ASCO Guidelines

An interview with Dr. Manish Shah from New York Hospital Weill Cornell Medical Center on "Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline." This guideline provides evidence-based recommendations on treatment options for patients with locally advanced esophageal adenocarcinoma and squamous cell carcinoma. Read the full guideline at www.asco.org/gastrointestinal-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. 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. Manish Shah from New York Hospital Weill Cornell Medical Center, lead author on "Treatment of Locally Advanced Esophageal Carcinoma," ASCO guideline. Thank you for being here, Dr. Shah. I'm so pleased to be here on this podcast for ASCO with you, Brittany. I'm very pleased to talk about this guideline and its significance to the oncologic community and to our patients. First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. But Dr. Shah, do you have any relevant disclosures that are directly related to this guideline topic? No, I have no conflicts as it relates to this topic. I do have research funding from Merck, Boston Biomedical, Oncolys, BMS, and Acelis, and no other conflicts and nothing specific to locally advanced esophageal cancer. Thank you. Then let's dive into this guideline. First, can you give us an overview of what this guideline covers? Sure. This guideline covers the management of locally advanced esophageal cancer, both adenocarcinoma and squamous cell cancer, because management of these diseases is very complicated, primarily as the epidemiology of this disease has shifted over the past several decades. About 20 to 30 years ago, squamous cell cancers of the esophagus was the predominant disease subtype. About 90% of patients that we would see with esophageal cancer were of squamous cell histology. However, with the rise in Barrett's esophagus and adenocarcinoma of the distal esophagus and GE junction, now, about 50% of esophageal cancers are adenocarcinoma histology. This distinction is important because, while the two diseases have significant overlap and treatment options, there are differences in sensitivity to various therapies. The guideline attempts to tease out these distinctions to provide the best evidence-based practice recommendations for the community. Great. So you mentioned that this covers both adenocarcinoma and squamous cell carcinoma. So what are the key recommendations of this guideline for patients with locally advanced esophageal adenocarcinoma? Sure. So for both squamous cell cancer and adenocarcinoma of the esophagus, locally advanced disease, the first and key recommendation is that multimodality therapy is considered and offered to both disease histologies. It's very important that these patients are treated through a multidisciplinary approach that involves a surgeon, typically a thoracic surgeon, but sometimes a general surgical oncologist as well, as well as a radiation oncologist and a medical oncologist. For adenocarcinoma of the esophagus, which is really becoming the most common type, the primary recommendation is that patients with locally advanced esophageal adenocarcinoma receive either preoperative chemotherapy with radiation or perioperative chemotherapy. Because there is no comparative study for these two options, we also provide a clinical vignette to help readers understand some of the key features that may sway one to one treatment versus another. For example, large bulky tumors where an R1 resection is more likely may be better suited for chemoradiotherapy, followed by surgery. An R1 resection, of course, is where the microscopic margin might still be positive. Additionally, patients who may not have a three-hole or a thoracic surgery as part of their surgical plan may not have an adequate lymph node dissection. That might be another reason to consider chemoradiotherapy, followed by surgery. And what is recommended for patients diagnosed with locally advanced esophageal squamous cell carcinoma? Yes. For squamous cell cancer, we recognize that these tumors are much more sensitive to radiotherapy. So the options that are recommended here, based on the evidence available, is that patients who receive preoperative chemotherapy and radiation or definitive chemotherapy and radiation, meaning chemotherapy and radiation with or without surgery. These are the recommendations for squamous cell cancer. So why is this guideline important, and how will it change practice? So we hope that our guideline will provide some clarity on a very murky field. The study suggests that there are several options available for patients with locally advanced esophageal squamous cell cancer and adenocarcinoma. And the guideline helps us frame the question and frame how we think about these options in offering patients the best practice that we can with regard to the available data. Additionally, the guideline may help define future research questions as well, as the gaps in knowledge are clear based on the guideline. For example, there are patients, a significant number of patients, who have a complete response to chemotherapy and radiation. Should all of these patients have immediate surgery, or can surgery safely be delayed? That's an ongoing question that is being examined in rectal cancers. And also, there is some data in esophageal cancer as well. And that might be an important question to ask, moving forward, for example. Great. And then finally, how will these guideline recommendations affect patients? We hope that through the guideline process and understanding the nuances of how to treat patients with locally advanced esophageal cancer, that based on histology, based on the size and bulk of the tumor, based on the likelihood of an R1 resection, or based on even the surgical approach, that patients will receive more uniform therapy and therapy that is more tailored to their particular condition and situation. In the end, we hope that patients will receive the right care and ultimately have better outcomes because their care is more uniform. It sounds like these guidelines could have a real impact for patients. So thank you for your work on these treatment of locally advanced esophageal carcinoma guidelines and for taking the time today to speak with me, Dr. Shah. Thank you. It's a pleasure to be here. 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/gastrointestinal-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.

