ASCO Guidelines

An interview with Dr. Philip Saylor from Massachusetts General Hospital on "Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline." This guideline includes recommendations for management of osteoporotic fracture risk in nonmetastatic disease and interventions for men with castration-resistant prostate cancer metastatic to bone. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines. Transcript [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines Podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.ASCO.org. My name is Brittany Harvey, and today I'm interviewing Dr. Philip Saylor from Massachusetts General Hospital, lead author on "Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline." Thank you for being here today, Dr. Saylor. Oh, it's my pleasure. First, can you give us a general overview of what this guideline covers and about the endorsement process? Yes. So the Cancer Care Ontario has a program in evidence-based medicine, and they periodically put out clinical practice guidelines for management of a whole variety of topics. And they relatively recently put out a publication on bone health and bone-targeted therapies in prostate cancer. And so that's a really big topic because bone health is such a big part of prostate cancer care across the entire range of scenarios that patients can face. And their guideline addresses topics all the way from osteoporosis and fragility fractures and that risk as it relates to GnRH agonist, androgen deprivation therapy that men can get for really any prostate cancer scenario, goes all the way from that to improving quality of life in patients who have bone metastases that have progressed despite systemic therapy. So it's really a very broad series of topics that they addressed. And so when they put out that guideline, ASCO identifies it as something that's very relevant to the ASCO community and goes through, then, a formal process of reviewing the methodology of those guidelines and then having an expert panel discuss the quality and evidence of the guidelines and really provide, if appropriate, an endorsement and some additional discussion of those topics. So what are the key recommendations of this guideline? They really have four sort of subtopics within this bone-themed guideline that are addressed and discussed in a fair amount of detail. And each one of those four topics deserves some of its own discussion. The first topic is osteoporosis and risk for just fragility fractures, like hip fracture and vertebral body compression fractures. That's one. The second is potential prevention of bone metastases in a patient that does not yet have bone metastases. The third one is management of castration-resistant prostate cancer metastatic to bone. And the fourth one is symptomatic management of men with CRPC metastatic to bone. So it is probably worth discussing each one of those, in some detail, one by one. So for the osteoporosis fracture risk question, Cancer Care Ontario, their recommendation really is that men with non-metastatic prostate cancer at high risk for fracture who are receiving ADT should be considered for the osteoporosis dosing of denosumab. And in situations or places where denosumab is not available, then patients can consider a bisphosphonate as an alternative. So we had a fair amount of discussion of that recommendation. We endorsed that recommendation. And I guess my personal emphasis would be that osteoporotic fracture risk is really the biggest challenge to that is not forgetting about it. So you can often have men who are in a good prostate cancer scenario, likely to be cured by their therapy. They're going to get some duration of ADT. And they look healthy as they sit there in clinic with you. They're likely to do well from a prostate cancer standpoint. And it just would be so easy not to adequately screen for osteoporotic fracture risk, and just not to remember that because so many of our discussions together in clinic are focused on the prostate cancer more than the broader health questions. And so, I mean, to me, I think not forgetting about this issue is really one of the most important things to emphasize in any discussion of osteoporosis. And so really, it's a fairly simple problem to screen for and manage. Most men should be, if they're going to be on any duration of ADT, should be tested with a bone density test, a DEXA scan. It's really a fairly inexpensive and easy test for getting a sense for where their bone health is as they begin. And I usually tell my patients in clinic that most men don't need any new prescription medicines to manage that risk, but we'll never figure out the ones who need it unless we go through the very disciplined systematic work of doing that screening. And then among those who really do deserve treatment, it's really denosumab at the osteoporosis dosing or a bisphosphonate. Really, any of those choices really works well for improving bone mineral density. One of the big ASCO discussion points is that denosumab is the only medicine that's been shown definitively to improve fracture risk in this setting. But that's really a product of denosumab being studied in a really large prospective randomized controlled trial. And so that's one where they required more than 1,000 patients in order to assess that fracture endpoint. So the reason, perhaps-- probably the most important reason that bisphosphonates have not been shown to improve fractures is that none of them have been studied in such a big study. The bone mineral density trials that have studied bisphosphonates are all on the order of maybe 30 to 100 patients rather than 1,000. So really, in many clinical settings, cost and convenience are important considerations. And when those are factored in, it's often very reasonable to use a bisphosphonate rather than denosumab, though either one really could be considered a gold standard. So that's point number one from the guidelines. Number two really discusses the issue of prevention of bone metastases. And so there are a couple of sub-recommendations from Cancer Care Ontario. But really, the most important point from that is that there is no bone-targeted drug that has been shown to prevent or delay the development of the first bone metastasis. So a number of different studies have tried to address this question in slightly different clinical scenarios. But the bottom line is, we don't use bone-targeted medicines to prevent the first bone metastasis. And so there's always been sort of an attractive potential effectiveness there because you think if your bone-targeted therapy changes the bone microenvironment, could the natural history of prostate cancer play out differently? But the answer is that we really don't have any convincing evidence of effectiveness on that front using any drug, in any situation. So that's a pretty easy one to summarize. For the third category of situation that's addressed in the guideline really relates to castration-resistant prostate cancer metastatic to bone. And so there are three sub-recommendations there. In that situation, either zoledronic acid or denosumab in monthly dosing at the skeletal event preventing dosing is a gold standard and reasonable to pursue. So that's one thing. In men with symptomatic disease, radium-223 can be considered, both to prevent skeletal events and to improve health-related quality of life. And then, finally, all radiopharmaceuticals can be considered in that situation for palliation of bone pain. And so we endorsed those recommendations as well. And we added a fair amount of discussion about how to optimally support men's health in those situations. For one thing, it's important to note that monthly zoledronic acid or monthly denosumab, whichever is pursued, is a fairly intensive osteoclast-targeted therapy. And so the studies that formally establish those as gold standards in that setting, they really only treated for about two years, plus or minus. So we don't know a lot about the safety of that intensity of therapy beyond two years. And so that's an important consideration, because there are many men who do well, thankfully, for a lot longer than two years in the castration-resistant setting with bone metastases. And so we really do, as clinicians, need to respect the possibility of toxicities, especially osteonecrosis of the jaw seems to be a much, much more common phenomenon with longer durations of treatment and with these more intensive regimens. So that's one thing that deserves a lot of attention by clinicians. The other thing is that dental evaluation and proactive dental care before and during any of these bone-targeted therapies is really an important issue not to miss. So the highest risk for having osteonecrosis of the jaw is in patients who are on one of these intensive regimens and then need to have invasive dental work when they're already been started on one of those regimens. Those are the jaws and mandibles that seem not to heal as well. And so ideally, every patient that is going to go on intensive osteoclast-targeted therapy really should be evaluated by a dentist with the question of whether there's any dental work that really needs to be done proactively before the start of one of those medicines. And so I always say I have to be humble as a medical oncologist to say I really know little to nothing about teeth. And so I have to reach out to my colleagues in the dental field to tell me which are the patients that need to do something ahead of time and heal before they start one of these medicines. So those are a couple of important points. And then the other thing that's really not a new piece of information but is important to emphasize is that it's really monthly therapy with denosumab or zoledronic acid should really be used only for patients with castration-resistant prostate cancer metastatic to bone. So the patients who are responding to their systemic therapy really seem not to benefit from the bone-targeted therapy. And that's likely because any systemic therapy that's controlling the prostate cancer, in general, that's active against the cancer, in