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This study aims to evaluate the effect of Bacillus Calmette-Guérin (BCG) instillation and radical cystectomy on high-risk NMIBC with squamous or glandular variants. We retrospectively reviewed the data of high-risk (T1 or CIS or HG or TaG1/G2 with multiple, recurrent, large tumor) NMIBC patients from January 2000 to December 2017. Comparative analysis of radical cystectomy, intravesical BCG, and observation groups was conducted in high-risk NMIBC with squamous or glandular histologic variants. Among the 1263 high-risk NMIBC patient, 62 (4.9%) were reported squamous or glandular histologic variants. Thirty patients underwent BCG instillation and 15 patients were subjected to radical cystectomy. Statistically significant differences were found between the three treatment groups in terms of underlying hypertension (p = 0.031), T stage (p = 0.022) and tumor multiplicity (p = 0.019). Similar 5-year OS (p = 0.893) and CSS (p = 0.811) were observed in each of BCG instillation and radical cystectomy group. BCG instillation showed survival benefit in both OS (p = 0.019) and CSS (p = 0.038) than in the observation group. In high-risk patients diagnosed with NMIBC bladder cancer with squamous or glandular histologic variants, both intravesical BCG and radical cystectomy showed survival gain. In conclusion, BCG instillation represents an appropriate treatment option in high-risk NMIBC with squamous or glandular histologic variant.

BCG instillation versus radical cystectomy for high-risk NMIBC with squamous/glandular histologic variants