An interview with Dr. Eric Roeland from Massachusetts General Hospital Cancer Center on "Management of Cancer Cachexia: ASCO Guideline." This guideline provides evidence-based recommendations on the clinical management of cancer cachexia in adult patients with advanced cancer. Recommendations are made on both pharmacologic and nutritional interventions. Read the full guideline at www.asco.org/supportive-care-guidelines 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 Brittany Harvey, and today I'm speaking with Dr. Eric Roland from Massachusetts General Hospital Cancer Center. Lead author on Management of Cancer Cachexia, ASCO Guideline. Thank you for being here, Dr. Roland. Well thank you very much. Before we get into the content of this guideline, I want to note that all conflict of interest disclosure information for the expert panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Roland, do you have any conflicts of interest to disclose? Yes, within the last two years, I've served as a consultant for Asahi Kasei Pharmaceuticals, DIG Consulting, Napo Pharmaceuticals, American Imaging Management, Immuneering Corporation, and Prime Oncology. I've also served on advisory boards for Herron Pharmaceuticals and Vector Oncology. And I serve as a member on the Data Safety Monitoring Boards for Oragenics, Kalyra Pharmaceuticals, and [INAUDIBLE] Life Sciences Pharmaceutical Company. Thank you. Then first, can you give us a general overview of what this guideline covers? Sure. We performed a systematic review of the literature regarding available evidence for nutritional and pharmacologic interventions for cancer cachexia. Specifically, we searched PubMed and the Cochrane Library for randomized controlled trials and systematic reviews published between 1966 in 2019. We focused our review on adult patients with advanced or incurable cancer. And given the highly variable nature of cancer cachexia, we specifically evaluated the endpoints of loss of appetite or anorexia, body weight, and lean body mass, or skeletal muscle. Our targeted audience included clinicians as well as patients and caregivers. Can you provide us with a little background on cancer cachexia? Yes, first I think it's incredibly important for us to define cancer cachexia, especially given its prevalence in cancer care. Traditionally, cancer cachexia has been defined as a certain amount of weight loss over a defined time period. However, cachexia is much more complicated than weight loss alone. It is a multifactorial syndrome characterized by loss of appetite, weight, and skeletal muscle, which leads to fatigue, functional impairment, increased treatment related toxicity, poor quality of life, and even reduced survival. And as clinicians, we need to try to identify any reversible causes contributing to cachexia and treat them. This of course, includes treating the underlying cancer when possible. Additionally, it's essential for patients to receive optimal palliation of all symptoms that may be interfering with the intake of calories, such as pain, nausea, vomiting, constipation, diarrhea, and depression. Therefore, as clinicians, we need to work in teams of experts that might include expertise in pain, palliative care, nutrition, physical occupational therapy, and mental health where available. We also need to introduce and discuss the term, cachexia, with our patients and their caregivers, who often have never heard of it before. They may not understand that this term is unique and very different from weight loss alone. I personally have found that describing the unique nature of cachexia and providing the information to patients and caregivers can be very helpful. Additionally, we need to recognize that food is a very complicated issue. And when we engage patients and caregivers around issues of food, we need to recognize that there are informational needs, but there are also emotional needs. And as clinicians, we help patients and caregivers gain access to evidence based information and interventions, but we equally need to ensure that they receive emotional support. Food represents hope and control in an uncontrollable situation. And not being able to eat or feed a loved one can cause severe distress. Therefore, we need to engage patients and caregivers regarding these emotional issues and make sure they feel heard. We can also reach out to our mental health colleagues, such as social workers and psychologists, who may help us support patients and caregivers in this difficult issue. Then, what are the key recommendations covered in this guideline? With regard to our systematic review, we identified 20 systematic reviews and 13 additional randomized controlled trials. And from this data, we made the following recommendations. First, we found limited data supporting the integration of dietary counseling with or without oral nutritional supplements. However, given the lack of harm and the critical role of educating patients and caregivers, we felt it was important to support referring patients with incurable cancer and loss of appetite and/or body weight to registered dietitian for assessment and counseling. It's critical for patients and caregivers to learn about practical and safe approaches to feeding. Specifically, registered dietitians may help develop strategies, such as shifting away from three larger meals per day towards frequent high protein, high calorie, nutrient dense snacks. Dietitians can also address questions regarding specific diets, including fad diets and unproven or extreme diets. Moreover, clinicians should not routinely offer enteral tube feeding or parenteral nutrition to manage cachexia in patients with incurable cancer. A short term trial of parenteral nutrition may be offered to a very select group of patients, such as patients with a reversible bowel obstruction, or short gut, or issues with malabsorption, but otherwise reasonably fit. We also can consider discontinuing previously initiated enteral parenteral nutrition near the end of life, as it is associated with net harm at that time. With regard to pharmacologic interventions, there are no FDA approved drugs to treat cancer cachexia. Yet there is sufficient data to support two pharmacologic interventions associated with improvements in appetite and/or body weight. And these include progesterone analogs, such as megestrol acetate and