Are cystoscopy and urinary cytology sufficient to identify candidates for subsequent biopsy after bacillus Calmette–Guérin treatment in patients with bladder carcinoma in situ?

Reading the latest European Association of Urology (EAU) guidelines on non-muscle-invasive urothelial carcinoma of the bladder [1,2], as well as the literature, it seems that there are no clear recommendations for the follow-up of patients with carcinoma in situ (CIS) in the bladder after adjuvant intravesical bacillus Calmette–Gue rin (BCG) immunotherapy. After an initial diagnosis of CIS lesions in the bladder, adjuvant therapy with intravesical BCG is recommended if cystectomy for other reasons is not performed. The EAU guidelines recommend that BCG installations are given according to the empirically 6 weekly schedule, and a maintenance full-dose intravesical BCG treatment should be given for 1–3 years in high-risk tumours such as CIS. However, there are no specific recommendations on how to manage follow-up after BCG installations in clinical practice. The efficacy of intravesical BCG treatment is often evaluated by cystoscopy and routine transurethral bladder biopsies under general anaesthesia, as CIS is not always recognizable in white-light cystoscopy (WLC). This follow-up regimen is not supported by solid data but was introduced as part of the Southwest Oncology Group (SWOG) protocols, where the aim was to evaluate the efficacy of BCG treatment [3,4]. Because bladder biopsy under general anaesthesia is an invasive and costly procedure with known complications, the need for routine biopsy has been questioned. Earlier studies found indications that an individual approach tailored from cystoscopic findings and cytology would be the best followup regimen after BCG treatment in patients with non-muscleinvasive bladder cancer [5,6]. Urine cytology has generally high sensitivity in bladder CIS [7] but its interpretation is user dependent [8]. However, in experienced hands the specificity exceeds 90% [9]. We have investigated whether cystoscopy and urine cytology are sufficient initial follow-up in patients treated with intravesical BCG for bladder CIS, to identify patients in whom further bladder biopsies are needed. For a 3 year period from April 2010 to April 2013, all patients diagnosed with CIS in the bladder, either CIS per se or concurrent CIS with bladder tumour, and treated with intravesical BCG, at Aalborg University Hospital were included prospectively in the study. After transurethral resection of the bladder, a 6 week course of weekly intravesical BCG (BCG Medac, containing RIVM strain in 50 ml saline) was given. Six to eight weeks after the last installation, WLC with transurethral biopsies were performed under general anaesthesia. Biopsies were taken as standardized predefined selected site biopsies (including the prostatic urethra in males) as well as from target lesions. At cystoscopy the findings were described as either normal or suspicious of relapse. Preoperative voided urine and peroperative bladder wash were collected for urine cytology. Cytological changes induced by BCG therapy are non-specific and reactive in nature and distinguishable from malignant changes in urothelial cells. The cytology was described as normal, atypical, possible urothelial carcinoma or showing neoplastic urothelial cells. The cytology and bladder biopsies were undertaken as a standard procedure in this department by local cytopathologists. Normal cytology was categorized as negative cytology whereas other results were categorized as positive cytology. Overall, 98 patients (45–89 years of age) diagnosed with CIS in the bladder underwent intravesical BCG treatment in the 3 year period. Thirty-six were excluded because study criteria were not met (fewer than the prescribed number of biopsies had been taken, or the urine or bladder wash had not been collected for cytology). In total, 62 patients were included in the study. The indication for BCG treatment was for one-third of the patients with CIS per se, one-third with