Neoadjuvant Versus Adjuvant Chemotherapy in Patients With Clinically Node-positive UTUC Who Underwent a Radical Nephroureterectomy - Karan Jatwani

March 27, 2023

Sam Chang and Karan Jatwani discuss a study looking at the impact of neoadjuvant or adjuvant chemotherapy for patients with invasive disease, T2 disease, and the role of nephroureterectomy and how these treatments may impact findings. The study analyzed the NCDB database from 2004 to 2018 and found that neoadjuvant chemotherapy use was associated with a significantly improved overall survival hazard among patients with clinically node-positive UTUC who underwent a radical nephroureterectomy. The findings may improve patient selection for future trials in the perioperative setting.


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

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Sam Chang: Hi, I'm Sam Chang. I'm a urologic surgeon at Vanderbilt in Nashville, Tennessee, and I'm here today with Karan Jatwani. Karan is a second year fellow. He and I have just met. But you have no idea how impressed I am with two different abstracts that were presented at GU ASCO 2023. So let's talk about one of them. All right?

Karan Jatwani: Sure.

Sam Chang: One of the abstracts that you all have presented is looking at the impact of neoadjuvant or adjuvant chemotherapy for patients with invasive disease, T2 disease, and the role of nephroureterectomy and how these treatments may impact findings. So give us an idea, a summary of your findings, and then we'll talk about maybe some questions after that.

Karan Jatwani: Sure. Thank you so much for the kind introduction. As you mentioned, I'm a second year fellow and I'm currently working at Roswell Park. And the project was with my mentor, Dr. Dharmesh Gopalakrishnan. And we were trying to look at, given how neoadjuvant chemotherapy is a debatable topic in upper tract urothelial cancer, we were trying to see if there is any difference in overall survival in patients who have gotten a neoadjuvant therapy versus adjuvant chemotherapy. So we essentially looked at locally advanced upper tract population. We included patients with any T stage and nodes one to three, but they were M0 and who have undergone radical nephroureterectomy. And we looked at patients who have received neoadjuvant versus adjuvant. And we analyzed the NCDB database, that's the National Cancer Database, from the years of 2004 to 2018. And we found out around 860 patients, around 500 of those have undergone adjuvant chemotherapy and 300 had gotten neoadjuvant chemotherapy.

Sam Chang: So you searched under... Your initial search variable was who underwent nephroureterectomy, correct?

Karan Jatwani: That is correct. That is correct.

Sam Chang: So immediately, you have the assumption that, okay, these patients are at least fit to go through nephroureterectomy.

Karan Jatwani: Exactly. Exactly. And given radical nephroureterectomy could end up leaving these patients to be ineligible later on in the adjuvant setting, we just wanted to see if there is any difference in mortality. And we saw that the overall survival in the neoadjuvant group was 47 months versus in the adjuvant group that was only 20 months. That was statistically significant. And we saw that this was... We did a multivariable regression and we saw that even after controlling for all the factors, including clinical T stage, this data was significant.

Sam Chang: Did you include performance status?

Karan Jatwani: Yes. We did include performance status, and we did include charts and comorbidity index.

Sam Chang: So you tried to match them as well as possible taking into account common factors that could impact on survival.

Karan Jatwani: Exactly.

Sam Chang: And because you always worry about some type of selection bias. But in looking at that, then those individuals that received neoadjuvant obviously fit enough to get that and that nephroureterectomy, but their survival was significantly different compared to those that received adjuvant.

Karan Jatwani: Yeah. And I think, again, all these datas have to be interpreted with caution and with-

Sam Chang: Sure. Hypothesis generating, for sure.

Karan Jatwani: Exactly. I think the whole idea was that this would probably improve the selection of the patient in the future and giving us some idea that actually neoadjuvant might be more beneficial than the adjuvant. And hopefully, this would yield into future trials in the more thoroughly setting of the perioperative setting than later.

Sam Chang: Curiously, I was wondering, did you ever look in that cohort that didn't receive neoadjuvant and did not receive adjuvant and just received nephroureterectomy for locally advanced disease?

Karan Jatwani: So that's a really good point, and that was one of the feedbacks that we got during our poster discussion this morning. And we are going to include that in the publication. So we are going to divide them into three groups in our publication, and we are going to look at all three groups.

Sam Chang: Do you have any idea? Can you share with us the findings? I know you don't want to be-.

Karan Jatwani: No. Honestly, because the thing is that even while selecting the group, we honestly did not look at that data. But this is more of an afterthought now that we are going to look at it once we go back.

Sam Chang: My only thought behind that is, yes, you've under gone this nephroureterectomy. Clearly, you have high volume, high risk disease. And then hence you get the chemotherapy, making the assumption, clearly you've got more advanced disease.

Karan Jatwani: Yes.

Sam Chang: In the neoadjuvant arm, there may be a percentage of patients that weren't as locally advanced, et cetera. But still, it's very much intriguing in terms of hypothesis generation. And what I always like to say is whenever there's hypothesis generating data that supports my biases, I support it 110%. But our bias has been in those patients with disease that we are worried about. We're worried about the loss of ability to give cisplatin-based chemotherapy.

Karan Jatwani: Cisplatin later on. Yep.

Sam Chang: We tend to lean towards neoadjuvant, understanding the impact of level one evidence. So what do you all do now at Roswell Park?

Karan Jatwani: So we essentially give patient gemcitabine-cisplatin for full cycle in these patients.

Sam Chang: And you tend to give it in the neoadjuvant setting?

Karan Jatwani: So again, it's clinician dependent. It's clinician dependent. Now again, the patient selection does come into play. So a lot of these patients would get upstaged during surgery, and then that can change the treatment decision later on. So that has to be... And this was something that we have been discussing even with my mentors and even during the poster session, that staging in upper tract is quite hard.

Sam Chang: It's very difficult.

Karan Jatwani: And we need better imaging modalities to improve that because that will essentially make our patient selection better.

Sam Chang: Your next research project, I'm looking forward to the findings from that. But Dr. Jatwani, thank you so much for spending some time with us. And kudos on your excellent work.

Karan Jatwani: Thank you so much. Thank you.