Risk Factors for Multiple Intravesical Recurrences of Non-muscle Invasive Bladder Cancer
Andrew J. Charap, BS1, Jorge Daza, MD1, Linda Dey, MD2, Alberto Martini, MD1, John Pfail, BS1, Ashkan Mortezavi, MD2, Gunnar Steineck, MD2, Lotta Renström-Koskela, MD2, Peter Wiklund, MD PhD1, John Sfakianos, MD1.
1Icahn School of Medicine at Mount Sinai, New York, NY, 2Karolinska Institute, Stockholm, Sweden.
Introduction:Currently available risk calculators such are useful in identifying patients with non-muscle invasive bladder cancer (NMIBC) at risk for recurrence yet cannot identify patients who are at risk of multiple recurrence. Using an untreated cohort, we aimed to identify risk factors for multiple-recurrent disease in order to better risk stratify patients with NMIBC and aid clinical decision-making.Methods:Our cohort consisted of 535 patients diagnosed with bladder cancer in Stockholm County between the years 1995-96. We included patients with pathologic Ta or T1 disease who were confirmed to have at least one recurrence of their disease during median follow up of 12 years. Patients were excluded if they underwent cystectomy after first recurrence of disease. Patients who received curative chemotherapy, curative radiation, or an intravesical agent such as BCG or mitomycin were excluded to eliminate the confounding effects of these treatments on disease recurrence. Of this cohort, we identified 136 with NMIBC who experienced a recurrence during the course of the study and met criteria for inclusion.Results:The median age of the cohort at diagnosis was 72 years. 89 participants (65%) were male and 118 (88%) had pathologic Ta disease. 37 patients (27%) had high grade disease. Multiple recurrences were identified in 94 (69%) patients, versus 42 (31%) patients who experienced only a single recurrence. We found that patients with multiple-recurrent disease were more likely to experience their first recurrence within 6 months of their initial diagnosis (OR 2.49, 95% CI 1.07 - 5.79). Interestingly, many of the parameters included in the EROTC risk calculator were not significantly associated with multiple recurrence versus single recurrence, such as multifocal disease (OR 1.83, 95% CI .82 - 4.08), high-grade disease (OR 1.07, 95% CI .47 - 2.45), or T1 disease (OR .51, 95% CI .18 - 1.39). (Figure 1).Conclusion:In this study of an untreated cohort of patients we compared the clinical characteristics of patients with multi- versus single-recurrent non-muscle invasive bladder cancer. We found that patients with multiple recurrences were more than two-and-a-half times as likely to have experienced a first recurrence within six months. This information is important for risk stratifying patients for intravesical treatment. 
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