corticosteroids. The optimal dose and timing of each drug remains unknown. Regarding megestrol acetate, data support its role in improving appetite, modest weight gain, and improvement in quality of life. However, the weight gain associated with megestrol acetate is primarily fat and not skeletal muscle. We also need to be aware of side effects of megestrol acetate, including an increased risk of thromboembolic events, edema, adrenal insufficiency, and even an increased risk of death. As for corticosteroids, the first published double-blind randomized study dates back all the way to 1974, which showed an improvement in appetite and sense of well-being. However, clinicians are aware of the multiple side effects associated with corticosteroid use, that often limit initiation and timing of their use. Additionally, the weight gain associated with corticosteroids is not skeletal muscle. As important as it is to know what drugs are evidence based, it is also important to note what pharmacologic approaches are not supported by evidence. There are many agents that have been evaluated in clinical trials without any evidence to support an improvement in cancer cachexia outcomes. One such drug that frequently is asked about is dronabinol or the general class of cannabinoids. Insufficient data was available to recommend dronabinol or medical cannabis, and they have notable side effects, including altered mental status and a higher risk of falls. Especially in the elderly. Why is this guideline important? And how will it impact practice? Cachexia is a very common clinical entity and causes lots of distress for patients and caregivers. Oftentimes, the issues regarding nutrition and weight loss can be the central focus of clinical appointments and conversations with oncologists. We need to ensure that patients and caregivers have access to evidence based information and recognize that some interventions may be associated with more harm than benefit. And finally, you've just spoken to this a bit, but how will these guideline recommendations affect patients? Primarily, I think these cancer cachexia guidelines will serve as a great educational resource. They will also allow patients to better understand the risks associated with some of the pharmacologic interventions. I also think it's critical to define the current state of evidence in cancer cachexia, as we have many new exciting clinical trials evaluating novel agents in the setting. Furthermore, as a cancer community, we need to ensure that interventional trials are focused on clinically meaningful endpoints, such as improvements in appetite, muscle mass, and quality of life. We also need to encourage a rigorous but expedited approval of these agents, given the lack of any FDA approved drugs in this setting. Lastly, we need to recognize this is a multi-modal syndrome that requires the help and expertise of our interdisciplinary colleagues. Supporting our patients and their caregivers with this very difficult syndrome requires as much help as possible. Great. Thank you for your work on these guidelines and for taking the time to speak with me today, Dr. Roland. Thank you so much, Brittany. I would also like to recognize and thank ASCO for its support of these guidelines, the talented ASCO staff, and the experts who contributed. Most of all, I'd like to recognize our patients and their caregivers. 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-cancer-guidelines. This guideline also has a companion, cancer.net podcast episode. Cancer.net is the patient information website of ASCO. And we encourage you to learn more by tuning into their episode. You can find their podcast and all ASCO podcasts at podcast.asco.org. 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.

An interview with Dr. Benjamin Levy from Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital on "Lung Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline." This guideline provides recommendations to clinicians on radiographic imaging and biomarker surveillance strategies after definitive curative-intent therapy in patients with stage I-III non–small-cell lung cancer and small-cell lung cancer. Read the full guideline at www.asco.org/thoracic-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, 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. Benjamin Levy from Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, author on "Lung Surveillance After Definitive Curative Intent Therapy ASCO Guideline." Thank you for being here, Dr. Levy. Thanks for having me. So first, can you give us a general overview of what this guideline covers? Yeah, I think that the general broad stroke intent of this consensus paper was to provide evidence-based guidelines and recommendations for practicing clinicians on what the optimal radiographic imaging and biomarker surveillance strategy should be for patients who received definitive curative intent therapy, and specifically for patients with stage I through III non-small-cell lung cancer, or patients who have received curative intent therapy for a limited-stage small-cell lung cancer. And importantly, this expert panel comprised a multidisciplinary team, and this included not only medical oncologists, but surgical oncologists, pulmonologists, radiologists, a general internist, a patient representative. So we had, I think, the relevant stakeholders to make the best recommendations we could based on the evidence. And we really framed our recommendations by answering five questions, and I think we can get to the five questions at a later time during this cast, but we try to answer these five questions in a systematic way. And really looked at the type-- was an evidence-based or was it informal consensus? What was the evidence quality? Was it low, was it intermediate, or was it high? And then finally, the strength of the recommendation. And importantly, we tried to answer these questions based on the evidence. We did a literature search, which culminated in a systematic review of more than-- close to 1,200 studies of which 14 studies were identified, and these 14 studies included meta-analysis, randomized control trials, case-controlled trials, and retrospective studies, and really by doing this, we wanted to come up with important guidelines. I think these guidelines are coming on the heels of a lot of confusion about what is the optimal