Penile Cancer: EAU-ASCO Guideline

Dr. Scott Tagawa and Dr. Oscar Brouwer come on the ASCO Guidelines podcast to discuss the new EAU-ASCO Collaborative Guidelines on Penile Cancer. These comprehensive guidelines cover pathological assessment of tumour specimens, diagnosis and staging, local treatment of penile carcinoma, radical inguinal lymph node dissection, prophylactic pelvic lymph node dissection, surgical management, neoadjuvant and adjuvant chemotherapy, radiotherapy, systemic and palliative therapies for advanced penile cancer, follow-up, and quality of life. They highlight key recommendations, and describe the importance of a patient-focused and multidisciplinary approach to management of penile cancer. Find more information about the guidelines at www.asco.org/genitourinary-cancer-guidelines The full text of the guideline is available at https://uroweb.org/guidelines/penile-cancer    Conflict of interest disclosures: Guideline Working Group  Dr. Scott Tagawa  Dr. Oscar Brouwer TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.  My name is Brittany Harvey, and today I'm interviewing Dr. Oscar Brouwer from the Netherlands Cancer Institute in Amsterdam, and Dr. Scott Tagawa from Weill Cornell Medical College in New York, co-chairs on the ‘ASCO-EAU Collaborative Guidelines on Penile Cancer’.  Thank you for being here, Dr. Brouwer and Dr. Tagawa. Dr. Scott Tagawa: Thanks very much. Dr. Oscar Brouwer: Yeah, thanks for having us. Brittany Harvey: Before we discuss this guideline, I'd just like to note that the guideline was led by the European Association of Urology, and the conflict of interest disclosures of the Guideline Working Group are publicly accessible through the European Association of Urology website linked in the show notes. Additionally, Dr. Brouwer's and Dr. Tagawa's individual disclosures are provided in the show notes of this episode.  So, to jump into the content of this guideline, first, Dr. Tagawa, could you give us a general overview of the purpose and the scope of this collaborative EAU-ASCO Guideline? Dr. Scott Tagawa: So, I think the key word there is collaborative. This was truly a collaborative effort, and I say that in a number of ways. So, the two key organizations, the EAU and ASCO, came together with a Memorandum of Understanding and got together from the very beginning in terms of developing the scope and then throughout the methodology for the guidelines. And then, on a practical basis, I'd say even more importantly, a collaboration between multiple physicians of different disciplines from across the world. Whether we're talking about surgeons, radiation oncologists, medical oncologists, pathologists, we had panel members from all over the world as well as patient representatives from all over the world. And patient representatives really played a key role in the development of this guideline.  By way of background, penile cancer in most places is considered a rare disease. For example, in the United States, we expect around 2000 cases per year. In the genitourinary world, the next rare cancer is going to be testis cancer, which is going to be four or five times higher than that per year and nowhere near prostate cancer, for instance. So, just kind of put that into perspective. But, importantly, a disease that is a worldwide issue in a number of different ways. That includes the kind of general stigma of being diagnosed with that, the physical and emotional consequences of the diagnosis, as well as treatment. And then, because in part of its rarity, the lack of prospective randomized trials to really guide clinicians and that, I would say, that total package underscores the importance of coming together with a guideline. Brittany Harvey: Great. Thank you for providing that background and perspective.  So then, next, Dr. Brouwer, I'd like to review the key recommendations of this comprehensive guideline. Starting with what are the key recommendations regarding diagnosis and staging of penile cancer? Dr. Oscar Brouwer: First of all, I guess just to underline what my colleague, Dr. Tagawa, just said, it's a worldwide guideline, international, multi-continental. I think that's quite a special thing. But it also poses a few challenges, of course, because cultural differences and treatments may differ, opinions as well, distances that patients have to travel, lots of factors there, and also economy, et cetera, et cetera. So, to find a consensus there has been one of the challenges. I think we did a good job there to really make it accessible to all patients and physicians, of course, in the world.  When talking about diagnosis, I think comparing our new guidelines to old guidelines really emphasizes the new 2022 WHO classification in which distinction between HPV-positive and HPV-negative disease is highlighted. We increasingly have some knowledge on the difference between the HPV-related and the non-HPV-related penile cancers. I'd say it's about 50-50, the distinction. So, 50% is HPV-related, and 50% not HPV-related. But what we know from other cancers, for instance, that HPV-positive disease is associated with better prognosis than HPV-negative. This distinction is not so clear in penile cancer yet. And one of the reasons is just the lack of data, a lack of perspective for large studies, so to say. So, what we're really highlighting and underlining in the new guideline is the importance of doing HPV testing in all patients that have penile cancer, and that tissue is taken from. We chose to go for the cheapest and easiest but reliable methods to do so. So, immunohistochemistry of p16, to be exact. This is one of the important, I think, recommendations, or maybe even more than a recommendation; obligations we set to all physicians treating penile cancer.  