Long-Term Toxicity in Testicular Cancer and AYA: Premature Mortality and Morbidity Illustrated - Zachary Klaassen
May 1, 2024
Zach Klaassen discusses his lecture on the topic of testicular cancer and survivorship during a discussion with Alicia Morgans. Highlighting the long-term effects of chemotherapy, Dr. Klaassen emphasizes the profound impact on young patients who often live decades post-diagnosis. His presentation addresses the serious long-term toxicities, noting that one in five survivors experiences significant morbidity. He discusses secondary malignancies and the profound, enduring mental health challenges these survivors face, shedding light on the necessity of a comprehensive survivorship care plan. Dr. Klaassen's focus underscores the importance of considering not just the immediate effects of testicular cancer treatments but also the extended health and well-being of survivors.
Biographies:
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Well Star MCG, Georgia Cancer Center, Augusta, GA
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, MA
Biographies:
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Well Star MCG, Georgia Cancer Center, Augusta, GA
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, MA
Read the Full Video Transcript
Alicia Morgans: Hi, I'm so excited to be here today with Dr. Zach Klaassen, who is joining me from the Georgia Cancer Center, where we are talking about his EAU 2024 lecture. We talked about testicular cancer and survivorship and all the things we really need to think about. Thank you so much for being here with me today.
Zach Klaassen: Of course, Alicia, always good chatting with you.
Alicia Morgans: Wonderful. So, Zach, I wonder if you can really show us some slides, give us an introduction to your lecture. Tell us what you talked about and why it's so important.
Zach Klaassen: Yeah, absolutely. So as I'm pulling these up, basically, the survivorship in all of cancer is so important, but I think we probably get a little bit, I don't want to say lackadaisical, but we sometimes forget about our young testicular cancer patients. These patients, because of how effective chemotherapy is, are often going to live 40 to 50 years after their diagnosis and often cure of testicular cancer. So I was asked to talk about the long-term toxicity, really focusing on morbidity and mortality for these patients. And certainly, this is a big topic. You could almost have its own session alone, let alone a ten-minute lecture at EAU. But I wanted to share a couple of slides on premature morbidity and then a slide on mortality. I know we're going to talk about some of the other aspects after we go through the slides. So this is an important study.
This study is out of the Journal of Clinical Oncology from 2018, and when we look at chemotherapy toxicity as a medical oncologist, the chemotherapy toxicity for these patients can be very vast and have many different symptoms, including peripheral neuropathy, difficulty hearing, among other things. But I like this study because it really shows what these authors described as the cumulative burden of morbidity. And so I've highlighted two ovals here, which I think are important. If you look at the right side, 20% of patients, that's one in five of your testicular cancer patients, have either a high, very high, or severe cumulative burden of morbidity after their chemotherapy. So I think that's an important number to keep in mind that one in five will have this over the course of years of follow-up. What's also important is that only 5% have none. Now, if you flip that on its side, that means 95% of your testicular cancer patients have some cumulative burden of morbidity after chemotherapy from testicular cancer.
So, in that context, without going into too many details of the types of chemotherapy toxicity they can get, we know that this is something that not only happens in the acute time when they're receiving their chemotherapy but certainly stays with them over the course of their survivorship care plan. The second thing we talked about was secondary malignancy. As we know, these are young patients, and this study is an older study, but it highlights a couple of things. So this is from 2012 again in JCO, and we look at the relative risks here. And so there's an escalation of relative risk when we look at surgery, which adds very little risk to secondary malignancy. When we think about radiotherapy, which we don't use much anymore, but in historical patients that we may still see in our practice, they may have had radiotherapy for their testicular cancer even five, 10, 15 years ago.
That increases their risk of secondary malignancy. And then, when we combine chemo and radiotherapy, that really increases their relative risk up to 4.5 times that of the standard population. So when we're thinking about these malignancies, as you can see on the right here, the solid malignancies—lung, colon, bladder, pancreas, and stomach cancer, as well as some of the leukemias, AML, and acute lymphoblastic leukemia—are included. Also, a topic that I know is near and dear to both of our hearts is mental health. And this was another study I talked about at EAU, probably the best long-term mental health study we've seen in testicular cancer. This came out in JCO in 2021 from folks in Ontario, Canada. The way this study is set up is that the Ontario Cancer Registry captures over 95% of testicular cancer patients. And what they're able to do is then follow them longitudinally.
