Comparing Therapy Approaches for Advanced Upper Tract Urothelial Carcinoma - Joon Kyung Kim
March 20, 2025
Sam Chang is joined by Joon Kyung Kim to discuss treatment approaches for node-positive upper tract urothelial carcinoma. Dr. Kim shares findings from an NCDB analysis comparing outcomes across three treatment strategies: chemotherapy alone, neoadjuvant chemotherapy with nephroureterectomy, and nephroureterectomy with adjuvant chemotherapy. Treatment patterns are shifting, with chemotherapy-only approaches increasing to 47% while adjuvant therapy has decreased by 20%. Neoadjuvant therapy shows the best survival outcomes (65% at three years compared to 53% for adjuvant and 20% for chemotherapy alone), with complete or partial pathological response in 23% of these patients. Dr. Kim emphasizes that surgical consolidation remains crucial despite these shifts, noting concerns about patients becoming ineligible for surgery after initial chemotherapy. He highlights ongoing immunotherapy trials that may further improve treatment options for this rare, aggressive disease.
Biographies:
Joon Kyung Kim, MD, Resident, Department of Urology, University of Kentucky College of Medicine, Lexington, KY
Sam S. Chang, MD, MBA, Urologist, Patricia and Rodes Hart Professor of Urologic Surgery, Vanderbilt University Medical Center, Chief Surgical Officer, Vanderbilt-Ingram Cancer Center Nashville, TN
Biographies:
Joon Kyung Kim, MD, Resident, Department of Urology, University of Kentucky College of Medicine, Lexington, KY
Sam S. Chang, MD, MBA, Urologist, Patricia and Rodes Hart Professor of Urologic Surgery, Vanderbilt University Medical Center, Chief Surgical Officer, Vanderbilt-Ingram Cancer Center Nashville, TN
Read the Full Video Transcript
Sam Chang: Hi, my name is Sam Chang. I'm a urologist in Nashville, Tennessee, at Vanderbilt University Medical Center. And we are quite honored to have a rising star in urology, Dr. Joon Kim, who's a resident at the University of Kentucky and pursuing a urologic oncology fellowship. I've known Joon for several years now as he's pursued a career in urologic oncology.
And he's going to give highlights of a presentation given at ASCO GU 2025, looking at actually the role of surgery and evaluation following actually different types of therapies for those patients who are thought to have more advanced disease and upper tract urothelial carcinoma. So Joon, thanks so much for spending some time with us, and we look forward to your presentation.
Joon Kyung Kim: Thank you so much for having me be able to present our data that we took a look at with evaluation of systemic therapy and surgical consolidation in patients with node positive upper tract urothelial carcinoma.
As you all know, upper tract urothelial carcinoma accounts for about 5% to 10% of upper tract cases. More than 50% of cases can be invasive at initial diagnosis, and up to 2/3 are high grade. Treatment for high grade UTUC often involves a radical nephroureterectomy with regional lymph node dissection. And post-operatively, node positive disease can be present in up to 25% of patients.
Timing of perioperative systemic therapy is multifactorial. A lot of this has stemmed from, been extrapolated from bladder cancer treatments. As you know, they’re both sort of a very similar disease also, but very distinct diseases for lower bladder cancer versus upper tract. Level one evidence currently exists only for the adjuvant space, and that’s with the recent POUT trial that showed benefits.
As for the neoadjuvant setting, again, a lot of these paradigms have been extrapolated from muscle invasive disease. Recently there’s been two phase II trials with Dr. Coleman and Dr. Margulis that have shown evidence of pathological response with favorable survival outcomes.
For node positive disease, regionally advanced disease, the treatment guidelines are even more unclear. Currently, the AUA and EAU guidelines recommend offering systemic therapy with consideration of consolidative surgery among individuals with partial or complete responses. So there’s nothing really distinct in that group to provide guidance.
So what we did was take a look at NCDB between 2018 and 2021, just to see how people are being treated up front or around for the management of this disease. So individuals with N1 through 3 disease were identified on non-metastatic and were looked at from individuals that received chemotherapy with or without nephroureterectomy.
And these were stratified into three groups, which included chemotherapy only, neoadjuvant chemotherapy, followed by a nephu, and nephu followed by adjuant chemo. This is just the flow diagram of our study population. And about 495 for the chemotherapy only, 411 for the nephu followed by chemo, and chemo followed by nephu about 297.
So what we saw amongst our patients was that for the chemotherapy only treatment groups, from 2018 to 2021, this has increased from about 33% of individuals receiving chemo only to 47%. Neoadjuvant treatment has also increased by about 6% over the past four years, and adjuvant treatment has decreased by about 20% over four years.
