Predicting Recurrence and Progression in Patients with Non-Muscle-Invasive Bladder Cancer : Systematic Review on the Performance of Risk Stratification Models

BACKGROUND: Several classifications have been reported to stratify non-muscle-invasive bladder cancer (NMIBC) in risk groups according to the probability of recurrence and progression. OBJECTIVE: To systematically review the current evidence regarding risk stratification of NMIBC. METHODS: The systematic review was performed in accordance with the PRISMA statement. Studies providing data on development and/or external validation cohorts of models and risk stratification tables for recurrence and/or progression for patients with NMIBC, reporting at least one discrimination measure (AUC or C-Index) were included. RESULTS: Twenty-five studies involving 22,737 patients were included. Six classifications were identified, three of them were predictive models (EORTC, CUETO, EAU 2021) and three were based on expert opinion (EAU 2020, AUA, NCCN). A high risk of bias was present in the majority of the studies. Certain heterogenicity was found among the studies regarding adjuvant therapy, postoperative instillation or second resection. The definition of oncological outcomes was not standardized in the included studies. CUETO and EORTC scoring systems are the most validated. In general, validations showed a poor discrimination capability to predict recurrence, slightly better for progression. The EAU 2021 model overestimates the risk of progression in patients treated with BCG. Carcinoma in situ is underrepresented in all the studies analyzed. CONCLUSIONS: The existing classifications show poor discrimination capability for recurrence and possibly helpful discrimination capability for progression in NMIBC patients. These results highlight the unmet need to develop novel accurate risk models for patients with NMIBC, which could be improved with the combination of clinicopathological and molecular information

Adjuvant single-dose upper urinary tract instillation of mitomycin C after therapeutic ureteroscopy for upper tract urothelial carcinoma: a single-centre prospective non-randomized trial

Purpose To address the safety and feasibility of upper urinary tract instillation of a single dose of mitomycin (ASDM) immediately after therapeutic ureteroscopy for upper tract urothelial carcinoma (UTUC) and to compare urothelial (ipsilateral or bladder) recurrence rates in the ASDM group and controls. Materials and Methods Between April 2015 and August 2018, 52 patients affected by UTUC were treated by endoscopic ablation, of whom 26 were selected for ASDM. Clinical and perioperative data and 30-day complications were recorded. The primary endpoint was urothelial recurrence-free survival (URFS) evaluated by second-look ureteroscopy and CT scan/ureteroscopy every 6 months. Results ASDM was administered via a single-J (19/25, 76%) or a double-J (6/25, 24%) in 25/26 (96%) patients. Median follow-up was 18 months (IQR 10-29). The urothelial recurrence rate was 23.5% and 55.5% in the ASDM group and controls, respectively (p=0.086). Mean URFS was 28.8 months in the ASDM group vs 18.8 months in controls (log-rank p=0.067). On multivariate Cox regression, ASDM was associated with a 7.7-fold lower risk of urothelial recurrence (HR=0.13; 95% CI 0.03-0.65; p=0.01). Clavien grade 64II complications occurred in 32% (8/25) and 30.7% (8/26) of the ASDM and control group, respectively (p=0.9). Two Clavien III complications occurred in the ASDM group: bladder haematuria after concomitant TURB and obstructive kidney failure in a single-kidney patient. Conclusions ASDM was well tolerated after therapeutic ureteroscopy. It appears to reduce the risk of urothelial recurrence in patients affected by low-grade UTUC without bladder tumour. Therefore, its use should be evaluated

T1G1 Bladder Cancer: Prognosis for this Rare Pathological Diagnosis Within the Non-muscle-invasive Bladder Cancer Spectrum

BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer