Results From the IGCCCG Update Consortium in Metastatic Seminoma And Nonseminomatous Germ Cell Tumors – Silke Gillessen

May 24, 2021

Silke Gillessen highlights the International Germ Cell Cancer Collaborative Group (IGCCCG) update model for both seminoma and non-seminoma patients highlighting two recently published articles in the Journal of Clinical Oncology, titled "Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium" and "Survival and New Prognosticators in Metastatic Seminoma: Results From the IGCCCG-Update Consortium."  The classification of the IGCCCG plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. Extrapulmonary visceral metastases were the only adverse prognostic factor among 660 advanced seminomas in the original classification of the IGCCCG treated between 1975 and 1990 and published in 1997. There are a number of rationales supporting the update of the IGCCCG risk classification including- not all patients had received cisplatin-based treatments, outcomes may have improved with current era management, and additional prognostic factors may exist. There were two goals of this update: To validate original IGCCCG criteria and to identify new prognostic factors that may explain the heterogeneity of outcomes in the original IGCCCG risk groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS).


Prof. Dr. Med. Silke Gillessen, Medical and Scientific Director, Oncology Institute of Italian Switzerland (IOSI), ​and Co-founder of the Advanced Prostate Cancer Consensus Conference (APCCC).

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University in Chicago in the United States. I'm so excited to have here with me today, a good friend and colleague, Dr. Silke Gillessen, who is the Head of the Medical Oncology Department and the Medical and Scientific Director of the Oncology Institute of Southern Switzerland. Thank you so much for being here with me today, Dr. Gillessen.

Silke Gillessen: Thank you very much, and for the introduction, and it's a pleasure cias always to be with you.

Alicia Morgans: Wonderful. And I just wanted to talk with you a little bit about two fantastic recent publications in the Journal of Clinical Oncology, in which you and colleagues really updated and perfected the prognostication models that you have developed over years and years, for both seminoma and non-seminoma patients. Can you tell us a little bit about the work that you've done?

Silke Gillessen: Yeah, so I have to say, it all started a long time ago with the IGCCCG that you probably know, and all GU oncologists know, that the classification that we are using every day for patients with testicular cancer to decide management of patients with metastatic disease. That classification was published in 1997. So the idea was actually that we had some years ago, as you say, I can't remember exactly, probably five or six years ago, is that we wanted to update this classification because obviously, we have made progress in the sense that we have probably better diagnostics, we have now, because, in that classification or the original classification, not all patients had received cisplatin or etoposide based chemotherapies that are now standard.

We have more centralization. So we just were wondering, because some smaller cases had shown that probably the prognosis is better currently than in these patients that had been collected for the 1997 classification. So we had actually two goals. So that was one goal, that we wanted to update the estimate of survival in patients with current treatment [inaudible 00:02:30]. And the second one was, we wanted to, because we know, you know as well, there are all these patients that are intermediate, but it's heterogeneous, and we wanted to try to find new prognosticators that would explain a bit of that heterogeneity in the single groups of poor, intermediate, and good prognosis.

Alicia Morgans: I completely agree. And I think we should acknowledge the effort that you and the team put forth to really do this work and to update our prognostic expectations for patients. It does look in your papers and in your work as if patients are living longer today than they were by the old classifiers and you and the team really did this work as a labor of love in fact. It's hard to find funding for this kind of work and you and your team spent many, many hours and your own dollars to get it done. So I really do want to commend you. And of course, you put all of your efforts and your brains into it as well. So, fantastic work. Can you tell me how did you actually update these models? What did you add to the models in order to make them better for today?

Silke Gillessen: So, first of all, maybe I have to say one word. So it's not like my collaborators. It's really all kind [inaudible 00:03:54] of colleagues and friends who are also interested in patients with testicular cancer, because this is really a smaller group compared to prostate cancer, maybe, but it's a very enthusiastic group and I have to really acknowledge that all of the people helped us and sent us the data and did everything for free. So we had to fund this with money from the Swiss Cancer Foundation, our money, and also money from Movember. So again, kudos to Movember, the statistical fellow who helped us with the very complicated statistics that we had to do. And so, yes, so really, really good news. So the old IGCCC classification still holds true. So even if this was a classification that had been done or published at least, in 1997, it still holds true.

