Smoke load prognostic impact on bacillus Calmette–Guérin (BCG) treated non-muscle invasive bladder cancer

Andrade, Danilo Leite; Moretti, Tomás Bernardo Costa; Neto, Wilmar Azal; Benedetti, Júlia; Reis, Leonardo Oliveira

doi:10.1007/s11255-020-02438-6

Cited by 12 publications

(5 citation statements)

References 23 publications

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“…At the time of diagnosis, between 75% and 85% of the tumors are non-muscle-invasive bladder carcinoma (NMIBC), and half of patients will experience recurrence within 1 year after transurethral resection–exclusive treatment, which significantly decreases by adjuvant intravesical bacille Calmette–Guérin (BCG) instillation [ 3 ]. NMIBC has been shown to be a heterogeneous and complex tumor [ 4 ] that varies in clinical and biological behavior, mainly according to stage and grade [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups

et al. 2022

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Purpose Current World Health Organization/International Society of Urological Pathology (2004 WHO/ISUP) grading of bladder urothelial carcinoma relies on the highest pathologic grade of the specimen and does not reflect the inherent qualitative and quantitative heterogeneity of disease. Materials and Methods We retrospectively studied consecutive urothelial high-grade cT1 (cT1HG) carcinomas submitted to adjuvant bacille Calmette–Guérin between 2008 and 2015 to evaluate the prognostic potential of grade 3 (presence or predominance) according to the 1973 WHO system concerning disease progression and cancer-specific death. Results Among 253 patients, grading distribution was 34.4% 1+2, 7.5% 2+1, 20.2% 2+2, 19.0% 2+3, 5.1% 3+2, and 13.8% 3+3. Recurrence was diagnosed in 115 (45.5%), progression in 83 (32.8%), and cancer-specific death in 50 patients (19.8%). Mean time to recurrence, progression, and death from disease were 35.9±31.7, 47.6±44.5, and 51.2±50.4 months, respectively. Grade 3 presence (2+3, 3+2, or 3+3) occurred in 96 (37.9%) and independently predicted time to progression (p<0.001; hazard ratio [HR], 3.11; 95% confidence interval [CI], 1.88–5.14). Grade 3 predominance (3+2 or 3+3) occurred in 48 (18.9%) and independently predicted time to disease-specific death. Conclusions Grade 3 presence and predominance are independent predictors of progression and disease-specific death and occur in about 40% and 20% of cT1HG, respectively. Describing qualitative and quantitative heterogeneity in urothelial carcinoma grading might improve the stratification of patients. This gives three prognostic high-grade groups based on WHO/ISUP 1973: prognostic grade group I (grade 3 absence), prognostic grade group II (grade 3 presence), and prognostic grade group III (grade 3 predominance).

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Section: Introductionmentioning

confidence: 99%

Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups

et al. 2022

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“…Among the clinical and pathological features, no significant association was observed between mGPS and age, gender, concomitant CIS, recurrence, progression, OS and CSS. Based on these results, we showed that the effects of tobacco smoke have a detrimental effect on both inflammation and oxidative stress which may lead to activation of angiogenesis and tumor progression, according to literature data [27,34,35]. Moreover, our data from Cox regression analysis showed that patients with mGPS of 1 were more likely to experience disease recurrence (univariable HR: 1.403; p < 0.0001; (multivariable HR: 1.542; p < 0.0001), compared to mGPS 0 patients.…”

Section: Discussionmentioning

confidence: 69%

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette–Guerin Immunotherapy

et al. 2022

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Background: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette–Guérin (BCG) therapy. Methods: We retrospectively reviewed patient’s medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. Results: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan–Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92–94), in patients with mGPS 0, 82.2% (CI 95% 78.9–85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4–70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97–99) in patients with mGPS 0, 90% (CI 95% 87–94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. Conclusions: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion.

