EAU 2025: Low-risk Recurrent NMIBC in the Elderly Patient – Fulguration as Day Care Protocol, Chemoablation in Mutated Tumors, and Active Surveillance Strategies with Urine Biomarkers

(UroToday.com) The 2025 European Association of Urology (EAU) Annual Congress held in Madrid, Spain was host to a plenary session on organ-sparing paradigms in kidney and bladder cancer. Drs. Marek Babjuk, Antoni Vilaseca Cabo, and Ashish Kamat discussed various strategies for the management of low-risk, recurrent non-muscle invasive bladder cancer (NMIBC) in elderly patients:

• Fulguration as day care protocol
• Chemoablation in mutated tumors (.e.g, FGFR altered [FGFRalt])
• Active surveillance strategies

The session began with a case presentation of an 84-year-old, fit female patient with the following bladder cancer history:

• August 2020: 2 cm bladder tumor   TURBT: TaG1 urothelial carcinoma
• February 2022: 0.8 cm recurrence   TURBT: TaG1
• March 2024: A likely TaG1 2cm recurrence, with a negative urinary cytology

What are the next steps in management?

Arguing in favor of in-office fulguration, Dr. Babjuk noted that the relevant clinical questions in this scenario are as follows:

• Can we discern low- from high-grade tumors at cystoscopy?
• What is the prognosis of such a patient?
• What are the available methods and are they safe/feasible?
• What are the oncological outcomes in such a scenario?

With regards to predicting low-grade disease at cystoscopy, Marlappan et al. have previously demonstrated that the overall positive predictive value for low-grade tumors at cystoscopy is 86% (88% for tumors <3 cm).¹ In other words, if a lesion appears to be low-grade on cystoscopy and then a TURBT is performed, the lesion is pathologically confirmed low-grade ~90% of the time. Thus, Dr. Babjuk argued that, in general, we may presume a low risk of high-grade recurrence in such patients with a history of recurrent low-grade tumors who have a low-grade appearing lesion on surveillance.

What is the prognosis of this patient? Based on the current EAU risk stratification model of 2021, this patient meets the criteria for intermediate-risk disease given that she has recurrent LG Ta lesions <3 cm with no CIS component. Her risk of disease progression at 5 years is ~5%, per the EAU risk classification model. However, when we apply the IBCG risk stratification to sub-stratify these intermediate-risk patients, we note that this patient has 0 high-risk factors (multiple lesions, tumor size >3 cm, early recurrence <1-year, frequent recurrences >1/year), and is thus in intermediate risk ‘low’ subgroup.

Based on the current evidence, she has a ‘negligible’ risk of progression with a ~30% risk of disease recurrence and should be treated similarly to low risk patients.¹

What do the current guidelines say about in-office fulgurations?

• EAU: Patients with small recurrent low-grade Ta tumors can be effectively and safely offered office fulguration (strong recommendation)
• AUA/SUO: In a patient with a history of low-grade Ta disease and a noted subcentimeter papillary tumor(s), a clinician may consider in-office fulguration as an alternative to resection under anesthesia (Expert opinion)
• NICE: Consider fulguration without a biopsy for people with recurrent NMIBC if they have all of the following:
  • No previous intermediate- or high-risk bladder cancer
  • A disease-free interval of at least 6 months
  • Solitary papillary recurrence
  • A tumor diameter of 3 mm or less 

Available methods for ablation include:

• Fulguration (e.g., monopolar ‘bugbee’ electrode’)
• Laser ablation
  • Ho:YAG, 980 nm diode laser, Nd:YAG
  • Thullium fiber laser

Importantly, it appears that currently available fulguration/laser ablation techniques are safe, with the following pooled results from a 2022 systematic review by Malde et al. published in European Urology Oncology:³

In addition to being safe, long-term follow-up of a cohort of 270 patients with recurrent low-grade Ta tumors treated with in office fulguration (mean follow-up: 11.7 years) demonstrated that the 10-year progression rate was only 3.1%.

What about the efficacy of in-office laser ablation? In 2023, Pedersen et al. published the results of a trial of 206 patients with tumors ≤1.5 cm randomized to either laser photocoagulation with a 980 nm diode laser or TURBT. After 4 months, the recurrence-free survival rate was 57% in the laser arm versus 49% in the TURBT arm. Complications were noted in 2% and 10% of patients in the ablation and TURBT arms, respectively.⁴

Dr. Babjuk concluded his argument by noting that in well-selected patients, in-office fulguration or laser ablation is feasible, safe, and effective.

Next, Dr. Vilaseca argued in favor of chemoablation in such a setting, specifically for mutated tumors (e.g., FGFRalt). He noted that TURBT, although not a major urologic procedure, is associated with significant, often underappreciated complication rates: 

What is the evidence for chemoablation for low-grade tumors? In 2012, Colombo et al. published the results of a phase II trial of neoadjuvant short-term intensive intravesical mitomycin C (3 instillations/week for 2 weeks prior to TURBT) versus a neoadjuvant weekly schedule (1/week x 6 weeks prior to TURBT) for low-grade, recurrent NMIBC. They demonstrated that the complete response rates were superior in the ‘intense’ neoadjuvant strategy arm (70% versus 44%).⁵

CALIBER, published in 2020,⁶ was a phase II feasibility trial whereby patients with low-risk NMIBC were randomized 2:1 to treatment with four once-weekly mitomycin-C 40-mg intravesical instillations (chemoablation arm) or to surgical management. Between February 2015 and August 2017, 82 patients with a visual diagnosis of recurrent low-risk NMIBC were enrolled from 24 UK hospitals (chemoablation, n = 54; surgical management, n =28), and followed for a median of 24 months. The 3 months complete response rate was 81% with surgical management versus 37% with mitomycin-C ablation. Amongst patients with a complete response at 3 months, the 12-months recurrence-free rates were identical in both groups (84%). Notably, amongst those with residual disease at 3 months, the 12-month recurrence-free proportion was lower in the surgical management group (40%), compared to the chemoablation group (84%). Ultimately, recruitment was suspended early as chemoablation did not meet the prespecified threshold of 45% complete responses at 3 months.