Taking a look at age, sex, insurance status, primary site of the tumor, such as renal pelvis versus ureteral, geographical location, and pathological stage all had significant associations with treatment. Patients in the CO group were generally older and more commonly male. Overall, no significant differences were seen in the Charlson Comorbidity Index.
Pathological response: complete pathological response was seen in about 7% of the patients assessed in the neoadjuvant arm. Partial response was seen among 16%. So about 23% had partial or complete response. Overall, the neoadjuvant group appeared to have exhibited the most favorable overall survival compared to their other counterparts at both the one-year and three-year points. So as you can see here, at about three years, 65% were alive, with overall survival in the neoadjuvant arm down to 53% for the adjuvant arm. And the chemotherapy only group had about 20% survival. And this is just a Kaplan-Meier curve showing this.
On multivariate analysis controlling for age, sex, and clinical stage, again, as seen with the overall survival of the adjuvant group and the chemotherapy only group, both had inferior overall survival compared to the neoadjuvant group. So overall, this appears to show that neoadjuvant chemotherapy has optimal survival outcomes in patients with node positive upper tract urothelial cancer. Again, taking note that this is a database review with what we all know that the NCDB isn’t perfect, but it just gives us a glimpse of what can be seen.
Also, one thing is that surgical consolidation appears to still be an important component in the treatment of node positive disease, as chemotherapy only confers worse survival across both groups. But one must also consider if we’re losing patients who receive chemotherapy up front. As you can see, the numbers have gone up for chemotherapy only groups and neoadjuvant groups, while there’s a decrease in the adjuvant group. So are we losing patients to disease progression or surgical ineligibility? So that’s something that needs to be further addressed in future studies as well. Thank you.
Sam Chang: Joon, great presentation. Whenever you look at these databases, just as you said, it gives you a glimpse of the real world. But it also begs questions on what really is going on with these patients. Do you think that overall, this decline in adjuvant chemotherapy use, is that just a reflection of patient selection? Is it a reflection of truly disease characteristics and changes? Or is it the shift towards doing other forms of therapy? What do you think is really going on?
Joon Kyung Kim: I think it’s a mixed picture. I think it is a shift that more people are considering neoadjuvant therapy. There’ve been several, again, prospective and retrospective studies that have seen the benefits in neoadjuvant therapy. The big importance of this is that a lot of individuals, up to 85%, can become ineligible post-operatively after the removal of their kidney. This can be changed if you change GFR parameters to 45. About 85% can be eligible preoperatively if you change parameters to 45 on certain studies. So that can provide some at least cisplatin treatment for these individuals before they lose ineligibility after getting their kidney removed.
Sam Chang: So at UK, if you have a patient in this particular kind of clinical situation where there’s concern for lymph node positive disease, more advanced disease, tell me kind of how you guys evaluate these patients and what your next steps are?
Joon Kyung Kim: Big part of it is it’s such a rare disease. So these are only coming in a handful a year, especially out of a smaller, more rural population is generally where we see this node positive disease. Oftentimes, we have to see their survival, how late, how much progressed they present. Oftentimes, we’ll get medical oncology involved and have a multidisciplinary discussion tumor board. More generally than not, offer chemotherapy.
Just again, a lot of these individuals that come with regional disease have worsened GFR as much of their kidneys have already been knocked off by disease. And a lot of the patient populations that are more prone to, although there was no Charlson Comorbidity Index difference seen in our NCDB study, oftentimes people with these more regionally or locally advanced diseases are more likely to have these comorbidities just given lack of health care, socioeconomic status, and things like that. So we try to get them consolidated, just again with how guidelines mention, and attempt systemic treatment, try to get them down stage as best as possible to give them the best shot.
Sam Chang: Now, I think you mentioned some key points. Multidisciplinary evaluation, basically not only a consolidation of opinion, but a consolidation then of therapy, and then post systemic therapy, which we tend to also use as the therapy of choice. But emphasizing the individual situation. Are they really symptomatic? Is the burden of disease really in the primary versus the lymph nodes, et cetera? All those things come into play.
And in those patients, if you perpetuate those that respond, you tend to do more as opposed to just the opposite, just as your study shows. The patients that tend to progress get less treatment. Survival tends to be shorter. It all fits along the line of disease progression. And so where do we go next, Joon? What’s y’all’s next study in terms of looking at upper tract disease?
Joon Kyung Kim: I think one interesting thing right now is, again, just with all of urothelial carcinoma, the sort of explosion of immunotherapy and its treatments and how beneficial it’s been for all stages, whether it’s local disease or metastatic disease with EV pembro in the urothelial space. Again, they’re the same disease, but also very distinct subtypes of the same disease. But there are studies looking at immunotherapy that have shown benefits with pathological response.