general, is going to prevent skeletal complications. We just have a lot fewer of those events, thankfully, when the disease is under control. And then, finally, the fourth category of recommendation addresses symptomatic castration-resistant prostate cancer metastatic to bone. And that's a situation where the radium-223 given in the typical once per month times six series of treatments is a gold standard, improves health-related quality of life and overall survival. I think one of the important discussion points on that front relates to recent clinical trial data that examines the use of other secondary systemic therapies in addition to the radium. So we have a prospective randomized study that looked at abiraterone with or without radium. And what it really showed was that the combination of abiraterone and prednisone with radium resulted at a very high rate of fractures and worsened overall survival. So that's really a combination that should absolutely not be pursued outside of a clinical trial. And so that's an important thing to know, but it's also sort of a cautionary tale that if we're tempted to combine other secondary medicines with our radium treatment, we really don't have a lot of evidence for the safety or efficacy of doing that. So that's the sort of thing that really should be reserved for clinical trials. And those are probably the most important-- those are the four main topics addressed by the guidelines. As you can tell, it really includes situations that are relevant to just about every man who receives systemic therapy for prostate cancer. Absolutely. And thank you for that comprehensive overview and those considerations of the guideline endorsement panel. Why if this guideline important? And how will it impact practice? So I think there's really sort of two main ways that it's important to the reader in 2020. I'd say, first of all, as a reminder and sort of educational promotion of awareness of the things that we already know but are easy to overlook. And I think the things that are really there are that it is easy to focus on the cancer therapy and easy to overlook the bone-targeted therapy. So as we have an increasing number of systemic therapies that are active against the cancer itself, and as we have sort of, in the best possible way, more options and more molecular considerations for our prostate cancer patients, we really can't forget to do the fundamentals, like doing monthly zoledronic acid or monthly denosumab in men with castration-resistant disease that's metastatic to bone. So I think that's the kind of thing that would be easy to forget, but that we shouldn't. And the second subtopic there would be screening for osteoporosis in any man who receives ADT. And again, that's something that-- osteoporosis or someone at high risk for fragility fracture, that's an asymptomatic situation until the fracture occurs. And then at that moment, you're really thinking back and saying, man, I wish I'd done something three years ago, or five years ago, or 10 years ago to improve bone health so that this wouldn't have happened in the first place. So it really is up to us as the clinicians caring for these prostate cancer patients to advocate for their general health in a way that includes their bone health. We just have to really not forget to screen for osteoporotic fracture risk. So I think those reminders of things that we already know but are really easy to miss, I think that's one aspect of this. And I think the other is just discussion of the data. It really adds some richness to the topics. And we do have these updates in an emerging field, particularly when it relates to radium-223. It seems like a drug really on, like, a drug strategy that could easily be paired with other drug strategies because it's reasonably well-tolerated. But we learned, really especially from that clinical trial experience of radium with abiraterone, we really learned that freewheeling combinations are not necessarily safe and not necessarily effective. And so we have to just be mindful of recently emerging data and have an ear to the ground about ongoing clinical trials, sort of how to best combine and sequence all the different medicines that are sort of in our back pocket. And finally, how will these guideline recommendations affect patients? Yeah. I mean, I think bone health is really just so important to every patient with prostate cancer. And it's almost, for clinicians, it's almost an educational issue where we have to help our patients understand how important bone health is. When we talk in clinic about a DEXA scan to look at bone density, a lot of men really look at me a little bit blankly. They think of osteoporosis more as this sort of issue that women deal with more so than men. But I always talk about, if you imagine having a hip fracture and needing hip surgery, or if you think about the pain and the postural changes that happen with vertebral body compression fractures, we really have to do something before any of those things occur. And most men agree with me if you put it in those practical terms. It's just the kind of thing that you have to take a couple of minutes out of your clinic visit to make sure that you address. And the other thing really is, in men who have more challenging prostate cancer metastatic to bone, even life-threatening prostate cancer, all the complications that can happen later in the course of disease, we really need to do the best possible job not only to keep men living longer, but also to make sure their quality of life is the best it can possibly be. And that's really-- and most of the time when prostate cancer starts to become a physical burden as it progresses, it's really a physical burden that's centered on bones and skeletal health. And that can have an effect on comfort. That can have an effect on mobility. And these things are hugely central to quality of life. So the impact on patients, all the way from osteoporosis to bone metastases, really, it's just such a central theme within the management of everybody who has to face prostate cancer. Thank you for your work on this important guideline, and thank you for your time today Dr. Saylor. Oh, it's my pleasure. We got to keep working to get the word out there and have the optimal management for all of our patients. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.ASCO.org/genitourinary-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Christina Annunziata from the National Cancer Institute on "Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline". This guideline provides recommendations for women diagnosed with epithelial ovarian cancer and their families on which individuals should receive risk evaluation, counseling, and genomic testing, and when they should be tested. Read the full guideline at www.asco.org/gynecologic-cancer-guidelines. Transcript [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at podcast.asco.org. My name is Brittany Harvey. And today, I am interviewing Dr. Christina Annunziata from the National Cancer Institute, co-chair on Germline and Somatic Tumor Testing and Epithelial Ovarian Cancer: ASCO Guideline. Thank you for being here Dr. Annunziata. Oh, it's my pleasure. Thank you. First, can you give us a general overview of what this guideline covers? Sure. So this guideline is covering the use of molecular testing in women diagnosed with ovarian cancer. And that's specifically what tests should be done and when to do them. And what are the key recommendations of this guideline? The key recommendations really are that all women diagnosed with ovarian cancer should be tested for certain gene mutations that are responsible for predisposing people to ovarian cancer and also that a genetic counselor should be involved in discussing the results of these tests with the person involved and with her family. In the guidelines, we go into specifics of which genes should be tested at what point in the course of the disease. And the guidelines mainly focus on the BRCA genes and mismatch repair genes because these are the ones with approved treatments for cancers with these mutations. What are the clinical questions that you addressed in this guideline? So we have three main questions when we started out. We wanted to know, first, in which individuals should risk evaluation counseling genomic testing for germline and somatic tumor alterations be performed. We also wanted to know, number two, which genomic alterations had actually demonstrated clinical utility to direct therapy for women with ovarian cancer. And third, what is the most appropriate sequence and timing of testing, meaning specifically at what point in the course of the diagnosis and the treatment of the women should we be performing this testing? So we came up with specific answers to each of these questions. And just to briefly summarize, for the first questions in which individuals should we test, we did find evidence that all women diagnosed with ovarian cancer should be offered germline testing for, specifically, BRCA1 and BRCA2 cancer susceptibility genes, irrespective of whether or not they had a family history of the disease. Also within that question, we found evidence that women who have non-high grade serous ovarian cancer, specifically clear cell endometrioid or mucinous ovarian cancer, should have somatic tumor testing for mismatch repair deficiency. And both of these recommendations are because there are FDA approved therapies for women with cancers with these particular genetic makeups. In the second question, we asked, which genomic alterations have demonstrated clinical utility? This goes specifically into, which specific genes should be tested in the germline and the somatic setting? And in that recommendation, specifically, we focused on, again, the BRCA1 and 2 genes and the mismatch repair deficiency genes. We did not make specific recommendations for the homologous recombination deficiency assays at this time. Those are still undergoing evaluation. And it's likely in the near future that we will amend this recommendation to specifically discuss those. In