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Oncology Decoded Live! Advancing Peri-Operative Bladder Cancer Care: Integration of Emerging Evidence into Clinical Practice

Test your knowledge of these often-overlooked but essential aspects of genetic and genomic testing.

Quiz: CUA guidelines on specimen and timing considerations with genetic testing

The inclusion of the test is supported by more than 25 studies demonstrating its clinical utility, including 2 studies published earlier this year.  

NCCN reaffirms Prolaris’ prognostic value in prostate cancer

Test your knowledge of this quiz on the Canadian Urological Association's recommendations for genomic profiling of tumors in prostate cancer.

Quiz: What CUA guidelines say about genomic profiling of tumors in prostate cancer

Test your knowledge of this quiz on the Canadian Urological Association's recommendations for germline genetic testing in prostate cancer management.

Quiz: CUA guidelines on germline genetic testing in prostate cancer

“Our study highlights the potential of epigenomic profiling from a simple blood draw to provide a real-time, non-invasive readout of PSMA expression that corresponds with treatment response," says Jacob E. Berchuck, MD.

Epigenomic cfDNA may accurately assess PSMA expression, Lu-PSMA response in mCRPC

Paul Sieber, MD, shares his thoughts on what the future holds for genetic testing in prostate cancer. 

Paul Sieber, MD, on the future of genetic testing in prostate cancer

, shares his thoughts on what the future holds for genetic testing in prostate cancer. Sieber is the medical director for clinical trials at Keystone Urology Specialists in Lancaster, Pennsylvania.

Well, I'm glad you asked that question, because we just had an article that some other of my peers signed off on. It's going to go to the 

 talking about everybody with prostate cancer getting germline testing out of the gate. Everybody, everybody. Do I think it's going to happen? I think so. In fact, we've got this article accepted. I think [we're] going to see that coming. I think it's going to force urologists to say, "I have to test everybody." It's going to become the standard of care, hopefully, in the next couple of years. We'll see. And certainly somatic testing is equally important, because there's a lot of people who don't have germline abnormalities, but they have somatic abnormalities, which is going to tailor their treatment going forward.

This transcript was AI generated and edited by human editors for clarity.

Videos

The future of genetic testing in prostate cancer is poised for significant change, with germline testing potentially becoming a standard practice for all patients. This shift is anticipated to compel urologists to adopt comprehensive testing protocols. The integration of somatic testing is equally crucial, as it addresses cases without germline abnormalities, allowing for personalized treatment strategies. The adoption of these testing practices is expected to enhance patient care by tailoring treatments based on individual genetic profiles, marking a pivotal advancement in prostate cancer management.

Sieber shares his thoughts on the potential for universal genetic testing to become a standard of care practice for patients with prostate cancer.

Daniel Kwon, MD, discusses the impact of the JNCI Cancer Spectrum paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits.” 

Daniel Kwon, MD, discusses study’s impact on veteran access to germline testing for prostate cancer

 paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits." Kwon is an assistant professor of medicine at the University of California, San Francisco.

Your research led to changes in the Veterans Benefits Administration Compensation and Pension Manual. How do you anticipate these changes will affect veterans' decisions about genetic testing in the future?

I'm hopeful that the decisions are more informed in terms of actual science. The science does not suggest that just because you have a service-connected prostate cancer related to Agent Orange or something, and you also have a hereditary connection between something you inherited and your prostate cancer, that for some reason, this genetic factor should nullify the service connection. It doesn't make sense. And so hopefully, now that this is reflected in language in the compensation and pension manual, that veterans are more reassured and with more sound information, they are more likely to participate in genetic testing as long as they go through the consent process and it's still in line with what they wish. Now, that's still quite a huge jump to get from just words on a page to veterans actually making decisions and changing behavior. So what's going on is that there is a dissemination plan from a lot of us in the VA genomics field advisory board, and we're trying to develop this plan to figure out what's the best way to get the word out there and implement the change that it leads to changes in behavior and decisions. So we're talking with various stakeholders at the VA, including patient advocacy groups, other physicians, leadership, to come up with this plan as we speak.

"I'm hopeful that the decisions are more informed in terms of actual science," says Daniel Kwon, MD.

Tim A. Richardson, MD, shares his thoughts on the need for more genetic testing in prostate cancer as more targeted therapies become available. 

Tim Richardson, MD, on genetic testing in the era of targeted therapies

, shares his thoughts on the need for more genetic testing in prostate cancer as more targeted therapies become available. Richardson is the director of the advanced prostate cancer program and the radioligand therapy infusion program at Wichita Urology in Kansas.