On the left side, we see compared to controls in the short term, leading up to the time of orchiectomy, which is in the middle of this left-hand graph, there's very little mental health resource utilization until orchiectomy. And we see that in the two years after orchiectomy, patients with testicular cancer, compared to the controls, have a significantly increased utilization of mental health resources. What's particularly striking is on the right side, when we reset the X-axis to less than two years, the time of orchiectomy at time 0.0 all the way up to 20 years after the orchiectomy, this curve continues to split, meaning that even with continued follow-up two decades after their orchiectomy, they continue to use more mental health resources compared to the general population. So I think this really highlights the fact that not only is this a traumatic time in their twenties or thirties when they're diagnosed with testicular cancer, but it often leads to the survivorship care plan for 20, 30, 40 years afterward. We have to be aware of the mental health of these patients.
The final study talks about premature mortality. I did present some other Norwegian data, but I'll focus on this study from China, which had 27,000 patients over almost two decades. On the left-hand side, we see the causes of mortality for localized testicular cancer. And we can see here very few testicular cancer mortalities, but the majority of these non-tumor mortalities for localized testicular cancer. What's particularly interesting on the bottom left, we see that suicide, accidents, and adverse events make up almost 20% of the early mortalities among localized testicular cancer patients. And I think, going again to the previous slide with the mental health, these patients are at risk of injury and accidents. And I think, again, being aware of those things for our localized patients, even years after their diagnosis. On the right, again, we see regional and distant metastases over half of these mortalities are from testicular cancer. But again, we still do see suicide and self-inflicted injury making up a portion of these mortalities as well. So those are the key studies I talked about, and I'll turn it back over to Alicia.
Alicia Morgans: Thank you so much for that, Zach. I think that we don't talk about some of those issues as much as we should. And I know there are still other outstanding concerns that we continue to investigate as an oncologic field, particularly in urologic oncology. What are some of the other things that you're thinking about when you're trying to care for patients with testicular cancer, and what else are we still trying to investigate?
Zach Klaassen: Yeah, I think we've heard about financial toxicity across the board for a lot of cancers over the last five to ten years. I know there's been some great work at Vanderbilt. Dave Penson has looked at that in prostate cancer. And when I was putting together this presentation, I only found one study out of Japan that looked at financial toxicity. And if we think about testicular cancer patients, they have a lot of reasons to be at risk of financial toxicity. One, they may be in school, so they're not earning any income, and so they're burdened with medical bills. Two, they may be the sole breadwinner for their household, and so they're stopping work for chemotherapy or recovering from an RPLND, resulting in a lack of income.
The third one is they probably have children, and you and I both have children; they're dependents, they're costly, we love them, but they're costly. And so that also adds to the fact that there are a couple of different factors that may contribute to their financial toxicity. Now, I will add for our U.S. listeners as well, a lot of these young men don't necessarily have health insurance when they're diagnosed. They're in their twenties and thirties, they think they're invincible. They get diagnosed with testicular cancer, and they may not have insurance as well. So that's potentially a fourth aspect of their care and follow-up that may lead to financial hardship.
Alicia Morgans: I couldn't agree more. And when you think about guys who are in their late teens and twenties, they're not always financially secure, even on a basic level. So when you add this in, they may or may not have insurance coverage in the U.S., and they also may not have even really been thinking about what happens in a situation where something traumatic occurs. And there are few things as traumatic in this age group as a diagnosis of cancer. So I think definitely I agree with you, work needs to be done, and really, I think there's a lot of information for us to continue to gather and to support these individuals, especially as we think about the broader implications for mental health. Financial toxicity leads to emotional traumatic stress, psychological distress. When you think about how to care for your patients with testicular cancer even next week, tomorrow, what are the things that you take from this presentation and the compilation that you've made to present at EAU to take into clinic tomorrow?
