Sandip M. Prasad, MD, MPhil1; Mark Schoenberg, MD, FACS2,3; Michael J. Louie, MD, MPH, MSc2; Sunil Raju, MBBS2; Andrew Meads, BS2; Brent Burger, MSc, MBA2; Victoria Tsurutis, PharmD, BCPS, BCMAS2; Nikky Ugwuoke, PharmD, MPH2; Veronica Lee, MD, FACC2; John P. Sfakianos, MD4
1Morristown Medical Center/Atlantic Health System and Garden State Urology, Morristown, New Jersey
2UroGen Pharma, Princeton, New Jersey
3Albert Einstein College of Medicine, Bronx, New York
4Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York
KEYWORDS:
Urinary bladder neoplasms; mitomycin; patient care; administration, intravesical
Abstract
Background: Low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC) is characterized by high recurrence rates and low progression, typically occurring in older individuals (at least 70 years of age) with multiple comorbidities. Transurethral resection of bladder tumor, a common treatment for NMIBC performed under general anesthesia, is associated with well-documented risks. UGN-102, a reverse thermal hydrogel formulation of mitomycin, is approved for the treatment of recurrent low-grade, intermediate-risk NMIBC in adult patients. This nonsurgical treatment option is administered intravesically in an outpatient setting without general anesthesia.
Methods: This narrative review was informed by a literature search from 2015 to April 2025 using keywords “UGN-102,” “mitomycin and NMIBC,” “TURBT,” and “LG [low-grade]-IR [intermediate-risk]-NMIBC.” Ten unique publications were identified; additional relevant articles were written by the authors of this article.
Results: Across the reviewed clinical trials, the proportions of the 449 patients with newly diagnosed or recurrent low-grade, intermediate-risk NMIBC treated with UGN-102 who achieved complete response (negative cystoscopy; negative urine cytology; and negative for-cause biopsy, if indicated) at 3 months after the first instillation were consistently high (64.8%-79.6%). The durability of these responses was notable, with an 80.6% probability of remaining disease free at 18 months after 3-month complete response in the ENVISION trial and a median duration of response of 42.1 months based on extended follow-up of complete responders in the OPTIMA II trial. Adverse events across the UGN-102 studies were mild to moderate and predominantly localized to the lower urinary tract.
Conclusions: As an alternative to transurethral resection of bladder tumor, UGN-102 offers durable disease control with an acceptable side effect profile.
At presentation, approximately 75% of patients with bladder cancer are diagnosed with non–muscle-invasive bladder cancer (NMIBC),1,2 a heterogeneous group of cancers with a wide range of recurrence and progression probabilities.3 The typical age at diagnosis of bladder cancer is 70 to 74 years in men and 75 to 79 years in women. The majority of cases occur in White men.4,5 International guidelines recommend the stratification of NMIBC into low risk, intermediate risk, and high risk of recurrence or progression based on a range of clinical and pathologic factors to inform prognosis and guide treatment.1,3,6-8 The European Association of Urology recently included a fourth category of very high-risk NMIBC.9 Guidelines jointly issued by the American Urological Association and the Society of Urologic Oncology define intermediate-risk NMIBC as a low-grade T1 tumor, a solitary high-grade Ta nonrecurrent tumor smaller than 3 cm, or a low-grade Ta tumor with specific features (ie, recurrent within 1 year, large tumor size [>3 cm], or multifocal in nature).3,6,10 Low-grade, intermediate-risk NMIBC is often multifocal in nature, with a high risk of recurrence but a low risk of progression to muscleinvasive bladder cancer.3,10,11
Low-grade, intermediate-risk NMIBC is often treated with transurethral resection of bladder tumor (TURBT) under general anesthesia. Multiple repeat TURBTs are typically needed to treat this highly recurrent disease, highlighting the critical unmet need for an alternative, nonsurgical treatment that provides a longer recurrence-free interval while minimizing potential adverse events (AEs).12