It’s such a rare disease. And a lot of these retrospective studies take years, even up to a decade, to gather all the patients with a collaborative or consortium. But it’ll be very interesting to see. There’s a few randomized controlled studies looking at neoadjuvant with adjuvant with the MSK group, and I believe an ECOG Toronto group, that are trying to look at comparing the two. So it’d be very interesting to see what comes out. And also adding there’s several immuno studies up in clinical trials recruiting, trying to see whether adding durvalumab or pembrolizumab can help benefit these patients.
Sam Chang: Well, Joon, thanks for again enlightening us with and your colleagues’ evaluation of the NCDB, looking at upper tract disease and the role of combination of systemic and surgical consolidation. I think it adds to our literature, obviously, but also adds to our knowledge base regarding how we should be evaluating these patients and treating them. So we look forward to future contributions. And thanks for spending some time with us on UroToday.
Joon Kyung Kim: Yeah, thank you so much for having me.
Sam Chang: Hi, my name is Sam Chang. I'm a urologist in Nashville, Tennessee, at Vanderbilt University Medical Center. And we are quite honored to have a rising star in urology, Dr. Joon Kim, who's a resident at the University of Kentucky and pursuing a urologic oncology fellowship. I've known Joon for several years now as he's pursued a career in urologic oncology.
And he's going to give highlights of a presentation given at ASCO GU 2025, looking at actually the role of surgery and evaluation following actually different types of therapies for those patients who are thought to have more advanced disease and upper tract urothelial carcinoma. So Joon, thanks so much for spending some time with us, and we look forward to your presentation.
Joon Kyung Kim: Thank you so much for having me be able to present our data that we took a look at with evaluation of systemic therapy and surgical consolidation in patients with node positive upper tract urothelial carcinoma.
As you all know, upper tract urothelial carcinoma accounts for about 5% to 10% of upper tract cases. More than 50% of cases can be invasive at initial diagnosis, and up to 2/3 are high grade. Treatment for high grade UTUC often involves a radical nephroureterectomy with regional lymph node dissection. And post-operatively, node positive disease can be present in up to 25% of patients.
Timing of perioperative systemic therapy is multifactorial. A lot of this has stemmed from, been extrapolated from bladder cancer treatments. As you know, they’re both sort of a very similar disease also, but very distinct diseases for lower bladder cancer versus upper tract. Level one evidence currently exists only for the adjuvant space, and that’s with the recent POUT trial that showed benefits.
As for the neoadjuvant setting, again, a lot of these paradigms have been extrapolated from muscle invasive disease. Recently there’s been two phase II trials with Dr. Coleman and Dr. Margulis that have shown evidence of pathological response with favorable survival outcomes.
For node positive disease, regionally advanced disease, the treatment guidelines are even more unclear. Currently, the AUA and EAU guidelines recommend offering systemic therapy with consideration of consolidative surgery among individuals with partial or complete responses. So there’s nothing really distinct in that group to provide guidance.
So what we did was take a look at NCDB between 2018 and 2021, just to see how people are being treated up front or around for the management of this disease. So individuals with N1 through 3 disease were identified on non-metastatic and were looked at from individuals that received chemotherapy with or without nephroureterectomy.
And these were stratified into three groups, which included chemotherapy only, neoadjuvant chemotherapy, followed by a nephu, and nephu followed by adjuant chemo. This is just the flow diagram of our study population. And about 495 for the chemotherapy only, 411 for the nephu followed by chemo, and chemo followed by nephu about 297.
So what we saw amongst our patients was that for the chemotherapy only treatment groups, from 2018 to 2021, this has increased from about 33% of individuals receiving chemo only to 47%. Neoadjuvant treatment has also increased by about 6% over the past four years, and adjuvant treatment has decreased by about 20% over four years.
Taking a look at age, sex, insurance status, primary site of the tumor, such as renal pelvis versus ureteral, geographical location, and pathological stage all had significant associations with treatment. Patients in the CO group were generally older and more commonly male. Overall, no significant differences were seen in the Charlson Comorbidity Index.
Pathological response: complete pathological response was seen in about 7% of the patients assessed in the neoadjuvant arm. Partial response was seen among 16%. So about 23% had partial or complete response. Overall, the neoadjuvant group appeared to have exhibited the most favorable overall survival compared to their other counterparts at both the one-year and three-year points. So as you can see here, at about three years, 65% were alive, with overall survival in the neoadjuvant arm down to 53% for the adjuvant arm. And the chemotherapy only group had about 20% survival. And this is just a Kaplan-Meier curve showing this.
