Metachronous bladder recurrences after prior treatment for primary upper tract urothelial carcinoma (UTUC) can occur in ~3-50% of patients. We aim to study the BCG efficacy in patients with primary high risk non-muscle invasive bladder cancer (P-NMIBC) and metachronous bladder recurrences after previous nephroureterectomy for UTUC (M-NMIBC).

We reviewed an IRB-approved prospective uro-oncology database of patients who underwent transurethral resection followed by BCG therapy for high grade NMIBC from 2017 to 2021. Clinicopathological parameters, intravesical therapies and the oncological outcomes were analyzed. Patients in the P-NMIBC group were matched to patients in the M-NMIBC cohort (control) via propensity score matching (PSM) to adjust for potential clinicopathological confounders. The primary outcomes were high grade (HG) intravesical recurrences after BCG and progression to muscle invasive disease (MIBC). Secondary outcomes were metastasis free and overall survival. Logistic and cox regression analyses were performed to elucidate independent variables associated with intravesical recurrences and disease progression.

Of the 183 patients diagnosed with NMIBC, 35 patients were identified to have a history of UTUC with radical nephroureterectomy. EAU risk stratification revealed 50 (27.3%) intermediate risk, 107 (58.5%) high risk and 26 (14.2%) very high risk groups. P-NMIBC patients were more likely to have symptomatic presentation (79.7% vs 22.9%), and a larger mean tumour size (3.6cm vs 1.2cm) than M-NMIBC. The mean follow-up duration for the study was 34 months. In the unmatched analysis, M-NMIBC was associated with increased risk of HG intravesical recurrence post BCG compared to P-NMIBC (P=0.006, HR 2.14, 95%CI: 1.25 – 3.65) and increased risk of progression to MIBC (P=0.007, HR 4.19, 95%CI: 1.47 – 11.95). For the propensity-matched analysis, the control group consisted of 35 M-NMIBC matched to 123 P-NMIBC patients for similar demographics, EAU risk score and BCG doses. M-NMIBC again demonstrated a higher HG intravesical recurrence rate (57.7% vs 22.8%, P=0.001, HR 2.67, 95%CI: 1.5 – 4.77), progression to MIBC (20% vs 5.7%, P=0.022, HR 1.2– 9.75, 95%CI: 1.2 - 9.75) and lower metastasis-free survival (20.0% vs 6.5%, P=0.033, HR 3.02, 95%CI: 1.09–8.35). Overall survival in both groups were not significantly different.

Our study indicates that BCG treatment may be less effective for NMIBC patients with a history of UTUC, with a higher risk of intravesical recurrences and disease progression. This is an important consideration when counselling patients for BCG treatment and overall prognostication.