Right now, most of the targeted therapies that we have are downstream—second-line, third-line, etc—when the patient is castration-resistant, but it also is a factor for the patient's family of risk of cancer. We typically recommend testing for somatic and germline mutations at diagnosis of metastatic disease. Some will do germline testing initially and then wait down the road for progression to do somatic; some will do the opposite.

In my practice, I try to do both early. With somatic testing, tissue tends to be a good lab to get, as opposed to a liquid biopsy. I want to use the tissue when it's fresh and new. So, at time of diagnosis of metastatic disease, I try to get somatic and germline. It's very important. We don't even really understand yet how important it's going to be, but down the road, everything is going to be targeted therapy. I think everyone agrees on that. We just don't know how and when. But there [are] new therapies coming out, for example, PTEN loss, AKT inhibitors, patients that maybe need to go on to taxotere-based chemotherapy, whether it's p53, [etc]. So, there's markers that that we don't even really use yet that are coming down the road that we know. Then obviously there [are] the main players with the BRCA1 and [BRCA]2, HRR mutations. Those can direct us to PARP inhibitors when the patient is castration resistant.

I think the biggest take-home message for the germline and somatic testing is we need to do more of it. Prostate is late to the game with that type of genetic testing. Breast cancer has been there for a long time. Ovarian cancer has been there for a long time, pancreatic cancer, etc. Prostate is late to the game. There's been a big push over the last 2 to 3 years to get urologists to think about genetic testing just like they think about doing a metastatic work-up for a high-risk patient. We're all used to ordering scans for a high-risk patient to make sure they don't have metastatic disease. I think genetic testing needs to move into that same paradigm where that comes into our head at the same time. We're getting there. It's picked up over the last 2 to 3 years. We still haven't caught up with those people that are treating breast, ovarian, etc. It's been ingrained in their head for years and years, but we need to keep pushing that, because before long, what we do, how we do it, and when we do it might solely be based off of those genetic testing results.

The importance of genetic testing in prostate cancer is emphasized as targeted therapies become more prevalent. Currently, most targeted treatments are used in later stages when the cancer is castration-resistant. Genetic testing, including somatic and germline mutations, should be conducted early in the diagnosis of metastatic disease. Prostate cancer lags behind other cancers like breast and ovarian in adopting genetic testing. There is a push to integrate genetic testing into standard practice, as future treatment decisions may heavily rely on these results.

“Before long, what we do, how we do it, and when we do it might solely be based off of those genetic testing results,” says Tim Richardson, MD. 

Daniel Kwon, MD, discusses how clinicians can use information from the JNCI Cancer Spectrum paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits” to counsel patients

Discussing germline testing for prostate cancer with veterans

 discusses how clinicians can use information from the 

 paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits” to counsel patients. Kwon is an assistant professor of medicine at the University of California, San Francisco.

How do you envision clinicians using the information from your study to better counsel veterans about germline testing, particularly regarding the potential impact on their benefits?

I think clinicians should take this information, especially those at the VA, but also clinicians outside the VA who take care of veterans, so it's not just VA oriented, and whenever they discuss germline testing, an important part of that is this pretest counseling process where you talk about the pros and the cons. Include some information that reassures them that their genetic test results [will] not affect their service connected benefits that are active right now, or if they're in the process of increasing or applying for new service-connected benefits, then it won't affect that either.

I guess something I should have gone into a bit more detail is this whole idea of like, what is a service-connected benefit, and what does that have anything to do with prostate cancer? Veterans who were exposed to certain agents while in the military in active service, for example, Agent Orange in the Vietnam War, or burn pits in the Middle East, and then later developed prostate cancer, that is a presumed connection between the exposure and the disease, where they automatically get benefits related to this service connection. These benefits can be quite significant. I won't go into detail, but you heard from one of the quotes that it's a monthly pension of sorts for the rest of their lives. And so this is a really important disability type of benefit for a lot of veterans.

This transcription was AI generated and edited by human editors for clarity.

Clinicians should incorporate insights from the JNCI Cancer Spectrum paper to effectively counsel veterans on germline testing, emphasizing that genetic test results will not impact their service-connected benefits. This reassurance is crucial during pretest counseling, especially for veterans exposed to agents like Agent Orange or burn pits, which are linked to prostate cancer. Understanding the significance of these benefits, which provide lifelong financial support, is essential for clinicians advising veterans. The information is relevant for both VA and non-VA healthcare providers treating veterans.

"Whenever they discuss germline testing, an important part of that is this pretest counseling process where you talk about the pros and the cons," says Daniel Kwon, MD.

