Introduction:

Bacillus Calmette-Guerin (BCG) therapy is standard of care following transurethral resection of high-risk non-muscle invasive bladder cancer. Following induction +/- 3-month maintenance, bladder biopsies may be performed to assess response to treatment. The benefit of this approach has not been rigorously tested, so the aim of our study was to evaluate the utility of these biopsies and to compare the recurrence and progression rate of patients who received biopsies versus those who were evaluated by cystoscopy and cytology only after induction with BCG. 

Methods:

We reviewed our prospective IRB approved institutional database (Caisis) of patients with non-muscle invasive bladder cancer bladder cancer and performed a retrospective review of all patients who underwent BCG induction therapy between 2005 and 2018.  All patients had urine cytology and either an office cystoscopy or cystoscopy with site directed biopsies under anesthesia. Patients with an abnormal office cystoscopy underwent resection or biopsy in the operating room. We determined the number of patients who developed recurrence or progression and calculated disease free survival (DFS), which was the time to recurrence or progression stratified by patients who had a positive vs negative cystoscopy and cytology after BCG induction. We determined how the addition of site directed biopsies would change these clinical parameters. Chi-square test , Student’s t-test, and logistic regression were used as appropriate with statistical significance defined as p < 0.05

Results:

120 patients were reviewed with an average follow-up of 88.5 months (mo). 51 patients had an office cystoscopy only with 45 and 6 patients with a negative and positive cytology, respectively. 14(31.1%) and 5(83.3%) patients who had a negative and positive cytology, respectively developed recurrence/progression with a DFS of 17.1 and 16 mo, respectively. 69 patients underwent site directed biopsies. Of the 44 patients with a negative biopsy and negative cytology, 11(25%) developed recurrence/progression and DFS was 55.9 mo. Of the 17 patients with a positive biopsy (3 T1HG, 5 Ta LG, 9 CIS) and negative cytology, 14(82.3%) developed recurrence of progression and DFS was 35.2 mo. Of the 7 patients with a positive biopsy (2 T1HG, 2 Ta LG, and 3 CIS) and positive cytology, 7(100%) developed recurrence/progression with DFS 12.27 mo. Lastly 1 patient had a negative biopsy and positive cytology and never developed recurrence/progression.

Conclusion:

After BCG induction therapy, nearly one-third of patients with a negative cystoscopy and negative cytology will recur/progress and this likelihood increases with a positive cytology. While patients with a negative biopsy and cytology do no recur at a lower rate, the DFS is signifcantly longer statistically. Furthermore, patients with a positive biopsy and negative cytology develop recurrence or progression at a higher rate with a shorter DFS (p<0.05) compared to patients with a negative biopsy. The DFS of patients with a positive biopsy and negative cytology compared to patients with a negative cystoscopy, however was significnatly longer (p< 0.05). This may be attributed to repeat induction therapy. Last, patients with a positive biopsy and cytology will with certainty recur (100%) with the shortest DFS (p<0.05). Thus the addition of biopsies with cytology after induction with BCG will better stratify patients to determine risk of recurrence or progression.

Funding: N/A