Subcategorization of T1 Bladder Cancer on Biopsy and Transurethral Resection Specimens for Predicting Progression

Abstract

Context.— Despite continued surveillance and intravesical therapy, a significant subset of patients with lamina propria–invasive bladder cancer (T1) will progress to muscle-invasive disease or metastases. Objective.— To analyze the value of pathologic subcategorization of T1 disease in predicting progression. Design.— Six substaging methods were applied to a retrospective cohort of 73 patients, with pT1 urothelial carcinoma diagnosed on biopsy/transurethral resection. Additionally, the immunohistochemistry for GATA3 and cytokeratin 5/6 (CK5/6) was performed to study the prognostic value of stratifying T1 cancers into luminal or basal phenotypes. Results.— On follow-up (mean, 46 months), 21 (29%) experienced at least 1 recurrence without progression, and 16 (22%) had progression to muscle-invasive disease and/or distant metastasis. No differences were noted between progressors and nonprogressors with regard to sex, age, treatment status, medical history, tumor grade, and presence of carcinoma in situ. Substaging using depth of invasion (cutoff ≥1.4 mm), largest invasive focus (≥3.6 mm), aggregate linear length of invasion (≥8.9 mm), and number of invasive foci (≥3 foci) correlated significantly with progression and reduced progression-free survival, whereas invasion into muscularis mucosa or vascular plexus, or focal versus extensive invasion (focal when ≤2 foci, each <1 mm) failed. Patients with luminal tumors had higher incidence of progression than those with nonluminal tumors (27% versus 11%), although the difference was statistically insignificant (P = .14). Conclusions.— Substaging of T1 bladder cancers should be attempted in pathology reports. Quantifying the number of invasive foci (≥3) and/or measuring the largest contiguous focus of invasive carcinoma (≥3.6 mm) are practical tools for prognostic substaging of T1 cancers.

International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer

“…Most studies revealed significant prognostic impact (disease recurrence, n=6 studies; disease progression, n=18 studies; recurrence-free survival, n=6 studies; progression-free survival, n=13 studies; cancer-specific survival, n=7 studies; overall survival, n=3 studies). Thirteen percent of studies (n=6) failed to show clinical impact, that is 5 (16%) histoanatomic and 1 (7%) semiquantitative study(s), all published between 2000 and 2018 9–54 …”

“…Most studies on semiquantitative methods included in our comprehensive literature review summarizing over 3700 patients showed an association with progressionfree survival or cancer-specific survival. 12,18,32,[44][45][46][47][48]51,52 Only 7% of studies on T1 subcategorization failed to show such an association, 13,14,20,26,36,39,44 most of which applied histoanatomic methods. Studies, comparing head-to-head histoanatomic and semiquantitative methodology also revealed a better performance in terms of prognostic impact for the latter.…”

“…Thirteen percent of studies (n = 6) failed to show clinical impact, that is 5 (16%) histoanatomic and 1 (7%) semiquantitative study(s), all published between 2000 and 2018. Thirteen of the 46 selected articles compared histoanatomic and semiquantitative methods head to head, and most of the studies (n = 8) identified significant prognostic impact associated with semiquantitative methods, 12,25,29,40,42,43,48,49 while a lesser number (n = 4) showed prognostic impact of both histoanatomic and semiquantitative methods. 28,46,52,54 Only one study reported significant prognostic impact for the histoanatomic, but not for the semiquantitative method.…”

“…To guide management decisions in T1 bladder cancer, it is a clinical priority to predict its prognosis 2,6,8 . Emerging data support T1 subcategorization as a predictor of oncological outcome 2–54 . Several studies have been conducted to identify the prognostic role of lamina propria invasion and to determine the best method to assess T1 subcategorization 9–54 .…”

Prospective Validation of the ROL System in Substaging Pt1 High-Grade Bladder Cancer: Results from a Prospective Mono-Institutional Confirmatory Analysis in BCG Treated Patients

“…In contrast, micrometric systems measuring the maximum extent of LP invasion at any direction overcome the anatomic issues and proved clinical significance. Interestingly, a recent retrospective study conducted on 73 patients compared 6 different substaging methods and showed that reporting the extent and/or the number of invasive foci represented the most practical approach not conditioned by orientation or artifacts [34]. The one proposed by Van Rhijn et al applies a 0.5 mm cut-off to classify tumors in T1m (microinvasive) and T1e (extensively invasive) [21].…”