surveillance strategies post-curative intent therapy for our lung cancer patients? So we recognize this confusion and tried our best to create guidelines that were reasonable to follow, and hopefully it can change practice. Great. So you just mentioned that there were five key questions that you looked at for this guideline. Yeah. Could you elaborate on what those questions are and the key recommendations of the guideline? Sure. So the crux of our recommendations, again, come on these five questions, and just a summary of these questions. One, what should be the frequency of surveillance imaging post-curative intent therapy? Two, what is the optimal imaging modality? Three, are there any patient factors such as performance status or age limits that would preclude surveillance? Four, is there a role for circulating biomarkers and surveillance? And then five, is there-- or what is the role of brain MRI imaging for surveillance of curative intent patients both non-small cell and small-cell? And just briefly in terms of-- I'll maybe go over briefly just the answers to these questions that we tried to hash out in this consensus work-- for the question, what should be the frequency of surveillance imaging? We recommended that patients should undergo surveillance imaging for recurrence every six months for two years. We then recommend that patients should undergo surveillance imaging for detection of new primary lung cancers annually after the first two years. And in question 2, what is the optimal imaging modality? We recommended a diagnostic chest CT that included the adrenals with contrast, that's preferred, or without contrast when conducting surveillance for recurrence during the first two years post-treatment. We did state that there was no evidence of any added benefit for CT of the abdomen and pelvis over a chest CT through the adrenals, that surveillance. We then, again, similar answer to recommendation 1, we do recommend a low dose screening for chest CT when conducting surveillance for new lung primaries after those first two years. And then I think importantly, we take a hard stand on PET scans as part of the answer to question 2, where we really should not be using PET scans as a surveillance tool in the surveillance starting post-curative intent therapy. Question 3, are there any patient factors such as performance status or age limits that would preclude surveillance? And for us, we make the recommendation that surveillance imaging may be permitted in some patients who are clinically unsuitable, have multiple medical comorbidities, or unwilling to undergo further treatment. Doesn't make a lot of sense to offer surveillance imaging if patients are stating that they're not going to undergo any further treatment. We also state that age should not preclude surveillance imaging, but there needs to be a consideration for overall health status and chronic medical conditions and patient preferences. Question 4 was, is there a role for circulating biomarkers in surveillance? And this is probably one of the more confusing parts of surveillance. Many physicians are still using CEA to monitor for a recurrence, and we really take a hard stand and say that clinicians should not be using circulating biomarkers as surveillance strategy for the detection of recurrence in patients who've undergone curative intent treatment, but we also do state that there is emerging data looking at ctDNA that may change this over the next four or five years, but we're certainly not there yet. So standard of care should not be-- to be using anything like that. And then question 5 is, are there-- or what is the role for brain MRI for surveillance in patients with both non-small-cell and small-cell? And our recommendations are a little nuanced here. We did say for patients with stage I through III non-small-cell lung cancer, clinicians should not be using a brain MRI for routine surveillance after curative intent therapy, and patients who have undergone curative intent treatment for small-cell and did not receive prophylactic cranial radiation, this is where we do say clinicians should offer a brain MRI every three months for the first year and then every six months for the second year for surveillance. So a little bit different surveillance strategies for patients whether you're small-cell or non-small-cell. So those are the broad stroke overviews of the recommendations that we put together in this consensus statement. And then can you speak to the importance of this guideline and these recommendations and how they will impact practice? I think that ASCO recognized how much confusion there was post-curative intent therapy. So I think this is the reason why these guidelines are so important. We need to keep in mind that health care resources that are utilized and be mindful of that. There's no real role for routine imaging less than the intervals that we're describing as they may obviously not be in touch with health care utilization and cost. The other thing is this idea that patients are getting scans so frequently that we're picking up on a lot of false positive information that can't be used, and so we recognize that as well. So I think that on the heels of the confusion coupled with cost considerations, as well as what we're picking up on frequent scans, we do have to make recommendations that will hopefully unify and harmonize practice across the country to better suit patients and also evidence-based practice. I think that's really important. And finally, how will these guideline recommendations affect patients? Yeah, I think patients hopefully, if physicians follow these guidelines, will be receiving the appropriate interval. I mean, look, we understand that two-thirds of patients with lung cancer who relapse will present with metastatic disease and that there have been limited data thus far on what should be the optimal interval for scans. But we understand also that patients who do relapse could present with potentially curable lung cancer, and in addition, there's been recent data to suggest that even patients with limited metastatic disease who was detected on recurrence may be cured or may have improved survival with certain strategies like local ablative therapy. So we hope that these guidelines can be firmly cemented into the practice for clinicians so that the appropriate interval is selected, but that also patients can benefit from these appropriately timed-out scans to improve outcomes for them. Great. Thank you for your work on these guidelines, and thank you for taking the time today to give an overview to our listeners, Dr. Levy. Thank you so much. 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/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

An interview with Dr. Jessica Geiger from Cleveland Clinic on "Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck: ASCO Guideline." This guideline provides evidence-based recommendations addressing diagnosis, surgery, radiation therapy, and systemic therapy for patients with squamous cell carcinoma of unknown primary in the head and neck. Read the full guideline at www.asco.org/head-neck-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 podcasts.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Jessica Geiger from Cleveland Clinic, author on Diagnosis and Management of Squamous Cell Carcinoma of Unknown Primary in the Head and Neck ASCO guideline. Thank you for being here, Dr. Geiger. Thanks, Brittany, for the invitation and the opportunity. First, can you tell our listeners what is squamous cell carcinoma of unknown primary in the head and neck and what this guideline generally covers? Sure. So cancer of unknown primary or carcinoma of unknown primary in the head and neck is metastatic squamous cell carcinoma found in cervical lymph nodes. And importantly, there's a lack of a primary mucosal tumor that's identified. So these patients comprise about 5% of all head and neck cancers. And it poses a challenge for all members of the treatment team, both from a diagnostic perspective but as well as treatment management; what is the best way to proceed for treatment with these patients? Now this guideline provides an up-to-date and evidence-based management for recommendations. And these recommendations are based on published literature. But where the data is lacking in the literature, expert panel consensus was utilized to provide recommendations. I'd like to discuss some of the key recommendations of this guideline. First, with regard to diagnosis of squamous cell carcinoma of unknown primary in the head and neck, what are the challenges, and what are the recommendations from the guideline? The diagnostic challenges come about when a patient presents with a neck mass. They often have imaging, a clinical exam. But again, about 3 to 5 percent of patients, we will be unable to locate where this tumor started. Squamous cells don't show up in the lymph nodes by themselves. They came from somewhere else. And part of the reason that this makes a diagnostic challenge if we're not able to readily see where the primary tumor is, oftentimes, it's very small in size. And so it's not picked up by imaging or by a physical exam. Also, these are sometimes difficult anatomic locations to evaluate. So all of this can pose a challenge to coming up with the right diagnosis. Now some of the recommendations for diagnosing these patients, obviously, we need to have a complete history and physical exam. And this physical exam should include a fiberoptic laryngoscopy, so a good lab endoscopy exam looking at all of the mucosal tissues, trying to find abnormalities, trying to see where exactly this cancer started. Now in order to make the diagnosis of squamous cell carcinoma, obviously, a biopsy needs to be done, and that is in the neck, where these suspicious nodes are. Either a fine needle aspiration or a core needle biopsy is recommended within these guidelines. The guidelines also indicate when to do additional pathologic testing. So this is for high-risk HPV, especially in neck nodes that are in level two or three. If high risk HPV testing is negative, then we give recommendations regarding Epstein-Barr virus testing, so looking to find is this nasopharynx primary cancer and then, of course, imaging guidelines. So the image modality of choice is a contrast enhanced CT of the neck, not just to elucidate and better evaluate the nodal burden of disease, which the patient presents with, but also to investigate for evidence of a mucosal primary. Now if that fails to produce a primary then we give recommendations regarding PET scans. And then what are the recommendations for surgery for a squamous cell carcinoma of unknown primary in the head and neck? There are many recommendations that we go into to address the surgical approach to a cancer with unknown primary. Now the previous question asked about diagnosis included in the surgical recommendations in our guidelines for diagnostic surgical interventions. So we can sort of branch point or divide recommendations for surgery, whether it's a diagnostic or a therapeutic procedure. And then in the therapeutic procedures, we can look more in detail at what surgery is recommended for a primary or the mucosal, and then how to how do we address the neck? So first, as part of diagnosis with surgery, all patients need a complete operative evaluation of the upper aerodigestive path. And this includes directed biopsies. So the surgeon goes in the operating room, gets a good look around. Any suspicion for any possible cancer is biopsied, as opposed to blind biopsies or random biopsies, which are not recommended. Now the recommendations for surgery also include when to do tonsillectomies and what tonsillectomies to do. So are these palatine tonsillectomies or lingual tonsillectomies? Do we perform them or recommend them on the ipsilateral side, or what is the role for a contralateral or even bilateral tonsillectomy? And I won't go into the specifics because they're all-- all the different scenarios are laid out within the guidelines, but the recommendations are based on the patient's nodal burden. So do they have bilateral lymph nodes; do they have lymph nodes just on one side; how big they are, that all plays a role into the recommendations regarding surgical intervention. Now if mucosal primary tumor is identified, there are clear recommendations and guidelines that every effort to clear the disease with negative margin is of paramount importance. So we're talking about a definitive oncologic surgery in this case. And the reason we want to stress that negative margins are the goal is because we're trying to avoid trimodal therapy. So we're trying to get to a good surgical resection. A positive margin left behind is likely going to lead to recommendations for postoperative radiation with the addition of radiosensitizing chemotherapy, which is what we do not want. We want to try to avoid toxicities with trimodal therapy. That brings me to then surgical management of the neck and the guidelines set forth in this document. So recommendations for neck surgical management are broken into whether the patient has what we consider small volume disease versus large volume disease. So for small volume disease, small lymph nodes on one side of the neck, we recommend a multidisciplinary discussion whether or not the patient should be best served with a definitive surgery involving a neck dissection or if they should have definitive radiotherapy. Again, our goal is to avoid trimodal therapy. So if there's obvious gross extranodal extension seen on imaging, then they would be best served with a primary radiation approach, as opposed to surgical. Similarly, any large volume disease, obviously, gross extranodal or extracapsular extension, definitive chemo radiotherapy is favored. Now a comment on management of the neck, if you're suspecting an oropharynx primary, which is the majority of cancer of unknown primaries of the head and neck, we give specific recommendations regarding what levels to routinely surgically dissect, levels IIa, III, and IV in that instance. In your discussion of the surgical recommendations, you began to touch on the radiation recommendations. Could you elaborate on those recommendations from ASCO on radiation therapy for this patient population? Of course. And again, when you refer back to the guideline and the recommendations, there are even more specific recommendations regarding when and how to use primary radiotherapy or adjuvant radiotherapy in this setting. So I'm not going to go into great detail for every single recommendation that is provided, but a nice overview is, basically, if a patient is receiving radiotherapy as the primary definitive management of cancer of unknown primary, obviously, we recommend treatment should be given to gross nodal disease but also to neck regions and mucosal anatomic regions, which are considered at risk for containing microscopic disease. So it's not just good enough to radiate what we see on imaging but also to consider the areas around it, the nodal echelons and other mucosal areas where there could be cancer. So for example, an HPV-related disease where it's likely oropharynx unilateral disease, there are specific locations to include. And this is also the same for HPV-negative disease. Now if we're worried about a possible nasopharynx cancer in the setting of E-Barr or EBV-positive disease, the mucosal radiotherapy can be limited to just the nasopharynx, but you want to radiate bilateral necks, level II through IV, and include the retropharyngeal lymph nodes. There are specific recommendations where unilateral versus bilateral neck irradiation is recommended. And again, I just encourage the listeners to refer back to the guideline itself for these specific instances. Also included within the radiotherapy guidelines and recommendations are specific doses. What doses do you use? Where do you use these doses? And these doses are extrapolated from known and well established evidence for traditional head and neck squamous cell carcinoma in which we know where the primary is, also, when to give post neck dissection kind of in the adjuvant setting, again, all extrapolated from known head and neck squamous cell carcinoma but very specific and laid out within the guidelines. And what does the expert panel recommend for systemic therapy for squamous cell carcinoma of unknown primary in the head and neck? Similarly, when we devised the recommendations for radiotherapy for this disease, the use of systemic therapy, when to use it, when to add it to radiation is also extrapolated from the head and neck guidelines and evidence for known head and neck cancer. So we recommend adding chemotherapy to definitive radiotherapy in advanced nodal disease, and we've defined what advanced nodal disease is based on the AJCC 8th Edition. So in HPV-negative disease, this is N2 or N3, in HPV-positive disease, multiple ipsilateral lymph nodes. If a lymph node is greater than three centimeters, we recommend adding chemotherapy to radiation in the definitive setting. Now, specifically, the chemotherapy that we recommend is cisplatin. Again, this is based on well-established studies and evidence in head and neck cancer. So patients who are medically fit and able to receive cisplatin, that is the treatment of choice. There are also recommendations regarding resected cancer of unknown primary. So with evidence of extranodal capsular extension, we recommend the addition of, again, cisplatin chemotherapy to postoperative radiotherapy, again, extrapolated from well-established head and neck studies. And then, again, if you are concerned that this is an Epstein-Barr-related nasopharynx cancer, stages II through IVA, again, AJCC 8th Edition, we recommend the addition of chemotherapy to radiation in those settings as well. Great. This guideline covers a lot of ground and many recommendations. Can you speak to why this guideline is important and how you envision it will impact practice? So this guideline is important because a fair amount of patients will be presenting with cancer of unknown primary. We stress through this guideline that this is very evidence-based recommendations and guidelines with a focus on a multidisciplinary approach to how to treat these patients. And finally, how will these guideline recommendations affect patients? Well, hopefully, this guideline will provide reassurance to patients that no matter where they are receiving treatment, they are receiving quality standard of care management, again, largely driven by evidence. And it doesn't matter whether they're treated by locally practicing experts and specialists or at a large institution, they're being treated by the standard of care that is accepted across the board. Well, thank you for your time today, Dr. Geiger, and for working on these comprehensive guidelines. You're very welcome. Thanks, Brittany. 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/head-neck-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 write and review the podcast and be sure to subscribe so you never miss an episode.

