Original Study| Volume 20, ISSUE 6, P595-603, December 2022

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Intravesical Therapy Compared to Radical Cystectomy Among Patients With Non-Muscle Invasive Bladder Cancer Requiring Additional Treatment After Induction BCG



      Many patients with recurrent high-risk non-muscle invasive bladder cancer after intravesical bacillus calmette-guerin (BCG) face a difficult decision between radical cystectomy (RC) or salvage intravesical therapy (IVT). We sought to determine if there is a difference in overall survival RC and IVT after previous treatment with BCG.


      We performed a retrospective cohort study of patients with Ta, T1, and Tis bladder cancer treated with induction BCG in the SEER-Medicare dataset from 2000 to 2015. We used a proportional hazards regression model to compare differences in survival between patients having RC and IVT. We adjusted for confounding using a propensity score and stratified our analysis according to timing of treatment and stage at diagnosis.


      We identified 3940 patients who received either IVT (79%) or RC (21%) following induction BCG. Among patients treated within 12 months of BCG, there was no significant difference in survival between RC and IVT (HR 0.92, 95% CI 0.81-1.04) and 17% of patients having early IVT ultimately required RC. Among patients treated at least 12 months after BCG, RC was associated with worse survival than IVT (HR 1.19, 95% CI 1.06-1.35) and 10% of patients having late IVT ultimately required RC.


      Among patients with bladder cancer who required additional treatments after induction BCG, we did not observe a difference in overall survival between IVT and RC within 12 months of starting BCG. While RC remains the gold-standard for high risk recurrent NMIBC after BCG, bladder preservation with IVT may be appropriate for well-selected patients.


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        • Morales A
        • Eidinger D
        • Bruce AW
        Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors.
        J Urol. 1976; 116: 180-183
        • Pinsky CM
        • Camacho FJ
        • Kerr D
        • et al.
        Intravesical administration of bacillus Calmette-Guerin in patients with recurrent superficial carcinoma of the urinary bladder: report of a prospective, randomized trial.
        Cancer Treat Rep. 1985; 69: 47-53
        • Cookson MS
        • Herr HW
        • Zhang ZF
        • et al.
        The treated natural history of high risk superficial bladder cancer: 15-year outcome.
        J Urol. 1997; 158: 62-67
      1. Administration USFD: Bacillus Calmette-Guerin-Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biologics for Treatment Guidance for Industry, 2018.

