The Use of Urine Mycobacterium tuberculosis Complex Polymerase Chain Reaction as a Predictive Factor for Recurrence and Progression After Intravesical Bacillus Calmette-Guérin Therapy in Patients with Non–muscle‑invasive Bladder Cancer

• Main Authors: Satoru Muto, Yan Lu, Hisamitsu Ide, Raizo Yamaguchi, Keisuke Saito, Kousuke Kitamura, Yasuhiro Noma, Hiroki Koyasu, Hisashi Hirano, Takeshi Ashizawa, Shuji Isotani, Masayoshi Nagata, Shigeo Horie
• Format: Article
• Language: English
• Published: Elsevier 2021-05-01
• Series: European Urology Open Science
• Subjects: Bladder cancer; Bacillus Calmette-Guérin; Non–muscle invasive; Mycobacterium tuberculosis complex polymerase chain reaction
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666168321000409

Background: Intravesical bacillus Calmette-Guérin (BCG) instillation is a standard treatment for non–muscle-invasive bladder cancer (NMIBC); however, not all patients benefit from BCG therapy. Currently, no surrogate marker exists to predict BCG efficacy, and thereby, identify patients who will benefit from this treatment. Objective: To evaluate the utility of urine Mycobacterium tuberculosis complex polymerase chain reaction (MTC-PCR) assay as a predictive marker for recurrence and progression following BCG therapy. Design, setting, and participants: A prospective analysis was carried out for of intermediate- or high-risk NMIBC patients who received BCG instillation for the first time. Urine samples, for MTC-PCR assay, were collected at baseline and annually for up to 10 yr after the last BCG instillation, including induction and maintenance therapy. The first postoperative sample for MTC-PCR was taken at 1 yr from the last instillation. Outcome measurements and statistical analysis: A survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence and progression after BCG treatment were assessed using Cox regression analysis. Results and limitations: During follow-up (median: 57 mo), 468/521 samples (89.8%) were MTC-PCR positive, and 108/123 patients (87.8%) exhibited MTC-PCR positivity at least once. Five-year recurrence- and progression-free survival in patients who were not MTC-PCR positive was significantly lower than in patients who were MTC-PCR positive at least once (p <  0.001). Using multivariable Cox regression analysis, MTC-PCR positivity at least once was a significant prognostic factor for recurrence (hazard ratio [HR]: 36.782, p <  0.001) and progression (HR: 47.209, p <  0.001). Conclusions: Patients who were not MTC-PCR positive, even once after BCG therapy, were extremely likely to exhibit recurrence and progression. Urine MTC-PCR may be an extremely useful, noninvasive surrogate marker to predict recurrence and progression following BCG therapy. Patient summary: Urine Mycobacterium tuberculosis complex polymerase chain reaction may be a novel biomarker capable of identifying patients at risk of recurrence and progression after bacillus Calmette-Guérin (BCG) immunotherapy.