Article of the week: The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non‐muscle‐invasive bladder cancer

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If you only have time to read one article this week, it should be this one.

The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non‐muscle‐invasive bladder cancer

Elisabeth E. Fransen van de Putte*, Judith Bosschieter*†, Theo H. van der Kwast‡^§, Simone Bertz^¶, Stefan Denzinger**, Quentin Manach††, Eva M. Compérat‡‡,

Joost L. Boormans^§§, Michael A.S. Jewett^¶¶, Robert Stoehr^¶, Geert J.L.H. van Leenders^§, Jakko A. Nieuwenhuijzen†, Alexandre R. Zlotta^¶¶***, Kees Hendricksen*,

Morgan Rouprêt††, Wolfgang Otto**, Maximilian Burger**, Arndt Hartmann^¶and Bas W.G. van Rhijn***^§§¶¶

*Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, †Department of Urology, VU University Medical Centre, Amsterdam, ^§Department of Pathology, ^§§Department of Urology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands, ‡Department of Pathology, ^¶¶Department of Surgical Oncology (Urology), Princess Margaret Cancer Center, University Health Network, ***Department of Urology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, ^¶Department of Pathology, University of Erlangen, Erlangen, **Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany, ††Academic Department of Urology and ‡‡Department of Pathology, Pitie-Salpétrière Hospital, Assistance-Publique Hôpitaux de Paris, Pierre et Marie Curie Medical School, University Paris, Paris, France

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Abstract

Objectives

To compare the prognostic value of the World Health Organization (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1‐BC), as both are currently recommended in international guidelines.

Patients and Methods

Three uro‐pathologists re‐revised slides of 601 primary (first diagnosis) T1‐BCs, initially managed conservatively (bacille Calmette–Guérin) in four hospitals. Grade was defined according to WHO1973 (Grade 1–3) and WHO2004 (low‐grade [LG] and high‐grade [HG]). This resulted in a lack of Grade 1 tumours, 188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554 (92%) HG tumours. We determined the prognostic value for progression‐free survival (PFS) and cancer‐specific survival (CSS) in Cox‐regression models and corrected for age, sex, multiplicity, size and concomitant carcinoma in situ.

Fig. 1. The median follow‐up for the 601 primary T1 urothelial bladder tumours was 5.9 years. PFS was grouped according to (a) the WHO1973 classification (Grade 2 vs 3, log‐rank test P < 0.001) and according to (b) the WHO2004 (LG vs HG, log‐rank test P = 0.077) classification. CSS was grouped according to (c) the WHO1973 classification (Grade 2 vs 3, log‐rank test P < 0.001) and according to (d) the WHO2004 classification (LG vs HG, log‐rank test P = 0.292).

Results

At a median follow‐up of 5.9 years, 148 patients showed progression and 94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard ratio [HR] 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On multivariable analysis, WHO1973 grade was the only prognostic factor for progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour size >3 cm (HR 1.8) were all independently associated with worse CSS.

Conclusion

The WHO1973 classification system for grade has strong prognostic value in T1‐BC, compared to the WHO2004 system. Our present results suggest that WHO1973 grade cannot be replaced by the WHO2004 classification in non‐muscle‐invasive BC guidelines.