Impact of smoking exposure on disease progression in high risk and very high-risk nonmuscle invasive bladder cancer patients undergoing BCG therapy

•High grade and very high grade NMIBC has the potential to reoccur and progress and the BCG intravesical therapy is an adjuvant gold standard treatment.•Smoking impacts appearance and oncological outcomes of NMIBC, even in BCG treated patients.•In the EAU21 risk group classification the high-risk patients with heavy long-term smoking exposure showed a higher risk of progression when compared to the high-risk group with poorer survival outcomes. The nonmuscle invasive bladder cancer treated with BCG instillations in patients who smoke could potentially lead to poorer oncological results in the light of the new EAU risk groups classification for NMIBC that did not include BCG treated patients or smoking status. Outcomes from 1313 patients with nonmuscle invasive bladder cancer treated with TURBT, re-TURBT and BCG instillations at 13 academic hospital centers, since 2002, has been included in this retrospective study. The study variables, including cumulative smoking exposure have been analyzed. A multivariable Cox proportional hazard model was used to assess associations between smoking variables and disease progression and repeated in the EAU high risk and very high-risk group. The statistical significance threshold was set at 0.05, and the statistical analysis was performed using Stata/SE version 17 (StataCorp, College Station, TX, USA). Cox regression analysis revealed in 1313 patients diagnosed with T1G3 NMIBC that patients with a history of heavy and long-term smoking faced a more than twofold increased risk of disease progression compared to nonsmoker patients (HR 2.35; 95% CI: 1.7-3.2; P < 0.01) and a significantly poorer PFS for patients with a history of heavy long-term smoke exposure (P < 0.01). Patients with heavy long-term smoking exposure according to the EAU21 high-risk group had a PFS comparable to very high-risk patients and high-risk patients with heavy long-term smoking exposure showed a higher risk of progression when compared to the high-risk group (HR 1.4; 95% CI: 1.3-1.6; P < 0.01). This study adds valuable information on the relationship between smoking and the progression of NMIBC and BCG therapy. The findings emphasize the need for healthcare providers to consider a patient's smoking history when managing NMIBC and express the need for individualized smoking cessation counseling and individualized treatment approach. [Display omitted]