For patients with low-grade, intermediate-risk NMIBC, adjuvant intravesical therapy with aqueous chemotherapeutic agents such as gemcitabine and mitomycin or with BCG vaccine should be considered as an adjuvant to TURBT.1-3
Aqueous mitomycin has a mechanism of tumor cell destruction ascribed to the inhibition of DNA synthesis.13 Most studies of mitomycin in NMIBC have been of aqueous formulations delivered intravesically in the adjuvant setting, but some studies have examined dose-intense regimens of 3 instillations per week for 2 weeks in the chemoablative setting.14 Intravesically administered aqueous gemcitabine has a dwell time of approximately 1 to 2 hours; it therefore seems likely that mitomycin has a similar dwell time when delivered as an aqueous solution.15 For these aqueous intravesical treatments, patients are usually advised not to void and to turn to optimize exposure of the entire bladder surface to the treatment. Although dose-intensive administration of intravesical aqueous mitomycin can achieve high complete response (CR) rates in patients with NMIBC, the need for frequent dose administration at short intervals is inconvenient and impractical both for patients and for treating health care professionals, and the treatment is often not durable.14
Recent research efforts have focused on alternative therapeutic approaches for intermediate-risk NMIBC that provide disease control while limiting morbidity and the negative effects of therapy on patients’ quality of life (QOL).16 Examples of new and investigational therapeutic approaches include novel drug-delivery systems such as UGN-102 for primary nonsurgical therapy and TAR-210 (erdafitinib), CG0070, and combination chemotherapy as adjuncts to TURBT.16
UGN-102 is a reverse thermal hydrogel containing mitomycin (75 mg in 56 mL), administered intravesically using a urethral catheter as a liquid under chilled conditions in an office or ambulatory setting (Figure 1). Routine urinary catheterization obviates the need for general anesthesia and its associated risks. The reverse thermal hydrogel converts to a semisolid depot when warmed to body temperature following instillation into the bladder. The semisolid gel depot dissolves in the urine. Patients reported visible gel in urine up to 24 hours (median, 5 hours) after instillation, allowing a sustained release of mitomycin and prolonged contact with the tumor cells (data on file). Reverse thermal hydrogel is especially useful for drug delivery in the bladder and upper urinary tract, where continuous dilution and excretion of aqueous medications through normal urine production and bladder voiding limit drug dwell time and, consequently, the therapeutic effect.
A pharmacokinetic study of UGN-102 administered through intravesical instillation in 6 patients with NMIBC found low systemic exposure to mitomycin, with a mean maximum serum plasma concentration at the target dose (75 mg) of 2.27 ng/mL (range, 0.19-8.94 ng/mL). This maximum, achieved approximately 2 hours following instillation, is less than 1% of the expected maximum serum plasma concentration after intravenous administration of mitomycin and is less than 1% of the mitomycin plasma concentration associated with myelosuppression (400 ng/mL).17
This article is a narrative review of the efficacy and safety results from late-phase clinical trials of UGN-102 to treat low-grade, intermediate-risk NMIBC in adult patients.
Figure 1. UGN-102 forms a semisolid gel when exposed to body temperature
This narrative review of the clinical efficacy and safety of UGN-102 in patients with low-grade, intermediaterisk NMIBC was informed by a literature search in the US National Library of Medicine’s PubMed database from 2015 to April 2025, using the keywords “UGN-102,” “mitomycin AND NMIBC,” “TURBT,” and “LG-IR [intermediate-risk]-NMIBC,” limited to clinical studies. Ten unique publications were identified. We added relevant articles compiled by the authors of this article and reviewed articles for inclusion that had cited or been cited by the articles in the primary search.