So, just in terms of diagnosis and in terms of staging, we all know that lymph node status is the most important factor determining survival. So, finding those lymph nodes, if they are involved with cancer, yes or no. So, if they are metastatic, yes or no, is of crucial importance. This has always been the case, but I think it cannot be emphasized enough. And in this new guideline, we again emphasize the importance of doing surgical lymph node staging in high-risk patients. And what's a little bit new is that we are more or less going to the direction of preferring central node biopsy as the best method to do so. You could also, of course, remove all the lymph nodes, what we call radical lymph node dissection. It's still possible inside our new recommendations, depending on availability of all the techniques or availability of expert centers in proximity. But I think we can all see that in terms of complication rates, central node biopsy is probably superior. So this is also one of the new things in terms of staging.  Brittany Harvey: Absolutely. Thank you for those highlights of diagnosis and staging in the guideline.  So, following those recommendations, Dr. Tagawa, and I know this is a large section, but what does the expert panel recommend for disease management of penile cancer? Dr. Scott Tagawa: A single-sentence summary would say a multi-disciplinary approach in an expert center when possible. Re-emphasizing one of the statements that Dr. Brouwer made about sentinel lymph nodes; it appears to be better, but clearly is not available everywhere. And if I just make this US-centric for a minute, just within this country, where there are centers that are able to do it and have that expertise, there are centers that are not so far away that may not be able to do that. So regional differences within a single country that’s what happens. So, anyway, multi-disciplinary input, I think, is important for many diseases, including penile cancer. A little bit of a segue, but one part of this guideline of which most of us are proud is that, front and center really, the introductory paragraph of the guidelines, where it really states that we need to really have this disease and the management patient-focused and that includes addressing some of the emotional aspects of the disease. Those are included in the management. But to kind of go through very quickly on a very high level, in the early stages management is mostly in the hands of the urologist. But sometimes there’s dermatologists and others, so when there is superficial disease, we talk about superficial therapy and I’m just going to leave it at that, many of them don’t have level 1 evidence, but there is, for instance, topical chemotherapy that can be helpful.  And then, as the disease becomes more invasive, so does the treatment. So there’s sections on organ or penile sparing that is a reasonable option that needs to be done in a good multi-disciplinary system. That is a good and sometimes a preferred option when there is adequate staging for earlier stage disease. And then the more invasive the disease becomes is when the management needs to become more multi-disciplinary both in terms of workup as well as treatment. Where there is a consideration for, in certain situations, particularly in very locally advanced where it becomes unresectable at least in some eyes, where we say, “Okay, we’re actually going to recommend starting off with chemotherapy,” the intent is for surgery with an alternative of chemotherapy and radiation. And currently, there are no head-to-head trials, but those are both reasonable approaches for the most locally advanced disease setting.  Taking a step back, if someone starts off with a little bit less locally advanced, so we’d say the alias, gross resectable, we would at least discuss in a multi-disciplinary setting what are the risk benefits of then post-operative therapy, whether that is radiation or chemotherapy, or both. I think all patients at least deserve the opportunity to have that discussion, and then that would be on an individual basis whether we decide to do that or not. Coming from the medical oncology-centric viewpoint where we really deal with systemic therapy, we don’t really have any randomized trials to say that one approach is preferred to another, so they’re kind of generic. But it does look like platinum chemotherapy, taxane chemotherapy are the most active current drugs. So when we’re looking at multi-agent therapy when the setting is a goal of cure, we’re generally saying platinum plus taxane combinations without being specific about doublets or triplets. Triplets when they can handle them, but not everyone can handle them.  And then for metastatic disease whether it’s current or at presentation metastatic disease, the old guidelines actually said ‘don’t even bother’, but now that we have some effective drugs, we would say that for palliative purposes to come in with systemic chemotherapy, the same drugs that we talked about before. And then, there may be additional therapeutic agents. So we’re now in the genomic era where there has been at least an initial look at what are the genomics of HPV related, non-HPV related, and there may be some targets, we just are a little bit too early to say that there are absolutely some targets, but there definitely are recommendations for participating in clinical trials. There are some trials that are specific to penile cancer. There are other ones that are non-specific or basket trials. Let’s say any disease that has EGFR positivity, a patient with penile cancer may be able to get into that clinical trial or maybe meet a therapy-based trial, so considerations for the trials, I think, are important.  Brittany Harvey: It sounds like multidisciplinary care is a key tenet of this guideline. You mentioned patient-focused care is also key in this guideline. So that leads nicely into my next question. But Dr. Brouwer, what are the key recommendations both for follow-up and quality of life?  