        • Chang SS
        • Boorjian SA
        • Chou R
        • et al.
        Diagnosis and treatment of non-muscle invasive bladder cancer.
        American Urological Association (AUA)/Society of Urologic Oncology (SUO) Guideline, American Urological Association2016
        • Catalona WJ
        • Hudson MA
        • Gillen DP
        • et al.
        Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer.
        J Urol. 1987; 137: 220-224
        • Koch GE
        • Luckenbaugh AN
        • Chang SS
        High-risk nonmuscle invasive bladder cancer: selecting the appropriate patient for timely cystectomy.
        Urology. 2021; 147: 7-13
        • Raj GV
        • Herr H
        • Serio AM
        • et al.
        Treatment paradigm shift may improve survival of patients with high risk superficial bladder cancer.
        J Urol. 2007; 177 (discussion 1286): 1283-1286
        • Anderson CB
        • McKiernan JM
        Complications of Radical Cystectomy and Urinary Diversion.
        in: Taneja SS Shah O Complications of Urologic Surgery: Diagnosis, Prevention, and Management. ed 5th. Elsevier, 2018: 433-444
        • Haas CR
        • McKiernan JM
        Salvage therapy using bacillus calmette-guerin derivatives or single agent chemotherapy.
        Urol Clin North Am. 2020; 47: 47-54
        • Steinberg G
        • Bahnson R
        • Brosman S
        • et al.
        Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group.
        J Urol. 2000; 163: 761-767
        • Lee CT
        • Dunn RL
        • Ingold C
        • et al.
        Early-stage bladder cancer surveillance does not improve survival if high-risk patients are permitted to progress to muscle invasion.
        Urology. 2007; 69: 1068-1072
        • Klabunde CN
        • Potosky AL
        • Legler JM
        • et al.
        Development of a comorbidity index using physician claims data.
        J Clin Epidemiol. 2000; 53: 1258-1267
        • Du XL
        • Fang S
        • Vernon SW
        • et al.
        Racial disparities and socioeconomic status in association with survival in a large population-based cohort of elderly patients with colon cancer.
        Cancer. 2007; 110: 660-669
        • Cole SR
        • Hernan MA
        Adjusted survival curves with inverse probability weights.
        Comput Methods Programs Biomed. 2004; 75: 45-49
        • Cole SR
        • Hernan MA
        Constructing inverse probability weights for marginal structural models.
        Am J Epidemiol. 2008; 168: 656-664
        • Austin PC
        Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis.
        Stat Med. 2016; 35: 5642-5655
        • Matulewicz RS
        • Frainey BT
        • Oberlin DT
        • et al.
        High-risk of adverse pathologic features in patients with clinical t1 high-grade bladder cancer undergoing radical cystectomy.
        J Natl Compr Canc Netw. 2016; 14: 1403-1411
        • Di Lorenzo G
        • Perdona S
        • Damiano R
        • et al.
        Gemcitabine versus bacille Calmette-Guerin after initial bacille Calmette-Guerin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial.
        Cancer. 2010; 116: 1893-1900
        • Khaled D
        • Taylor J
        • Holzbeierlein J
        Salvage therapy for non-muscle-invasive bladder cancer: novel intravesical agents.
        Urol Clin North Am. 2020; 47: 119-128
        • Gallagher BL
        • Joudi FN
        • Maymi JL
        • et al.
        Impact of previous bacille Calmette-Guerin failure pattern on subsequent response to bacille Calmette-Guerin plus interferon intravesical therapy.
        Urology. 2008; 71: 297-301
        • Li R
        • Metcalfe MJ
        • Tabayoyong WB
        • et al.
        Using grade of recurrent tumor to guide further therapy while on bacillus calmette-guerin: low-grade recurrences are not benign.
        Eur Urol Oncol. 2019; 2: 286-293
        • Tilki D
        • Reich O
        • Svatek RS
        • et al.
        Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients.
        J Urol. 2010; 183: 1757-1763
        • Lamm D
        • Herr H
        • Jakse G
        • et al.
        Updated concepts and treatment of carcinoma in situ.
        Urol Oncol. 1998; 4: 130-138
        • Balar AV
        • Kulkarni GS
        • Uchio EM
        • et al.
        Keynote 057: Phase II trial of pembrolizumab for patients with high-risk non-muscle invasive bladder cancer unresponsive to bacillus calmette-guerin (abstract).
        JCO. 2019; 37: 350
        • Boorjian SA
        • Alemozaffar M
        • Konety BR
        • et al.
        Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.
        Lancet Oncol. 2021; 22: 107-117
        • DeCastro GJ
        • Sui W
        • Pak JS
        • et al.
        A phase i trial of intravesical cabazitaxel, gemcitabine and cisplatin for the treatment of nonmuscle invasive bacillus calmette-guerin unresponsive or recurrent/relapsing urothelial carcinoma of the bladder.
        J Urol. 2020; 204: 247-253
        • Steinberg RL
        • Thomas LJ
        • Brooks N
        • et al.
        Multi-institution evaluation of sequential gemcitabine and docetaxel as rescue therapy for nonmuscle invasive bladder cancer.
        J Urol. 2020; 203: 902-909
        • Haas CR
        • Barlow LJ
        • Badalato GM
        • et al.
        The timing of radical cystectomy for bacillus calmette-guerin failure: comparison of outcomes and risk factors for prognosis.
        J Urol. 2016; 195: 1704-1709
        • Packiam VT
        • Labbate CV
        • Boorjian SA
        • et al.
        The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis.
        Urol Oncol. 2021; 39: 436.e1-436.e8