In 2023, the DaBlaCa13 trial was published in The Journal of Clinical Oncology.⁷ This was a Danish randomized clinical trial of 120 patients with a history of Ta low- or high-grade NMIBC who were included upon recurrence and randomized to:

• Intervention: Intravesical mitomycin-C (40 mg/40 mL) three times a week for 2 weeks and TURBT or office biopsy only if the response was incomplete
• TURBT or office biopsy and 6 weekly adjuvant instillations

This trial demonstrated that fewer patients in the intervention group required a procedure (71% versus 100%). There were no differences in the 12-months recurrence-free survival rates (36% versus 43%, p=0.5).

Novel bladder chemoablative treatment options are emerging. Dr. Vilaseca highlighted UGN-102, a reverse thermal gel containing mitomycin, that was evaluated in ATLAS a randomized phase III trial of UGN-102 once weekly for 6 weeks versus TURBT in patients with new or recurrent low-grade, intermediate-risk NMIBC.

Tumor-free complete response 3 months after initial treatment was achieved by 65% of UGN-102-treated patients and 64% of TURBT patients. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± TURBT and 50% for TURBT patients.⁸

Another promising, emerging option in this space is TAR-210, which is designed to release sustained local erdafitinib, a pan-FGFR inhibitor, intravesically for 3 months. At AUA 2024, Dr. Vilaseca presented the first safety and efficacy results of an open-label, multicenter phase I study (NCT05316155) that evaluated TAR-210 in patients with NMIBC whose tumors harbor select FGFRalt.

This study included two cohorts:

• Cohort 1; High-risk NMIBC (HG Ta/T1, no CIS, papillary only), BCG-experienced/unresponsive and not undergoing radical cystectomy. All patients in this cohort had a TURBT with complete resection of all visible disease prior to treatment.
• Cohort 3: Intermediate-risk NMIBC (LG Ta/T1 disease) and visible target lesions prior to treatment (chemoablation design)

The baseline characteristics were as follows:

In cohort 3 (chemoablation cohort), 90% achieved a complete response, with 28/31 achieving this response by week 12.

Significantly, TAR-210 provided sustained erdafitinib release in the urine over 90 days with very low plasma concentrations: 

The adverse event profile was favorable, and there were no dose-limiting toxicities.

Dr. Vilaseca concluded his argument in favor of ablation as follows:

• TURBT is associated with some adverse events, and NMIBC is associated with high recurrence rates
• Chemoablation for low- to intermediate-risk NMIBC is feasible
• In a pooled meta-analysis of mitomycin-C, BCG, epirubicin, and gemcitabine, the complete response rate was 51%⁹
• Thermogels for mitomycin-C can improve complete response rates up to 65% in ATLAS and up to 80% in ENVISION¹⁰
• FGFR-directed chemoablation can achieve complete response rates in 90% of cases 

Finally, Dr. Kamat argued in favor of surveillance in this scenario. While the patient in question has, by definition, EAU intermediate-risk disease, this group includes a heterogenous population of candidate patients:

• Recurrent low-grade disease (case example presented)
• Primary, large (>3 cm) LG Ta
• High-grade Ta with, at most, one high-risk clinical feature

Dr. Kamat noted that the updated 2022 IBCG guidelines provide further nuance and guidance for the management of intermediate-risk patients. The IBCG risk classification stratifies patients based on the number of risk factors present, as follows, with the 5-year risks of recurrence and progression with sequential intravesical gemcitabine + docetaxel summarized below:¹¹

Importantly, this scoring system can be used to predict the subsequent time of surveillance. In an analysis of 163 patients with low-grade Ta/T1 NMIBC followed for a median of 33 months, patients with 0 risk factors, such as the patient in the case example, were over 2-fold more likely to continue active surveillance compared to patients with ≥3 risk factors (59% vs 24%). Multivariable analysis adjusted for age, T stage, and sex demonstrated that the IBCG intermediate-risk NMIBC scoring system was associated with subsequent rates of surveillance discontinuation and performance of a TURBT (1-2 risk factors: HR=1.66, p=0.072; ≥3 risk factors: HR=3.21, p<0.001).¹² 

Furthermore, when the IBCG intermediate-risk NMIBC scoring system is applied, we note that low-grade, intermediate-risk NMIBC patients with 0 risk factors have 3-year recurrence-free survival rates of 86%, including 92% for high-grade recurrences.¹³

Based on the current evidence, the following algorithm for the management of primary low-grade Ta disease, which incorporates active surveillance as an option for IBCG intermediate-risk NMIBC with ≤2 risk factors, has been proposed:

• Marek Babjuk, MD, PhD, Professor, Department of Urology, 2nd Faculty of Medicine, Hospital Motol, Prague, Czech Republic
• Antoni Vilaseca Cabo, MD, Hospital Clínic de Barcelona, Barcelona, Spain
• Ashish Kamat, MD, MBBS, Professor of Urology, and Wayne B. Duddleston Professor of Cancer Research, University of Texas, MD Anderson Cancer Center, Houston, TX

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the European Association of Urology (EAU) 2025 Annual Meeting, Madrid, Spain, Fri, Mar 21 – Mon, Mar 24, 2025. 

References:

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4. Pedersen GL, Erikson MS, Mogensen K, et al. Outpatient Photodynamic Diagnosis-guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis-guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial. Eur Urol. 2023; 83(2): 125-30.
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