The Role of Adjuvant Chemotherapy, Versus Observation, in Patients With Upper Urinary Tracts With Variant Histology Undergoing a Radical Nephroureterectomy - Karan Jatwani
March 27, 2023
Sam Chang and Karan Jatwani discuss the role of adjuvant chemotherapy, versus observation, in patients with upper urinary tracts with variant histology undergoing a radical nephroureterectomy. The study, which analyzed data from the National Cancer Database from 2004 to 2018, found no difference in overall survival between patients who received chemotherapy and those who did not. The study focused on a rare disease with rare subtypes and did not examine chemotherapy regimens. Drs. Chang and Jatwani discuss how the data may be used in clinical practice.
Biographies:
Karan Jatwani, MBBS, Hematology and Oncology Fellow, Roswell Park Comprehensive Cancer Center, Buffalo, NY
Sam S. Chang, M.D., M.B.A. Patricia and Rodes Hart Endowed Chair of Urologic Surgery Professor Department of Urology at Vanderbilt University Medical Center
Biographies:
Karan Jatwani, MBBS, Hematology and Oncology Fellow, Roswell Park Comprehensive Cancer Center, Buffalo, NY
Sam S. Chang, M.D., M.B.A. Patricia and Rodes Hart Endowed Chair of Urologic Surgery Professor Department of Urology at Vanderbilt University Medical Center
Read the Full Video Transcript
Sam Chang: Hi, I'm Sam Chang. I'm a urologic surgeon at Vanderbilt University and that's in Nashville, Tennessee. I'm fortunate here to have Dr. Karan Jatwani. Karan is actually a second year fellow in hematology oncology at Roswell Park, and he's going to be discussing actually, one of the two abstracts that he'd had to present at GU ASCO 2023. And this one looks at actually, kind of a small cohort of patients, patients that have varying histologies at the time of nephroureterectomy.
Karan Jatwani: Yes.
Sam Chang: And the impact of actually, adjuvant chemotherapy or chemotherapy versus observation. And these were in node negative patients, correct?
Karan Jatwani: That is correct.
Sam Chang: Right.
Karan Jatwani: That is correct.
Sam Chang: So give us an overview. Tell us what you found.
Karan Jatwani: Yeah. We were essentially, looking at patients who had muscle invasive disease, but no negative. And we were trying to see, especially in the variant histology population that has been associated with inferior outcomes to begin with, and if there was any difference in, if they have undergone radical nephroureterectomy and they have received adjuvant chemotherapy after, or they were just put on observation, which is also a fairly commonly used strategy. And we looked at the data from 2004 to 2018 in NCDB and we found-
Sam Chang: National Cancer Database.
Karan Jatwani: Mm-hmm. National Cancer.
Sam Chang: Which more than 70% of patients with cancers of all types are treated at NCDB facilities.
Karan Jatwani: That is correct.
Sam Chang: And the findings that included what?
Karan Jatwani: So essentially, we found out around 500 patients, 520 patients, which again, tells you that how rare this disease is, over the course of 15 years. And around 380 patients underwent observation, and only 140 of them underwent adjuvant chemotherapy. And in that, we found out that there was no difference between, in overall survival, in patients who have undergone observation versus adjuvant chemotherapy. Now this has again, comes with the caveat that, this is a retrospective database.
Sam Chang: Sure.
Karan Jatwani: And this does not include the findings from the POUT trial, because POUT trial was recently published, and this is still 2018. So from that aspect, again, this does generate interesting findings that, if there is no negative disease and muscle invasive disease, does adjuvant chemotherapy has any role in it or not?
Sam Chang: Right. Especially the variant histologies that you focused on. And then remind me, did the POUT trial basically, was an exclusion criteria-
Karan Jatwani: Yeah.
Sam Chang: ... to have variant histologies?
Karan Jatwani: Yeah.
Sam Chang: This is the first that I know of, because it is a upper tract disease, rare entity. You throw in varying histologies, rarer entities.
Karan Jatwani: Make it more rare. Exactly.
Sam Chang: Now knowing and looking at NCDB database, it's very hard to get too granular. Are you able to tell if it was cisplatinum versus carboplatin, or any type of specific chemotherapy regimens?
