Analysis of T1 Bladder Cancer on Biopsy and Transurethral Resection Specimens

Abstract

Urothelial carcinoma of the bladder invasive into lamina propria on biopsy or transurethral resection of bladder tumor, termed "T1" disease, progresses to muscularis propria invasion in a subset of patients. Prior studies have proposed histopathologic metrics to predict progression, although methods vary widely and it is unclear which method is most robust. This poses a challenge since recent World Health Organization and American Joint Commission on Cancer editions encourage some attempt to substratify T1 disease. To address this critical problem, we analyzed T1 specimens to test which T1 quantification method is best to predict progression and to then establish the optimal cut-off. Progression was analyzed for all patients or for patients with definitive muscularis propria only. Multivariate analysis and outcomes modeling controlled for additional histopathologic features. Our results suggest that aggregate linear length of invasive carcinoma (ALLICA) measured by optical micrometer is far superior to other methods (P=3.067×10) and could be applied to 100% of specimens. ALLICA retained significance in multivariate analysis and eliminated contribution of other histopathologic features to progression. The best cut-off for ALLICA using a 30% false-positive threshold was 2.3 mm and using a 10% false-positive threshold at 25 mm, although the latter severely limited patients who could achieve this threshold. After comparison of all proposed methods of T1 quantification, we recommend the adoption of the ALLICA measurement and a cut-off of ≥2.3 mm as the best predictor of progression, acknowledging that additional nonhistopathologic methods may be required to increase broad applicability and further reduce the false-positive threshold.

The Genitourinary Pathology Society Update on Classification of Variant Histologies, T1 Substaging, Molecular Taxonomy, and Immunotherapy and PD-L1 Testing Implications of Urothelial Cancers

“…An ideal T1 subcategorization method must be reproducible and broadly feasible, especially in TUR fragments, and predictive of outcome (ie, able to discriminate tumors with the highest risk for recurrence and progression) 87,91–93. Since 1989, >45 studies were conducted applying different methods for T1 subcategorization in bladder cancer 92–100…”

“…87,[91][92][93] Since 1989, > 45 studies were conducted applying different methods for T1 subcategorization in bladder cancer. [92][93][94][95][96][97][98][99][100] Most of the methods can be classified broadly into histoanatomic-based and micrometric techniques (Table 5, Fig. 4).…”

“…Histoanatomic-based substaging is the most investigated technique which uses muscularis mucosae (MM) and/or vascular plexus (VP) as landmarks to assess the depth of LP invasion. 92,93,[95][96][97][98][99][101][102][103] Staging of the depth of LP invasion can be performed in relation to MM/VP either through a 2-tiered (T1a/T1b) or 3-tiered (T1a/T1b/T1c) method, with more studies applying the 2-tiered approach; nevertheless, many pathologists agree that the 3-tiered system is too complicated in daily practice, preferring the 2-tiered approach. MM is known to be an inconsistent layer in LP which forms a near-continuous or continuous layer in only ∼40% of cystectomy sections.…”

“…Micrometric technique measures the extent of LP invasion, usually by use of an ocular micrometer or microscopic field. 95,98,102,103,[107][108][109][110] Methods vary with those using 0.5 mm [such as T1microscopic(m)/T1extensive(e), where multifocal invasive carcinomas are also considered as extensive] or 1 mm [such as Rete Oncologica Lombarda (ROL)1/ROL2] cutoffs and measuring the aggregate linear length of invasive carcinoma being the more studied. 93,95,98,111 Without reliance on identifiable LP landmarks, micrometric techniques are more broadly feasible, applicable in > 99% of T1 TURs.…”

Predictive value of GATA3 and Ki-67 expression in biopsy and transurethral resection specimens in patients with urothelial carcinoma of the urinary bladder

“…Study from 2018 is one of the rare studies which described a method for determining the depth of invasion within pT1 stage, but in biopsy or TUR specimens. Defining the linear extent of urothelial carcinoma with optical micrometer and the cut-off value of 2.3 mm after regression analysis, made this system 100% accurate for all included specimens, because the system did not require specific specimen orientation and did not depend on the presence of muscularis mucosa, histologic subtypes, lymphovascular invasion and CIS [18].…”