The Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute presents a succinct summary of all the testicular cancer clinical updates you need to know from ASCO 2022.
we'll be concluding the geo oncology conference highlights from 20 to 2022 with updates and testicular cancer and germ cell tumors presented by dr to worry. Great, thank you jake. I can't start my video either. I guess I'm not the host um that we will proceed nonetheless. So these are my disclosures. So there were there were two uh presentations that I wanted to share from germ cell tumors kind of echoing the theme of kind of how this conference was for G you in general, there's never that much that's going on in testicular cancer. But every so often we do kind of advanced some of our knowledge about the overall management of disease. And so I think there were two things that are worth mentioning this conference. The 1st 1 is an abstract from Memorial Sloan Kettering. Looking at germline genetics in germ cell tumors and really trying to understand if these may have any impact on clinical management of patients. And so as many of us are familiar with the Memorial's located has done a really nice job of tumor and genetic profiling Of patients that come through their center. And so for this study court, they were able to leverage 477 men, the most the majority of whom had testicular cancer, but some also the primary media cycle germ cell tumors. And they were able to do germline sequencing either through next generation sequencing or also panels and uh then they analyze this to look for what they called pathogenic gene variants. I mean they looked for associations between these variances and site of disease histology or other other clinical factors. So this pie chart shows that The vast majority of patients did not have what was called a pathogenic germline variant, about 11% did. And when you classified by the penetrates of these alterations, the in Richmond in the high penetrates group was for DNA damage type genes such as BRCA 12 which in power bi too. Although these were admittedly very rare. There were moderate penetrates alterations such as those in check to or A T. M. And check to. Has notably been described previously by Ella van Allen here at Dana Farber and the rest of the alterations were of low penetrates. One question that is really important in any sort of DNA alteration within the cancer. Either germline or within the cancer genome. Is is there by like an activation in these jeans? Because you could expect that the phenotype may vary if only one copy is altered or not. That's not a hard and fast rule. But it's certainly worth knowing. And so what was interesting is that in the context of all very very small numbers only the check too and A T. M. And P 53 ta damage type genes were altered at the biological level. Looking at the association between either pathogenic or likely pathogenic variants and some of the clinical characteristics that were able to be captured. There was nothing that was significant, mainly probably due to numbers but there was a trend at least towards likely pathogenic variants being enriched in primary media spinal. And these are also to us that are just overall enriched for three alterations as well. So that was the first study. The second study is one of late relapses and testicular cancer, a report from the Sweeney Tech, a group presented by Dr Hanson and colleagues. And so late relapses are in a special problem in testicular cancer because they tend to represent less curable disease. But as the authors pointed out in this abstract, there really is a wide incident in the range of how much weight real actors are actually happening and how these patients end up doing. And a lot of it's based on older data. And so the authors were interested in using some of their data to try and update the field in this. And just as a matter of terminology, I've included here on the right what we mean by these different relapse parameters. So technically within germ cell tumor treatment, a late relapse qualifies as anything where the disease relapses after two years of treatment, the risk of relapse in Seminole man non seminar was really highest in the first two years anyways. Uh then they classified other relapses is very late if they occurred after five years and then extremely late relapse uh 10 years or later, The cohort of patients is a northern European won a total of 5700 patients relatively evenly mixed between semin oma and non semin oma. And I think what is a particular strength of this court is that there's 3500 patients from the latter kind of portion of the accrual of these patients. So they started carrying these patients in the 80s. And treatment has drastically changed since that in terms of supportive care and just our ability to manage patients with even severe disease. And so it's nice to have a somewhat larger population from a somewhat more recent time point. And so this is the data, a total of 400 patients out of 5700 had a relapse. And this was across the entire spectrum from patients with clinical stage one, who were just managed with surveillance to stage three, that were managed with chemotherapy. You can see that the majority of relapses were uh in the late relapse years two through 5 and then very few relatively speaking, occurred after five years. As expected, the median time to relapse was less than a year. Um Late relapses once happening after two years did take uh on media out to almost five years. And the exciting thing from this data is that the overall survival of 10 years, even in these patients with relapses was quite good when looking at the different causes of death and patients that did relapse. Um Patients who had clinical stage one ah Patients who had clinical stage one disease. Of the 61 patients, only eight patients died and only four of them from their testicular cancer, suggesting that these patients are quite have quite salvageable disease. But for patients with late relapses who had medicine disease, especially those who had gotten chemotherapy prior, the chance of dying from their cancer was much much higher. Looking at that that specific group. So the overall survival of patients in this cord after a late relapse. For patients who are initially treated with chemotherapy, the numbers are definitely improving. And really the number you want to look at is from the 1995 to 2009 Tenure overall and cancer specific survival, which is still 2/3 which is actually pretty good for relative to historic numbers. And you can even see that on this slide. So not all these patients are curable, but it's still a reasonable a reasonable chance even in the late relapse setting. And so the authors concluded that there was just overall low rates of late relapses. There were more relapses in clinical stage one patients that were managed with surveillance, but these patients had disease that was very salvageable and curable still. Um But for patients who were initially treated with chemotherapy, uh you know, it's harder to cure that disease, but we're doing better over time. And so this suggests that there's probably some granularity that we need to really look into for late relapses specifically thinking that even though a year three relapses lay relapse the prognosis may actually be quite good. I'm gonna. And those are the two that I wanted to discuss. Happy to take. Any questions. I don't see any questions in the chat dr Sweeney any comments. two things. I think we need to start to discussed with our genetics team. are we reaching a threshold if we're seeing 5% of these patients with tuna have a Exxon mutation, should we be starting to send them routinely off for testing? Which would lead to cascade testing to family members Because testis cancer is a very heritable disease when you look into it in first degree relatives. If we see check to and bracket then that really does play into the role. So I think we need to speak with memorial Sloan Kettering and the N. C. C. M. Team to see if we should think about getting that as a recommendation. Not yet for everyone. But I think that's where we're heading with that. The other thing is Tony made a good point. How do you know what the late relapses Second primary. It takes a bit of thinking where is the relapse? Where was the primary etcetera that. But I think we can get a feel for it based on the side of relapse and the markets. The key message is if you do document it is a light relapse markers are elevated. It's not unreasonable to think about re trying chemotherapy. The chemotherapy to shrink it to make surgery more viable than the only real reliable curative therapy is surgical reception even if it's multi stage, multi location, multi times receptions. Um So surgery is the main stay of treatment. Chemotherapy especially if the markets are elevated is a reasonable thing to do bulk it but don't rely even if they go into a complete remission, go away and they come back and chris you're making, you're making no delineation between patients with late relapses who never got chemotherapy versus patients who have lately relapses who received chemotherapy up front. The late relapses even if they didn't get chemotherapy they may be a bit more chemotherapy sensitive but I would not rely on chemotherapy to be chemo curable. And the other thing to realize that a lot of these terry thomas may make a bit of a, so that's another reason why to take it out and many of them transform to another to another histology territory with transformation which you may use some histology director chemotherapy to try and get some shrinkage but against surgery is the main table, especially for the sack homes. So surgery surgery, surgery and optional lecture of chemotherapy is how I think about it. But the one kicker, one thing I would say is A late relapse cinema say five years out on active surveillance that's been slowly growing for five years that's very curable with chemotherapy for sure. And my other comments are really related to non Semin Emma. Alright, well thanks chris. Thanks. Hello and thank you to all the presenters and discuss and attendees um for for coming today. And we will look forward to regrouping after Esma this fall. Have a good night, everyone.
