Abstract
Simple SummaryThe 2016 World Health Organization classification system distinguishes between urothelial carcinomas (UCs) with divergent differentiation (DD) and those with variant morphologies (VMs), which until now had been considered to indicate highest-risk cases. Intravesical Bacillus Calmette–Guérin (BCG) treatment is an alternative therapeutic and adjuvant option after transurethral resection of a bladder tumor. However, data comparing oncological outcomes after intravesical BCG treatment among pure UC, UC with DD, and UC with VMs are sparse. This is a retrospective study to investigate the outcomes of bladder-preservation therapy using intravesical BCG treatment on cases of bladder UCs with DD or VMs. We followed the outcomes of 1490 patients with pure UCs, UC with DD, or UC with VM. We found that concomitant VMs, not DD, was more likely to result in cancer-specific death. The VM-associated risk was significant for cancer-specific mortality only, not for recurrence-free or progression-free survival rates.The 2016 World Health Organization classification newly described infiltrating urothelial carcinoma (UC) with divergent differentiation (DD) or variant morphologies (VMs). Data comparing oncological outcomes after bladder-preservation therapy using intravesical Bacillus Calmette–Guérin (BCG) treatment among T1 bladder pure UC (pUC), UC with DD (UC-DD), and UC with VMs (UC-VM) are limited. We evaluated 1490 patients with T1 high-grade bladder UC who received intravesical BCG during 2000–2019. They were classified into three groups: 93.6% with pUC, 4.4% with UC-DD, and 2.0% with UC-VM. Recurrence-free, progression-free, and cancer-specific survival following intravesical BCG were compared among the groups using multivariate Cox regression analysis, also used to estimate inverse probability of treatment weighting-adjusted hazard ratio and 95% confidence interval for the outcomes. Glandular differentiation and micropapillary variant were the most common forms in the UC-DD and UC-VM groups, respectively. Of 1490 patients, 31% and 13% experienced recurrence and progression, respectively, and 5.0% died of bladder cancer. Survival analyses revealed the impact of concomitant VMs was significant for cancer-specific survival, but not recurrence-free and progression-free survival compared with that of pUC. Our analysis clearly demonstrated that concomitant VMs were associated with aggressive behavior in contrast to concomitant DD in patients treated with intravesical BCG.
Highlights
Bladder cancer is the 10th most common cancer, with roughly 549,000 initially diagnosed cases and 200,000 deaths reported annually according to 2018 worldwide cancer statistics [1]
In the urothelial carcinoma (UC)-divergent differentiation (DD) group, 38 (69%) and 27 (41%) patients had glandular differentiation and squamous differentiation, respectively, whereas trophoblastic differentiation was not seen in our cohort
We investigated the impact of concomitant DD and variant morphologies (VMs) in TUR specimens in T1/HG
Summary
Bladder cancer is the 10th most common cancer, with roughly 549,000 initially diagnosed cases and 200,000 deaths reported annually according to 2018 worldwide cancer statistics [1]. Non-muscle-invasive bladder cancer (NMIBC; Ta, T1, and Tis) is a heterogeneous disease accounting for approximately 70% of initially diagnosed bladder cancers [2]. Most of NMIBC can be treated with the combination of transurethral resection of a bladder tumor (TURBT) and intravesical treatment of chemotherapy and Bacillus. The European Association of Urology guidelines 2019 specify characteristics of the highest-risk subset from high-risk non-muscle invasive bladder cancers (NMIBCs) [3]. Patients are stratified into highest-risk NMIBC when the tumor has at least one of the following five aggressive factors: i) T1/high-grade (HG) urothelial carcinoma (UC) with concomitant bladder carcinoma in situ (CIS); ii) multiple and/or large and/or recurrent. Clinical practice guidelines suggest that intravesical BCG treatment is still an alternative therapeutic and adjuvant option after transurethral resection of a bladder tumor (TURBT) for high-/highestrisk NMIBCs [4,5,6]. Clinicians may judge that not all the patients with highest-risk NMIBC require RC because of the highly heterogenic nature of highest-risk NMIBC [7]
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