Zach Klaassen: I think the main thing is that we have to be on the lookout for mental health for sure. Every single testicular cancer patient I have experiences some degree of shock and depression. Why me? How did I get this? And so I think not only at that initial visit when you see them but in the follow-up, I offer just like to my bladder cancer patients, the prostate cancer patients, the NCCN distress thermometer, which I think is really helpful. It's quick. It doesn't add anything to the clinic workflow. It just gives a snapshot in having metrics, whether the thermometer is five or higher or seven or higher, whatever metric you want, just to have an idea of where they're coming into the clinic at for each visit. And I think that's important. Also, relying on your team, such as nurse navigators, nurse practitioners, PAs, APPs, social workers—these young fellows need a lot of support, not just getting through treatment, but also in follow-up and having those counselors available as well from a psycho-oncology side is huge, not just in the immediate diagnosis period but following long-term as we've seen from the Canadian study.
Alicia Morgans: I couldn't agree more. And I think this is a time when cancer centers, when urologic oncologists, medical oncologists, all of us need to also support the patient by ensuring that they have community-based resources because we don't always have within our clinical sphere the degree of mental health support that can be necessary to support our patients. So, really, really fantastic. So, as you think about the overall conclusion and the message to listeners, what would that be, Zach?
Zach Klaassen: I think the main thing is that testicular cancer has been regionalized to centers of excellence, which I think is important, once you get past the orchiectomy. Whether we're discussing multidisciplinary tumor boards, we're talking about appropriate indications for surgery, how to do the surgery properly, all those things are well-established. But I think we have to look at this as not just treating the testicular cancer but treating the testicular cancer patient. And I think that the summary from this entire talk at EAU was that there's more to it than just giving chemo and doing surgery and doing surveillance scans and seeing that we have secondary malignancies. They should be getting family or general practitioner follow-up so they're getting screened for colon cancer, screened for all the things that are maybe outside of our scope, and really, really engaging the entire team to make sure that we're not missing these men who are really going through a hard time. I think it takes a team effort and really putting the patient first, not just the cancer.
Alicia Morgans: Absolutely. And these younger men, whether they're 20, 30, 40, are vulnerable people who are also at a point where they can make some pivots in their medical care and focus on their mental health, focus on their cardiovascular health, all of the aspects that they need. And I so appreciate you bringing all of this to light. We should absolutely bring you into, and you already are part of, the survivorship fold, and so I appreciate you sharing this information, and of course, leading your efforts in survivorship at your institution and beyond, at the AUA and beyond. So thank you so much for your time and expertise.
Zach Klaassen: Always a pleasure, Alicia. Thanks so much.
Alicia Morgans: Hi, I'm so excited to be here today with Dr. Zach Klaassen, who is joining me from the Georgia Cancer Center, where we are talking about his EAU 2024 lecture. We talked about testicular cancer and survivorship and all the things we really need to think about. Thank you so much for being here with me today.
Zach Klaassen: Of course, Alicia, always good chatting with you.
Alicia Morgans: Wonderful. So, Zach, I wonder if you can really show us some slides, give us an introduction to your lecture. Tell us what you talked about and why it's so important.
Zach Klaassen: Yeah, absolutely. So as I'm pulling these up, basically, the survivorship in all of cancer is so important, but I think we probably get a little bit, I don't want to say lackadaisical, but we sometimes forget about our young testicular cancer patients. These patients, because of how effective chemotherapy is, are often going to live 40 to 50 years after their diagnosis and often cure of testicular cancer. So I was asked to talk about the long-term toxicity, really focusing on morbidity and mortality for these patients. And certainly, this is a big topic. You could almost have its own session alone, let alone a ten-minute lecture at EAU. But I wanted to share a couple of slides on premature morbidity and then a slide on mortality. I know we're going to talk about some of the other aspects after we go through the slides. So this is an important study.
