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Título

THE GLEASON PROGNOSTIC PERSPECTIVE APPLIED TO THE UROTHELIAL CARCINOMA HETEROGENEITY

Resumo

PURPOSE: Current World Health Organization/International Society of Urological Pathology (2004/WHO/ISUP) bladder urothelial carcinoma grading relies on the highest pathologic specimen grade, not reflecting its inherent heterogeneity. METHODS: We propose and validate a grading system that considers the primary (most common) and secondary (second most common or higher grade even focal). The highest-grade area was considered as 1, 2 or 3 according to the 1999 World Health Organization system. The number was repeated when only one grade was seen. A final score was obtained which ranged from 2 (1+1) to 6 (3+3). RESULTS: We studied 312 consecutive bladder transurethral resections (TUR) between 2008 and 2015. Considering non-muscle invasive carcinomas, the grading distribution was 19% 1+1, 15.4% 1+2, 7.5% 2+1, 20.2% 2+2, 19% 2+3, 5.1% 3+2 and 13.8% 3+3. Recurrence was diagnosed in 115 (36.9%), progression in 83 (26.6%) and cancer-specific death in 50 patients (16%). Meantime to recurrence, progression, and death of disease was 31.7 ± 35.9, 44.5 ± 47.6 and 50.4 ± 51.2 months, respectively. Compared to all other grades, grade 3 presence (2+3, 3+2 or 3+3) independently predicted progression, p=0.0205, and grade 3 predominance (3+2 or 3+3) independently predicted death of disease, p=0.0346. Progression rates were significantly higher in the presence of grade 3: grades 2+3 p=0.004, HR 4.4 (1.6-12 95%CI), 3+2 p=0.0003, HR 8.3 (2.6-26.3 95%CI), and 3+3 p=0.0012, HR 5.45 (1.97-15.2 95%CI); and (1.7-16.7 95%CI) while disease-specific mortality was significantly higher in grades 3+2 p=0.004, HR 6.4 (1.8-22.7 95%CI) and 3+3 p=0.0031, HR 5.45. CONCLUSIONS: Grade 3 presence and predominance are independent predictors of progression and death of disease, respectively. Including heterogeneity in urothelial carcinoma grading engenders a significantly better stratification of patients.

Palavras Chave ( separado por ; )

bladder cancer, tumor heterogeneity, histological grading, combined numbers, prognosis