the third question, what is the most appropriate sequence and timing of the testing? That goes into, when should we be doing this in the course of the disease? And we did want to emphasize that women with ovarian cancer should be tested at the time of diagnosis because of the specific implications for therapies. If they have not had testing at the time of initial diagnosis-- let's say they were diagnosed several years ago-- then they should be tested at the time of their first recurrence or subsequent recurrences if those have already happened. And again, these have implications for treatment. Why is this guideline important, and how will it impact practice? So one of the most important recommendations is that all women should be tested at the time of the initial diagnosis. In practice today, we estimate that only about 1/3 of women are actually being tested at the time of diagnosis. This testing is important, especially for the BRCA genes, because this has implications for the choice of treatment because of recent FDA approvals for PARP inhibitors in this setting. And how will these guideline recommendations affect patients? Our goal is to ensure that all women have access to the best treatments for their ovarian cancer. In order to achieve this goal, doctors need to be aware of best practices, and patients need to understand the results in the context of their disease. This is why we recommend that the results of the gene testing be delivered to the patient in conjunction with a genetic counselor because this has been shown to increase understanding of the tests and follow through on the recommended treatments. In some settings, we know it may be difficult to arrange these discussions with a genetic counselor, so we hope that these guidelines will emphasize the importance of this step. Well, thank you for your overview of these and for your work on these guidelines. And thank you for taking the time today to come on the show, Dr. Annunziata. Oh, you're very welcome. And thank you for the opportunity to highlight these guidelines. And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/gynecologic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available and iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. [MUSIC PLAYING]

An interview with Dr. Edouard Trabulsi from the Sidney Kimmel Medical College at Thomas Jefferson University on "Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline." This guideline outlines techniques available and provides recommendations on appropriate use of imaging for specified patient subgroups. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. My name is Shannon McKernin, and today I'm interviewing Dr. Ed Trabulsi from the Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania, lead author on "Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline." Thank you for being here today, Dr. Trabulsi. Thanks, Shannon. Thanks for inviting me. So first, can you give us a general overview of what this guideline covers? Sure. So the purpose of this guideline, and it's fairly broad, is to try to come up with some recommendations and strategies for appropriate imaging for patients with advanced prostate cancer. Also, that includes patients that are newly diagnosed that are high or very high risk for having micrometastatic disease. Also, patients that have been treated and are suffering recurrence of disease as indicated by rising PSA. And then also, patients with metastatic disease, either on initial diagnosis, or on treatment and who are contemplating changing treatments. Also, it has a wide range of different patient populations that all fit in the category of advanced prostate cancer. And the idea is to try to figure out or make some recommendations on strategies for what imaging is appropriate for each of those groups of men. So what are the key recommendations for this guideline? Well, the big impetus for this guideline is the awareness of what we would consider next-generation imaging, meaning that there's a large group of new or novel imaging studies available and on the horizon. And we're trying to figure out the best way to fit them in in the context of traditional imaging in what we would call conventional imaging. So that would be-- conventional imaging would be imaging tests like CAT scan, radionuclide bone scan, prostate MRI, that sort of thing. Next-generation imaging would include some of the newer PET imaging scans, using different tracers and isotopes, and some of the new SPECT imaging scans, as well as full body MRI. And so how to interweave those different imaging tests is really what's proving to be not as straightforward as we'd like. And so we realized that we need to really approach this based on a clinical disease state model. So not just one monolithic category of advanced prostate cancer, but looking at specific scenarios. And we developed this guideline as a scenario-based algorithm. So the initial diagnosis of prostate cancer of men that are at high risk, what images we think about there; for men that have been treated and their PSA is rising, and so forth. And so we shouldn't jump to next-generation imaging across the board. We really should look very specifically at circumstances where these new, novel, and unfortunately, expensive imaging tests could have real clinical impact. So patients that are newly diagnosed that are high risk who have suspicious or equivocal conventional imaging, so they have a CAT scan or a bone scan or something that we're really not sure if something that we're seeing there might be an indication of disease, that's a good spot where next-generation imaging might be very helpful. For patients that have been treated and their PSA is rising, say, after surgery or, say, after radiation, and they get traditional, what we would call conventional imaging, and we don't see a source for the PSA, well, that is another scenario where a patient-- or a category where next-generation imaging should be considered. In that specific space, there actually are two PET imaging studies that have been approved by FDA in the US with C-11 choline, as well as the fluorine-18 fluciclovine scans. And then also overseas, or not yet approved in the US, there are other PET-based agents that are being used in that specific space. Another important aspect of this is that it should have real clinical impact. So if you have a man who unfortunately may be suffering, or evidence of recurrence of disease after surgery or radiation, but because of their comorbidities or age or patient preference, they're not necessarily going to be aggressive with additional therapy, then we probably don't need to chase some of these next-generation imaging studies in that man. In the confirmed metastatic patient population, that is a little more unclear in terms of what the benefit of next-generation imaging would be outside of the setting of a clinical trial. And in those patients, if it is thought that there would be a change in clinical treatment based on the results of the scan and of next-generation imaging, then that would be a scenario where those might be considered. But we wouldn't necessarily recommend them across the board. And so why is this guideline so important? And how will it change practice? Well, it's important and timely because of the tidal wave that we are expecting of novel, next-generation imaging that is going to become closer and closer to clinical practice. Patients are aware of these studies, and they're asking for them, even if they're not currently available or approved by an FDA or covered by a third-party insurance. There's been a plethora of research studies and new imaging tracers in Europe, Southeast Asia, and Australia. And so trying to get ahead of where they might fit in, and which patients might benefit now and in the future, was really one of the main drivers to come out with a strong position statement on the appropriate use of imaging. There's a lot of controversy about some of the implications of the next-generation imaging, such as the potential for false positives and the attendant prognostic tests, that that might trigger false negatives, and potentially offering clinicians or patients a more optimistic outlook than may be really present. And so figuring out specific scenarios and specific patient populations that would benefit from next-generation imaging is the real goal of this guideline. And so finally, how will these guideline recommendations affect patients? Well, the ultimate goal is to improve patient care and improve patient outcomes. And so by coming up with some reasonable templates and framework of where some of the next-generation imaging will fit in on a patient's disease spectrum and disease course will help them both to potentially indicate when treatment changes may be necessary, or to isolate areas of disease, and to importantly and accurately give their correct stage. And then that will translate, or we hope and expect, with more information and more accuracy in diagnosis, in better treatment plans and better patient outcomes. Great. Thank you for your work on this important guideline on Optimum Imaging Strategies for Advanced Prostate Cancer. And thank you so much for your time today, Dr. Trabulsi. Thank you so much. Thanks for having me. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline and find additional resources, such as the guideline pocket card, go to www.asco.org/genitourinary-cancer-guidelines. And you can find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or the Google Play Store. And if you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

An interview with Dr. Kimberly Allison from Stanford University School of Medicine and Dr. Antonio Wolff from Johns Hopkins University on "Estrogen and Progesterone Receptor Testing in Breast Cancer Guideline: ASCO/CAP Guideline Update." This guideline updates key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen and progesterone receptor testing in breast cancer guideline, and focuses on low estrogen receptor expression cases. Read the full guideline at www.asco.org/breast-cancer-guidelines.