An interview with Dr. Nadine Tung from Beth Israel Deaconess Medical Center in Boston, MA on "Management of Hereditary Breast Cancer: ASCO, ASTRO, and SSO Guideline." This guideline covers recommendations for the management of patients with breast cancer with germline mutations in breast cancer susceptibility genes. Read the full guideline at www.asco.org/breast-cancer-guidelines

An interview with Dr. Pauline Funchain from Cleveland Clinic in Cleveland, OH on "Systemic Therapy for Melanoma: ASCO Guideline." This guideline provides recommendations on systemic therapy options for adult patients with cutaneous and noncutaneous melanoma. Read the full guideline at www.asco.org/melanoma-guidelines

An interview with Dr. Gabriela Chiorean from the University of Washington, Fred Hutchinson Cancer Research Center, Dr. Mary Chamberlin from Dartmouth-Hitchcock Medical Center, and Dr. Pritesh Lohar from the HCG Cancer Center, on "Treatment of Patients With Late-Stage Colorectal Cancer: ASCO Resource-Stratified Guideline." This guideline provides guidance for resource-constrained settings on the management of late-stage CRC. Read the full guideline at www.asco.org/resource-stratified-guidelines.

An interview with Dr. Sharon Giordano from MD Anderson Cancer Center and Dr. Michael Hassett from Dana-Farber Cancer Institute on "Management of Male Breast Cancer: ASCO Guideline". This guideline provides recommendations concerning the management of male breast cancer; addressing five main areas where treatment for men differs from the approach used for women with breast cancer: adjuvant endocrine therapy, endocrine therapy for advanced/metastatic cancer, adverse effects of endocrine therapy, germline genetic testing, and survivorship. Read the full guideline at www.asco.org/breast-cancer-guidelines.

An interview with Dr. Nasser Hanna from Indiana University Simon Cancer Center and Dr. Gregory Masters from Helen F. Graham Cancer Center and Research Institute on "Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update." This guideline provides recommendations on systemic therapy treatment options for patients with stage IV non-small-cell lung cancer (NSCLC) without driver alterations in epidermal growth factor receptor or ALK, based on histology, PD-L1 status, and/or the presence or absence of contraindications. Read the full guideline at www.asco.org/thoracic-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 podcasts.asco.org. My name is Brittany Harvey. And today, I'm interviewing Dr. Nasser Hanna from Indiana University's Simon Cancer Center and Dr. Gregory Masters from Helen F. Graham Cancer Center and Research Institute, co-chairs on therapy for stage IV, non-small cell lung cancer without driver alterations, ASCO and CCO Joint Guideline Update. Thank you for being here today Dr. Hanna and Dr. Masters. Thank you. Glad to be with you. My pleasure. Thanks. First, Dr. Hanna, can you give us a general overview of what this guideline covers? Sure. So the ASCO guidelines for the treatment of patients with stage IV, non-small cell lung cancer were last updated in 2017. And since that time, there has been a tremendous amount of change that has taken place. The 2017 guidelines included recommendations for basically three subgroups-- those patients with non-small cell lung cancer who have certain targetable DNA mutations and those who do not have those mutations but have a PD-L1 score of 50% or higher and then everyone else. But because of the rapid and vast changes that have taken place, we decided to make a separate guideline for those with targetable DNA mutations and to focus this current guideline on those without the targetable mutations. So within that context, this guideline categorizes patients by whether their tumors have a PD-L1 score of 0% to 49% or those who have a PD-L1 score or 50% or greater. And within those categories, recommendations are characterized based upon whether the patient has squamous cell histology or non-squamous cell histology. And we also consider whether patients are candidates for chemotherapy or perhaps even those that decline chemotherapy and whether they have any contraindications for immunotherapy. So what distinguishes these guidelines from other guidelines is our attempt to adhere to the strongest available evidence-based medicine. And while not every iteration of clinical management can be covered, these guidelines provide oncologists with a strong, evidence-based roadmap to treat the vast majority of patients with non-small cell lung cancer. So as a result of this collective effort by ASCO staff and the guideline writing committee, this report offers a substantial amount of change to the recommendations from the clinical practices guidelines provided in 2017. In 2017, the only recommendations for the use of immunotherapy were in the first line setting for patients who had a PD-L1 score of greater than 50% and in the second line setting of patients progressing after first line chemo. But these updated guidelines include the incorporation of immunotherapy in all subgroups of patients regardless of histology and PD-L1 score. So as a result, there are about three times the number of options to consider in the first line setting with these new guidelines compared to the 2017 guidelines. However, the 2020 guidelines provides a preferred treatment regimen for each situation to simplify the decision making process for most patients. And what are those key recommendations of this guideline update for patients without driver alterations? So the key changes for 2020 is the incorporation