Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer?

Jackson, Bettie S.; Mohammed, Aza; Mayer, Nick; Dormer, John; Griffiths, T.R. Leyshon

doi:10.1159/000375411

Cited by 14 publications

(13 citation statements)

References 22 publications

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“…MPUC is associated with aggressive behavior and poor survival most probably due to frequent lymphatic invasion and metastases [5,15]. In comparison with MPUC of the upper urinary tract both malignancies present with similar aggressive characteristics [16].…”

Section: Discussionmentioning

confidence: 99%

Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype

et al. 2018

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Comprehensive molecular analyses of urothelial bladder cancer (UBC) have defined distinct subtypes with potential therapeutic implications. In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC, alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed, and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. Additionally, HER2 amplification status was assigned by chromogenic in situ hybridization. Sanger sequencing of exon 4 and 8 was used to test for HER2 mutations. Kruskal-Wallis test was calculated to compare marker distribution between proportions of the MPUC component. HER2 2+/3+ staining scores were identified in 39.6% of 91 analyzed MPUCs and were not differentially distributed among the proportion of the MPUC component (P = .89). Additionally, CISH analysis revealed 30% of HER2-amplified tumors independently of the MPUC fraction. In 6/90 evaluable MPUCs, a p.S310F HER2 mutation was detected. Overexpression of luminal markers was observed in the majority of MPUC. Our investigations of the largest cohort of analyzed MPUC demonstrate that HER2 overexpression and amplifications are common genetic alterations and identification of overexpressed luminal markers allows subclassification to the luminal subtype. These findings highlight the need of histomorphological recognition of MPUC and analysis of HER2 status and the luminal molecular subtype for potential targeted therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype

et al. 2018

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“…Interestingly, controversies exist regarding the socalled non-invasive micropapillary component [98,112], which may be interpreted as micropapillary-like features in NMIBC and CIS, and therefore should not be classified as true MV [8,16,42,[113][114][115][116][117]. The pattern of superficial MV-UC has been associated with an improved OS when compared with invasive MP (63 vs. 47 months, p = 0.05) in an MV-NMIBC series managed conservatively [118]. In keeping with this, progression to T1 disease occurred in only 2 out of 16 patients with pTa MV-UC managed with surveillance in a recent series [119].…”

Section: Micropapillary Variantmentioning

confidence: 99%

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

et al. 2021

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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.

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“…Further, most of the specimens of patients who underwent deferred RC showed advanced disease after intravesical therapy with BCG suggesting no beneficial effect in this histological subtype ( 64 , 65 ). Recently Jackson et al aimed to identify patients who might be managed without immediate RC distinguished all non-muscle invasive MPBC tumors (n=40) into superficial (pTa) and invasive carcinomas (pT1) ( 66 ). Unsurprisingly, the authors reported that superficial MPBC is associated with higher survival rates (median OS 63 vs. 47 months), and concluded, that those might therefore be managed more conservatively with TUR-BT and possible deferred RC in selected patients ( 66 ).…”

Section: Micropapillary Carcinomamentioning

confidence: 99%

“…Recently Jackson et al aimed to identify patients who might be managed without immediate RC distinguished all non-muscle invasive MPBC tumors (n=40) into superficial (pTa) and invasive carcinomas (pT1) ( 66 ). Unsurprisingly, the authors reported that superficial MPBC is associated with higher survival rates (median OS 63 vs. 47 months), and concluded, that those might therefore be managed more conservatively with TUR-BT and possible deferred RC in selected patients ( 66 ). Still there is evidence that intravesical therapy is less effective in variants as compared to UC, with progression rates of up to 70% after 8 months, therefore advocating generously for early RC in all non-muscle invasive MPBC ( 14 , 63 ).…”

Section: Micropapillary Carcinomamentioning

confidence: 99%

Variant histology in bladder cancer: how it should change the management in non-muscle invasive and muscle invasive disease?

Klaile¹,

Schlack²,

Boegemann³

et al. 2016

Transl. Androl. Urol.

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Bladder cancer (BC) is a frequent type of carcinoma with an estimated incidence of approximately 100,000 men and women each year in the European Union (EU) with an associated mortality of 30,000 of these patients. In more than 70% the disease is diagnosed in a non-muscle invasive stage with the chance of minimally invasive, local treatment only, which might be required repetitively due to high rate of recurrence. In contrast, muscle invasive or metastatic stages need multimodal treatment strategies including surgical treatment and chemotherapy (CTX) in neoadjuvant (NAC), adjuvant, or palliative settings. Therapy recommendations and guidelines mainly refer to the most common histological type of BC, pure urothelial carcinoma (UC). However, BC can be classified as urothelial and non-UC. Non-urothelial BC and variants of UC account for up to 25% of all BCs. Further discrimination can be made into epithelial and non-epithelial non-UC. Most of the non-UCs are of epithelial origin (approximately 90%) including squamous-cell carcinoma, adenocarcinoma and small-cell carcinoma. Non-epithelial tumors are rare and include variants as sarcoma, carcinosarcoma, paraganglioma, melanoma and lymphoma. Even though it is unclear whether the prognosis of non-urothelial cancer truly differs from that of UC, there is evidence that additional variant histology might prognosticate an impaired prognosis. Accordingly, aggressive behavior and often advanced stages at primary presentation are frequently observed in non-UC arguing for radical and sometimes different treatment strategies as compared to pure UC. This review aims to summarize the available data for the most common histological variants of non-urothelial BC.

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Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer?

Cited by 14 publications

References 22 publications

Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype

Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype

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

Variant histology in bladder cancer: how it should change the management in non-muscle invasive and muscle invasive disease?

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