Intermediate-risk (IR) non muscle invasive bladder cancer (NMIBC) represents a diverse cohort of patients whose tumors do not distinctly align with either low- or high-risk classifications, leading to varied therapeutic approaches. This heterogeneity, largely driven by tumor grade, is evident in the differing classifications across major guidelines, including those from the AUA, EAU, NCCN, NICE, and IBCG (Table 1) [[1], [2], [3], [4], [5]]. Accurate risk stratification is essential for guiding treatment decisions. The World Health Organization (WHO) updated its classification for urothelial carcinomas in 2004, with further revisions in 2016 and 2022 [6]. The new system categorizes tumors into low-grade (LG) and high-grade (HG), replacing the older 1973 system's Grade 1(G1), Grade 2 (G2), and Grade 3 (G3) categories. A key change was reclassifying some G2 tumors as HG, increasing the number of HG cases. While the WHO 1973 and WHO 2004/2022 systems predict tumor progression, hybrid models provide better prognostic accuracy by addressing the overlap between these categories [7,8].

Intravesical immunotherapy with bacillus Calmette-Guérin (BCG) or chemotherapy is the recommended treatment option for IR-NMIBC [1,9]. BCG has been pivotal in refining NMIBC risk classification by identifying that HG tumors are most responsive to BCG therapy. BCG's effectiveness in reducing tumor progression has led to critical updates in classification systems to enhance patient treatment strategies [[10], [11], [12]]. Sequential intravesical Gemcitabine and Docetaxil (Gem/Doce) is currently recommended after BCG failure for patients unfit for cystectomy [1,13]. The Gem/Doce combination has shown promising results, with a 2-year recurrence-free rate of 82% for high-risk NMIBC and 71% for IR-NMIBC [[14], [15], [16]]. Given recent global shortages of BCG and certain patients' contraindications or intolerances to BCG, Gem/Doce presents a viable alternative. Previous studies have demonstrated this regimen's effectiveness in high-risk NMIBC settings, justifying its evaluation in intermediate-risk populations. The success of this regimen could influence real-life risk classification by improving treatment outcomes, potentially necessitating updates to existing stratification models.

In our study, we aim to determine whether there is a significant difference in outcomes between HG and LG IR-NMIBC under intravesical therapy and to compare the efficacy of Gem/Doce vs. BCG in treating IR-NMIBC.