Karan Jatwani: Yeah. I think, that's one of the limitations that the granularity come for chemotherapy regimens we couldn't get, but we did get histologies, and we noticed that patients who had small cell histology, or micropapillary or adenocarcinoma histology, they were more likely to get adjuvant chemotherapy.
Sam Chang: Sure.
Karan Jatwani: And also, patients who were younger, significantly got more adjuvant chemotherapy than patients who were older. Again, these were all, this is before any control. This is before any regression was done. And once we controlled for every factor, we saw that there was no difference between these two-
Sam Chang: Right.
Karan Jatwani: ... in terms of overall survival.
Sam Chang: Well, just as you said, this type of study raises questions, raises thoughts, is not in any way definitive, but to be honest, it's going to be very difficult in this small population. It's almost like a rare, it is a rare tumor with rare subtypes. It will be difficult to succeed in any type of large scale prospective study.
Karan Jatwani: Yeah.
Sam Chang: It may happen. But if it doesn't, how do you all use this data now at Roswell Park? Say, I'm in Nashville, I perform a nephroureterectomy. The nodes are negative. We've got a T2 cancer.
Karan Jatwani: Yeah.
Sam Chang: Margins are negative.
Karan Jatwani: Yeah.
Sam Chang: Bladder's clear.
Karan Jatwani: Yeah.
Sam Chang: Let's make it easy. Let's make, the GFR is still 52.
Karan Jatwani: Yeah.
Sam Chang: So could get platinum based.
Karan Jatwani: Yeah.
Sam Chang: Or depending on upon the subtype, whatever.
Karan Jatwani: Yeah.
Sam Chang: So if I have that patient and I'm just treating them, what should I do with him or her?
Karan Jatwani: I think, again, this is particularly where I feel the shared patient decision making comes into play. Because you have to be honest with your patients, and disclose to them that, we don't have good data. And this is a rare disease-
Sam Chang: Sure.
Karan Jatwani: ... as you mentioned. And we don't know if there would be micrometastatic disease there or not. Now the flip side is that, you might have side effects from the chemotherapy itself. So if you have a grade two neuropathy, or if you have poor renal function, would you want them to go through this? Again, it depends on the clinician, but probably not. Right?
Sam Chang: Right.
Karan Jatwani: So these are the things where, I think, shared participation decision making plays a critical role. Because there will be disease states where we might not have the best data, and this just tells you that we are facing a critical need to have a better way of selecting patients whom we can give these therapies, which can potentially be harmful for those patients.
Sam Chang: So right, I think that discussion with the patient of, we don't really know. Here are the possibilities.
Karan Jatwani: Yeah.
Sam Chang: We could do surveillance.
Karan Jatwani: Yeah.
Sam Chang: We could give adjuvant chemotherapy.
Karan Jatwani: Yeah.
Sam Chang: Now how about throwing this out at you? What about adjuvant nivolumab in this population? So only 20% in that trial.
Karan Jatwani: In the trial, yeah.
Sam Chang: We can't really tease out specifics.
Karan Jatwani: Yeah.
Sam Chang: And also, didn't include variant histologies.
Karan Jatwani: Yeah, that's true.
Sam Chang: So you have all these, these are the patients you discuss in tumor board.
Karan Jatwani: Yeah. Exactly.
Sam Chang: These are the patients that, you go over specific things about patient desires, risks, et cetera.
Karan Jatwani: Yeah. Yeah. Yeah.
Sam Chang: Well, thank you so much for talking about your data.
Karan Jatwani: Yeah, for sure.
Sam Chang: Thank you for raising questions.
Karan Jatwani: Thank you so much.
Sam Chang: Any study that raises more questions always-
Karan Jatwani: Always.
Sam Chang: ... is, I think, of benefit. And is this in any way affecting or changing the practice now at Roswell Park?
Karan Jatwani: I think it would be, again, as you said, that these just raises questions and makes, these are hypothesis generating questions. Changing practice, I think, you can only rely on the better evidence, right? And this is a retrospective study. I know in the past also, there are certain disease states where we use retrospective data as in evidence.
Sam Chang: Right.