Dr. Oscar Brouwer Yeah so we have, like Dr. Tagawa already said, we have quite an elaborate section, not only in the introduction of the guideline but also a separate chapter at the end, really, to acknowledge the psychosocial, sexual impact this disease can have on patients. And again, I think it's more or less a plea for a form of centralized care for such a rare disease. We have a set of recommendations that we give in terms of follow-up and quality of life, and mainly several points that should really be discussed with patients, and support should be offered. So things like psychological sexual help, but also lymphedema therapist, physiotherapy in terms of complication management. And this mainly goes for patients that undergo lymph node surgery or treatment. And in our experience, if you don't see the disease often enough, you don't have all these things in place in your hospital to offer dedicated people that can do this. So I think that's something to consider in the future for healthcare in general when treating rare diseases such as these. But, yeah, like Dr. Tagawa said, our patient representatives have had a big role in this, and we're happy with that. So I recommend everyone to read it. Brittany Harvey: Absolutely. You've both mentioned that this is a rare disease. So, in your view, Dr. Tagawa, what is the importance of this guideline, and how will it impact clinicians? Dr. Scott Tagawa: There are certain centers that have high volume and certain countries that will have a high volume. For instance, areas in Brazil have a high volume. Whether there's a high volume or a low volume, like an average center in the United States, there haven't been any recent guidelines out there from any organization. So, the EAU has had an old guideline that was really out of date - updating that, number one. And number two, having the backing of two major organizations in the EAU and ASCO, I think is quite important to get this out there on a true international basis. Because not just in this disease, but in most diseases, when there is standardization of care, there's overall better outcomes, whether it's at the center that sees a lot or the centers that rarely see any. I think this document provides guidance, and, actually, take a step back for those that are interested, on the EAU website will be the entire very comprehensive guideline. So, someone that wants to get a lot of details, it's there, very comprehensive and honestly long, but it's, I think, an excellent reference document. And then, published in European Urology will be the summary guideline that has all the key points of the guidelines and summary in the text that will refer to the overall guideline for someone that wants to get through it on a quicker basis. That will also be published on the ASCO website just to kind of get that out there. A little bit of the side in terms of answering your question is that this is a rare tumor. We want everyone to have access to the best care possible, and if nothing else, it provides guidance in a setting where most clinicians don't have a lot of expertise. Brittany Harvey: Definitely. And thank you for highlighting both the summary and full text of the comprehensive guideline. We'll provide those links in the show notes, too, for easy access for any listeners.  And then, finally, you've both mentioned the impact this has for patients. But Dr. Brouwer, in your view, how will these guideline recommendations affect patients with penile cancer?  Dr. Oscar Brouwer: Well, of course, it's our hope that it will be very beneficial for patients around the world. I think it cannot be emphasized enough that this initiative, in which ASCO, in this case United States group, has collaborated with the European one to make an international multi continental guideline, is quite rare, in urological cancers is the first one. I'm not even sure if there are many others like these. I do really believe it makes sense for rare diseases to not have several guidelines. It's confusing which guideline to choose, especially if there are contradictions. So I guess this initiative is the first step towards having more comprehensive, literal guidelines for such a rare disease. And I really do hope that it will help clinicians, especially when they don't have experience treating this disease, to really look at this guideline first. And in turn, of course, I hope that will benefit patients because they'll have, hopefully, access to better quality care that way. And especially, like we already touched upon, also the importance of early access to support and to palliative care throughout the whole disease process. I really hope that is something that will be offered to patients worldwide more frequently now because it is not only about treating the disease itself but also about the consequences, of course. And I really do think that people will benefit from that in terms of quality of life. Brittany Harvey: Absolutely. I want to thank you both so much for your work on this comprehensive EAU-ASCO Guideline and for talking with me today and sharing your insights, Dr. Brouwer and Dr. Tagawa. Dr. Scott Tagawa:  Thank you very much. It was a pleasure. Dr. Oscar Brouwer: You're welcome. I would just like to add also a short opportunity, maybe just to thank all the panel members because it has been a huge effort. Not only an update, it has been actually rewritten from the ground up. So a lot of panel members, not only from the United States and Europe but also Canada, South America, patient representatives, all the associates that have helped. So it has been a big effort, and I congratulate and thank everyone. And thank you, Brittany, for the interview. Brittany Harvey: Definitely, it was a large group and multidisciplinary effort. So thank you to them as well. And also, thank you to all our listeners for tuning in to the ASCO Guidelines Podcast. 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