An interview with Dr. Scott Eggener of University of Chicago Medicine on "Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline." This guideline provides recommendations for available tissue-based prostate cancer biomarkers geared toward patient selection for active surveillance, identification of clinically significant disease, choice of postprostatectomy adjuvant versus salvage radiotherapy, and to address emerging questions such as the relative value of tissue biomarkers compared with MRI. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines TRANSCRIPT If you like what you hear from the ASCO podcast, please let us know. Take our listener survey and help shape the future of the ASCO Podcast Network. Visit podcast.asco.org, and click on the survey link. Once again, that's podcast.asco.org. The survey will just take a few minutes to complete and will help us get to know you better. Thank you so much for listening. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at podcast.asco.org. My name is Shannon McKernin. And today I'm interviewing Dr. Scott Eggener from the University of Chicago Medicine, lead author on molecular biomarkers in localized prostate cancer ASCO Guideline. Thank you for being here today, Dr. Eggener. Thanks for having me, Shannon, and covering the guideline. So first, can you give us a general overview of what this guideline covers? Yeah, this guideline has been two years in the making and is an overview of the available molecular biomarkers to help clinicians and patients make smart decisions for men with localized prostate cancer. And that's in the newly diagnosed setting, as well as for certain patients that have undergone surgery and are considering adjuvant radiation therapy. And so what are the key recommendations for this guideline? So there was a lot of data that the team looked through with the help of the ASCO home office, and a Herculean amount of work went into it. There's a lot of commercially available tests out there. Most of them are quite expensive. And we are trying to make sense of the available literature and provide a guide to clinicians on what these tests are, which patients they might be relevant for, and how to interpret them. The key takeaways that the data that's been published for most of these biomarkers are purely prognostic. And there is good science and good data supporting them. But they have not been embedded in a rigorous fashion or within trials or validated to have the highest level of evidence. However, they can be used in certain situations to add additional info for the patient and clinician to try to make smart decisions based on prognostic information. Another key recommendation is that there are select patients that these can be helpful for. And we dive into a lot of the details on who these patients may be. Number one is a patient newly diagnosed with prostate cancer who is trying to determine whether to do treatment of the prostate cancer or embark on active surveillance. And some of those decisions are relatively easy and straightforward. But when the clinician and the patient are looking for all pieces of information to influence one way or the other, genomic or molecular biomarkers can be useful at that critical fork in the road. However, we made it very clear multiple times throughout the guideline that our group's recommendation is that the biomarkers should not be reflexively ordered for every individual newly diagnosed with prostate cancer. It seems wasteful and not an appropriate use of resources. The other situation clinically where these can be used are for men that have had previous surgery and are considering secondary radiation therapy, which can be given in an adjuvant or salvage manner. And there are some data suggesting that a specific test by Decipher, a genomic classifier, can be used to help inform whether adjuvant radiation would be appropriate or not. So that was a good overview. And this guideline also includes some special commentary sections with additional research questions that the expert panel wanted to address. So can you tell the listeners a little more about these important considerations? Yeah, it's critically important to know that these tests are not black and white. And they don't always clarify a data-based path forward. But we tried to emphasize in many different areas that integrating genomic or molecular information can be integrated into optimizing decisions. And the special commentary really dives into a lot of those details on working with the pathologists on selecting the appropriate biopsy sample to send to one of these laboratories. It gets into some of the specifics on interpreting the data, as well as the role of CLIA-approved labs and non-CLIA-approved labs for certain staining that's done internally within organizations or with biomarker panels. And so would you be able to expand a little more about which patients may benefit from having molecular biomarkers? Yeah, the sweet spot for some of these biomarkers include a couple different patient groups. The first one is what I alluded to earlier-- the man newly diagnosed with prostate cancer deciding whether to do active surveillance, which is a monitoring program, or to have treatment of the prostate typically by either surgery or radiation therapy. Again, worth emphasizing-- these tests are not appropriate for every newly diagnosed patient. And I would argue even for the man deciding between surveillance and treatment, there are specific men, perhaps those with higher volume low risk prostate cancer or lower volume favorable intermediate risk prostate cancer, that provides the ideal patient that may benefit from some of these tests. The second clinical scenario that was discussed amongst the group were patients where treatment intensification might be valuable. Again, these biomarkers are purely prognostic, and there's no high level evidence suggesting that treatment intensification leads to better outcomes. Although intuitively, the higher risk profile a patient has, either by clinical factors or biomarkers, there is a conceptual rationale that treatment intensification might prove beneficial. And the third category of patients that may benefit are those who have had prostatectomy where the pathology shows some adverse features, and there's a high likelihood of recurrence, and the clinician's decision is to guide the man on whether pure adjuvant radiation in the setting of an undetectable PSA or early salvage therapy at the time of biochemical recurrence would be more valuable. And there is one test that is commercially available that can help inform that decision. Great, so finally, what do you envision as the future of molecular biomarkers for localized disease? As we took an overview of the landscape in 2018 and 2019 of these molecular biomarkers, much of the group thought this was version 1.0 or 2.0 in this space. And it is our hope and likely scenario that not only will we have better data on some of the currently available biomarkers with higher levels of evidence from either correlative science from randomized trials or formally embedded into randomized trials, but also that there's a large amount of work being done to improve the quality of biomarkers and that, in the future, we'll see improvements on the currently available ones or newer biomarkers coming around that will be valuable for these men as they make decisions along their prostate cancer course. Great. Thank you for your work on this important guideline. And thank you for your time today, Dr. Eggener. Thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline and find additional resources such as the guideline's pocket card, go to www.asco.org/genitourinary-cancer-guidelines. And you can find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or in the Google Play Store. And if you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

An interview with Dr. Melissa Dillmon on the Patient-Centered Standards for Medically Integrated Dispensing: ASCO/NCODA Standards. The interview covers the findings of the systematic review, which were consistent with the NCODA patient-centered standards for patient relationships and education, adherence, safety, collection of data, documentation and other areas. NCODA standards were adopted and used as basis for these ASCO/NCODA standards. Additional information is available at www.asco.org/mid-standards.

An interview with Dr. Charles Shapiro from Mount Sinai Hospital in New York and Dr. Joan Neuner from Medical College of Wisconsin, co-chairs of "Management of Osteoporosis in Survivors of Adult Cancers with Nonmetastatic Disease: ASCO Clinical Practice Guideline." This guideline includes recommendations on assessing risk factors and interventions, including pharmacologic and nonpharmacologic options. Read the full guideline at www.asco.org/survivorship-guidelines TRANSCRIPT Hi. My name is Clifford Hudis, and I am the CEO of the American Society of Clinical Oncology as well as the host of the ASCO in Action podcast. About twice a month, I interview thought leaders in healthcare care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues. You can find the ASCO in Action podcast on Apple podcasts or wherever you are listening to this show, and you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content, and offer enriching insight into the world of cancer care at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. My name is Shannon McKernin and today on the ASCO Guidelines Podcast, I'm interviewing Dr. Charles Shapiro from Mount Sinai Hospital in New York, and Dr. Joan Neuner from the Medical College of Wisconsin, Milwaukee, co-chairs of management of osteoporosis in survivors of adult cancers with non-metastatic disease ASCO clinical practice guideline. Thank you for being here, Dr. Shapiro and Dr. Neuner. Thanks a lot. Pleasure to be here. So first, can you give us a general overview of what this guideline does cover? This guideline covers very important topics, that of osteoporosis and that of cancer survivorship. It's the coalescence of these two common problems that is the impetus for this guideline. It covers risk factors and what you can do as a cancer survivor to mitigate your risk. It covers screening and identification of the best test to use to measure your bone density, and it covers how to treat or pull the trigger for anti-osteoporosis drugs based on the guidelines that are contained within the document. And what are the key recommendations for this guideline? So we developed this guideline with three key guideline questions in mind. And they really required a fairly extensive search of the literature to address them. And we did that by looking to some of the literature outside of cancer in osteoporosis screening in other patients as well. So I'll sort of talk about it in terms of the three key questions. So the first question we had was, which patients with non-metastatic cancer are at increased risk for developing osteoporotic fractures? So that first question was, which patients are we really addressing in this guideline? And