Karan Jatwani: But I think in this case, I would say that it would be hard for us to be completely black and white and say, "Okay, there is no overall survival benefit, and we are not going to go ahead and do the chemotherapy with you."
Sam Chang: Understood.
Karan Jatwani: I think it will make you pause and make you think for sure but, for each patient, but I don't know if we can completely change the paradigm based on this.
Sam Chang: Great. Well thanks again for your work, and spending some time with us. And we look forward to future studies-
Karan Jatwani: Thank you so much.
Sam Chang: ... as you finish your fellowship.
Karan Jatwani: Yes.
Sam Chang: And look forward to your career rise.
Karan Jatwani: Thank you so much.
Sam Chang: Thanks very much.
Karan Jatwani: Thank you. Thank you.
Sam Chang: Hi, I'm Sam Chang. I'm a urologic surgeon at Vanderbilt University and that's in Nashville, Tennessee. I'm fortunate here to have Dr. Karan Jatwani. Karan is actually a second year fellow in hematology oncology at Roswell Park, and he's going to be discussing actually, one of the two abstracts that he'd had to present at GU ASCO 2023. And this one looks at actually, kind of a small cohort of patients, patients that have varying histologies at the time of nephroureterectomy.
Karan Jatwani: Yes.
Sam Chang: And the impact of actually, adjuvant chemotherapy or chemotherapy versus observation. And these were in node negative patients, correct?
Karan Jatwani: That is correct.
Sam Chang: Right.
Karan Jatwani: That is correct.
Sam Chang: So give us an overview. Tell us what you found.
Karan Jatwani: Yeah. We were essentially, looking at patients who had muscle invasive disease, but no negative. And we were trying to see, especially in the variant histology population that has been associated with inferior outcomes to begin with, and if there was any difference in, if they have undergone radical nephroureterectomy and they have received adjuvant chemotherapy after, or they were just put on observation, which is also a fairly commonly used strategy. And we looked at the data from 2004 to 2018 in NCDB and we found-
Sam Chang: National Cancer Database.
Karan Jatwani: Mm-hmm. National Cancer.
Sam Chang: Which more than 70% of patients with cancers of all types are treated at NCDB facilities.
Karan Jatwani: That is correct.
Sam Chang: And the findings that included what?
Karan Jatwani: So essentially, we found out around 500 patients, 520 patients, which again, tells you that how rare this disease is, over the course of 15 years. And around 380 patients underwent observation, and only 140 of them underwent adjuvant chemotherapy. And in that, we found out that there was no difference between, in overall survival, in patients who have undergone observation versus adjuvant chemotherapy. Now this has again, comes with the caveat that, this is a retrospective database.
Sam Chang: Sure.
Karan Jatwani: And this does not include the findings from the POUT trial, because POUT trial was recently published, and this is still 2018. So from that aspect, again, this does generate interesting findings that, if there is no negative disease and muscle invasive disease, does adjuvant chemotherapy has any role in it or not?
Sam Chang: Right. Especially the variant histologies that you focused on. And then remind me, did the POUT trial basically, was an exclusion criteria-
Karan Jatwani: Yeah.
Sam Chang: ... to have variant histologies?
Karan Jatwani: Yeah.
Sam Chang: This is the first that I know of, because it is a upper tract disease, rare entity. You throw in varying histologies, rarer entities.
Karan Jatwani: Make it more rare. Exactly.
Sam Chang: Now knowing and looking at NCDB database, it's very hard to get too granular. Are you able to tell if it was cisplatinum versus carboplatin, or any type of specific chemotherapy regimens?
Karan Jatwani: Yeah. I think, that's one of the limitations that the granularity come for chemotherapy regimens we couldn't get, but we did get histologies, and we noticed that patients who had small cell histology, or micropapillary or adenocarcinoma histology, they were more likely to get adjuvant chemotherapy.
Sam Chang: Sure.
Karan Jatwani: And also, patients who were younger, significantly got more adjuvant chemotherapy than patients who were older. Again, these were all, this is before any control. This is before any regression was done. And once we controlled for every factor, we saw that there was no difference between these two-
Sam Chang: Right.
Karan Jatwani: ... in terms of overall survival.
