Reverse-thermal mitomycin gel (UGN-101) was recently approved by the United States Food and Drug Administration (FDA) as a kidney-sparing treatment modality for low-grade noninvasive upper tract urothelial carcinoma (UTUC) [1]. The availability and approval of this therapy were propelled by results from the OLYMPUS trial, which demonstrated that 58% of patients had a complete response to induction therapy, half of whom continued to have no evidence of disease after 12 mo [2], [3]. However, the OLYMPUS trial required patients to have residual UTUC lesions and excluded patients with poor performance status, coexisting bilateral UTUC, and an estimated glomerular filtration rate (eGFR) of <30 ml/min [2]. Considering these exclusions, uncertainties arose regarding the generalizability of these results in clinical practice, in which patients have various comorbidities and indications for therapy.

Post-commercialization studies have confirmed that these concerns are relevant, revealing that administration indications, techniques, and patient factors are quite heterogeneous and differ from those in the original OLYMPUS trial cohort [4]. These variations included the administration route (antegrade vs retrograde) [5], use of UGN-101 as a chemoablative versus an adjuvant agent [6], and the presence of high-grade and superficially invasive disease [4], [5]. Most importantly, these real-world data have highlighted the use of UGN-101 in patients with “imperative” indications for therapy, that is, patients in whom nephroureterectomy (RNU) is not a viable option. Prior studies have defined imperative indications to include patients who would be functionally anephric after RNU, such as those with a solitary kidney, bilateral UTUC, or renal insufficiency, and those not eligible for surgery [7], [8], [9]. These select patients deserve a personalized approach for management of their malignancy, as corroborated by the European Association of Urology (EAU) recommendation of kidney-sparing management options for patients with a solitary kidney or impaired renal function, assuming that no compromise to survival will occur [10]. Taken together, the evidence indicates that further study is critically needed to better understand the role of UGN-101 for UTUC in this comorbid population.

With this in mind, we sought to examine the use, efficacy, and safety profile of UGN-101 in patients with UTUC and imperative indications for therapy. This will aid urologists in counseling patients with UTUC and these comorbidities, allowing patients to make informed decisions that balance oncologic control, risk of therapy, and the morbidity of end-stage renal disease.