OBJECTIVE: To investigate the impact of ageing on survival outcomes in Bacillus Calmette-Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. METHOD: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. RESULTS: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. CONCLUSIONS: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.

2nd Faculty of Medicine Hospital Motol Department of Urology Charles University Prague Czech Republic

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Experimental and Clinical Biomedical Science University of Florence Florence Italy

Department of Urology Città Della Salute E Della Scienza University of Torino School of Medicine Turin Italy

Department of Urology Clinico San Carlos University Hospital Madrid Spain

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Faculdade de Medicina Do ABC Santo André Brazil

Department of Urology Fundació Puigvert Autonoma University of Barcelona Barcelona Spain

Department of Urology Hospital Beneficencia Portuguesa de Sao Paulo São Paulo Brazil

Department of Urology Hospital Israelita Albert Einstein São Paulo Brazil

Department of Urology Ng Teng Fong General Hospital National University Health System Singapore Singapore

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Surgical Sciences San Giovanni Battista Hospital University of Studies of Torino 10024 Turin Italy

Division of Urology Rabin Medical Center Petah Tikva Israel

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Research Center for Evidence Based Medicine Iranian EBM Center A Joanna Briggs Institute Center of Excellence Tabriz University of Medical Sciences Tabriz Iran

S H Ho Urology Centre Faculty of Medicine Department of Surgery The Chinese University of Hong Kong 4 F LCW Clinical Sciences Building Prince of Wales Hospital Shatin Hong Kong

Urology Unit Azienda Ospedaliero Universitaria Delle Marche Università Politecnica Delle Marche Ancona Italy

Urothelial Cancer Working Group European Association of Urology Young Academic Urologists Amsterdam Netherlands

Zobrazit více v PubMed

Zhang Y, Rumgay H, Li M, Yu H, Pan H, Ni J (2023) The global landscape of bladder cancer incidence and mortality in 2020 and projections to 2040. J Glob Health 13:04109 PubMed PMC

Shariat SF, Sfakianos JP, Droller MJ, Karakiewicz PI, Meryn S, Bochner BH (2010) The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int 105:300–308 PubMed PMC

Teoh JY, Kamat AM, Black PC, Grivas P, Shariat SF, Babjuk M (2022) Recurrence mechanisms of non-muscle-invasive bladder cancer - a clinical perspective. Nat Rev Urol 19:280–294 PubMed

Kukreja JB (2023) Non-muscle-invasive Bladder Cancer: Side-by-Side Guideline Comparison. Eur Urol Focus. 10.1016/j.euf.2023.05.004 PubMed

Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Dominguez Escrig JL, Gontero P, Liedberg F, Masson-Lecomte A, Mostafid AH et al (2022) European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Eur Urol 81:75–94 PubMed

Redelman-Sidi G, Glickman MS, Bochner BH (2014) The mechanism of action of BCG therapy for bladder cancer–a current perspective. Nat Rev Urol 11:153–162 PubMed

Lobo N, Brooks NA, Zlotta AR, Cirillo JD, Boorjian S, Black PC, Meeks JJ, Bivalacqua TJ, Gontero P, Steinberg GD et al (2021) 100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19. Nat Rev Urol 18:611–622 PubMed PMC

Teoh JY, Huang J, Ko WY, Lok V, Choi P, Ng CF, Sengupta S, Mostafid H, Kamat AM, Black PC et al (2020) Global trends of bladder cancer incidence and mortality, and their associations with tobacco use and gross domestic product per capita. Eur Urol 78:893–906 PubMed

Hong Kong population projections for 2022–2046 released [https://www.info.gov.hk/gia/general/202308/15/P2023081500304.htm]

Hieber C, Grabbe S, Bros M (2023) Counteracting immunosenescence-which therapeutic strategies are promising? Biomolecules 13:1085 PubMed PMC

Contieri R, Grajales V, Tan WS, Martini A, Sood A, Hensley P, Bree K, Lobo N, Nogueras-Gonzalez GM, Guo CC et al (2023) Impact of age >70 years on oncological outcomes in patients with non-muscle-invasive bladder cancer treated with Bacillus Calmette-Guérin. BJU Int 133:63–70 PubMed PMC

Liu K, Zhao H, Chen X, Nicoletti R, Vasdev N, Chiu PK, Ng CF, Kawada T, Laukhtina E, Mori K et al (2023) A territory-wide study investigating the dose and efficacy of different Bacillus Calmette-Guérin strains in patients with intermediate- and high-risk non-muscle-invasive bladder cancer. Eur Urol Oncol. 10.1016/j.euo.2023.09.014 PubMed

EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023. ISBN 978–94–92671–19–6

Kresovich JK, Xu Z, O’Brien KM, Weinberg CR, Sandler DP, Taylor JA (2019) Methylation-based biological age and breast cancer risk. J Natl Cancer Inst 111:1051–1058 PubMed PMC

Harrison H, Thompson RE, Lin Z, Rossi SH, Stewart GD, Griffin SJ, Usher-Smith JA (2021) Risk prediction models for kidney cancer: a systematic review. Eur Urol Focus 7:1380–1390 PubMed PMC

Deuker M, Rosiello G, Stolzenbach LF, Martin T, Collà Ruvolo C, Nocera L, Tian Z, Roos FC, Becker A, Kluth LA et al (2021) Sex- and age-related differences in the distribution of metastases in patients with upper urinary tract urothelial carcinoma. J Natl Compr Canc Netw 19:534–540 PubMed

Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK (2020) Prostate cancer incidence and survival, by stage and race/ethnicity - United States, 2001–2017. MMWR Morb Mortal Wkly Rep 69:1473–1480 PubMed PMC

Herr HW (2007) Age and outcome of superficial bladder cancer treated with Bacille Calmette-Guérin therapy. Urology 70:65–68 PubMed

Oddens JR, Sylvester RJ, Brausi MA, Kirkels WJ, van de Beek C, van Andel G, de Reijke TM, Prescott S, Witjes JA, Oosterlinck W (2014) The effect of age on the efficacy of maintenance bacillus Calmette-Guérin relative to maintenance epirubicin in patients with stage Ta T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911. Eur Urol 66:694–701 PubMed

Sylvester RJ, Brausi MA, Kirkels WJ, Hoeltl W, Calais Da Silva F, Powell PH, Prescott S, Kirkali Z, van de Beek C, Gorlia T, de Reijke TM: Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder. Eur Urol 2010;57:766-773 PubMed PMC

Oddens JR, Sylvester RJ, Brausi MA, Kirkels WJ, van de Beek C, van Andel G, de Reijke TM, Prescott S, Alfred Witjes J, Oosterlinck W (2016) Increasing age is not associated with toxicity leading to discontinuation of treatment in patients with urothelial non-muscle-invasive bladder cancer randomised to receive 3 years of maintenance Bacille Calmette-Guérin: results from European Organisation for Research and Treatment of Cancer Genito-Urinary Group study 30911. BJU Int 118:423–428 PubMed

Ershler WB, Socinski MA, Greene CJ (1983) Bronchogenic cancer, metastases, and aging. J Am Geriatr Soc 31:673–676 PubMed

Fisher CJ, Egan MK, Smith P, Wicks K, Millis RR, Fentiman IS (1997) Histopathology of breast cancer in relation to age. Br J Cancer 75:593–596 PubMed PMC

Gödde D, Degener S, Walles C, Keller R, Graf K, Tosch M, Krege S, Musch M, Kvasnicka HM, Ackermann M, et al: Degenerative changes in aging human pelvic lymph nodes-a reason to rethink staging and therapy of regional malignancies? Cancers (Basel) 2023, 15 PubMed PMC