The Impact of Upper Tract Urothelial Cancer Treatments Based on the National Cancer Database’s Findings

Eun-mi Yu, MD, from the Inova Schar Cancer Institute, in Fairfax, VA, details her research on upper tract urothelial cancer treatments presented at the 2023 ASCO Annual Meeting, and how insight into the different features of metastatic presentation can be educational.

Transcript:

Eun-mi Yu, MD: Hello. I'm Eun-mi Yu. I'm a genitourinary medical oncologist at the Innova Shar Cancer Institute. My colleagues, Dr Aragon-Ching, Dr Wang and I completed this study here at Innova. I very much look forward to discussing our study and thank you very much for having me today. 

Can you give me some background for your study and what prompted you to undertake it?

Dr Yu: The primary objective of our study was to evaluate trends and differences between different types of cancers involving the urinary tract. Specifically, we looked at upper tract versus bladder, urothelial and non-urothelial cancers, such as squamous, sarcomatoid, small cell or neuroendocrine and adenocarcinomas. In general, upper tract and non-urothelial urinary tract cancers are less common and portend a worse prognosis compared to primary bladder urothelial cancers. In the clinic responses to systemic therapies can vary widely, and, in particular, we have observed that patients presenting with visceral metastases tend not to respond as well to immune checkpoint inhibitors. So, we pursue this analysis to try to identify any differences in survival outcomes among the various types of urinary tract cancers patients present with.

Can you briefly describe how this study was conducted?

Dr Yu: So, we use the de-identified data set from the national cancer database acquired from 2004 to 2017. We looked into the demographics presenting stage response to treatment and survival outcomes of bladder and upper tract, urothelial cancers and non-urothelial cancers. We captured urothelial carcinoma cases by including urothelial carcinoma, not otherwise specified transitional cell carcinoma. Papillary transitional cell carcinoma and spindle cell trapped transitional cell carcinomas in research for non-urothelial histologies. We included sinus and adenocarcinomas, adenocarcinoma papillary, adeno carcinomas with mixed up types. Neuroendocrine carcinomas not otherwise specified, large and small cell carcinomas and not otherwise specified characterizing and spindle cell types and squamous. We use the Chi-square test, the capital Myer method, and log rank test for data analysis.

And what were the key findings of this study?

Dr Yu: A total of 649,939 cases, of whom 603,423 were urothelial and 19,516 patients were non-urothelial, or both bladder and upper tract cancers were identified. 62% of your urothelial and 58% of non-urothelial cases were men. The Median age at diagnosis was similar between urothelial and nonurothelial carcinoma patients at 71.4 and 70.1 years respectively. So a greater proportion of non-urothelial cases presented with stage 3 or 4 disease compared to urothelial cases among patients presenting with stage 4 disease, overall survival was worse for non-urothelial cancer patients. The median overall survival was 6.14 months in stage 4 non-urothelial patients compared to almost 8 months for urothelial carcinoma patients, but in static sites, evaluated, included bone, brain, liver, lung, and distant lymph nodes. The median overall survival was longest for those with urothelial carcinomas and distant lymph node metastases. Patients with visceral metastases comparatively did more poorly. Patients with lung metastases tended to do better than those with liver, bone and brain metastases, with the exception of patients with non-urothelial cancers, who appear to have a longer median overall survival. If they had bone metastases compared to other sites of metastases. Also, the use of chemotherapy appeared to result in an improved overall survival to a greater extent in nonurothelial versus urothelial cancer patients with a median overall survival of 73.5 months versus 17.3 months respectively and for patients treated with immunotherapy, the median overall survival was 116 months for urothelial carcinoma patients and 64.5 months for non-urothelial patients.

How do you think your research will impact future analysis on effects of treatment and patterns of metastasis for upper tract urothelial cancer?

Dr Yu: I think this study highlights a few areas of unmet need in genitourinary oncology. While there has been significant progress in the treatment of advanced urothelial cancers, there's no clear standard of care for patients with non-urothelial histologies in particular. We hope that our findings increase awareness of patients with less common cancers involving the urinary tract who need more effective treatment strategies.

Can you explain further why patients with distant lymph nodes have a slightly better overall survival rate?

Dr Yu: So that's a very good question we don't have a clear explanation for this, but this is a pattern that has been observed and well documented in other solitude malignancies, including prostate cancer as an example. I think that at least in part it may be a reflection of the heterogeneity of urinary tract tumors and tumor microenvironments. Perhaps cancer cells that metastasize to lymph nodes may behave more indolently compared to those that spread to other organs due to the biology of the tumor itself, as well as the characteristics of the metastatic site. This is certainly something that should be studied further.