biopsy seems to be significantly safer even without the use of antibiotics. Saying that there are some caveats. The transperineal could be a little bit more painful than a transrectal biopsy, but depending on how you use it, what medications you use to control the pain, patients tolerate it very well, it's significantly safer based on the current data. So I don't see any rational, at least in my practice, to be using a transrectal biopsy.

Dale Shepard, MD, PhD: And then once we've got that biopsy, we know that a person has prostate cancer, we think about staging. You mentioned before about newer imaging modalities, and instead of the traditional bone scan and CT scan, how do things like PSMA PET scans and other imaging, how are those changing what we do?

Alberto Pieretti, MD: Yeah, so PSMA scan is significantly more sensitive than a regular bone scan or a regular CT scan to detect a metastatic disease. Even in the localized setting, it could also let us know where other areas of the cancers could be localized if the biopsy miss it or not. And what it allows to do is, first of all, when we're talking about local disease or locally advanced disease, the data about doing at least surgery in locally advanced disease is we don't have level one evidence to prove that there is a major benefit of that. There was a recent randomized trial where there could be a little bit of advantage, but there are a lot of questions if that should change the standard.

So again, if you have a PET scan that is showing a couple of nodes, then there has to be a truly discussion with the patient, "Is surgery the best option for you if you're still going to need androgen deprivation therapy and radiation therapy after surgery?" So I think it allows to guide the treatment for the patients better. And when the diseases advance, if we're thinking to use radiation associated with androgen deprivation therapy, being able to localize the disease better will allow us to target therapy to this disease.

Dale Shepard, MD, PhD: And when we think about localized disease and how you think about managing, certainly with the more advanced imaging, you have people that we might pick up metastatic disease we wouldn't have in the past, and the relevance of that, what factors are you using to decide active surveillance versus radiation versus surgery?

Alberto Pieretti, MD: Yeah, so nowadays we have very good data about active surveillance and the role of active surveillance. We have trials that have 15 years old to follow-up the ProtecT trial. The GÖTEBORG study has 25 years old. And in patients with low-risk disease, we really are not seeing difference in terms of overall survival. And this was in an era where they didn't have MRI, that the biopsies were not as precise as they are right now. So in theory, we don't like to extrapolate the data, but now that we have better images, modalities, and better techniques to biopsy these patients, most likely it's even safer than what it was before. So in patients who have very low-risk prostate cancer that have what we call a Gleason 6 or a Grade Group 1, they have a small volume of disease. If you read like the NCCN guidelines, they only treatment option is actually active surveillance. We're not advocating for other types of treatment.

For patients who have low-risk prostate cancer, which means is that you have still a Gleason 6 or Grade Group 1, your PSA is below 10, but you have multiple cores with low-risk prostate cancer, the preferred treatment options continue to be active surveillance, and we should be pushing for that. There is some role to surgery and radiation, and at the end it's the discussion between the surgeon, the radiation oncologist, and the patient. And I think it's very fair that we provide accurate data about why are we treating and what are the goals, so the patients could take the appropriate decision.

Dale Shepard, MD, PhD: How does patient preference and patient concern about active surveillance play in? Certainly, as you said, we've known active surveillance has been a really viable option for a long time. Are patients accepting of that?

Alberto Pieretti, MD: Yeah, so I think it really depends on the provider and how you pass the information to your patients. If you sit down with your patients, you explain the guidelines, you share the guidelines and you share the data, even if the disease has the name cancer, they will understand that this is not a threat and that they could monitor this very carefully. This is actually a very hot topic in urology is, should we change the name of the Gleason 6 prostate cancer and get rid of the word cancer to get rid of that anxiety? And I think it's a fair question. I don't feel that in my personal practice this is a big problem, but it's also because I sit down, I share with them the guidelines, I have these trials up in my computer so I could share the data. When the patients see the data, then they understand that there's really not a threat. But I understand that that doesn't happen with all the providers in all the practices, so a change may benefit a good proportion of these patients.

Dale Shepard, MD, PhD: Yeah. Tell us a little bit about other ways of testing, things like genomic testing, molecular markers, have impacted how we think about treating prostate cancer.

Alberto Pieretti, MD: This is actually, it's also another hot topic because there are a lot of genomic tests over there. Some of them are part of our guidelines, but if you read some papers, it really doesn't change what we do in a lot of the cases. I typically try to not use any genomic tests in patients with very low-risk and low-risk prostate cancer. But that is in my personal practice. Some people will use it in the low-risk to see if they do treatment or not. But then when you go into these details about the genomic test, we're talking about the risk of developing a known disease and you see the percents and the numbers, we're talking about years for that to develop. And then you go back to your ProtecT trial and the GÖTEBORG, in that area they didn't have any of these genomic tests. And yes, we understand that if you do active surveillance, you have a 50% chances that you may need treated, but treating the disease too early may not change the long-term outcome and it could cause more harm.

And that's where the question about, are these genomic tests pushing for an early treatment and not changing the long-term outcome? And that is the question that is still to debate. I use it for those patients who have what we call unfavorable intermediate-risk prostate cancer, which is Gleason 7, three plus four, with a small volume of the disease and a low PSA. When the patients have questions, if they want to do active surveillance or not, I use the genomic score to try to help the patients to take a decision in that scenario.