Kara Cossis, PA-C, MPH, discusses the role of advanced practice providers (APPs) in expanding and encouraging the use of genetic testing for prostate cancer

Kara Cossis, PA-C, MPH, on the role of APPs in genetic testing

, discusses the role of advanced practice providers (APPs) in expanding and encouraging the use of genetic testing for prostate cancer. Cossis is a physician assistant at Chesapeake Urology in Towson, Maryland.

I think there's a very good role for APPs to introduce the genetic testing to the patients to help explain what exactly we're testing for, why we're testing for it, what it means potentially for their cancer treatments. And then, as the results come back, to be able to review the results with a patient. But then also, [to] know how to interpret them, to either be able to treat them internally with the practice—if those particular treatments exist—or to refer them out, say to a partner with medical oncology if there's additional treatments they qualify for, but they may not have in house.

Advanced practice providers (APPs) play a crucial role in promoting genetic testing for prostate cancer. They are instrumental in educating patients about the purpose and implications of genetic testing, which can influence cancer treatment decisions. APPs are also responsible for interpreting test results and determining appropriate treatment pathways. This may involve managing treatments within their practice or referring patients to medical oncology partners for additional options. Their involvement ensures a comprehensive approach to patient care, enhancing the integration of genetic testing into clinical practice.

APPs can help in introducing genetic testing and in the interpretation of results, according to Kara Cossis, PA-C, MPH. 

Tim A. Richardson, MD, outlines the 2 key scenarios for utilizing genetic testing in clinical practice. 

Tim A. Richardson, MD, outlines key avenues for genetic testing in prostate cancer

, outlines the 2 key scenarios for utilizing genetic testing in clinical practice. Richardson is the director of the advanced prostate cancer program and the radioligand therapy infusion program at Wichita Urology in Kansas.

There are really 2 avenues of genetic testing: genomic markers, or genomic testing, vs what we call real genetic testing, like germline/somatic testing. One is used in one situation; one is used in the other. So, let's start with the most common patient, the localized disease patient that is either a candidate for active surveillance vs a candidate for treatment. We will order genomic testing on those patients in certain situations. In general, it's going to be those patients that were on the fence between watching them on active surveillance vs treating them.

The other situation that we would order that type of test would be a patient that we know we want to treat but we're trying to decide if we want to intensify treatment by adding some adjuvant androgen deprivation therapy to their radiation would be the most common situation. On the flip side, [there are] the patients that are metastatic, high-risk, locally advanced. Those patients are oftentimes ordering what we call germline testing plus/minus somatic testing, which is a different type of test, but that's more to not only educate them and their family on their risk of cancer, but also to direct with targeted therapies down the road. So, 2 different avenues, but by far the most common is probably going to be that localized patient that maybe has intermediate-risk disease or high-volume, low-risk disease, and you need some genomic markers to help you decide on treatment vs active surveillance.

Genetic testing in clinical practice involves two primary avenues: genomic testing and germline/somatic testing. Genomic testing is typically used for localized prostate cancer patients to determine the need for active surveillance or treatment, and to decide on treatment intensification with adjuvant therapies. Germline and somatic testing are more relevant for metastatic, high-risk, or locally advanced cases, aiding in risk assessment and guiding targeted therapies. The most frequent application is in localized patients with intermediate-risk or high-volume, low-risk disease, where genomic markers inform treatment decisions.

Tim A. Richardson, MD, outlines the 2 key scenarios for utilizing genetic testing in clinical practice.

Tim A. Richardson, MD, outlines key settings for genetic testing in prostate cancer

Daniel Kwon, MD, discusses implications from the JNCI Cancer Spectrum paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits.” 

Germline testing study’s implications for veteran access to prostate cancer treatments

 paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits.” Kwon is an assistant professor of medicine at the University of California, San Francisco.

The finding that veterans with service-connected disability benefits were hesitant to undergo germline testing due to fear of benefit loss is significant. Could you discuss the implications of this finding for veterans' access to potentially life-saving treatments?

Well, they may be missing out on potentially life-saving treatments, and their family might also be missing out on some benefits as well. To get into that, germline testing is part of precision oncology, which has been revolutionary in the field of prostate cancers and other cancers as well, like bladder cancer. And so there have been a number of large phase 3 studies that have shown that PARP inhibitors are effective, with increased survival, improved quality of life in men with castrate-resistant prostate cancer and those who have DNA damage repair mutations, whether it's germline or somatic mutations, and particularly benefiting 

 alterations and a few others.And so a veteran might have 1 of these or harbor 1 of these mutations, but because they're not doing germline testing, might be missing out on something that they could benefit from. Not only that, but there are implications personally for their risk of other types of cancers, and also similar implications for their family members, and so if the veteran were to test positive, they might have children or other living blood relatives who might also be positive and never find out, and they might never be able to potentially find cancer early or prevent cancer altogether by having this cancer risk information for them.