UGN-102 (ZUSDURI [mitomycin] for intravesical solution) is approved by the US Food and Drug Administration for the treatment of adult patients with recurrent low-grade, intermediate-risk NMIBC.18 Three late-phase clinical trials investigated the safety and efficacy of UGN-102 in patients with low-grade, intermediate-risk NMIBC at the target dose of 75 mg instilled intravesically once weekly for 6 weeks: OPTIMA II (ClinicalTrials.gov identifier NCT03558503),19 ATLAS (NCT04688931),20 and ENVISION (NCT05243550).21 Low-grade Ta NMIBC was diagnosed using cold cup biopsy (with visible tumor left in situ); negative voiding cytology was used for high-grade disease. Intermediate-risk disease was defined as instances with 1 or 2 of the following criteria: the presence of multiple tumors, a solitary tumor larger than 3 cm, and early or frequent recurrence (≥1 occurrence of low-grade NMIBC within 1 year of the current diagnosis). The full trial designs, inclusion and exclusion criteria, and safety and efficacy outcomes have been reported previously19-21 and are briefly summarized in this article. In all 3 studies, CR was defined as negative cystoscopy; negative urine cytology (ie, not consistent with the presence of urothelial carcinoma); and, if indicated (ie, if any remaining lesions appeared, even if they appeared necrotic), negative for-cause biopsy at 3 months after the first instillation.19-21
OPTIMA II was a phase 2b, open-label, single-arm trial conducted across 20 sites in the United States and Israel (Figure 2, Table 1).19
In total, 63 patients with recurrent (77.8%) or newly diagnosed (22.2%) low-grade, intermediate-risk NMIBC were enrolled in the study and received at least 1 instillation of UGN-102; 57 patients (90.5%) received all 6 instillations; 6 patients withdrew from treatment because of AEs. The mean patient age was 70.5 years, and most patients were male (60.3%) and White (87.3%), which is reflective of the general epidemiologic pattern of low-grade, intermediate-risk NMIBC in the United States (Table 2).4,5
A total of 41 (65.1% [95% CI, 52.0-76.7]) patients achieved the primary end point of CR at the 3-month evaluation, of whom 39 (95.1%) remained disease free at 6 months, 30 (73.2%) at 9 months, and 25 (61.0%) at 12 months. The median duration of response (DoR) was not reached by the 12-month data cutoff point, but the probability of durable response 9 months after CR was estimated to be 69.9% (95% CI, 51.8-82.3) by the Kaplan-Meier method. Of the 41 patients who achieved CR at the 3-month assessment, 13 (31.7%) had documented disease recurrence, 2 of whom had evidence of disease progression. Twenty-five of the 41 (61.0%) patients had a sustained CR at 12 months, and 17 (41.5%) patients entered a long-term follow-up study.22
At the 5-year long-term follow-up analysis, among the 41 patients who had achieved CR in the parent study, median follow-up was 35.8 months (95% CI, 10.8-61.0), and the median estimate of DoR was 24.2 months (95% CI, 9.7-42.1). Among the 17 patients with long-term follow-up, median follow-up was 50.4 months (95% CI, 27.0-not estimable), and median DoR was 42.1 months (95% CI, 24.2 to not estimable).22
Figure 2. Study designs of the OPTIMA II, ATLAS, and ENVISION trials19-21 Abbreviations: CR, complete response; NMIBC, non–muscle-invasive bladder cancer; TURBT, transurethral resection of bladder tumor. a Complete response was defined as visual confirmation and negative urine cytology as well as for-cause biopsy. The primary end point in ENVISION and OPTIMA II was CR at 3 months; the primary end point in ATLAS was disease-free survival.
Treatment-emergent AEs (TEAEs) in OPTIMA II were mainly of mild or moderate severity. There were no treatment-related or procedure-related serious TEAEs (Table 4).
ATLAS was a prospective, phase 3, open-label, randomized controlled trial conducted at 72 sites across the United States, Europe, and Israel (Figure 2, Table 1).20
Of the 396 patients screened, 142 were randomly assigned to UGN-102 with or without TURBT and 140 to TURBT alone (Figure 2). In the UGN-102 with or without TURBT arm, 138 (97.2%) patients received at least 1 instillation of UGN-102; 132 (95.7%) of these 138 patients received all 6 UGN-102 installations, while 6 discontinued treatment (5 as a result of AEs and 1 other). In the TURBT alone arm, 132 (94.3%) patients received TURBT at baseline.
The median patient age in the UGN-102 with or without TURBT arm was 68.0 years and in the TURBT alone arm was 67.0 years; most patients were male (UGN-102 with or without TURBT, 73.9%; TURBT alone, 66.4%) and White (UGN-102 with or without TURBT, 98.6%; TURBT alone, 99.3%) (Table 2). Multifocal tumors were present in 82 patients (60.3%) randomly assigned to the UGN-102 with or without TURBT arm and in 94 patients (70.1%) in the TURBT alone arm. Tumors larger than 3 cm were found in 67 patients (49.3%) in the UGN-102 with or without TURBT arm and 59 patients (44.7%) in the TURBT alone arm. Recurrent low-grade, intermediate-risk NMIBC was present in 54 patients (38%) in the UGN-102 arm and 65 (46%) patients in the TURBT alone arm.
