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T1 bladder cancer: current considerations for diagnosis and management

Nature Reviews Urology volume 16, pages 23–34 (2019)Cite this article

Subjects

Abstract

Stage T1 bladder cancers invade the lamina propria of the bladder and, despite sharing many of the genetic features of muscle-invasive bladder cancers, are classified as non-muscle-invasive or ‘superficial’ tumours. Yet, patients with T1 bladder cancer have an overall mortality of 33% and a cancer-specific mortality of 14% at three years after diagnosis, suggesting that these patients have a high risk of progression and, accordingly, require meticulous surgery, endoscopic surveillance and clinical decision-making. We hypothesize that the variability in the outcomes of patients with T1 bladder cancer is a result of both tumour heterogeneity and pathological staging, as well as inconsistencies in risk stratification, endoscopic resection and schedules of delivery of BCG. Owing to limitations in clinical staging, patients with T1 bladder cancer are at risk of both undertreatment with persistent use of BCG despite recurrence, and overtreatment with early cystectomy. Understanding the molecular features of T1 bladder cancers and how they respond to BCG therapy could improve biomarkers for risk stratification to align therapy with biological risk.

Key points

  • Non-muscle-invasive bladder cancers (NMIBCs) comprise ~70% of all bladder cancers and T1 tumours represent 20% of all NMIBCs.

  • Patients with T1 high-grade (T1HG) bladder cancer have a 10-year recurrence rate of ~77%, a 10-year progression rate of ~42% and a 10-year cancer-specific mortality of ~15%.

  • Staging T1 cancers can be challenging; substaging made on the basis of muscularis mucosae invasion has been performed, but has not been universally adopted.

  • T1 bladder cancer with aggressive features (such as lymphovascular invasion and variant histology) might warrant early cystectomy as progression to muscle-invasive disease after BCG is associated with poor survival outcomes.

  • Among patients receiving maintenance BCG therapy, data suggest that full-dose BCG therapy for 3 years is the most beneficial regimen.

  • No clear predictive biomarker of T1 bladder cancer progression has been identified; challenges remain in the identification of tumours (or patients) that are BCG unresponsive or have occult aggressive cancer.

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Fig. 1: Proposed pathways of bladder cancer upstaging from T1 tumours to MIBC.
Fig. 2: Risk factors associated with recurrence and progression in T1 bladder cancer.
Fig. 3: Treatment algorithm for T1 high-grade bladder cancer.

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Acknowledgements

The authors would like to acknowledge M. K. Keeter for helpful discussions of the manuscript. J.J.M. is supported by a VA Merit Award (BX003692-01) and a SEED Award from the Hope Foundation.

Reviewer information

Nature Reviews Urology thanks L. Dyrskjot, B. W. G. van Rhijn and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Department of Urology, Northwestern University, Chicago, IL, USA

    Brian Jordan & Joshua J. Meeks

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The authors contributed equally to this manuscript.

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Correspondence to Joshua J. Meeks.

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J.J.M. is a consultant for Merck, AstraZeneca and Ferring, and receives research funding from Abbvie, Tesaro, NextCure and Epizyme. B.J. declares no competing interests.

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Glossary

Non-muscle-invasive bladder cancer

(NMIBC). Tumour stages Ta, Tis and T1, which show no evidence of muscle invasion (stage T2).

Muscle-invasive bladder cancer

(MIBC). Tumour stage ≥T2, with evidence of muscle invasion.

T1 high-grade bladder cancer

(T1HG bladder cancer). Following the 2004 International Society of Urological Pathology (ISUP) change in pathology classification, T1HG included some grade G2 and all G3.

Lymphovascular invasion

(LVI). The presence of tumour cells in the lymphatic or vascular channels, usually identified by CD31 or CD34 immunostaining.

T1 low-grade bladder cancer

(T1LG bladder cancer). Following the 2004 International Society of Urological Pathology (ISUP) change in pathology classification, T1LG included grades G1 and some G2.

Nested variant

A variant histology in which the tumour has a benign appearance, simulating von Brunn’s nests, and invades the lamina propria or deeper.

Papillary bladder cancer

Describes a cytoarchitecture of non-muscle-invasive bladder cancer with a central fibrovascular core surrounded by epithelial cells, in contrast with the ‘flat’ cancer found in CIS and sessile invasive tumours.

Enhanced cystoscopy

Cystoscopy with blue light or narrow band imaging.

Mapping biopsies

Small biopsies performed of normal-looking tissue to identify occult carcinoma in situ.

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Jordan, B., Meeks, J.J. T1 bladder cancer: current considerations for diagnosis and management. Nat Rev Urol 16, 23–34 (2019). https://doi.org/10.1038/s41585-018-0105-y

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