Sam Chang: Well, just as you said, this type of study raises questions, raises thoughts, is not in any way definitive, but to be honest, it's going to be very difficult in this small population. It's almost like a rare, it is a rare tumor with rare subtypes. It will be difficult to succeed in any type of large scale prospective study.
Karan Jatwani: Yeah.
Sam Chang: It may happen. But if it doesn't, how do you all use this data now at Roswell Park? Say, I'm in Nashville, I perform a nephroureterectomy. The nodes are negative. We've got a T2 cancer.
Karan Jatwani: Yeah.
Sam Chang: Margins are negative.
Karan Jatwani: Yeah.
Sam Chang: Bladder's clear.
Karan Jatwani: Yeah.
Sam Chang: Let's make it easy. Let's make, the GFR is still 52.
Karan Jatwani: Yeah.
Sam Chang: So could get platinum based.
Karan Jatwani: Yeah.
Sam Chang: Or depending on upon the subtype, whatever.
Karan Jatwani: Yeah.
Sam Chang: So if I have that patient and I'm just treating them, what should I do with him or her?
Karan Jatwani: I think, again, this is particularly where I feel the shared patient decision making comes into play. Because you have to be honest with your patients, and disclose to them that, we don't have good data. And this is a rare disease-
Sam Chang: Sure.
Karan Jatwani: ... as you mentioned. And we don't know if there would be micrometastatic disease there or not. Now the flip side is that, you might have side effects from the chemotherapy itself. So if you have a grade two neuropathy, or if you have poor renal function, would you want them to go through this? Again, it depends on the clinician, but probably not. Right?
Sam Chang: Right.
Karan Jatwani: So these are the things where, I think, shared participation decision making plays a critical role. Because there will be disease states where we might not have the best data, and this just tells you that we are facing a critical need to have a better way of selecting patients whom we can give these therapies, which can potentially be harmful for those patients.
Sam Chang: So right, I think that discussion with the patient of, we don't really know. Here are the possibilities.
Karan Jatwani: Yeah.
Sam Chang: We could do surveillance.
Karan Jatwani: Yeah.
Sam Chang: We could give adjuvant chemotherapy.
Karan Jatwani: Yeah.
Sam Chang: Now how about throwing this out at you? What about adjuvant nivolumab in this population? So only 20% in that trial.
Karan Jatwani: In the trial, yeah.
Sam Chang: We can't really tease out specifics.
Karan Jatwani: Yeah.
Sam Chang: And also, didn't include variant histologies.
Karan Jatwani: Yeah, that's true.
Sam Chang: So you have all these, these are the patients you discuss in tumor board.
Karan Jatwani: Yeah. Exactly.
Sam Chang: These are the patients that, you go over specific things about patient desires, risks, et cetera.
Karan Jatwani: Yeah. Yeah. Yeah.
Sam Chang: Well, thank you so much for talking about your data.
Karan Jatwani: Yeah, for sure.
Sam Chang: Thank you for raising questions.
Karan Jatwani: Thank you so much.
Sam Chang: Any study that raises more questions always-
Karan Jatwani: Always.
Sam Chang: ... is, I think, of benefit. And is this in any way affecting or changing the practice now at Roswell Park?
Karan Jatwani: I think it would be, again, as you said, that these just raises questions and makes, these are hypothesis generating questions. Changing practice, I think, you can only rely on the better evidence, right? And this is a retrospective study. I know in the past also, there are certain disease states where we use retrospective data as in evidence.
Sam Chang: Right.
Karan Jatwani: But I think in this case, I would say that it would be hard for us to be completely black and white and say, "Okay, there is no overall survival benefit, and we are not going to go ahead and do the chemotherapy with you."
Sam Chang: Understood.
Karan Jatwani: I think it will make you pause and make you think for sure but, for each patient, but I don't know if we can completely change the paradigm based on this.
Sam Chang: Great. Well thanks again for your work, and spending some time with us. And we look forward to future studies-
Karan Jatwani: Thank you so much.
Sam Chang: ... as you finish your fellowship.
Karan Jatwani: Yes.
Sam Chang: And look forward to your career rise.
Karan Jatwani: Thank you so much.
Sam Chang: Thanks very much.
Karan Jatwani: Thank you. Thank you.