At the 3-month evaluation, a total of 92 (64.8% [95% CI, 56.3-72.6]) patients who received UGN-102 at baseline and 87 (62.1% [95% CI, 53.6-70.2]) patients who received TURBT at baseline achieved CR; 12 (8.5%) patients in the UGN-102 arm and 9 (6.4%) in the TURBT alone arm showed progression to high-grade disease (Table 3). Residual disease was found in 26 (18.3%) patients in the UGN-102 arm, 24 (92.3%) of whom subsequently underwent TURBT. In the TURBT alone arm, residual disease was found in 22 (15.7%) patients, 18 (81.8%) of whom underwent subsequent TURBT. Disease-free survival at 15 months after random assignment to the UGN-102 arm was 72.0% (95% CI, 63.1-79.2) and to the TURBT alone arm was 49.5% (95% CI, 39.6-58.6). Of the patients who achieved CR at the 3-month evaluation, the estimated DoR 12 months after CR was 79.6% (95% CI, 69.3-86.8) in the UGN-102 arm and 69.6% (95% CI, 57.6-78.9) in the TURBT alone arm. The between-arms hazard ratio for DoR in ATLAS was 0.49 (95% CI, 0.26-0.93), favoring the UGN-102 arm. Median DoR was not estimable for either arm because of low recurrence rates; the most common AE with UGN-102 was dysuria, which occurred in 30.4% of patients in ATLAS.
Treatment-emergent AEs were reported in 104 (75.4%) patients in the UGN-102 with or without TURBT arm and in 63 (47.7%) patients in the TURBT alone arm; serious TEAEs were found in 12 (8.7%) and 7 (5.3%) patients, respectively (Table 4). Two serious TEAEs were reported to be due to treatment or procedure in the UGN-102 arm while 1 TEAE (postoperative hematuria) in the TURBT alone arm was considered treatment related. It should be noted that the schedule of TEAE collection was considerably different between the 2 arms during the study’s first 3 months; in the UGN-102 arm, events were collected at each instillation, weekly for the first 6 weeks, and then by monthly telephone follow-up. Treatment-emergent AE collection was less frequent in the TURBT alone arm because TEAE occurrence was collected only by monthly telephone follow-up.20 This difference likely resulted in ascertainment bias, with underreporting of TEAEs in the TURBT alone arm. Rates of AEs were generally similar between the UGN-102 and TURBT alone arms after the first 3 months.
The trials’ sponsor ceased enrollment after 282 of the planned 632 patients were randomly assigned, deciding to pursue an alternative phase 3 study for UGN-102 without knowledge of the postrandomization data. As a result, the trial was underpowered to determine whether UGN-102 with or without TURBT was statistically superior to TURBT alone. Further, patients in the TURBT alone arm did not receive post-TURBT adjuvant chemotherapy.
ENVISION is an ongoing prospective, pivotal, phase 3, single-arm study that is being conducted at 56 sites in 10 countries (Figure 2, Table 1).21 Of the 318 patients with recurrent low-grade, intermediate-risk NMIBC who were screened, 240 have been enrolled, all of whom received at least 1 UGN-102 instillation; 228 patients (95.0%) received all 6 weekly instillations, while 26 withdrew or stopped treatment (3 because of AEs, 10 withdrew consent, 1 withdrew at investigator discretion, 1 was nonadherent to treatment, 7 were lost to follow-up, 4 stopped for other reasons). The median age of study patients was 70.0 years, and most patients were male (61.3%) and White (97.5%) (Table 2). A total of 191 (79.6% [95% CI, 73.9-84.5]) patients had a CR at the 3-month visit (Table 3). Of these patients, the probability of remaining disease free for 12 months following the 3-month visit was 82.3% (95% CI, 75.9-87.1). With a median follow-up of 13.9 months, the median DoR was not estimable at the interim analysis (ie, April 4, 2024). A subsequent analysis with a median follow-up of 18.7 months following the 3-month visit showed that the probability of remaining disease-free at 18 months was 80.6% (95% CI, 74.0-85.7) according to Kaplan-Meier analysis.23
Treatment-emergent AEs were reported in 137 (57.1%) patients (Table 4). Most were mild to moderate, and the majority were resolved or resolving by the time of the interim analysis. Serious TEAEs occurred in 29 (12.1%) patients; 2 were attributed to treatment with UGN-102 (urinary retention and urethral stenosis), both of which resolved.21
The ENVISION trial demonstrated that primary treatment of recurrent low-grade, intermediate-risk NMIBC with UGN-102 resulted in a clinically significant CR rate with robust DoR, indicating that UGN-102 can be a well-tolerated and valuable alternative to TURBT in these patients.