Dale Shepard, MD, PhD: Makes sense. How about germline testing in prostate cancer?

Alberto Pieretti, MD: Yeah, so I actually think that that is a different story. I think germline testing has a huge impact in prostate cancer. The guidelines are strongly advocated for germline testing in patient with high-risk of metastatic disease. I think it has two major benefits. If you have a germline mutation and you have family members, it allows to screen for different cancers in that patient. But it also allow us to test the family members to understand which one are at risk of developing this type of cancer so we could offer early screening, and that typically will be associated with a better outcome. And then nowadays in advanced prostate cancer, we could target some of these genes, and this has been tested in randomized trials. And using medications like ARB inhibitors are associated with an improvement in the recurrence and the survival of the disease.

Dale Shepard, MD, PhD: When we think about prostate cancer, there's oftentimes a number of players, so they're community practices, they're the large urology practices, there's the academic centers. How much does the management of prostate cancer currently vary between different settings, and are there particular patients that really need to be seen at an academic center?

Alberto Pieretti, MD: To me, it's not so much of the academic. I would like to see that the patient have a person who is really trained in cancer, like a urologic oncologist. Someone who knows all the studies, who understands the biology disease, who is trained in prostate cancer. I would like them to talk with the medical oncologist and a radiation oncologist so they don't get a bias from one of the providers in terms of the best treatment options. So if the community or the big practices are offering that, I think the majority of those groups are going to offer good care. But the problem is that in the majority of the community practice, they don't provide that, which is different than an academic center. When you go to an academic center, this basically becomes a guarantee for the patient. And having a multidisciplinary care involving all this group is typically associated with better survival, better patient satisfaction, which is something huge in this particular disease.

Dale Shepard, MD, PhD: What about clinical trials? Is there anything that is being studied in clinical trials right now that you're waiting to see the results and may change practice?

Alberto Pieretti, MD: Yeah, I think that if we want to talk about clinical trials, we may spend a couple of hours, but the key, there's so many clinical trials that are promising in prostate cancer. Obviously, the big stone in localized prostate cancer is high-risk disease, because high-risk disease is a disease that a lot of the patients, more than 50% of them, may need more than one treatment option. We have been trying neoadjuvant therapy, meaning giving therapy before surgery, and the data has not been the best. New phase two trials are quite promising that we may be integrating neoadjuvant therapies in the future. So we're waiting for the phase three results, and hopefully these are going to be positive so this will impact in a positive way our outcomes and a patient's life expectancy and quality of life.

There are other therapies like lutetium, a targeted radiation therapy that in metastatic disease are quite promising. Now we're starting to bring lutetium to early phases of the disease, and I think that has the potential to change the outcomes and try to minimize the long-term need of androgen deprivation therapy. Which, at the end I think it has the biggest impact in the quality of life of the patients in the long-term.

Dale Shepard, MD, PhD: Where are we now in terms of thinking about resection of primary tumors for metastatic disease?

Alberto Pieretti, MD: Yeah, a couple of minutes ago we were talking about this. There was a randomized trial that was published not more than three days ago. It was a trial where they did best systemic therapy alone or best systemic therapy with surgery. It turns out that there was a cancer-specific survival benefit for those patients who had surgery, but that trial was closed early because it was in the ERA where the STMP trial came out. So they felt that because the STMP trial shows that radiation therapy was a benefit, they cannot keep the trial open just with observation alone without offering treatment to the localized prostate cancer.

So we don't have an overall survival benefit in that trial. We do not have a recurrence-free survival benefit. We have a cancer-specific survival. So while this trial is showing a light at the end of the tunnel, I don't think surgery is the standard of care. We do have two or three big trials that we are comparing this with radiation therapy, and we're still waiting for the results of that. One of the problems in prostate cancer is that this really has become a chronic disease. We have so many lines of treatments at different stages, that when we like to look for overall survival, we may have to wait 10, 15 years to have the definitive result.

Dale Shepard, MD, PhD: And then, since this is a chronic disease at this point, and you mentioned about androgen deprivation and symptoms, how are we best addressing quality of life issues like sexual health and urinary function and things like that?

Alberto Pieretti, MD: Yeah, I think the first thing is what is the life expectancy of the patient, what is the baseline sexual function of the patient, and what are the urinary symptoms? Depending on that, those three factors, then we have to take into consideration how aggressive is the prostate cancer, does he really need treated? That's the benefit of active surveillance is that we're really not compromising long-term outcomes for the huge majority of the patients, but in the meantime, we're preserving their sexual function, which is a big thing. And then as these cancers could be more life-threatening, then those things have to be put in the balance, and then the patient has to decide what is the best for them. In those patients who have a lot of urinary symptoms and they have localized disease, typically surgery offers a better option than the radiation therapy. But at the end, it's the patient's decision based on our guidelines.

Dale Shepard, MD, PhD: Very good. Well, lots of things happening in prostate cancer, all the way from biopsy all the way through advanced treatments, and appreciate you joining us with some insights today.

Alberto Pieretti, MD: I agree, and thanks for the invitation. It was a pleasure to talk with you.

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