Gem-doce and BCG yield similar outcomes for upper tract urothelial cell carcinoma

In this video, Ryan L. Steinberg, MD, discusses the background and notable findings from the Urologic Oncology paper “Sequential endoluminal gemcitabine and docetaxel vs. Bacillus Calmette–Guérin for the treatment of upper tract carcinoma in situ.” Steinberg is a clinical assistant professor of urology at the University of Iowa in Iowa City.

Transcription:

Please describe the background for this study.

As we all know, upper tract urothelial cell carcinoma is a pretty uncommon entity relative to urothelial cell carcinoma of the bladder, with worse oncologic outcomes, and the standard of care for many years has been radical nephroureterectomy when patients have high-risk lesions. But this has many side effects, both recovery after surgery as well as the risk for renal deterioration from removing 1 of the kidneys. And so selectively endoluminal treatments or topical therapy with things like BCG have been explored in select populations to try to prevent the need to remove the kidney and preserve that renal function. In this case, sequential gemcitabine and docetaxel is a couplet therapy that we have utilized here at the University of Iowa for many years, specifically for urothelial cell carcinoma of the bladder. And when BCG ultimately has gone on multiple shortages, we transition to utilizing the gemcitabine and docetaxel in select patients for their upper tract urothelial cell carcinoma. And in this paper, we report our findings with that assessment.

What were some of the notable findings? Were any of them surprising to you and your coauthors?

In this study, patients were treated either with BCG or gemcitabine and docetaxel at the discretion of the treating provider, and then we retrospectively in the study went and reviewed those who had been treated. We had found 27 patients that were treated with BCG and 26 that were treated with gemcitabine and docetaxel. We didn't have any significant differences between the groups with regards to risk factors for upper tract urothelial cell carcinoma, history of prior bladder cancer, or even the prior number of treatments that had been received if they had been treated in their bladder. Ultimately, we found that in this retrospective evaluation, there was no significant difference in recurrence-free survival in those who are treated with gemcitabine and docetaxel as compared to BCG, where roughly just over 50% of each were still recurrence free at 24 months. This is good initial data in a retrospective fashion to show or suggest that gemcitabine may or may not be able to be considered equivalent to BCG, but only future prospective trials would be needed to really identify whether that would be the case. One surprising finding that we did identify in this study is some patients were treated with retrograde catheter placement to instill the agents, and others received the treatments through a percutaneous nephrostomy tube. And at least on our multivariate analysis, which was somewhat limited by the smaller cohorts, we identified a hazard ratio nearly 4 times that for patients treated with nephrostomy tubes as compared to retrograde catheter placement. We don't definitively know why this is the case. We have a few theories; specifically, that when we did place the retrograde catheters for placement, we made a pretty concerted effort to have those placed into the upper pole of the kidney. And since the kidney naturally sits or tips slightly backwards,with the upper pole more posterior than the lower pole, this area may allow the kidney to better fill with the agent prior to drainage down the ureter and may ultimately lead to better coverage or actual contact of the agents with the urothelium. Similarly, nephrostomy tubes, given the concern often from interventional radiology, placing these and having a pleural injury, were preferentially placed often in the renal pelvis or potentially in the lower pole where certain parts of the kidney may not ultimately, if it was instilled in that way, come into contact with the agents. [It's] still unclear exactly what the mechanism of this is but definitely something that warrants more investigation.

This transcription was edited for clarity.