Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes

Abstract

Background and Objective: The histologic variants of urothelial carcinoma (UC) are tumors arising from within the urothelium in which some component of the tumor morphology is other than urothelial.They are underdiagnosed, aggressive and have varying pathologic response rates to systemic chemotherapy.There are no consensus guidelines on the use of systemic chemotherapy in variant histology (VH) of UC. We performed a contemporary review on pathologic response rates to neoadjuvant systemic therapy and survival outcomes following radical cystectomy in order to provide a rationale for clinical practice recommendations on the management of UC with VH.Methods: A PubMed literature search was conducted for all English articles from inception reporting either pathological response rates to neoadjuvant treatment or survival outcomes after radical cystectomy in non-metastatic VH of UC.Key Content and Findings: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy was shown to be a beneficial treatment strategy in UC with VH. The micropapillary, plasmacytoid, nested and sarcomatoid histologic variants were associated with worse survival outcomes compared to conventional UC and UC with squamous or glandular differentiation despite initial downstaging with chemotherapy. There is evidence of improved survival in patients with sarcomatoid differentiation receiving NAC compared to RC alone. The major prognostic factors that affect survival outcomes in VH of UC include histologic variant subtype, patient age, presence of lymphovascular invasion, hydronephrosis, nodal metastasis and advanced T stage at diagnosis. Recent studies demonstrate that VH of UC are heterogenous tumors and responsiveness to NAC may be a function of the molecular subtypes present.Conclusions: Based on these findings, NAC to achieve pathologic downstaging prior to radical cystectomy is recommended for MIBC with VH. Biomarkers identified by molecular profiling with immunohistochemistry will need to be validated as predictors of response to NAC in future trials.

A nested variant of urothelial carcinoma of the urethra and urinary bladder: A case report and review of literature

“…14 In a recent narrative review, the use of NACT is recommended for pathologic downstaging, as a higher pathologic stage on surgery portends a worse survival outcome. 15 Based on this data, our patient was put on NACT, which was not beneficial in her case.…”

“…Hajiran and colleagues retrospectively reviewed 768 patients with clinical muscle invasive bladder cancer, 173 with variant histology, and reported that similar response rates were seen in all pathologies, and that both pure urothelial carcinoma and variant histology cohort demonstrated a survival benefit with this approach 14 . In a recent narrative review, the use of NACT is recommended for pathologic downstaging, as a higher pathologic stage on surgery portends a worse survival outcome 15 . Based on this data, our patient was put on NACT, which was not beneficial in her case.…”

PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis

“…Urinary bladder urothelial carcinoma (UBUC) presents micropapillary sarcomatoid, squamous, and glandular variations. It is accessible to TUR (transurethral resection) and local chemotherapy; hence, it has a good prognosis [56][57][58].…”

Glycocalyx analysis of bladder cancer: three-dimensional images in electron microscopy and vicia villosa lectin as a marker for invasiveness in frozen sections

“…Histologic variants of urothelial carcinoma comprise tumors arising from within the urothelium, in which some components of the tumor morphology are other than the urothelium ( Chalasani et al, 2009 ). The micropapillary, plasmacytoid, nested, and sarcomatoid histologic variants of urothelial carcinoma have been linked with poorer survival outcomes than conventional urothelial carcinomas and urothelial carcinomas with squamous or glandular differentiation, despite undergoing chemotherapy-induced downstaging ( Ogbue et al, 2022 ).…”