of immunotherapy into nearly all settings in the first line setting, regardless of tumor histology and regardless of PD-L1 score. For those patients who have a PD-L1 score of 50% or higher, single agent pembrolizumab remains the preferred treatment for most patients. But new evidence does provide a rationale for giving select patients chemotherapy, either carbo and pemetrexed if they have non-squamous, or carbo plus paclitaxel or nab-paclitaxel for squamous plus the addition of pembrolizumab in this subgroup of patients. For those patients with PD-L1 scores of 0% to 49% who are eligible and willing to take chemotherapy, these new guidelines recommend chemotherapy plus pembrolizumab. For those who have a PD-L1 score of 1% to 49% are not appropriate for chemo or decline chemotherapy, these guidelines suggest single agent pembrolizumab as a reasonable option. The guidelines also provide the option of alternative chemo immunotherapy regimens to be used in patients with non-squamous, non small-cell that were not included in the prior guidelines. And while these are not necessarily preferred for most patients, select patients can be considered for these regimens, which include the immunotherapy drug, atezolizumab, and combination chemo with atezolizumab and bevacizumab. And the guidelines provide some commentary on potential scenarios in which these options should be considered. Dr. Masters, why is this guideline important, and how will it change practice? Well, the new ASCO CCO joint non-small cell lung cancer guideline update is important in that it clarifies recommendations for an international audience and is co-sponsored by the American Society for Clinical Oncology and Cancer Care Ontario. These guidelines were developed through a rigorous, evidence-based process with a broad range of experts, including a multidisciplinary team of clinicians, researchers, data specialists, and patient representatives. The new guideline update provides a comprehensive review and analysis of the current literature on the treatment of advanced non-small cell lung cancer. The current update also includes a data supplement with evidence tables, slide sets, and links to patient information through cancer.net, ASCO's patient information website. In an increasingly complicated environment for oncologists, managing patients with advanced cancer, we're learning how to incorporate molecular testing and other biomarkers. And this guideline will help change day-to-day practice for clinicians as they implement these recommendations. This guideline will help clarify the optimal treatment strategies for non-small cell lung cancer patients without driver gene mutations and allow individualization based on tumor histology and immunotherapy biomarkers, such as PD-L1 testing. At the same time, the update allows clinicians to use their individual judgment and experience to incorporate unique, intangible characteristics of patients. It also emphasizes the importance of patient preferences in deciding the optimal care for an individual affected by advanced non-small cell lung cancer. And finally, how will these guideline recommendations impact patients? The broad range of experts who've contributed to these guidelines includes a multidisciplinary team, including clinicians, researchers, data specialists, and patient representatives. This assures patients of a consensus opinion based on the available clinical research on treating advanced non-small cell lung cancer. It provides clinicians with the best up-to-date distillation of the many complicated trials of chemotherapy and immune checkpoint inhibitor therapy in an area where patient-centered, precision medicine dictates the optimal treatment strategies. We incorporate molecular testing in these guidelines, although this particular guideline is directed at patients without driver gene mutations. We include recommendations on implementation of chemotherapy and immunotherapy based on the best available data on biomarker testing for PD-L1. We recognize, however, that new research continues into treatment strategies and molecular analysis to help guide incorporation of targeted therapy and immunotherapy. We recognize that new treatment options and combinations will become available, and new testing techniques will help guide the decision process in the future. We plan to continue to analyze the available research and update these guidelines as clinically indicated to provide the best options for our patients. Most of our patients will still be treated with palliative intent. But a growing number of patients have sustained control of their cancer with recent studies and updates suggesting that up to 25% of patients may have control of their disease for five years or longer. Now that more patients can maintain their quality of life with prolonged survival, with the current therapy, it is also critical that we continue to look to patient reported outcomes as an important way of defining the best options for our patients. Thank you both for your work on this ASCO CCO guideline update for therapy for stage IV, non-small cell lung cancer without driver alterations and for coming on the podcast today to provide an interview, Dr. Hanna and Dr. Masters. Thanks for having us on the program. And we have enjoyed being part of the process. Thank you. And thank you to all our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/thoracic-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've 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. 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]