So it still makes a very good difference of different prognostic groups. So this is, I think very reassuringly that the classification is really good as it is. And what we saw in the overall survival estimate is really also fantastic that we saw that the overall survival has improved in all the groups. So this is again like what we [inaudible 00:05:16] failed, what we had seen in smaller series, but now we really have the data on, that is obviously very good news for our patients. Yeah.

So I guess that is the most for me, in a way the most important message. It is still working, the classification, so it still really holds true and we have improved overall survival, but we still have to say, that for the non-seminoma patients with poor prognosis, that are in the poor prognostic group from the original IGCCCG, the five-year overall survival went from 48% to 67%. So there is still a third of these young patients, most of the time who are dying from the disease. And we discussed that before, right. We really need new treatments for these patients. I think that is very important, whereas in the good prognosis group, for example, the five-year overall survival in the non-seminoma patients went from 92% to 96%. So they are really doing good already. And I guess that is a nice message to have.

Alicia Morgans: It absolutely is. And certainly, a message of hope for the majority of these patients, being young men who do want to have a long life ahead of them and to know that they can predict how that will go and hope that things are getting better for these patients, as our therapies are improving and we are getting access for these patients to those therapies is also really, really important. So if you had to give a final message from your group to the listeners, what would that be on your updated prognostic papers?

Silke Gillessen: So I guess for both of us interesting would be, so we have two papers, the seminoma, and the non-seminoma. So again, the most important message may be is that the classification still holds true and that the overall survival is improved or has improved. For the non-seminoma, interestingly, we found LDH at the cutoff of 2.5 to make a difference in the big group of good prognosis patients. So there were the patients who have high LDH who didn't do as well as the other patients in [inaudible 00:07:48] different prognosis seminoma groups. But they did a bit more in the intermediate group. As you know, the intermediate group in the original classification is just one point that isn't having non-pulmonary visceral metastasis. So this is a very small group, so I guess now we know that probably in that good prognosis seminoma group, there is a group that doesn't do as well.

And that's the patients with the high LDH higher than 2.5 [inaudible 00:08:23] upper limit of normal. For the non-seminoma, we have much more patients for the prognosticators. And there we found two interesting new prognosticators that he puts into the new model. One was having pulmonary metastasis, so the presence of pulmonary metastasis added some information for the prognosis. And interestingly, I think most of us wouldn't have thought that age, as a continuous value, also added information for the prognosis. So every decade of life increases your risk of progression by about 25%.

And I think that is a very interesting finding. We don't know. So this is really, that is retrospective data. So we can't say why we don't have the exact doses of chemotherapy. So it seems that the chemo [inaudible 00:09:25] set people's plans, the same in older patients and in the young patients, but we don't know if the whole dose was given or if there were compromises for dose or if they were delayed. I think the other important message for me is that we also, with the patients who are a bit older [inaudible 00:09:43] and found that in kind of the setting of a particular amount is already, I mean, 40 or something, that is normally young for us. And we should really try with everything that we have to really make the chemotherapy be given in time, not delayed, not dose reduced if not necessary. So I think this is something where we should be very strict as a community to try to get the chemotherapy as planned.

Alicia Morgans: I agree. And it's such an interesting comment. It reminds me of conversations that leukemia doctors have had when there are these patients who, for ALL, for example, typically it is very young patients, but if you become a 20-year-old or a 25-year-old, or a 27-year-old, who has ALL your prognosis is worse somehow just related to age. And their thought was exactly the same that it might be that we are not pushing the chemotherapy schedule as we would with the younger patients if we're not. And that certainly we should try to use those more intensive chemotherapy strategies, even in older patients for that population. For our population, for testicular cancer, we just need to stick to the schedule and get the dose in, the whole dose and keep supporting those patients to get all of their treatments completed on time and in their entirety.

So really important and a good message to pass along. So again, I thank you for your work, for your time today. I commend your entire group for the work that you have done and for really helping to keep us moving forward in testicular cancer. We are as we talked about earlier, not necessarily changing our drugs right now, but we are still trying to move the ball forward and we are trying to improve our outcomes for our patients. It sounds like we are. And I sincerely appreciate you sharing that message and these updates with us.

Silke Gillessen: Thanks, Alicia.