"We found a sizeable and statistically significant uptick in compliance with genetic testing and compliance with post-test genetic counseling in patients who underwent testing after the implementation of the standardized protocol," says Siddharth Ramanathan.
A recent study found that the implementation of a guideline-based genetic testing protocol for patients with prostate cancer had a positive impact on testing compliance and the timeliness of test results.1 In this interview, study authors Savitha Balaraman, MD, Howard Korman, MD, FACS, Siddharth Ramanathan, and Andrew Korman discuss the findings in more depth, touching on how urologists can approach this going forward.
Balaraman is a medical oncologist at Michigan Healthcare Professionals Hemotology and Oncology, Howard Korman is a urologist at Comprehensive Urology, Ramanathan is a medical student at the Oakland University William Beaumont School of Medicine, and Andrew Korman is a clinical research consultant at Comprehensive Urology.
Howard Korman: All this started when the [National Comprehensive Cancer Network] NCCN guidelines came out recommending genetic testing for [patients with] prostate cancer. As a clinician, we're in a 20-office group with 35 [physicians] and 15 mid-level providers, and we were trying to figure out how we could roll this out in a way that made sense for us financially and in terms of the patients getting the care they needed to meet these criteria. We'd also been hearing stories of lawsuits with people that were not genetic tested. We now know that it was hitting the court systems, and this is really actually a scary proposition.
We were already doing something called no error, which is a buccal swab to prove DNA provenance of specimens. There was a test called UroSEEK that was out that was also a buccal swab that could be used for genetic testing. The pathway we created led for anybody who has Gleason 8 through 10 or had a certain family history from the family history intakes we had done with our medical assistants before the biopsy, anybody who qualified, we could then use the genetic material that we already had from the swab in the office and do a genetic test for it.
We thought this would be pretty elegant. We wouldn't have to drag people back for a blood test. We thought we might increase compliance. We sit at a tumor board, this multidisciplinary tumor board with radiation oncology and Savitha often represents medical oncology and who has the eye for papers and what is important to the rest of the world looked at that and said, "Hmm, I wonder what the compliance rates are now, and how they changed," so Savitha, I'll let you pick it up from there.
Balaraman: As Dr. Korman mentioned, we have been doing genetic testing even before the NCCN guidelines came out in the appropriate patient with family history. Once the Philadelphia Consensus Conference released the specific guidelines, not just about family history, but about the person's Gleason grade and stage of cancer, we realized we were on the right track. We quickly—Dr. Korman's group—implemented a protocol where they identified all high-risk patients, and those high-risk patients were then counseled before the test was done. If they approved for us to run the test, the patient then had the buccal swab tested for genetic markers that were inherited either from the mother or the father.
The importance of this is multifold. Prostate cancer, as you know, is the most common cancer in men and the second most common cancer of deaths in men after lung cancer. When you talk about a person with prostate cancer, there often is a very strong family history. Even though a genetic mutation may only be recognized in 10% to 15% of patients, inherited risk factors are present in about 60% of the patients.
So, when you have about 270,000 patients every year who are diagnosed with prostate cancer, if 10% to 12% of them have an abnormal gene, that's not a small number. That gene could affect how aggressively their cancer behaves. It could affect how we screen them in the future if we decide not to treat them at this time because their cancer appears to be an indolent or low-risk cancer, or they may be eligible for newer clinical trials. They may be eligible for newer medicines if they have stage 3 or stage 4 disease. Last but not least, we could prevent second cancers in that individual if we knew what cancers they were at risk for, and also help decrease the chance or detect cancers early in their family members with what is called cascade testing, which is where we test family members for this particular gene that the person has.
This mechanism or protocols that Dr. Korman's group put together as urologists and uro-oncologists helped us as medical oncologists treat patients better, counsel them better, hopefully prevent second cancers, and also counsel their family members. That was the background of the study.
Ramanathan: It was an elegant design in that we had a built in pre- and post- group just by way of how Dr. Korman and the rest of the group implemented this protocol. The pre-test group had just been receiving standard genetic testing without any protocol in place. The post-test group was the 2 years’ worth of patients who received genetic testing through the UroSEEK company through a more standardized approach.