how do we assess whether they're at potentially increased risk? So in response to that, we strongly recommend that oncologists teaming with other physicians, including primary care doctors like myself, evaluate their patients to determine whether they're high risk. And so we provide a lot of details in an extensive document. But in our bottom line, we have a summary of the most common and the most severe risk factors. And those include things like advanced age, current smoking, excessive alcohol consumption, and a history of prior fractures, so already showing that they're at high risk for fractures. So we recommend you look to that list. And then add in your own clinical judgment, particularly about patients who have added risks from their cancer treatments. And so we do also talk about those patients. And in particular, we call out patients with specific anticancer therapies, for example, aromatase inhibitors given to breast cancer patients, antiandrogens or GnRH agonists given to breast cancer and prostate cancer patients and call out how they're at particular risk. And finally, in response to this question, we also recommend that you consider using a risk assessment tool. And here, I mention that we had to look to the non-cancer literature. So here, the WHO actually developed something called the Fracture Risk Assessment Tool, or FRAX. And we do recommend that you use this tool or something like it to help you to assess whether your patient is at high risk. And those are readily available on the web. Search FRAX-- F-R-A-X-- to use it. And, of course, we have links in the guideline. So that addresses the first question, which again was, which patients are at increased risk? And we have a list of risk factors that you should be considering and some references, particularly FRAX, to help you with thinking about those risk factors and how important any specific risk factor is. Our second question really dovetailed right on that. And that was, how should patients who are at increased risk, you've identified as part of that first question, to be at increased risk for osteoporotic fractures be screened? And here again, we look to the standard recommendations for patients who don't have cancer as well. And there are two ways that you could move towards, should you screen your patient or not? One could be your patient had one of those risk factors that we talked about and are listed in the document. The other is you use that FRAX tool and patients are more than average risk. And then we recommend patients be screened using one of the standard screening tools. The most common one, is called dual X-ray absorptiometry. And I want to specifically mention central dual X-ray absorptiometry, which means that the test is done on the hip and the lumbar spine. Those are readily available. All major medical centers have them, and many clinics have them as well. And so we do recommend that for screening. And then we offer some specifics about how frequently you might screen, because that's another question that often comes up. And so then our final question is once you determine that your patient is at high risk because their bone density test and/or their FRAX test shows that patients are at high risk, we do encourage talking to them about treatment options. And the first thing I want to say is essentially everyone that our guideline addresses, which is all patients who currently have or who are survivors of non-metastatic cancer, that they should consume a diet with adequate calcium and vitamin D. And so that's generally considered to be 1,000 to 1,200 milligrams of calcium and at least 800 to 1,000 IUs, international units, of vitamin D. We also strongly recommend exercises and call out some specifics. That you want to work on balance, flexibility, and resistance, if possible. And that you quit smoking and limit alcohol consumption. All very good things for the body generally, but also very good for the bones. Obviously, the meat of this guideline is also about pharmacologic intervention specifically. And since Dr. Shapiro treats so many patients with this, I'm going to ask him if he wants to comment further on specifics about pharmacologic treatments, when you think patients should get them. So thanks, Joan. So pharmacologic interventions include RANK ligand inhibitors, like Denosumab or IV or oral bisphosphonates. So clearly, if your patients are at risk, that means a hip fracture predicted at 3% or more or a non-hip vertebral fracture at 20% or more-- and you get these numbers from the FRAX calculator and other calculators in common usage-- then you pull the trigger and use one of these agents. Now we couldn't distinguish between the agents in terms of what's one was preferred. It depends on patient preference, comfort with the doctor in terms of how comfortable the doctor is using the agent, and other factors that go into the decision about which biphosphonate to use. Generally, the IV Zoledronic Acid and sub-cu Denosumab are used in the cancer populations. But oral biphosphonates can be used as well. And why is this guideline so important? And how will it change practice? Well, this guideline is so important because we know from survey studies that osteoporosis and preventing osteoporosis and treating osteoporosis in the cancer survivor population is underutilized. And this is an important point, because many people, especially with breast and prostate cancer and colorectal cancer and bone marrow transplants, will be long-term survivors. And we don't want to cure a patient just to have them fracture 10 or 20 years later. So that's the importance of the guideline. So it's the recognition that osteoporosis is treated the same, whether you're a cancer survivor or not. But the cancer treatments we use in routine practice can cause osteoporosis and bone loss. And that's the importance of this recommendation, as well as the particulars of who's at risk, the risk factors, screening, and pulling the trigger for treatment. So that's basically in a nutshell, why this guideline is so important and how it will change practice, because we hope that the guideline stimulates us, as health practitioners, to screen our patients for osteoporosis, recognize risk factors, and how to pull the trigger on treatment to prevent or treat osteoporosis in this population. It doesn't matter who follows patient, but the patient has to know who's going to follow the bone density and treatment for osteoporosis, whether it's comfort that an oncologist has with the whole process of screening and risk factors and pulling the trigger for bisphosphonates or Denosumab or endocrinologists, the rheumatologist, the primary care physician. The patient's got to know who's going to be responsible for what aspects of care, survivorship care. And this is a big part of survivorship care. So the treatment summary, which is a document that the patients get and is given to the primary care provider, should specify who will take responsibility for what aspects of survivorship care. And this is a big aspect of survivorship care, osteoporosis screening and treatment, if necessary. So it doesn't matter who does it, as long as it gets done. I would jumped in if I could, Charlie. Yes, so please jump in. So I guess the only other point that I wanted to make about how it might change practice is osteoporosis guidelines have been out since the late '90s, early 2000s. And so many patients probably have thought about osteoporosis and their risk in the past. But I did want to note that there have been a number of studies in the last five years showing that in primary care-- so family medicine and general internal medicine, like I practice-- that we're actually ordering fewer bone densities than we did in the past. And all the reasons for that aren't clear. Perhaps it's because of some concerns about the rare side effects of some of these medicines. Perhaps it's because the guidelines aren't clear because the data is not clear about how often we should test people who don't seem to be at high risk once they've had a first test. But nonetheless, there seems to already be some effects of this that the hip fractures, which had been decreasing are starting to look like they're rising again. So it really is important then if we're not going to screen very frequently everybody, that we are screening the people who really need it. And so then this guideline it calls that out that these are patients who because either their cancer treatment and the debilitating nature of that in some cases or the specific medications puts them at particular risk. Those are the ones that we can't omit this. Great. Finally, how will these guideline recommendations affect patients? You know, I think we're hoping that this will help in the care of cancer survivors and spark people to use things like survivorship care plans. Or if those don't work in your institution, other ways to make clear what the patients who are survivors are at risk for, both related to their cancer and outside their cancer, so that we can all work as teams of health care providers to make sure all of the things on those lists addressed. So we're hoping that with some very clear recommendations about how to address bone health that we can help those teams serve patients that they can. Obviously, it can also provide some really essential information for patients who are wondering what the things that need to be wondering about in this new phase of survivorship after cancer that they're dealing with. Dr. Shapiro, did you have anything to add to that question? Hopefully, we can prevent fractures in our cancer survivors by following these guidelines. It's really important that we prevent osteoporosis and hip fractures and vertebral fractures, because we don't want to cure the patient just that saddle them with osteoporosis and breaking a hip or breaking vertebral body 10 or 20 years down the line. So this will hopefully affect patients positively. And we intended the guideline to be for patients in terms of risk factors. And if you need a biphosphonate or anti-osteoporosis drug, then it's clear indications in the document who gets it and who doesn't. So I think that the effect we hope would be great on patients, that part of general health is osteoporosis screening. And just because you're a cancer patient doesn't absolve you from participating in all the health recommendations, including osteoporosis screening. As with all ASCO Survivorship Guidelines, we do hope that this one informs many conversations between patients, survivors, and providers. Thanks to your overview here today and your work on this guideline, more clinicians will be informed of the risk factors and possible interventions for osteoporosis and survivors of non-metastatic cancers. So I want to thank you both for coming on the podcast to discuss this guideline with me today. Thanks for having us. Yes, thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/survivorship-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast. And be sure to subscribe, so you never miss an episode.