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“…BCG immunotherapy was reported to be less effective in smokers compared to non-smokers (Ślusarczyk et al 2019 ; Abd Elwahab et al 2021 ; Lammers et al 2011 ). Another study confirmed that greater lifetime smoke exposure (especially over 20 pack-years) confers a risk factor for recurrence and progression of NMIBC treated with BCG (Andrade et al 2020 Aug). Such observation might reflect not only the carcinogenesis and mutagenesis in urothelial cells induced by smoke but also the immunomodulatory effects of tobacco smoking.…”

Section: Discussionmentioning

confidence: 73%

“…We also did not study the effect of smoking intensity and load on prognosis, because of the heterogeneity of reported data in single papers. Andrade et al showed that smoke load, especially over 20 pack-years influenced recurrence and progression risk in BCG-treated pT1 NMIBC (Andrade et al 2020 ). Rink et al showed that heavy long-term smokers (≥ 20 years; ≥ 20 cigarettes per day) had the worst prognosis followed by light long-term (≥ 20 years; < 20 cigarettes per day), heavy short-term and light long-term smokers (Rink et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…In all studies the definition of the progression included the development of muscle-invasive disease (MIBC) and in the majority of studies any increase in T stage or grade was also regarded as progression. We excluded the studies reporting only smoking intensity or smoking time but not precisely the smoking status (former/current/never or smoker/nonsmoker) (Andrade et al 2020 ). Studies with a single analysis for the cohort of both NMIBC and MIBC or studies in which the information on tobacco use was not precise were also excluded (Nerli et al 2018 ; Zhang et al 2021 ; Ahirwar et al 2008 ).…”

Section: Methodsmentioning

confidence: 99%

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The impact of smoking on recurrence and progression of non-muscle invasive bladder cancer: a systematic review and meta-analysis

Ślusarczyk

Zapała

et al. 2022

J Cancer Res Clin Oncol

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Objectives Although smoking is a well-recognized causative factor of urothelial bladder cancer and accounts for 50% of cases, less is known about the prognostic significance of smoking on non-muscle invasive bladder cancer (NMIBC) prognosis. This systematic review and meta-analysis aimed to evaluate the effect of smoking on the risk of NMIBC recurrence and progression. Materials and methods We systematically searched Medline, Web of Science and Scopus databases for original articles published before October 2021 regarding the effect of smoking on NMIBC recurrence and progression. Information about smoking status and the number of events or odds ratio or hazard ratio for event-free survival must have been reported to include the study in the analysis. Quality In Prognosis Studies tool was utilized for the risk of bias assessment. Results We selected 64 eligible studies, including 28 617 patients with NMIBC with available data on smoking status. In a meta-analysis of 28 studies with 7885 patients, we found that smokers (current/former) were at higher risk for recurrence (OR = 1.68; 95% CI 1.34–2.09; P < 0.0001) compared to never smokers. Subgroup analysis of 2967 patients revealed that current smokers were at a 1.24 higher risk of recurrence (OR = 1.24; 95% CI 1.02–1.50; P = 0.03) compared to former smokers. A meta-analysis of the hazard ratio revealed that smokers are at higher risk of recurrence (HR = 1.31; 95%CI 1.15–1.48; P < 0.0001) and progression (HR = 1.18; 95%CI 1.08–1.29; P < 0.001) compared to never smokers. Detrimental prognostic effect of smoking on progression, but not for recurrence risk was also noted in the subgroup analysis of high-risk patients (HR = 1.30; 95%CI 1.09–1.55; P = 0.004) and BCG-treated ones (HR = 1.15; 95%CI 1.06–1.25; P < 0.001). Conclusion In conclusion, patients with non-muscle invasive bladder cancer and a history of smoking have a worse prognosis regarding recurrence-free and progression-free survival compared to non-smokers.

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Smoke load prognostic impact on bacillus Calmette–Guérin (BCG) treated non-muscle invasive bladder cancer

Cited by 12 publications

References 23 publications

Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups

Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette–Guerin Immunotherapy

The impact of smoking on recurrence and progression of non-muscle invasive bladder cancer: a systematic review and meta-analysis

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