Long-term risk of progression of carcinoma in situ of the bladder and impact of bacille Calmette–Guérin immunotherapy on the outcome

Abstract

Objective. This study aimed to determine the long-term risk of cancer progression of carcinoma in situ (CIS) of the urinary bladder, and whether intravesical bacille Calmette–Guérin (BCG) immunotherapy can reduce the risk of progression of CIS.Material and methods. From a prospectively enrolled cohort of bladder cancer patients treated at Århus University Hospital Skejby, Denmark, between 1994 and 2008, all 163 cases with CIS in the bladder, and a history free of invasive bladder cancer (stage T1–4) at least 1 year prior to inclusion were included in the study. Results. Median follow-up was 51 (0–253) months for progression. Initial treatment consisted of transurethral resection (TUR) alone (109 patients) or TUR plus BCG (54 patients). Twenty-eight patients underwent delayed treatment with BCG. Twenty-one patients in the TUR-alone group (19%) and 42 BCG-treated patients (51%) were free of disease at the end of follow-up (p < 0.001). Progression occurred in 18 BCG-treated patients (22%) versus 31 patients (41%) treated by TUR alone. The 10-year progression-free survival was 62% overall, 50% without BCG and 71% after BCG treatment (p = 0.04). BCG reduced the risk of progression by 46% (hazard ratio 0.54, 95% confidence interval 0.3–0.97). Thirteen patients (9%) experienced progression in the prostate and nine (6%) showed extravesical progression (upper urinary tract or metastases). This was independent of BCG treatment. Conclusion. CIS in the absence of invasive (T1) disease carried a 10-year risk of progression of 29–48%. Although BCG was effective against CIS, this effect was limited to the bladder. BCG provided a marginal, but significant reduction in the overall long-term risk of progression.

Key Words::

• BCG
• carcinoma in situ
• disease-free survival
• disease progression
• urinary bladder neoplasms

Acknowledgements

We wish to thank Bente Pytlich, Connie Sørensen and Gitte Stougaard for technical assistance collecting the data. Our uropathologists Søren Hoyer and Benedicte Parm Ulhøi, Institute of Pathology, Århus University Hospital, contributed with administrative support and valuable advice, which is gratefully acknowledged.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.