The 1973 WHO Classification is more suitable than the 2004 WHO Classification for predicting prognosis in non-muscle-invasive bladder cancer

Abstract

Background: Predicting the recurrence and progression of Non-muscle-invasive bladder cancer(NMIBC) is critical for urologist. Histological grade provides significant prognostic information, especially for prediction of progression. Currently, the 1973 and the 2004 WHO classification co-exist. Which system is better for predicting rumor recurrence and progression still a matter for debate.

Methodology/principal findings: 348 patients diagnosed with Non-muscle invasive bladder cancer were enrolled in our retrospective study. Paraffin sections were assessed by an experienced urological pathologist according to both the 1973 and 2004 WHO classifications. Tumor recurrence and progression was followed-up in all patients. During follow-up, corresponding 5-year recurrence-free survival rates of G1, G2 and G3 were 82.1%, 55.9%, 32.1% and the 5-year progression-free survival rates were 95.9%, 84.4% and 43.3%, respectively. The 5-year recurrence-free survival rates of papillary urothelial neoplasm of low malignant potential (PUNLMP), low-grade papillary urothelial carcinoma(LGPUC) and high-grade papillary urothelial carcinoma (HGPUC) were 69.8%, 67.1% and 42.0% respectively and the 5-year progression-free survival rates were 100%, 90.9% and 54.8% respectively. In multivariate analysis, the 1973 WHO classification significantly associated with both tumor recurrence and progression(p=0.010 and p=0.022, respectively); the 2004 WHO classification correlated with tumor progression(p=0.019), while was not proved to be a variable that can predict the risk of recurrence(p=0.547). Kaplan-Meier plots showed that both the 1973 WHO and the 2004 WHO classifications were significantly associated with progression-free survival (p<0.0001, log-rank test). For prediction of recurrence, significant differences were observed between the tumor grades classified using the 1973 WHO grading system (p<0.0001, log-rank test), while a significant overlap was observed between PUNLMP and LG plots using the 2004 WHO grading system(p=0.616, log-rank test).

Conclusion/significance: Both the 1973 WHO and the 2004 WHO Classifications are effective in predicting tumor progression in Non-muscle invasive bladder cancer, while the 1973 WHO Classification is more suitable for predicting tumor recurrence.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Kaplan-Meier estimates of progression-free survival rates after transurethral resection (TUR) of the bladder tumor according to the 1973 WHO classification.

Figure 2. Kaplan-Meier estimates of progression-free survival rates after transurethral resection(TUR) of the bladder tumor according to the 2004 WHO classification.

Figure 3. Kaplan-Meier estimates of recurrence-free survival rates after transurethral resection (TUR) of the bladder tumor according to the 1973 WHO classification.

Figure 4. Kaplan-Meier estimates of recurrence-free survival rates after transurethral resection (TUR) of the bladder tumor according to the 2004WHO classification.

Figure 5. Histologic grading of urothelial tumors: (A) The 2004 WHO classification Papillary urothelial neoplasm of low malignant potential (PUNLMP); (B) the 1973 WHO classification grade 3 urothelial carcinoma.

Figure 6. The relationship of the 1973 and 2004 WHO classification in our patients.

Figure 7. Kaplan-Meier plots of progression-free survival between G3 and G2′(HGPUC but not containing G3 tumors).