Veterans with service-connected disability benefits are hesitant to undergo germline testing due to fears of losing benefits, potentially missing out on life-saving treatments. Germline testing is crucial in precision oncology, particularly for prostate cancer, as it identifies DNA damage repair mutations that can be targeted with PARP inhibitors, improving survival and quality of life. The lack of testing not only affects veterans but also their families, who may unknowingly carry cancer risk mutations, missing opportunities for early detection or prevention of cancer.

"[Veterans] may be missing out on potentially life-saving treatments, and their family might also be missing out on some benefits as well," says Daniel Kwon, MD.

Kara Cossis, PA-C, MPH, outlines challenges and opportunities with genetic testing in prostate cancer. 

Kara Cossis, PA-C, MPH, on challenges, opportunities with genetic testing 

, outlines challenges and opportunities with genetic testing in prostate cancer. Cossis is a physician assistant at Chesapeake Urology in Towson, Maryland.

Probably the biggest challenges are figuring out a streamlined process within the office to actually order it. It's everything from who's going to identify the patient, who's going to fill out the paperwork, who they're going to actually use, the industry partners they're comfortable using, how is that information sent out, how is it received, how is it interpreted, and who deals with the results? That's one of the challenges. I think one of the other challenges is finding the right match. There are different companies that do germline only. There are different ones do somatic only. There are some that do both. Looking for that streamlined process, where you can find an industry partner, where it's more integrated, and there is a one-stop-shop.

Opportunity wise, I always say that if you don't perform the test, then you're limiting treatment options for your patients. There are really 3 main goals of doing these particular tests. One is to assess the patient's individual cancer risk. It will tell them, do they either carry an abnormal gene, or does their tissue have an abnormal gene that would potentially open the door for other treatments for them, for the future, as their cancer progresses. The other thing is, especially if it's in the germline testing, it will open the door for being able to be more proactive in their biological children's life. If they had a positive mutation, then they can make sure that their children are being screened appropriately and monitored and seeking proactive care. Then it also is going to help them with their individual cancer risk assessment, especially in germline, because they're testing to see if there are other potential cancers that they may be at risk for.

Genetic testing in prostate cancer presents challenges and opportunities. Streamlining the testing process involves identifying patients, completing paperwork, selecting industry partners, and managing results. Different companies offer germline, somatic, or both types of testing, necessitating a comprehensive approach. Genetic testing expands treatment options by assessing individual cancer risk and identifying abnormal genes, which can guide future treatment decisions. Germline testing also benefits patients' biological children by enabling proactive screening and care. Overall, genetic testing aids in personalized cancer risk assessment and management.

“Opportunity wise, I always say that if you don't perform the test, then you're limiting treatment options for your patients,” says Kara Cossis, PA-C, MPH. 

Daniel Kwon, MD, discusses the background and notable findings from the JNCI Cancer Spectrum paper, “Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits.”

Daniel Kwon, MD, on germline testing for prostate cancer in veterans with service-connected benefits

 discusses the background and notable findings from the 

Please give an overview of this study and its notable findings.

This study is at the San Francisco VA Medical Center, and we were trying to understand how veterans were making decisions about germline testing for their prostate cancer. We had the anecdotal experience that some veterans were declining testing because of some concerns about service-connected benefits, and how that might play into whether they want to get germline testing or not. But this has never been formally studied, so we did a qualitative study where we looked at veterans with at least locally advanced prostate cancer who hadn't had germline testing before and before their upcoming oncologist visit, where they would discuss germline testing at that time, we recruited them. We looked at patients recruited between early 2022 and November 2023, and we consented them. We recorded the conversations between their oncologists and them, and then 7 days after the appointment, we did a semi-structured interview where we asked questions exploring their decision-making process and what considerations they had behind their decision whether it was yes or no. We eventually recruited 32 patients, and this was across 7 oncologists. In the recordings, it looked like about 38% of the oncologists brought up service-connected benefits as 1 factor that veterans do have these concerns about. 88% of veterans agreed to testing, and 12% did not. The math turns out to 28 out of 32 agreeing, and 4 declining. But we stratified these veterans based on their service connection status. It's interesting; everybody who was not service connected for their prostate cancer actually agreed to testing. And among the 14 who were service connected for their prostate cancer, 4 declined testing, so a third of those were service-connected declined testing. The great thing about qualitative data is we get some really representative and rich quotes about veterans' own perspectives behind their decisions. We have all that, and I can actually pull one up and read one out to you right now. A succinct one is this particular patient who said, "I could lose my VA benefits, and then I would lose my life, my way of life. I would be standing in the soup kitchen, and I'm not willing to subject my life to that." So this is a patient who was service connected for the prostate cancer and declined testing because they were concerned that positive test results might nullify their benefits, which their livelihood depends on.

