EAU Oncology Section perspective: Gemcitabine/docetaxel - a new option for European centres in the management of NMIBC

Data on efficacy

In patients with HR-NMIBC who are BCG-naïve, recent findings are promising. A retrospective study which analysed 107 patients treated between 2013-2021 with Gem/Doce showed excellent results, with recurrence-free survival (RFS) rates of 85% at 1 year. At 15 months median follow-up, no patient had disease progression or died from bladder cancer (5). Similarly, another phase II single arm trial by Patel et al. focused on 25 BCG- naïve patients treated with Gem/Doce showed a 100% complete response rate at 3 months and no disease progression at a median follow-up of 20 months (6). Gem/Doce has also demonstrated activity in IR-NMIBC. McElree et al. reported a 2-year RFS of 71%, with significantly better outcomes among treatment-naïve patients (79%) compared to those previously treated (64%; p = 0.04) (7).

There is currently a lack of clinical randomised trials using GemDoce in U-BCG NMIBC patients. In retrospective analyses, high-grade-RFS (HG-RFS) rates of 60-65% at 1 year and 46-60% at 2 years have been reported (3,8). More recent data suggest improved efficacy: Taylor et al. reported a 1-year HG-RFS of 74% in a U-BCG cohort (9). Across studies, progression rates remain relatively consistent, with a 5-year progression ranging 8-18% (8,9). 

EuroGemDoce group: First results

The first European results on intravesical GemDoce for U-BCG patients derived from the EuroGemDoce group in 2025 (10). In this study, Scilipoti et al. examined 75 NMIBC patients previously exposed to BCG, of those 49 (65%) were U-BCG. At 9 months median follow-up, 1-year RFS, HG-RFS, cystectomy-free survival, and progression-free survival were 73%, 81%, 95%, and 95%, respectively. Treatment was well tolerated; only 5 patients (8%) had grade 3–5 adverse events (AEs). These results were possible due to a strength collaboration with 12 academic centres across Italy, Spain, France, Poland, and Germany and in collaboration with the Young Academic Urologist within the EAU guidelines group. 

The EuroGemDoce collaboration forms the foundation on which we are building future projects aimed at comparing oncological outcomes of U-BCG patients received GemDoce versus other treatment approaches, radical cystectomy or BCG rechallenge. The EuroGemDoce initiative lays the groundwork for further comparative analyses of Gem/Doce versus radical cystectomy and BCG rechallenge in U-BCG patients. These ongoing efforts are expected to strengthen the case for Gem/Doce as a viable therapeutic alternative in this setting.

Future perspectives

However, the need for prospective trials is crucial and lacking for GemDoce, especially in the U-BCG NMIBC setting. The phase 3 BRIDGE trial (currently enrolling) aims to compare the efficacy of Gem/Doce versus BCG in BCG-naïve HR-NMIBC patients (11). Lastly, another RCT (NCT06374914, not yet enrolling) from Turkey plans to provide intravesical GemDoce for U-BCG patients, aiming to investigate oncological outcomes, and compare these findings with a U-BCG cohort treated with upfront RC (12). 

Finally, there is a pressing need for validated protocols tailored to patient risk stratification, dosing, and bladder dwell times. Future research should prioritise individualised treatment strategies to optimise outcomes in this high-risk population.

------

Conflict of interest statement

All authors declare no conflict of interest relative to the content of the paper.

References

1. Gontero P, Birtle A, Capoun O, Compérat E, Dominguez-Escrig JL, Liedberg F, 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 Dec;86(6):531–49.
2. Balasubramanian A, Gunjur A, Weickhardt A, Papa N, Bolton D, Lawrentschuk N, et al. Adjuvant therapies for non-muscle-invasive bladder cancer: advances during BCG shortage. World J Urol. 2022 May;40(5):1111–24.
3. Steinberg RL, Thomas LJ, Brooks N, Mott SL, Vitale A, Crump T, et al. Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer. J Urol. 2020 May;203(5):902–9.
4. Steinberg RL, Thomas LJ, O’Donnell MA, Nepple KG. Sequential Intravesical Gemcitabine and Docetaxel for the Salvage Treatment of Non-Muscle Invasive Bladder Cancer. Bladder Cancer. 2015 Apr 30;1(1):65–72.
5. McElree IM, Steinberg RL, Martin AC, Richards J, Mott SL, Gellhaus PT, et al. Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer. J Urol. 2022 Sep;208(3):589–99.
6. Patel SH, Gabrielson AT, Chan S, Schwartz D, Collins C, Singla N, et al. A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder. J Urol. 2024 Jul;212(1):95–103.  
7. McElree IM, Orzel J, Stubbee R, Steinberg RL, Mott SL, O’Donnell MA, et al. Sequential intravesical gemcitabine and docetaxel for treatment-naïve and previously treated intermediate-risk nonmuscle invasive bladder cancer. Urol Oncol. 2023 Dec;41(12):485.e1-485.e7.
8. Chevuru PT, McElree IM, Mott SL, Steinberg RL, O’Donnell MA, Packiam VT. Long-term follow-up of sequential intravesical gemcitabine and docetaxel salvage therapy for non-muscle invasive bladder cancer. Urol Oncol. 2023 Mar;41(3):148.e1-148.e7.
9. Taylor J, Kamat AM, Annapureddy D, Khene ZE, Howard J, Tan WS, et al. Oncologic Outcomes of Sequential Intravesical Gemcitabine and Docetaxel Compared with Bacillus Calmette-Guérin in Patients with Bacillus Calmette-Guérin-Unresponsive Non-Muscle Invasive Bladder Cancer. Eur Urol Oncol. 2024 Dec 17;
10. Scilipoti P, Longoni M, de Angelis M, Zaurito P, Massiet A, Dutto D, et al. Gemcitabine and docetaxel for high-risk non-muscle-invasive bladder cancer: EuroGemDoce group results. BJU Int. 2025 Jan 11;
11. Kates M, Chu X, Hahn N, Pietzak E, Smith A, Shevrin DH, et al. Background and Update for ECOG-ACRIN EA8212: A Randomized Phase 3 Trial of Intravesical Bacillus Calmette-Guérin (BCG) Versus Intravesical Docetaxel and Gemcitabine Treatment in BCG-naïve High-grade Non-muscle-invasive Bladder Cancer (BRIDGE). Eur Urol Focus. 2023 Jul;9(4):561–3.
12. https://clinicaltrials.gov/study/NCT06374914.