Three studies have investigated the patient perspective on therapy with UGN-102 for low-grade, intermediate-risk NMIBC.24-26 The phase 3b Home Instillation study (NCT05136898) investigated patients’ and health care professionals’ perspectives on the administration of UGN-102 at the patient’s home rather than in an outpatient clinical setting.26 In substudies of the OPTIMA II and ENVISION trials, patients with low-grade, intermediate-risk NMIBC were interviewed about their experiences with UGN-102 therapy and prior TURBTs.24,25 The full study designs, inclusion and exclusion criteria, and outcomes have been previously reported but will be briefly summarized in this article.24-26 For the OPTIMA II, ATLAS, and ENVISION studies, patientreported symptom burden was evaluated using the European Organisation for Research and Treatment of Cancer 24-item Quality of Life Questionnaire for NMIBC at baseline and 3 and 12 months after treatment initiation.
In the UGN-102 clinical trial program for patients with low-grade, intermediate-risk NMIBC, instillations of UGN-102 were performed in an outpatient setting.19-21 This single-arm, phase 3b, open-label study in patients with low-grade, intermediate-risk NMIBC investigated the feasibility of administering 5 weekly instillations of UGN-102 in the home setting by a trained home health professional, following the first instillation at the investigative site by a qualified physician (Table 1).26 After each instillation, patients, home health professionals, and investigators were asked to rate their experience compared with office instillation and their overall experience.
Of the 8 included patients, the median age was 75 years; 5 (62.5%) patients were male; all were White and had recurrent low-grade, intermediate-risk NMIBC; and 6 (75.0%) completed all 6 weekly instillations. The results of the patient questionnaires showed that most patients highly rated each domain of their home instillation experience, including comfort, safety, and preference, and most evaluable patients (5/6 [83.3%]) would recommend home instillations of UGN-102 rather than TURBT to other patients.26 Investigators furthermore considered home instillation to be “not different” from office instillations for 5 of 6 (83.3%) evaluable patients. In this small, 3-month study, 6 (75.0%) patients achieved CR, and the safety profile was characterized primarily by mild to moderate urinary symptoms.26
Of the 63 patients enrolled in OPTIMA II,19 44 completed a quarterly patient-reported outcome questionnaire (the European Organisation for Research and Treatment of Cancer 24-item Quality of Life Questionnaire for NMIBC), and 10 were interviewed after the study to collect their impressions of treatment.24 UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating or flatulence, or malaise, but sexual function mildly worsened. Patients’ future health worries were reported to have improved following treatment with UGN-102. Demographic data were not shown to be correlated with changes in patient-reported outcomes. An association was found between worsening sexual function and new-onset low-grade, intermediate-risk NMIBC (as opposed to recurrent disease). Overall, interviewed patients would recommend UGN-102 to other patients and would choose UGN-102 over surgery.24
All US patients included in ENVISION were eligible for inclusion in an interview substudy, irrespective of their response at 3 months.25 Prospective semistructured interviews (20-45 minutes in length) were conducted by independent investigators from the University of North Carolina over the phone at enrollment (before initiating UGN-102) and 3 months after initiating UGN-102, when the primary ENVISION study end point was assessed. The enrollment interviews focused on patients’ previous experience with TURBT and its impact on their daily routines and responsibilities. The 3-month interviews compared the relative impact of TURBT with that of UGN-102 on their daily routines and responsibilities.
Of the 41 eligible patients, 29 (70.7%) completed both interviews. Most of these patients (20 [68.9%]) were at least 65 years old at enrollment, and most were male (18 [62.0%]) and White (24 [82.7%]).
