Intravesical Bacillus Calmette–Guérin Treatment for T1 High-Grade Non-Muscle Invasive Bladder Cancer with Divergent Differentiation or Variant Morphologies

• Main Authors: Makito Miyake, Nobutaka Nishimura, Kota Iida, Tomomi Fujii, Ryoma Nishikawa, Shogo Teraoka, Atsushi Takenaka, Hiroshi Kikuchi, Takashige Abe, Nobuo Shinohara, Eijiro Okajima, Takuto Shimizu, Shunta Hori, Norihiko Tsuchiya, Takuya Owari, Yasukiyo Murakami, Rikiya Taoka, Takashi Kobayashi, Takahiro Kojima, Naotaka Nishiyama, Hiroshi Kitamura, Hiroyuki Nishiyama, Kiyohide Fujimoto
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Cancers
• Subjects: urinary bladder neoplasms; Bacillus Calmette–Guérin (BCG); immunotherapy; divergent differentiation; variant morphology; survival
• Online Access: https://www.mdpi.com/2072-6694/13/11/2615

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.