© 2017 European Association of Urology Context Tumour grade is an important prognostic indicator in non–muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. Objective To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. Evidence acquisition A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Evidence synthesis Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Conclusions Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. Patient summary This article summarises the utility of two different grading systems for non–muscle-invasive bladder cancer. Both systems predict progression and recurrence, although pathologists vary in their reporting; suggestions for further improvements are made. All available data were collected and the prognostic performance and reproducibility of the 1973 and 2004/2016 World Health Organization (WHO) grading systems for non–muscle-invasive bladder cancer (NMIBC) were compared in the systematic review. We found that current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. In each category of the 1973 WHO classification (grade [G] G1, G2, G3), the risks of recurrence and progression were higher than in the corresponding category of the 2004/2016 WHO classification (papillary urothelial neoplasms with low malignant potential, low grade, and high grade [HG]). We confirmed the tendency to classify most patients as G2 in the 1973 WHO classification. On the contrary, a significant weakness of the 2004/2016 WHO classification is that it gives almost no prognostic information in T1 patients, nearly all of whom are classified as HG. Intra- and interobserver variability was slightly less in the 2004/2016 WHO classification. We could not confirm that the 2004/2016 WHO classification outperforms the 1973 WHO classification in the prediction of recurrence and progression. Current European Association of Urology recommendations for grading of NMIBC indicate that both the 1973 WHO and the 2004/2016 WHO classification should be used until new international multicentre studies and individual patient data analyses assess the real prognostic value of the 1973 and 2004/2016 WHO classifications.
- 1973 World Health Organization classification
- 2004/2016 World Health Organization classification
- Non–muscle-invasive bladder cancer