Three main themes emerged from the patients’ responses: (1) TURBT interfered more than UGN-102 therapy with patients’ daily activities and responsibilities (including work); (2) although urinary symptoms were similar between TURBT and UGN-102, patients described more bleeding and catheter issues associated with TURBT as well as a longer time to resume normal sexual activity; for UGN-102, patients reported challenges keeping the gel in the bladder during instillations and intense internal itching; and (3) most patients (90%) would recommend UGN-102 to other patients as a less invasive, less painful, and less time-consuming option than TURBT.25
Typically performed under general anesthesia for all lesions except those amenable to office fulguration, TURBT is associated with predictable surgical morbidity, including bleeding, infection, dysuria, and injury to the bladder.27,28 A previously unappreciated additional source of morbidity is repetitive general anesthesia in older patients (at least 70 years of age), which can contribute to cognitive decline and can be associated with cardiopulmonary complications.29,30 Up to 70% of patients with NMIBC experience recurrence within 5 years of TURBT, and tumor size, multifocality, and histologic grade all contribute to recurrence risk.1,31
A recent review article by the International Bladder Cancer Group highlighted the value of deintensification of treatment for low-grade NMIBC to include active surveillance for small, solitary Ta tumors; chemical ablation; and office fulguration.32 Factors affecting the need for treatment deintensification include TURBT-related morbidity, AEs associated with general anesthesia, the economic burden of NMIBC, and the psychological effects and negative impact on QOL associated with hospital stays and time in the operating room.32 The authors recommended considering chemoablation in patients who are not candidates for TURBT, noting that the intensive regimens needed for chemoablation with aqueous mitomycin necessitate frequent office visits.32 Another option for deintensification is office fulguration and laser ablation, an option that is currently recommended by the European Association of Urology for small low-grade Ta tumors9 and by the American Urological Association and the Society of Urologic Oncology for tumors less than 1 cm in diameter.3 The postfulguration response rates vary considerably, with recurrence rates of 13% to 73% reported and 1 study reporting progression to high-grade disease in 23% of patients with recurrent low-grade NMIBC treated with office fulguration.33
The patients newly diagnosed and with recurrent low-grade, intermediate-risk NMIBC included in the UGN-102 clinical development program tended to be older (median age range, 67-70 years across the studies). They also had a relatively high disease burden, with 60.3% to 82.8% having multiple tumors, 18.6% to 49.3% having an aggregate tumor size larger than 3 cm, and 24.6% to 51.7% having had low-grade NMIBC episodes within the year before their current diagnosis.
Across studies, the proportions of patients treated with UGN-102 who achieved CR at 3 months were consistently high (64.8%-79.6%).19-21 Responses were consistently durable, with an 80.6% probability of remaining disease free at 18 months in the extended follow-up of patients in ENVISION23 and a median DoR of 42.1 months with a median duration of follow-up of 50.4 months in the extended follow-up of patients in OPTIMA II.22 Across the UGN-102 studies, AEs were mainly mild to moderate, predominantly localized (lower urinary tract), and manageable, demonstrating a favorable benefit-risk profile.19-21
When presented with the treatment option of receiving intravesical chemoablation with UGN-102 instead of TURBT, 90% of patients with NMIBC expressed a preference for intravesical chemoablation.19-21 Studies investigating the patient perspective on the use of UGN-102 demonstrated a clear preference for UGN-102 over TURBT24,25 in that UGN-102 interfered with their daily lives less than TURBT, and many patients would recommend UGN-102 to other patients with low-grade, intermediate-risk NMIBC over TURBT.24,25 The potential for UGN-102 to be administered in the home setting adds a potential extra layer of convenience for patients and physicians26 and could reduce the burden of low-grade, intermediate-risk NMIBC on health care professionals and payers.
UGN-102 is a nonsurgical treatment approved by the Food and Drug Administration that has consistently shown robust, clinically significant, and durable CR in patients with newly diagnosed or recurrent low-grade, intermediate-risk NMIBC, with a favorable safety profile that can be managed in routine urologic practice.
