Non-Muscle Invasive Bladder Cancer with Variant Histology: Biological Features and Clinical Implications

Abstract

Background: The most common bladder cancer (BC) histotype is pure urothelial carcinoma (UC), which may undergo divergent differentiation in some cases. Variant histology (VH) presents along variable morphologies, either single or combined between them or with pure UC. From a clinical standpoint, the vast majority of BC is diagnosed at non-invasive or minimally invasive stages, namely as non-muscle invasive BC (NMIBC). There is a wide range of therapeutic options for patients with NMIBC, according to their clinical and pathological features. However, current risk stratification models do not show optimal effectiveness. Evidence from the literature suggests that VH has peculiar biological features, and may be associated with poorer survival outcomes compared to pure UC. Summary: In order to describe the biological features and prognostic/predictive role of VH in NMIBC, and to discuss current treatment options, we performed a systematic literature search through multiple databases (PubMed/Medline, Google Scholar) for relevant articles according to the following terms, single and/or in combination: “non-muscle invasive bladder cancer,” “variant histology,” “micropapillary variant,” “glandular differentiation,” “squamous differentiation,” “nested variant,” “plasmacytoid variant,” and “sarcomatoid variant.” We extracted 99 studies including original articles, reviews, and systematic reviews, and subsequently analyzed data from 16 studies reporting on the outcome of NMIBC with VH. We found that the relative rarity of these forms as well as the heterogeneity in study populations and therapeutic protocols results in conflicting findings overall. Key Messages: The presence of VH should be taken into account when counseling a patient with NMIBC, since it may upgrade the disease to high-risk tumor and thus warrant a more aggressive treatment.

Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer

“…Recently, many studies found varieties of diagnostic and prognostic biomarkers for cancer (32)(33)(34), few of which were utilized in clinical administration. A good biomarker can help identify cancers in the early stage, risk stratification, prognosis improvement, outcome prediction, variant histology (35), and targeted therapy (36). In this context, it is important to identify biomarkers that enable accurate prediction of recurrence, progression, and clinical outcome in bladder cancer.…”

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

“…As regards to genito-urinary tumors, clones SP263, SP142, 28-8, and 22C3 have been approved as assays to identify urothelial carcinoma patients that are most likely to benefit from various immunomodulants. To select eligible patients, each clone should be evaluated on the basis of specific score system and/or cut-off criteria (SSCC), according to current guidelines based on the results from large clinical trials: Atezolizumab (SP142; SSCC: ≥5% of positive immune cells); avelumab, durvalumab, and tislelizumab (SP263; SSCC: ≥25% of positive tumor or immune cells); nivolumab (28-8; SSCC: ≥1% of positive tumor cells); and pembrolizumab (22C3; CPS score) [167,168]. Such discrepancies in the recommended algorithms of evaluation reveal defective harmonization of PD-L1 immunohistochemical testing.…”

M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer

“…In addition, while univariate and multivariate Cox regression analysis indicated that the m6A score may be an independent prognostic factor, a study has suggested distinguishing between invasive and non-invasive micropapillary carcinoma of the bladder, as the latter may not predict a poor prognosis ( 30 ). Variant histology may be related to survival outcomes ( 31 ). Further studies on the relationship between variant histology and m6A are still needed.…”