An interview with Dr. Kala Visvanathan from Sidney Kimmel Comprehensive Cancer Center, and Johns Hopkins Bloomberg School of Public Health on the guideline update. This update adds anastrozole to the options of pharmacologic interventions for breast cancer risk reduction based on recent practice changing data. Read the full guideline at www.asco.org/breast-cancer-guidelines. TRANSCRIPT Hi. My name is Clifford Hudis, and I am the CEO of the American Society of Clinical Oncology as well as the host of the ASCO in Action podcast. About twice a month, I interview thought leaders in health care and experts in oncology. And we provide analysis and commentary on a wide range of cancer policy and practice issues. You can find the ASCO in Action podcast on Apple Podcasts or wherever you are listening to this show. And you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Kala Visvanathan from the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, and Johns Hopkins Bloomberg School of Public Health, co-first author on "Use of Endocrine Therapy For Breast Cancer Risk Reduction: ASCO Clinical Practice Guidelines Update." Thank you for being here, Dr. Visvanathan. Thank you as well for having me. So can you tell us about the phase III randomized trial, which provided the signal for this update? Yes. This was the IBIS-II trial that was reported out by Cuzick, et al in 2014. It was a double-blind, randomized placebo-controlled trial that assessed the safety and efficacy of Anastrozole, the aromatase inhibitor Anastrozole, at 1 milligram per day for five years. And the primary endpoint was the reduction of the incidence of breast cancer in postmenopausal women at increased risk of developing breast cancer. The trial itself was reported out with a median follow up of five years and the intention-to-treat analysis actually revealed that 85 women in the placebo group and 40 women in the Anastrozole group had developed both invasive and noninvasive breast cancer. What it showed was that there was a reduction in the incidence of breast cancer of 53% overall. It included both invasive and non-invasive breast cancer after a seven-year followup. And importantly, in subgroup analysis, similar to the other hormone endocrine therapy prevention trials, it also showed that the reduction in breast cancer risk among invasive cancers was limited to those individuals with ER-positive and PR-positive tumors. And the reduction in breast cancer incidence was among hormone-positive breast cancers. Another interesting point to mention here was that the five-year adherence was only slightly less in the Anastrozole arm compared to placebo. So it was well tolerated. And that was 68% in the Anastrozole group compared to 72% in the placebo group. And in all the subgroup analysis, there was no significant difference, except when they stratified by hormone replacement, women who had no prior hormone replacement, they saw a clear risk reduction. And this was not seen in women with prior hormone replacement therapy. And so what are the key recommendations for the update of this guideline? So based on these results, the update really adds Anastrozole as another option for endocrine prevention in women at increased risk. So specifically, we say that Anastrozole 1 milligram per day orally for five years should be discussed as an alternate to tamoxifen, raloxifene or exemestane in postmenopausal women for the reduction of breast cancer in women at increased risk. We also clarify further who are the women most likely to benefit from Anastrozole or the other endocrine prevention drugs. And these are women diagnosed with atypical hyperplasia, either ductal or lobular, or lobular carcinoma in situ or women with an estimated five-year risk of at least 3% based on the NCI Breast Cancer Risk Assessment tool or a 10-year risk of at least 5% based on the IBIS Tyrer-Cusick Risk Calculator. But we also give parameters for other risk models, and that is a relative risk of at least four times the population risk for women in the age group 40 to 45 and two times that of the population age group from 45 to 69. I think this is an important part of the recommendations, because up till now, the recommendations for women at increased risk have really followed the eligibility criteria for these trials, which were often a five-year risk, for example, of 1.7% in the NSABP trials. And here, we're trying to really highlight the importance of considering this women at higher risk where there is a clear benefit when you look at benefit-risk ratios. We also talk about the fact that Anastrozole should not be prescribed in women who are premenopausal and that it is really important that both patients and health care providers discuss the benefits and risks of Anastrozole along with the other risk-reduction agents when they are considering prescribing this. And then lastly, the importance of talking about specific adverse effects of Anastrozole, because here we're talking about a population of women at increased risk who are cancer free. And that includes baseline fracture risk, a measurement of bone mineral density as well as other adverse effects like joint stiffness, arthralgias, vasomotor symptoms, hypertension, dry eyes and vaginal dryness. So we think it's important that they have this discussion with women before the study. So what are some of the clinical considerations for the use of endocrine prevention pharmaceutical agents for breast cancer risk reduction? So in this guideline, we have introduced this section called Clinical Considerations to try to tackle some of the challenging questions that providers have when considering prescribing endocrine prevention. So I urge people to have a look at this section, because it's really a question-answer format. So one of the things we talk about first is what I just alluded to, how do you identify women at risk, where the benefit of endocrine prevention outweighs the risks? And we go through different risk calculations, and we give examples of clinical patients who fit into these risk categories. The second thing, which I think is an important thing, is we talk about a new study that came out while we were preparing this guideline update. And this was by De Censi, et al. And it's been published in the JCO on low-dose tamoxifen. This was a randomized trial in women with intra-epithelial neoplasia. So this includes women with atypical hyperplasia, lobular carcinoma, or ductal carcinoma in situ. So slightly different population. And the women were randomized to tamoxifen at 5 milligrams a day-- so this is 1/4 of the standard 20-milligram dose-- or placebo for three years. So remember-- or endocrine prevention trials were for five years. So this was a shorter duration. And then a median followup of five years, they reported out the results, and they saw half the number of neoplastic events, so DCIS or invasive cancer, compared to placebo. So the results were very comparable to the original NSABP-P1 trial and very promising. So the further I think, what has been a sometimes prevented uptake of these agents, has been the adverse effects of tamoxifen, for example, equal to uterine cancer. And in this study, they did not see an increase in the number of serious adverse effects, including deep venous thrombosis and endometrial cancer. They still saw an increase in hot flashes. So I think this is very promising data and could be an alternate option for some patients, where side effects are a problem or they're reticent to take prevention given the side effects. Another thing we tackle is the question of age when you start recommending hormone prevention. And here, this relates to we talk about at 70, not so much that you would stop it at 70, but at that age or 70 or above, you would actually make sure you're taking into consideration their life expectancy. So they should have a life expectancy of 10 years or greater. And you're also taking into consideration their breast cancer risk. So the question there was, is there an upper age limit for endocrine risk reduction therapy? And we think that, at least the panel thought that, in women 70 years of age or older, you should actually consider both the short-term risk. It should be at least in the range of 1% or more per year. So that would be women with atypical hyperplasia, a family history, or some with carcinoma in situ. We want to make sure they're active and that they have a life expectancy of 10 or more years. Another question we tackled here was, what is the duration of endocrine therapy in this setting for breast cancer risk reduction? And this comes in the context that now, in the treatment setting, a subset of women are given, for example, tamoxifen for more than five years. In terms of data, with the exception of raloxifene, where we do have longer-term data that is greater than five years, in women at increased risk of breast cancer from the osteoporosis prevention trial, where we see that even with women taking raloxifene for more than five years still have a benefit in terms of the breast cancer risk reduction. We don't really have data for any of the other agents in the preventive setting. So there is currently no data from randomized trials that any of these agents, except for raloxifene, should be given for longer than five years. And that is in the setting of women with osteoporosis. And then the last question that we tackle is to look at how you decide between taking an aromatase inhibitor endocrine prevention therapy or a SERM. And this is really only in postmenopausal women, because we still only have one option for premenopausal women, and that is tamoxifen. Here, we just go through step by step sort of the process of thinking about the side effects for each of these agents. And in the context of the woman who is considering endocrine therapy and tailoring it to their age, what symptoms they have, or other comorbidities. Finally, how will these guideline recommendations affect conversations between providers and women at increased risk for breast cancer? So I think, firstly, these guidelines, again, bring attention to breast cancer prevention and the need for us as a community, both providers and women, to move this field forward. And what do I mean by that is we need to be more systematic about identifying women who are truly at increased risk and then subsequently having these discussions with them about the options available. And so I think this guideline adds another agent to the list of agents we now have that can be used to reduce breast cancer risk or breast cancer incidence and also provide the opportunity to-- we look at this and think about how we might incorporate discussions on breast cancer risk reduction into clinical practice. We do also want to stress the importance of discussions on lifestyle factors or risk reduction in addition to these agents. So I think hopefully this guideline helps to, again, refocus attention on the issue and encourage both women to ask their providers about their breast cancer risk and then providers to re-look at this question about breast cancer prevention and how to identify those who are at risk and then discuss endocrine prevention in those at higher risk. I think this is particularly important as we think about our aging population and the increase we are expecting in breast cancer over the next 10 to 20 years. And then also, as we think about breast cancer is now the number-one cancer diagnosed, well, the prevention becomes even more important. Great. Thank you for your work on this guideline. It sounds like there may be many important conversations which happen between women and their providers based on the work and the research about breast cancer risk reduction. So thank you again for coming on the podcast to share with us today, Dr. Visvanathan. Thank you. I would like to thank ASCO for having these podcasts and also shining a light on breast cancer prevention and getting this information out to its listeners. