Although lymph node (LN) status and the LN burden determine the outcome of bladder cancer patients treated with cystectomy, compelling arguments have been made for the incorporation of LN density into the current staging system. Here, we investigate the relationship between LN density and clinical outcome in patients with LN-positive disease, following radical cystectomy for bladder cancer. PubMed, SCOPUS, the Institute for Scientific Information Web of Science, and the Cochrane Library were searched to identify relevant published literature. Fourteen studies were included in the meta-analysis, with a total number of 3311 patients. Of these 14 publications, 6 studies, (533 patients), 10 studies (2966 patients), and 5 studies (1108 patients) investigated the prognostic association of LN density with disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS), respectively. The pooled hazard ratio (HR) for DFS was 1.45 (95 % confidence interval [CI], 1.10–1.91) without heterogeneity (I2 = 0 %, p = 0.52). Higher LN density was significantly associated with poor DSS (pooled HR, 1.53; 95 % CI, 1.23–1.89). However, significant heterogeneity was found between studies (I2 = 66 %, p = 0.002). The pooled HR for OS was statistically significant (pooled HR, 1.45; 95 % CI, 1.11–1.90) without heterogeneity (I2 = 42 %, p = 0.14). The results of the Begg and Egger tests suggested that publication bias was not evident in this meta-analysis. The data from this meta-analysis indicate that LN density is an independent predictor of clinical outcome in LN-positive patients. LN density may be useful in future staging systems, thus allowing better prognostic classification of LN-positive bladder cancer.

Intravesical bacillus Calmette–Guerin (BCG) instillation is widely used as an adjuvant therapy after transurethral resection of bladder tumor (TURBT) in patients with intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). However, the effective dose, duration, and strain of BCG have not yet been clearly determined. We aimed to elucidate the relationship between dose, duration, and strain of BCG and clinical outcomes in NMIBC patients treated with TURBT. We conducted a literature search in Embase, Scopus, and PubMed databases for all relevant articles published up to October 2016 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The relative risks of clinical outcomes, including recurrence, progression, cancer-specific mortality, and all-cause mortality according to dose (standard vs low), duration (induction vs maintenance), and strain of BCG were presented as the pooled risk ratio (RR) and 95% confidence interval (CI). Nineteen studies meeting the inclusion criteria were finally selected in this meta-analysis. The risk of recurrence was significantly highly observed in case of low-dose BCG (RR, 1.17; 95% CI 1.06–1.30) and induction BCG (RR, 1.33; 95% CI 1.17–1.50) only group without heterogeneity among the included studies. Although there were no significant differences between dose or duration and other clinical outcomes. On direct comparison in each study comparing BCG strains, the Tice stain showed a relatively high probability of recurrence compared with the Connaught (RR, 1.29; 95% CI 1.01–1.64) and RIVM (RR, 2.04, 95% CI 1.28–3.25) strains. Funnel plot testing revealed no significant publication bias. The use of standard dose and maintenance BCG instillation may be effective to reduce recurrence rate after TURBT for NMIBC. Further large scale, well-designed, and prospective studies, with stratification of the patients into risk group at randomization, will be required to determine the optimal guideline of BCG use to improve clinical outcomes in NMIBC.

Kim HS, et al. Investig Clin Urol. 2021 Jul;62(4):361-377. https://doi.org/10.4111/icu.20200602