This study is out of the Journal of Clinical Oncology from 2018, and when we look at chemotherapy toxicity as a medical oncologist, the chemotherapy toxicity for these patients can be very vast and have many different symptoms, including peripheral neuropathy, difficulty hearing, among other things. But I like this study because it really shows what these authors described as the cumulative burden of morbidity. And so I've highlighted two ovals here, which I think are important. If you look at the right side, 20% of patients, that's one in five of your testicular cancer patients, have either a high, very high, or severe cumulative burden of morbidity after their chemotherapy. So I think that's an important number to keep in mind that one in five will have this over the course of years of follow-up. What's also important is that only 5% have none. Now, if you flip that on its side, that means 95% of your testicular cancer patients have some cumulative burden of morbidity after chemotherapy from testicular cancer.
So, in that context, without going into too many details of the types of chemotherapy toxicity they can get, we know that this is something that not only happens in the acute time when they're receiving their chemotherapy but certainly stays with them over the course of their survivorship care plan. The second thing we talked about was secondary malignancy. As we know, these are young patients, and this study is an older study, but it highlights a couple of things. So this is from 2012 again in JCO, and we look at the relative risks here. And so there's an escalation of relative risk when we look at surgery, which adds very little risk to secondary malignancy. When we think about radiotherapy, which we don't use much anymore, but in historical patients that we may still see in our practice, they may have had radiotherapy for their testicular cancer even five, 10, 15 years ago.
That increases their risk of secondary malignancy. And then, when we combine chemo and radiotherapy, that really increases their relative risk up to 4.5 times that of the standard population. So when we're thinking about these malignancies, as you can see on the right here, the solid malignancies—lung, colon, bladder, pancreas, and stomach cancer, as well as some of the leukemias, AML, and acute lymphoblastic leukemia—are included. Also, a topic that I know is near and dear to both of our hearts is mental health. And this was another study I talked about at EAU, probably the best long-term mental health study we've seen in testicular cancer. This came out in JCO in 2021 from folks in Ontario, Canada. The way this study is set up is that the Ontario Cancer Registry captures over 95% of testicular cancer patients. And what they're able to do is then follow them longitudinally.
On the left side, we see compared to controls in the short term, leading up to the time of orchiectomy, which is in the middle of this left-hand graph, there's very little mental health resource utilization until orchiectomy. And we see that in the two years after orchiectomy, patients with testicular cancer, compared to the controls, have a significantly increased utilization of mental health resources. What's particularly striking is on the right side, when we reset the X-axis to less than two years, the time of orchiectomy at time 0.0 all the way up to 20 years after the orchiectomy, this curve continues to split, meaning that even with continued follow-up two decades after their orchiectomy, they continue to use more mental health resources compared to the general population. So I think this really highlights the fact that not only is this a traumatic time in their twenties or thirties when they're diagnosed with testicular cancer, but it often leads to the survivorship care plan for 20, 30, 40 years afterward. We have to be aware of the mental health of these patients.
The final study talks about premature mortality. I did present some other Norwegian data, but I'll focus on this study from China, which had 27,000 patients over almost two decades. On the left-hand side, we see the causes of mortality for localized testicular cancer. And we can see here very few testicular cancer mortalities, but the majority of these non-tumor mortalities for localized testicular cancer. What's particularly interesting on the bottom left, we see that suicide, accidents, and adverse events make up almost 20% of the early mortalities among localized testicular cancer patients. And I think, going again to the previous slide with the mental health, these patients are at risk of injury and accidents. And I think, again, being aware of those things for our localized patients, even years after their diagnosis. On the right, again, we see regional and distant metastases over half of these mortalities are from testicular cancer. But again, we still do see suicide and self-inflicted injury making up a portion of these mortalities as well. So those are the key studies I talked about, and I'll turn it back over to Alicia.
Alicia Morgans: Thank you so much for that, Zach. I think that we don't talk about some of those issues as much as we should. And I know there are still other outstanding concerns that we continue to investigate as an oncologic field, particularly in urologic oncology. What are some of the other things that you're thinking about when you're trying to care for patients with testicular cancer, and what else are we still trying to investigate?
Zach Klaassen: Yeah, I think we've heard about financial toxicity across the board for a lot of cancers over the last five to ten years. I know there's been some great work at Vanderbilt. Dave Penson has looked at that in prostate cancer. And when I was putting together this presentation, I only found one study out of Japan that looked at financial toxicity. And if we think about testicular cancer patients, they have a lot of reasons to be at risk of financial toxicity. One, they may be in school, so they're not earning any income, and so they're burdened with medical bills. Two, they may be the sole breadwinner for their household, and so they're stopping work for chemotherapy or recovering from an RPLND, resulting in a lack of income.
The third one is they probably have children, and you and I both have children; they're dependents, they're costly, we love them, but they're costly. And so that also adds to the fact that there are a couple of different factors that may contribute to their financial toxicity. Now, I will add for our U.S. listeners as well, a lot of these young men don't necessarily have health insurance when they're diagnosed. They're in their twenties and thirties, they think they're invincible. They get diagnosed with testicular cancer, and they may not have insurance as well. So that's potentially a fourth aspect of their care and follow-up that may lead to financial hardship.
Alicia Morgans: I couldn't agree more. And when you think about guys who are in their late teens and twenties, they're not always financially secure, even on a basic level. So when you add this in, they may or may not have insurance coverage in the U.S., and they also may not have even really been thinking about what happens in a situation where something traumatic occurs. And there are few things as traumatic in this age group as a diagnosis of cancer. So I think definitely I agree with you, work needs to be done, and really, I think there's a lot of information for us to continue to gather and to support these individuals, especially as we think about the broader implications for mental health. Financial toxicity leads to emotional traumatic stress, psychological distress. When you think about how to care for your patients with testicular cancer even next week, tomorrow, what are the things that you take from this presentation and the compilation that you've made to present at EAU to take into clinic tomorrow?
Zach Klaassen: I think the main thing is that we have to be on the lookout for mental health for sure. Every single testicular cancer patient I have experiences some degree of shock and depression. Why me? How did I get this? And so I think not only at that initial visit when you see them but in the follow-up, I offer just like to my bladder cancer patients, the prostate cancer patients, the NCCN distress thermometer, which I think is really helpful. It's quick. It doesn't add anything to the clinic workflow. It just gives a snapshot in having metrics, whether the thermometer is five or higher or seven or higher, whatever metric you want, just to have an idea of where they're coming into the clinic at for each visit. And I think that's important. Also, relying on your team, such as nurse navigators, nurse practitioners, PAs, APPs, social workers—these young fellows need a lot of support, not just getting through treatment, but also in follow-up and having those counselors available as well from a psycho-oncology side is huge, not just in the immediate diagnosis period but following long-term as we've seen from the Canadian study.
Alicia Morgans: I couldn't agree more. And I think this is a time when cancer centers, when urologic oncologists, medical oncologists, all of us need to also support the patient by ensuring that they have community-based resources because we don't always have within our clinical sphere the degree of mental health support that can be necessary to support our patients. So, really, really fantastic. So, as you think about the overall conclusion and the message to listeners, what would that be, Zach?
Zach Klaassen: I think the main thing is that testicular cancer has been regionalized to centers of excellence, which I think is important, once you get past the orchiectomy. Whether we're discussing multidisciplinary tumor boards, we're talking about appropriate indications for surgery, how to do the surgery properly, all those things are well-established. But I think we have to look at this as not just treating the testicular cancer but treating the testicular cancer patient. And I think that the summary from this entire talk at EAU was that there's more to it than just giving chemo and doing surgery and doing surveillance scans and seeing that we have secondary malignancies. They should be getting family or general practitioner follow-up so they're getting screened for colon cancer, screened for all the things that are maybe outside of our scope, and really, really engaging the entire team to make sure that we're not missing these men who are really going through a hard time. I think it takes a team effort and really putting the patient first, not just the cancer.
Alicia Morgans: Absolutely. And these younger men, whether they're 20, 30, 40, are vulnerable people who are also at a point where they can make some pivots in their medical care and focus on their mental health, focus on their cardiovascular health, all of the aspects that they need. And I so appreciate you bringing all of this to light. We should absolutely bring you into, and you already are part of, the survivorship fold, and so I appreciate you sharing this information, and of course, leading your efforts in survivorship at your institution and beyond, at the AUA and beyond. So thank you so much for your time and expertise.
Zach Klaassen: Always a pleasure, Alicia. Thanks so much.