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Anna Falanga on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guideline Update." The guideline revises several previous recommendations. Most notably, direct oral anticoagulants (DOACs) have been added as options for VTE prophylaxis and treatment. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of ASCO's podcasts at podcast.asco.org TRANSCRIPT Hi, my name is Clifford Hudis and I am the CEO of ASCO and the host of the ASCO in Action Podcast. About twice a month, I interview thought leaders in health care and experts in oncology, and we provide analysis and commentary on a wide range of cancer policy and practice issues. You can find the ASCO in Action Podcast on Apple Podcasts or wherever you are listening to this show, and you can find all 9 of ASCO's podcasts which cover a wide range of educational and scientific content and offer enriching insight into the world of cancer care at podcast.asco.org Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin. And today I'm interviewing Dr. Anna Falanga from the hospital Papa Giovanni XXIII in Bergamo, Italy. Senior author on "Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer: ASCO Clinical Practice Guidelines Update." Thank you for being here today, Dr. Falanga. Yes, thank you. I am very happy to talk on the update of the ASCO VTE guidelines. So this guideline was first published in 2007 with an update in 2013 and a reaffirmation in 2015. So what prompted this 2019 update? Thanks for this first question. I think that an update was urgently needed at this time. You know, before, the ASCO guidelines were published in 2007. And then an update was made in 2013, and the second one in 2015. But in 2015 was basically a confirmation of the previous 2013 update. Now the update was urgently needed, because in the very recent years there has been even more evidence of the relevance and impact of a venous thromboembolism in the cancer patients. But in addition, and very importantly, new data from prospective randomized clinical trials with the new drugs for the management of VT in the oncological patients have become available. In particular, as you know, low molecular weight heparins were largely used in the setting of the treatment and trauma prophylaxis in the cancer patients. And actually, the low molecular weight tapering have been the standard of treatment for many years. However, recently the results of prospective randomized clinical trials of direct oral anticoagulant, particularly, the anti-Xa inhibitors, Edoxaban and Rivaroxaban, for cancer associated with [INAUDIBLE] treatment support the role of this new oral agent in the VT management in this setting. And this is related to new politics in the VT management in these patients. So what are the key recommendations for this guideline update? The main changes to the previous recommendations are first that Rivaroxaban and Edoxiban, the two anti-Xa inhibitors oral anticoagulants have been added as an option for routine treatment in cancer patients in this update. Also, now we may offer thrombo prophylaxis with Apixaban, Rivaroxaban, or low molecular weight tapering to selected high-risk outpatients with cancer. And about other changes of these new guidelines compared to the last one include that patients with brain metastases have been addressed in the VT type treatment sections, whereas before, only patients with the primary tumors were mentioned in the previous edition. And finally, the recommendation regarding long-term postoperative thromboprophylaxis with low molecular weight heparin expanded to patients undergoing a major open or laparoscopic abdominal or pelvic surgery. These are the main changes that all I think are very, very important. Why is this guideline so important? And how does it affect practice? Well, I think that the question how these changes affect our practice is a very important question, because I believe that these guidelines reflect the new evidence that we have from the new data. And this data clearly expand our possibility to choose now between the different treatment options in the single patient in the cancer population. For instance, the new data show that treatment with [INAUDIBLE] anticoagulants compared to low molecular weight heparin lower the risk of a recurrent thrombosis. But in some instances there's a higher risk of bleeding, particularly in the gastrointestinal and urinary tract cancer patients. So therefore it is evident that the patient selection and the individualization of a therapy based on the patient characteristics and the type of cancer-- all these become very important. And we have the possibility now to choose between different treatments, or in the same patients we can change from one treatment to the other according to the face of the disease or complications if the patient is in a phase that is assuming chemotherapy with many side effects like nausea and vomiting. Of course, in these cases a parenteral injection is preferable for the management of a venous thromboembolism. Whereas in other instances, a long-term and oral intake is surely more convenient. So it depends also from the level of risk. But now for the six months treatment we can offer different choice of the oral treatment and also for high-risk patients the primary prophylaxis with Apixaban Rivaroxoaban, and a low molecular weight tapering can be chosen. And what should patients be aware of when it comes to VTE risks and treatments? I think that patients should be educated about the risk of a cancer associated with VTE. You know, there is that evidence that they are educated about it. And they know a lot better about neutropenia, and the fever associated with this the neutropenic condition and the other side effect. But they know very little about the possibility that they can experience venous thromboembolism. s So I think they should be taught on how to recognize the symptoms and alert their physician. You know, sometimes the symptoms are indistinguishable It can be just a little pain in the calf. And patients must know that these are to be considered important. They must alert their physician to undergo some test-- objective test-- to see if there is a real thrombosis in the leg or not. This is extremely important, because one important consequence of venous thromboembolism of the extremities is a pulmonary embolism that can be also fatal. So they must know about that. Also, I think they should know about the risk of bleeding associated with the anticoagulant treatment, and also that this risk of bleeding can be different in the different type of tumors. Finally, I think that also they must be told about the once they have, for instance, and episode of venous thromboembolism they have to receive a treatment for that, and these are usually six months to the minimum, and then we'll decide. So they must know what these are the efficacy and the safety profiles of the different drugs. They must know the differences in the route of administration and the other characteristics of the drug. So I think that their shared decision with the patients of the type of treatment must be an integral part of the decision making and is certainly desirable. Great. It sounds as though there's some important considerations for patients and important conversations which may be prompted by this guideline. So thank you for taking your time to discuss this with me today, Dr. Falanga. I thank you very much for this interview and talk that our colleagues and also the patients will be happy with these new guidelines of ASCO. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Noam Yarom, Dr. Charles Shapiro, Dr. Deborah Saunders and Dr. Doug Peterson on "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." This guideline addresses the prevention and management of MRONJ in patients with cancer. This guideline is intended for oncologists and other physicians, dentists, dental specialists, oncology nurses, clinical researchers, oncology pharmacists, advanced practitioners, and patients with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines Find all of the ASCO podcasts at podcast.asco.org TRANSCRIPT Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today, I'm interviewing a panel of authors from "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." So could I have you each introduce yourselves for the listeners today? Thank you, Shannon. I'm Dr. Deborah Saunders. I'm the president of the International Society of Oral Oncology and was the section head for the Systematic Review on "Medication-Related Osteonecrosis of the Jaw," with MASCC and ISOO. I was a proud part of the steering committee and one of the authors. Thank you, Debbie. My name is Dr. Douglas Peterson. I am professor of oral medicine in the School of Dental Medicine at the University of Connecticut Health Center in Farmington, Connecticut. I am also a faculty member in the Head and Neck Cancer Oral Oncology Program at the university's Neag Comprehensive Cancer Center. I'm a member of the steering committee for this clinical practice guideline and one of the co-authors as well. In addition, and as of June 2019, I have been serving as chair elect during this next year for ASCO's Clinical Practice Guidelines committee. Thank you, Doug. My name is Noam Yarom. I'm an all medicine specialist from the Sheba Medical Center in Tel Aviv University in Israel. I'm serving as a culture of this guideline, and it is a pleasure to be with you today. Thanks, Noam. I am Dr. Charles Shapiro, professor of medicine at the Mt. Sinai Hospital in New York. And I'm co-chair of the guideline "Medical-Related Osteonecrosis of the Jaw." And I'm happy to be here. Thank you all for being here today to discuss this guideline on the podcast. So first, can you give us a general overview of what this guideline covers. Sure. So you know, ASCO and MASCC, as well as ISOO decided that it would be great to provide a practical evidence-based approach in a multidisciplinary type setting to address this important topic that impacts all of our professions, that being medication-related osteonecrosis of the jaw. It's terminology and its definition and the path that's varied and even part of this publication identifies the need for us to move forward with a concise definition and similar terminology, that being medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw is defined as the presence of an exposed or bone that is probable by a probe in a patient that has a history or is undergoing present use of a bone-modifying agent. This being in the absence of any patients having received any radiation to the head and neck and the absence of metastatic lesions to the jaw. The importance of us identifying this definition and agreeing on the terminology allows us to move forward in future publication to better compare