Babjuk M, Burger M, Compérat EM, et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) – 2019 update. Eur Urol. 2019;76(5):639-657. doi:10.1016/j.eururo.2019.08.016
Monteiro LL, Witjes JA, Agarwal PK, et al. ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer. World J Urol. 2019;37(1):51-60. doi:10.1007/s00345-018-2438-9
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Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021-1029. doi:10.1016/j.juro.2016.06.049
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Bladder Cancer. Version 3.2023. Updated May 25, 2023. Accessed June 5, 2023. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
Kamat AM, Witjes JA, Brausi M, et al. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer. J Urol. 2014;192(2):305-315. doi:10.1016/j.juro.2014.02.2573
Gontero P, Birtle A, Capoun O, et al. European Association of Urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ)—a summary of the 2024 guidelines update. Eur Urol. 2024;86(6):531-549. doi:10.1016/j.eururo.2024.07.027
Tan WS, Steinberg G, Witjes JA, et al. Intermediate-risk nonmuscle-invasive bladder cancer: updated consensus definition and management recommendations from the International Bladder Cancer Group. Eur Urol Oncol. 2022;5(5):505-516. doi:10.1016/j.euo.2022.05.005
Leblanc B, Duclos AJ, Bénard F, et al. Long-term followup of initial Ta grade 1 transitional cell carcinoma of the bladder. J Urol. 1999;162(6):1946-1950. doi:10.1016/s0022-5347(05)68075-5
De Nunzio C, Franco G, Cindolo L, et al. Transuretral resection of the bladder (TURB): analysis of complications using a modified Clavien system in an Italian real life cohort. Eur J Surg Oncol. 2014;40(1):90-95. doi:10.1016/j.ejso.2013.11.003
Paz MM, Zhang X, Lu J, Holmgren A. A new mechanism of action for the anticancer drug mitomycin C: mechanism-based inhibition of thioredoxin reductase. Chem Res Toxicol. 2012;25(7):1502-1511. doi:10.1021/tx3002065
McNall S, Hooper K, Sullivan T, Rieger-Christ K, Clements M. Treatment modalities for non-muscle invasive bladder cancer: an updated review. Cancers (Basel). 2024;16(10):1843. doi:10.3390/cancers16101843
Palou J, Carcas A, Segarra J, et al. Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer. J Urol. 2004;172(2):485-488. doi:10.1097/01.ju.0000131770.14409.7f
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US Food and Drug Administration. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. Updated June 12, 2025. Accessed July 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-intravesical-solution-recurrent-low-grade-intermediate-risk-non-muscle
Chevli KK, Shore ND, Trainer A, et al. Primary chemoablation of low-grade intermediate-risk nonmuscle-invasive bladder cancer using UGN-102, a mitomycin-containing reverse thermal gel (Optima II): a phase 2b, open-label, single-arm trial. J Urol. 2022;207(1):61-69. doi:10.1097/JU.0000000000002186
Prasad SM, Huang WC, Shore ND, et al. Treatment of low-grade intermediate-risk nonmuscle-invasive bladder cancer with UGN-102 ± transurethral resection of bladder tumor compared to transurethral resection of bladder tumor monotherapy: a randomized, controlled, phase 3 trial (ATLAS). J Urol. 2023;210(4):619-629. doi:10.1097/JU.0000000000003645
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Published: October 5, 2025.
Conflict of Interest Disclosures: S. M. Prasad has received principal investigator funding from Janssen, Merck, Pfizer, and UroGen Pharma. M. Schoenberg, M. J. Louie, S. Raju, A. Meads, B. Burger, V. Tsurutis, N. Ugwuoke, and V. Lee are employees and/or stockholders of UroGen Pharma. J. P. Sfakianos has received honoraria from Natera; is a consultant for Pfizer, CG Oncology, Ferring, and UroGen Pharma; and has received research funding from Irrimax Corporation.
Funding/Support: UroGen Pharma funded the study.
Author Contributions: S. M. Prasad, M. J. Louie, V. Tsurutis, and N. Ugwuoke participated in conceptualizing, reviewing, and editing the manuscript. M. Schoenberg, J. P. Sfakianos, S. Raju, A. Meads, B. Burger, and V. Lee read and approved the final article.
Data Availability Statement: No new data were generated for this article.
Acknowledgments: We thank the study investigators, patients, and carers who participated in the UGN-102 clinical study program and associated studies. This manuscript was sponsored by UroGen Pharma. Literature search, medical writing, and editorial assistance were provided by Patrick Crowley, PhD, and Jaqui Hodgkinson, DPhil, MBA, of Excerpta Medica, funded by UroGen Pharma in accordance with current Good Publication Practice guidelines. OPTIMA II: NCT03558503 (BL005); ATLAS: NCT04688931 (BL006); ENVISION: NCT05243550 (BL011); Home Instillation: NCT05136898 (BL010).
Citation: Prasad SM, Schoenberg M, Louie MJ, et al. Review of UGN-102: a reverse thermal gel containing mitomycin for the treatment of recurrent, low-grade, intermediate-risk non–muscle-invasive bladder cancer. Rev Urol. 2025;24(3):e77-e91.
Corresponding author: Sandip M. Prasad, MD, MPhil, Morristown Medical Center, 100 Madison Ave, Morristown, NJ 07960 (sandip.prasad@atlantichealth.org)