We found a sizeable and statistically significant uptick in compliance with genetic testing and compliance with post-test genetic counseling in patients who underwent testing after the implementation of the standardized protocol. I don't have the numbers in front of me right now, but I believe it was something like 33% compliance with genetic testing prior to implementation, all the way up to 96% or 97% compliance with genetic testing after the implementation of this protocol. It was really an astounding increase and something that we thought would be useful for the urology and uro-oncology community in general to hear about.
Andrew Korman: I would say one of the main take-home messages is that genetic testing seems like it's a mainstay in health for prostate cancer patients. As Dr. Balaraman said, 10% to 15% of the 270,000, that's [about] 30,000 patients a year who genetic testing can help catch for prostate cancer in advance and help people get treated early onset.
Also, just the importance of creating the workflow and educating doctors and educating patients and getting insurance providers on board. It seems like this is the future of where prostate cancer treatment is going. That's essentially the main takeaway of this study.
Ramanathan: That was really well put, and tacking on to that is we talked about it a little bit in the discussion portion of the manuscript, but one of the primary barriers to widespread implementation—there's provider discomfort, there's lack of access to resources—but also a significant lack of information regarding successful protocols in the literature. Even if providers and large groups are willing to implement a practice such as this, there's not as much information available out there on how exactly to go about it. So, I think this certainly is an important first step in starting to bridge that gap.
Howard Korman: In terms of other things to be mentioned, other concerns people will have, there will be a discomfort with the urologists in terms of genetic counseling and who does it. We happen to have a genetic counselor down the block, but we could quickly flood her practice to the point where nobody could get in. The genetic testing companies that do the tests, whether it be someone doing a blood test or a buccal swab, they usually have a genetic counseling hotline that people can call.
We do recommend that in practices that we have a couple champions in each practice, and as urologists, are trained in how to do the basic genetic counseling to the patients. We did that with a couple of doctors, help them get busy in their practice. Telemedicine was a great adjunct to that. It was a great way to do it. Patients didn't have to come in and drag their families in. All the members of the family could be on the call if they wanted to.
That's another nuance of the thing. It's one thing to get it ordered, it's another thing to get the insurance company to pay for it, which is a huge thing, because it can be a $1500 test. It's another thing to figure out what to do with the information.
Ramanathan: This was really an introductory step in evaluating how we implemented the protocol. On top of that, we are going to do a deeper dive into what the actual results of the genetic tests were. So first off, we need to figure out how many patients have a negative genetic test, how many patients have VUS, or variants of uncertain significance, identified on genetic testing, and then obviously, how many patients had positive genetic testing results.
Then taking that a step further, we're going to evaluate what the treatment and monitoring protocols were for the subsets of patients to see if they had any change in the treatment paradigm and if any patients were enrolled into clinical trials. For patients with variants of uncertain significance, what the long-term outcome of those were and if, potentially, newer treatments became available as monitoring was ongoing, whether these patients were enrolled. So, really a deeper dive into the post-genetic testing treatment and management of these patients is what the next step is going to be.
Balaraman: A lot of times, providers are short on time, because you have 3 or 4 things that you want to address with the patient, and genetic counseling pre-test can be a rather elaborate process. When a patient is signed in and waiting to see a physician, having a web-based system where they can meet with the genetic counselor, get pre-test counseling done before the physician meets them, and then the physician can consent the patient, get the testing done, and the post-test counseling can also be done through a web-based or a telemedicine-based pathway.
The genetic testing companies out there should be able to take this new technology and run with it, because one of the biggest roadblocks to genetic testing was that we didn't have enough genetic counselors. Now, with technology opening up the world for genetic testing, that should no longer be a barrier for patients or physicians.
1. Ramanathan Si, Korman A, Ramanathan Sa, et al. Positive impact of implementing a comprehensive genetic testing protocol for prostate cancer patients in a multi-disciplinary uro-oncology practice. Urol Pract. Published online January 1, 2023. Accessed February 22, 2023. doi:10.1097/UPJ.0000000000000350.