On multivariate analysis controlling for age, sex, and clinical stage, again, as seen with the overall survival of the adjuvant group and the chemotherapy only group, both had inferior overall survival compared to the neoadjuvant group. So overall, this appears to show that neoadjuvant chemotherapy has optimal survival outcomes in patients with node positive upper tract urothelial cancer. Again, taking note that this is a database review with what we all know that the NCDB isn’t perfect, but it just gives us a glimpse of what can be seen.
Also, one thing is that surgical consolidation appears to still be an important component in the treatment of node positive disease, as chemotherapy only confers worse survival across both groups. But one must also consider if we’re losing patients who receive chemotherapy up front. As you can see, the numbers have gone up for chemotherapy only groups and neoadjuvant groups, while there’s a decrease in the adjuvant group. So are we losing patients to disease progression or surgical ineligibility? So that’s something that needs to be further addressed in future studies as well. Thank you.
Sam Chang: Joon, great presentation. Whenever you look at these databases, just as you said, it gives you a glimpse of the real world. But it also begs questions on what really is going on with these patients. Do you think that overall, this decline in adjuvant chemotherapy use, is that just a reflection of patient selection? Is it a reflection of truly disease characteristics and changes? Or is it the shift towards doing other forms of therapy? What do you think is really going on?
Joon Kyung Kim: I think it’s a mixed picture. I think it is a shift that more people are considering neoadjuvant therapy. There’ve been several, again, prospective and retrospective studies that have seen the benefits in neoadjuvant therapy. The big importance of this is that a lot of individuals, up to 85%, can become ineligible post-operatively after the removal of their kidney. This can be changed if you change GFR parameters to 45. About 85% can be eligible preoperatively if you change parameters to 45 on certain studies. So that can provide some at least cisplatin treatment for these individuals before they lose ineligibility after getting their kidney removed.
Sam Chang: So at UK, if you have a patient in this particular kind of clinical situation where there’s concern for lymph node positive disease, more advanced disease, tell me kind of how you guys evaluate these patients and what your next steps are?
Joon Kyung Kim: Big part of it is it’s such a rare disease. So these are only coming in a handful a year, especially out of a smaller, more rural population is generally where we see this node positive disease. Oftentimes, we have to see their survival, how late, how much progressed they present. Oftentimes, we’ll get medical oncology involved and have a multidisciplinary discussion tumor board. More generally than not, offer chemotherapy.
Just again, a lot of these individuals that come with regional disease have worsened GFR as much of their kidneys have already been knocked off by disease. And a lot of the patient populations that are more prone to, although there was no Charlson Comorbidity Index difference seen in our NCDB study, oftentimes people with these more regionally or locally advanced diseases are more likely to have these comorbidities just given lack of health care, socioeconomic status, and things like that. So we try to get them consolidated, just again with how guidelines mention, and attempt systemic treatment, try to get them down stage as best as possible to give them the best shot.
Sam Chang: Now, I think you mentioned some key points. Multidisciplinary evaluation, basically not only a consolidation of opinion, but a consolidation then of therapy, and then post systemic therapy, which we tend to also use as the therapy of choice. But emphasizing the individual situation. Are they really symptomatic? Is the burden of disease really in the primary versus the lymph nodes, et cetera? All those things come into play.
And in those patients, if you perpetuate those that respond, you tend to do more as opposed to just the opposite, just as your study shows. The patients that tend to progress get less treatment. Survival tends to be shorter. It all fits along the line of disease progression. And so where do we go next, Joon? What’s y’all’s next study in terms of looking at upper tract disease?
Joon Kyung Kim: I think one interesting thing right now is, again, just with all of urothelial carcinoma, the sort of explosion of immunotherapy and its treatments and how beneficial it’s been for all stages, whether it’s local disease or metastatic disease with EV pembro in the urothelial space. Again, they’re the same disease, but also very distinct subtypes of the same disease. But there are studies looking at immunotherapy that have shown benefits with pathological response.
It’s such a rare disease. And a lot of these retrospective studies take years, even up to a decade, to gather all the patients with a collaborative or consortium. But it’ll be very interesting to see. There’s a few randomized controlled studies looking at neoadjuvant with adjuvant with the MSK group, and I believe an ECOG Toronto group, that are trying to look at comparing the two. So it’d be very interesting to see what comes out. And also adding there’s several immuno studies up in clinical trials recruiting, trying to see whether adding durvalumab or pembrolizumab can help benefit these patients.
Sam Chang: Well, Joon, thanks for again enlightening us with and your colleagues’ evaluation of the NCDB, looking at upper tract disease and the role of combination of systemic and surgical consolidation. I think it adds to our literature, obviously, but also adds to our knowledge base regarding how we should be evaluating these patients and treating them. So we look forward to future contributions. And thanks for spending some time with us on UroToday.
Joon Kyung Kim: Yeah, thank you so much for having me.