Cystoscopy and Systematic Bladder Tissue Sampling in Predicting pT0 Bladder Cancer: A Prospective Trial

Abstract

Purpose: Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates.

Materials and methods: Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology.

Results: A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (>pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility.

Conclusions: Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

Keywords: cystectomy; cystoscopy; neoadjuvant therapy; urinary bladder neoplasms.

Figure 1:

Consort Diagram for trial accrual across each cohort

Figure 2:

Agreement between SEE (seeT) and final pathology (pT) for the combined cohort (n=61).

Figure 3:

Gross pathology from a cystoprostatectomy specimen of a 66 y.o. male patient who underwent NAC with MVAC for cT3 HG UC. SEE with TUR (Cohort B) demonstrated seeT0 disease (muscle in specimen), while pT3a disease was noted upon extirpation: (A) Bivalved specimen with TUR site posterior lateral to left ureteral orifice and adjacent shallow diverticulum are inked green (white arrow); (B) Bisection of specimen through the TUR site demonstrates extensive submucosal pT3b high grade tumor (black arrows), which is deep to the extensive TUR (inked green) at this site.