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

Abstract

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.

T1 bladder carcinoma with variant histology: pathological features and clinical significance

“…6), although, our risk categorization is mostly based on cancer specific survival following guidelines supported therapy. A challenging point is that there were no cases of plasmacytoid carcinoma in our series, similar to Miyake's recent study of 1490 cases of HGT1 carcinoma; this is probably due to the rarity of the histologic variant in HGT1 carcinomas, with no reported series to date in the English literature [12,39]. It seems reasonable to include plasmacytoid morphology as part of our high-risk category.…”

“…The current WHO revision includes urothelial carcinoma with divergent (squamous, glandular, and trophoblastic) differentiation, nested, microcystic, micropapillary, lymphoepithelioma-like (LELC), plasmacytoid/signet ring cell/diffuse, sarcomatoid, giant cell, poorly differentiated, lipid-rich, and clear cell (glycogen-rich) as histologic variants [28]. The presence of any variant or combinations thereof is considered high risk in NMIBC; [12] the NCCN clinical guidelines also recommend immediate radical cystectomy for HGT1 with micropapillary, plasmacytoid, or sarcomatoid variants, and the AUA guidelines of NMIBC include the presence of any histologic variant as a high-risk category [31,32]. The true incidence of variant histology in HGT1 urothelial carcinoma is uncertain, mainly based on limited reports of short case series, and ranges from 6.4 to 23% [33,34].…”

“…On the other hand, micropapillary, nested, glandular, and basaloid variants showed lower CSS rates than squamous, inverted, microcystic, villous-like, and LELC variants whose patients remained alive over 150 months of follow-up. Miyake et al, [12] in an extensive series of 1490 patients with NMIBC, recently reported an incidence of 6.4% with variant histology. These patients are more likely to result in cancer-related death than those with conventional urothelial carcinoma or with divergent differentiation, similar to our findings concerning risk stratification; in fact, our cases with divergent squamous differentiation were included as part of the low-risk category, and cases such as micropapillary and nested carcinomas remained as aggressive, life-threatening high-risk diseases.…”

“…The role of variant histology to stratify patients at risk in HGT1 bladder carcinomas remains uncertain due to the limited number of related studies. Most reports on HGT1 with variant histology are reporting on micropapillary carcinoma or, rarely, nested carcinoma [4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The fact that some pathologists do not recognize or report about one-half of cases with variant histology in their practice is an additional limitation; therefore, the risk associated with variant histology in HGT1 carcinomas might indeed be underrecognized [21,22].…”

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

“…Five additional articles present original investigations regarding invasive bladder cancer. Miyake et al [21] present a retrospective study of a very large series of patients with T1 high-grade urothelial carcinoma and evaluate the prognostic role of divergent differentiation and variant morphologies when Bacillus Calmette-Guérin (BCG) endovesical treatment is used. This topic presents the clinical implications of urothelial cancer heterogeneity and is of particular interest in this era of BCG shortage, where new treat modalities such as chemo-hyperthermia to optimize adjuvant treatment after transurethral resection are being investigated [22,23] or even early cystectomy [24] are controversial.…”