Moving into the beyond the results and what we did with this, this has been an issue that physicians and veterans have known about for years, and there had already been prior to the study or concurrent to the study a process in which the VA Genomic Medicine Field Advisory Board was presenting anecdotal experiences to the VBA. We took some of these research findings, so now we have formal data, in October 2023 to the VBA, also got the Office of General Counsel involved, and lot of great discussion, great work. I wasn't a part of that, but some of my colleagues were. And in December 2023, the Veterans Benefits Administration changed some of the language in the compensation and pension manual that has to do with adjudication of service-connected benefits such that now there are some protections. And so specifically the language now is that genetic test results showing predisposition to a disease are not sufficient to rebut the evidentiary presumption of service connection or to sever service connection that has already been granted. So we hope that this new language mitigates some of the concerns that veterans have.

The study at the San Francisco VA Medical Center explored veterans' decision-making regarding germline testing for prostate cancer, focusing on concerns about service-connected benefits. Conducted between early 2022 and November 2023, it involved 32 veterans and revealed that 38% of oncologists mentioned service-connected benefits as a concern. While 88% agreed to testing, 12% declined, with a notable decline among those with service-connected prostate cancer. The findings prompted changes in the Veterans Benefits Administration's compensation and pension manual, ensuring genetic test results do not affect service connection status.

"We were trying to understand how veterans were making decisions about germline testing for their prostate cancer," says Daniel Kwon, MD.

Dr. Vince on “Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set.” 

Dr. Vince on evaluation of prostate cancer polygenic risk scores

study “Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set.” Vince is an assistant professor of urologic oncology at Case Western Reserve University and University Hospitals Urology Institute, as well as the director of Minority Men's Health at University Hospitals Cutler Center for Men in Cleveland, Ohio.

Please describe the background for this study.

Just for general background, polygenic risk scores incorporate what we call SNPs, which are obtained from what we call GWAS, which is a genome-wide association study. By looking at these SNPs, we're trying to look at the hereditability of prostate cancer. There have been a number of GWAS studies that have developed polygenic risk scores for prostate cancer. And what they found is that there is a really strong association for most polygenic risk scores with the incidence of prostate cancer or the risk of developing prostate cancer. However, what we know is that it is much bigger than just whether or not you develop prostate cancer. Because there's a whole debate among a lot of people in terms of, should we be diagnosing people with low-risk prostate cancer, that's pretty indolent? The reason why some of the guidelines changed in the past to recommend against prostate cancer screening was because we were overdiagnosing low-risk disease and overtreating people with low-risk disease. So now, we know there's a move to try to shift from just diagnosing anyone with prostate cancer, to purely being able to focus in on those men with clinically significant disease. That way, they can move on to biopsies and things like that and potential treatment. What we wanted to do with this was to look at 1) Out of the polygenic risk scores that have been published, how do they perform on an external data set with the association for incidence of prostate cancer and then for those top-performing polygenic risk scores, how do they associate with the aggressiveness of prostate cancer; in other words, does an increase in polygenic risk score correlate with increasing disease aggressiveness?

Considering 16 PRSs were evaluated, can you elaborate on the specific criteria used to identify the top-performing ones for further analysis of aggressive prostate cancer?

In terms of the 16 polygenic risk scores that were selected in general, our external data set from the University of Michigan was predominantly men of European ancestry. And so we wanted to use those polygenic risk scores that would develop on men of exclusively European ancestry. That way, it will be a strong correlation. And then the first step was, again, to look at the association with the incidence of prostate cancer for an increasing polygenic risk score. And what we found is that across the board, all 16 scores did relatively well with the association between an elevated polygenic risk score and prostate cancer incidence. However, what we did was those top 3 performing - so when we look at what we call an odds ratio, those risk scores that have the strongest association with prostate cancer incidence, we then took those polygenic risk score constructs and then applied it to evaluating disease aggressiveness. And so that's how we selected those top 3 polygenic risk scores to determine what to evaluate the association between disease aggressiveness with the increasing score.

This transcription was edited for clarity.

"What we found is that across the board, all 16 scores did relatively well with the association between an elevated polygenic risk score and prostate cancer incidence," says Randy A. Vince Jr, MD, MS.

Genomic Testing

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