outcome and provide better prevention and treatment for our patients moving forward. And what are the key recommendations of this guideline? There are six clinical questions associated with this clinical practice guideline as well as a series of recommendations built within each of the clinical questions. Clinical question one is directed to the preferred terminology and definition for osteonecrosis of the jaw, both of the maxilla and the mandible, as associated with pharmacologic therapies in oncology patients. The panel recommends that the term medication-related osteonecrosis of the jaw, MROJ, be used when referring to bone necrosis associated with pharmacologic therapies. As Dr. Saunders has described, the definition contains three key elements-- current or previous treatment with a bone-modifying agent or angiogenic inhibitor, exposed bone, or bone that can be probed through an intra or extra-oral fistula in the maxillofacial region and that has persisted for longer than eight weeks. And third, no history of radiation therapy to the jaws and no history of metastatic disease to the jaws. Clinical question two is directed to specific steps that should be taken to reduce the risk of MRONJ. The recommendation begins with emphasizing the absolute importance of interprofessional communication of the oncology team with the dental team in advance of initiating the bone-modifying agent. For patients with cancer who are scheduled to receive a bone-modifying agent in a non-urgent setting, a comprehensive oral care assessment, including dental examination and periodontal examination and an oral radiographic exam when feasible to do so should be undertaken prior to initiating the BMA therapy. Once the dental care plan has been developed, it should be discussed with the dental team, the patient, and the rest of the oncology team and then implemented based on medically necessary dental procedures. These procedures should be performed prior to the initiation of the bone-modifying agent. Once the bone-modifying agent is implemented, there should be ongoing followup by the dentist on a routine schedule, for example, every six months following initiation of the BMA therapy. It's also important to realize that there are a series of modifiable risk factors which should be emphasized with the patient. For example, poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes mellitus, and tobacco use are all factors that have been associated with development of a MRONJ. All of these modifiable risk factors should be addressed, where appropriate, with the patient in advance of the bone-modifying agent. As far as elective dental alveolar surgery, these procedures, if they are not medically necessary, for example, extractions or alveoloplasties or implants, they should not be performed during active therapy with a bone-modifying agent being given at an oncologic dose. Now, exceptions to this may be considered when a dental specialist with expertise in prevention and treatment of MROJ has reviewed the benefits and risks of the proposed invasive procedures with the patient and the oncology team. In general, however, elective dental alveolar surgical procedures should be deferred while the patient is undergoing active therapy with a bone-modifying agent. If the dental alveolar surgery is performed, the patient should be evaluated by a dental specialist on a systematic and frequently scheduled basis, for example, every six to eight weeks until there is full mucosal coverage of the surgical site. And once again, communication between the dental team and the rest of the oncology team is absolutely paramount in assuring ongoing comprehensive care of the patient. Interestingly, there are still questions in the literature relative to whether or not there should be temporary discontinuation of bone-modifying agents prior to dental alveolar surgery. Unfortunately, there remains insufficient evidence to support or refute the need for discontinuation of the bone-modifying agent prior to dental alveolar surgery. And so the administration of the bone-modifying agent may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. So it really becomes an individual judgment call by the treating physician relative to whether or not to temporarily discontinue the bone-modifying agent prior to dental alveolar surgery. Clinical question three involves the staging of MROJ. There are a number of well-established staging systems in the literature addressing severity and extent of MROJ. For example, the 2014 American Academy of Oral and Maxillofacial Surgeons Staging System is one example. Another example is the National Cancer Institute's Common Terminology Criteria For Adverse Events. And there is a 2017 International Task Force on O and J Staging System for MROJ that is available as well. So there are at least three well-established, widely utilized staging systems for MROJ. Having said this, it's important in the view of the panel that the same staging system should be used throughout an individual patient's MROJ course of care. And optimally, the staging should be performed by a clinician experienced with the management of MROJ. Clinical question four involves management of MROJ directly. Here, the recommendations talk in terms of initial treatment of MROJ, which is centered in conservative measures. Now, these conservative measures may include antimicrobial mouth rinses, antibiotics if clinically indicated, effective oral hygiene, and conservative surgical intervention such as a removal of a superficial bone spicule. In cases, however, of refractory MROJ, more advanced MROJ, aggressive surgical interventions, for example, mucosal flap elevations, bloc resections of necrotic bone may be used if MROJ is persisting and severely affects function despite conservative initial treatment. Clinical question five involves bone-modifying agents and whether they should be temporarily discontinued after a diagnosis of MROJ has been established. And once again, there is insufficient evidence to support or refute the discontinuation of the bone-modifying agents after a diagnosis of MROJ has been established. The bone-modifying agent may be deferred at the discretion of the treating physician, again in discussion with the patient and the oral health care provider. And finally, clinical question six involves what outcome measures that should be utilized in clinical practice to describe the response of MROJ lesion to treatment. During the course of MROJ treatment, the dentist, dental specialist, should communicate with a medical oncologist in an ongoing way, both the objective and subjective status of the lesion. The guideline presents a scale that can be utilized to describe the trajectory of the MROJ-- resolved, improving, stable, or progressive. The clinical course of MROJ may impact both local and systemic treatment decisions relative to the cessation or the recommencement of bone-modifying agents. So once again, it becomes very, very important that the ongoing interprofessional communication relative to the clinical course of MROJ-- resolved, improving, stable, or progressive-- be discussed with the oncology team. Great. Thank you, Dr. Peterson. So on that last note, how can oncologists, dental specialists, and dentists all work together to manage medication-related osteonecrosis of the jaw? Throughout these guidelines, we do emphasize the importance of collaboration among the cancer care team, dentist, and dental specialists in order to coordinate care and modify risk factors. It is very important that cancer care team and the dental care team speak the same language. Therefore, we spend time on clarifying the definitions, the diagnostic criteria, and staging of MROJ. As been said earlier, we have developed a new system to evaluate the response to treatment, which is based both on objective findings and symptoms. By using this scale, oncologists and dentists would be able to communicate more easily for the benefit of the patients. We emphasized the need for multidisciplinary discussion in a few critical points throughout the course of bone-modifying agent therapy. And it is most important in case of a planned oral surgery in a patient without MROJ or before aggressive surgical treatment of refractory MROJ. And how will these guideline recommendations affect patients, and what should they talk to their doctors about? There are a number of things that patients, providers, dental specialists, and medical oncologists can do to lessen the risk and prevent MROJ. Because the key to MROJ is prevention. Once MROJ is established, it's difficult to treat, impacting a patient's quality of life. So we want to prevent, reduce the risk of developing MROJ. Patients can do a number of things-- pursue good oral hygiene, stop smoking, or reduce smoking, and control their diabetes, for example. Those things lessen the risk of MROJ. Providers, dental providers, dental specialists, who are specialized in the area or providers, dentists otherwise in the community, when they encounter a patient that's contemplating bone-modifying agents, they can do what's called a complete dental screening exam, which involves a complete examination of the mouth, Panorex X-rays and X-rays as clinically indicated. We want to identify work in the mouth that needs to be repaired before initiating bone-modifying agents. That way, we don't have to deal with an emergent situation when it could be preventable prior to bone-modifying agents, because one of the single highest risk factors for MROJ is emergent dental work while you're on bisphosphonate or another anti-resorptive agent-- bone-modifying agents. So a dental screening exam is critical to prevent or reduce the risk of MROJ. And medical oncologists have a role too in communication with the dental specialists and really think hard about the indications for bone-modifying agents, whether it be for osteoporosis, whether it be for metastatic disease, and whether it be for anti-cancer effects. And finally, where can both patients and clinicians go to get more information on this topic or to find a dentist or a dental specialist? Now, as far as websites, ASCO, MASCC, and ISSO all have websites you can go to to find out more information about MROJ. Yeah, I think that's great advice. Our links for additional information are listed in the Clinical Practice Guideline as well. This is a really first step at a framework in trying to manage a side effect that affects our patients but is very multidisciplinary. And like Dr. Shapiro was saying, really the best way to prevent this is with proper communication between the dentist and the oncologist and making the patient aware of what is needed prior to commencement of these treatments. Well, it certainly sounds as though there are some important considerations for clinicians and patients. And I really hope that this guideline is widely read and makes a real impact on the management of osteonecrosis and the communication between oncologists, dental specialists, and dentists. So from me and all of our listeners, thank you all for coming on the podcast today to discuss "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." Thank you. Thank you for having us. Thank you very much for this opportunity to contribute to this important discussion. Thank you for allowing me to participate in this important podcast. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.