Presence and predominance of histological grade 3 define cT1HG bladder cancer prognostic groups

Abstract

Purpose: Current World Health Organization/International Society of Urological Pathology (2004 WHO/ISUP) grading of bladder urothelial carcinoma relies on the highest pathologic grade of the specimen and does not reflect the inherent qualitative and quantitative heterogeneity of disease.

Materials and methods: We retrospectively studied consecutive urothelial high-grade cT1 (cT1HG) carcinomas submitted to adjuvant bacille Calmette-Guérin between 2008 and 2015 to evaluate the prognostic potential of grade 3 (presence or predominance) according to the 1973 WHO system concerning disease progression and cancer-specific death.

Results: Among 253 patients, grading distribution was 34.4% 1+2, 7.5% 2+1, 20.2% 2+2, 19.0% 2+3, 5.1% 3+2, and 13.8% 3+3. Recurrence was diagnosed in 115 (45.5%), progression in 83 (32.8%), and cancer-specific death in 50 patients (19.8%). Mean time to recurrence, progression, and death from disease were 35.9±31.7, 47.6±44.5, and 51.2±50.4 months, respectively. Grade 3 presence (2+3, 3+2, or 3+3) occurred in 96 (37.9%) and independently predicted time to progression (p<0.001; hazard ratio [HR], 3.11; 95% confidence interval [CI], 1.88-5.14). Grade 3 predominance (3+2 or 3+3) occurred in 48 (18.9%) and independently predicted time to disease-specific death.

Conclusions: Grade 3 presence and predominance are independent predictors of progression and disease-specific death and occur in about 40% and 20% of cT1HG, respectively. Describing qualitative and quantitative heterogeneity in urothelial carcinoma grading might improve the stratification of patients. This gives three prognostic high-grade groups based on WHO/ISUP 1973: prognostic grade group I (grade 3 absence), prognostic grade group II (grade 3 presence), and prognostic grade group III (grade 3 predominance).

Keywords: Histology; Prognosis; Urinary bladder neoplasms.

Fig. 1. Kaplan–Meier time to progression curve. Grade 3 presence: no (n=157; 62.1%) versus yes (n=96; 37.9%). HR, hazard ratio; CI, confidence interval.

Fig. 2. Kaplan–Meier time to disease-specific death curve. Grade 3 predominance: no (n=205; 81.0%) versus yes (n=48; 18.9%). HR, hazard ratio; CI, confidence interval.

Fig. 3. Prognostic impact and treatment decision of cT1HG based on World Health Organization/International Society of Urological Pathology (WHO/ISUP) 2004 versus 1973 grade 3 absence (prognostic grade group I), presence (prognostic grade group II), or predominance (prognostic grade group III). Grade 3: intense pleomorphism and disorganization with frequent mitoses. Grade 2: moderate pleomorphism and disorganization with hyperchromatic nuclei. Grade 1: uniform and orderly distributed nuclei without hyperchromasia or mitotic figures. BCG, bacille Calmette–Guérin.