Клинико-морфологический анализ и прогностические критерии рецидивирования и прогрессии неинвазивных уротелиальных раков мочевого пузыря

Abstract

Уротеліальний рак сечового міхура (УРСМ) виявляється в 75% на стадії неінвазивного зростання, проте рецидив неінвазивних УРСМ (НУРСМ) виникає в 30-85%. Це визначає необхідність пошуку надійних критеріїв прогнозу клінічного перебігу захворювання. Досліджено операційний матеріал пацієнтів УРСМ за 2011-2015 рр. (1041 випадок). НУРСМ був розділений на 3 групи: без рецидивів (I група, 46 випадків), первинні пухлини з рецидивом (II група, 46 випадків) і з прогресією (III група, 14 випадків). I і II групи були взяті з однаковим диференціюванням G. Число НУРСМ склало 72,9% (759/1041 випадків). З комплексу клініко- морфологічних ознак прогностичними критеріями рецидиву НУРСМ можна вважати розмір пухлини >3 см (p <0,001), мультифокальне зростання (p <0,05), сума балів 5-9 при проміжному ризику рецидиву за алгоритмом Європейської організації з дослідження та лікування раку (EORTC) (р <0,01). Критеріями прогресії НУРСМ можна вважати розмір пухлини >3 см (р <0,01), G2-G3 (p <0,05) і високий ризик прогресії за алгоритмом EORTC (р <0,01).

Уротелиальный рак мочевого пузыря (УРМП) выявляется в 75% на стадии неинвазивного роста, однако рецидивирование неинвазивных УРМП (НУРМП) возникает в 30-85%. Это определяет необходимость поиска надежных критериев прогноза клинического течения заболевания. Исследован операционный материал пациентов УРМП за 2011-2015 гг. (1041 случай). НУРМП был разделен на 3 группы: без рецидивов (I группа, 46 случаев), первичные опухоли с рецидивом (II группа, 46 случаев) и с прогрессией (III группа, 14 случаев). I и II группы были взяты с одинаковой дифференцировкой G. Число НУРМП составило 72,9% (759/1041 случаев). Из комплекса клинико-морфологических признаков прогностическими критериями рецидивирования НУРМП можно считать размер опухоли >3 см (p<0,001), мультифокальный рост (p<0,05), сумма баллов 5-9 при промежуточном риске рецидивирования по алгоритму Европейской организации по исследованию и лечению рака (EORTC) (р<0,01). Критериями прогрессии НУРМП можно считать размер опухоли >3 см (р<0,01), G2-G3 (p<0,05) и высокий риск прогрессии по алгоритму EORTC (р<0,01).

Urothelial cancer is the fifth most frequent type of cancer in the world. Urothelial bladder cancer (UBC) is diagnosed in 75% cases at non-invasive stage, however, the recurrence of non-invasive urothelial bladder cancer occurs in 30-85% of cases. Considering this fact, the reliable criteria for prognosis of clinical course of disease should be determined. The aim of the research was to evaluate clinical and morphological characteristics of patients operated for urothelial bladder cancer in Kharkiv during 2011-2015 years and to determine the recurrence and progression criteria for non-invasive urothelial bladder cancer. The surgical material of patients-residents of Kharkiv with urothelial bladder cancer for 2011-2015 years (1041 cases) was studied. The number of urothelial bladder cancer cases corresponded to the total number of UBC cases registered in Kharkiv region according to the official statistics. Non-invasive urothelial bladder cancer cases were distributed into 3 groups: non-relapse (I group, 46 cases), primary tumors with relapse (II group, 46 cases) and with progression (III group, 14 cases). The I and II groups presented with the similar G differentiation. The number of cases with non-invasive urothelial bladder amounted to 72.9% (759/1041 cases). The prognostic system according to EORTC group algorithm was used, in which each risk factor affecting the prognosis criteria (size, number of tumors, degree of its differentiation, level of invasion to the bladder wall and surrounding tissues, presence of concomitant cancer in situ, relapse rate) was assigned the score. The study included cases without relapses in anamnesis. The relationship between studied features was determined applying Pearson chi-square test. Urothelial bladder cancer at the non-invasive stage was diagnosed in 72.9% (759 cases). Differentiation of noninvasive bladder cancers G1 was in 395 (52%) cases, G2 – in 236 (31.1%) cases, G3 – in 128 (16.9%) cases. Tumor size greater than 3 cm and multifocal growth, which were associated with recurrent non-invasive urothelial bladder cancer in comparison with non-relapse non-invasive urothelial bladder cancer (p <0.001 and p <0.05, correspondingly) can be considered as the significant recurrence criteria among the main clinical and morphological features of non-invasive urothelial bladder cancer. It was detected 26.6% (16/60) of cases with multifocal cancers among recurrent non-invasive urothelial bladder cancers and only 6.5% (3/46) among non- relapse (p <0.05). While distributing the primary tumors according to the size, namely, up to 3 cm and more than 3 cm, it was determined 70% (42/60) cases among recurrent non-invasive urothelial bladder cancers and 28.3% (13 of 46) among non-relapse ones. The differences between the groups were not observed considering the differentiation of non-invasive urothelial bladder cancer with distribution to a low and high grade malignancy according to present-day WHO histological classification of cancers. However, the tendency for increased incidence of high grade malignancy among III group was determined − 42.9% (6/14) compared to I and II groups − 27.7% (20/72) (p = 0.08). The gradation of transitional cell cancers on G1, G2 and G3 used in prognostic EORTC system detected the statistically significant decrease in differentiation of III group non-invasive urothelial bladder cancer compared to I and II groups due to the less number of G1 tumors. Consequently, non-invasive urothelial bladder cancer recurring with progression was associated with the decrease in the number of highly differentiated forms. When evaluating non-invasive urothelial bladder cancer according to EORTC algorithm in the group of intermediate risk of recurrence (with 1-9 scores), the recurrence and recurrence with progression were characteristic for noninvasive urothelial bladder cancer with 5-9 scores compared to score 1-4 (p <0.01 and p <0.001), which determined the expediency of intermediate risk group distribution into two subgroups with the scores 1-4 and 5-9. The present-day system of risk progression evaluation for urothelial bladder cancer according to EORTC algorithm assessed with the high degree of reliability the prognosis for recurrence with progression of non-invasive urothelial bladder cancer. Thus, the absence of recurrence was associated with the groups of small (with 1-6 scores) and intermediate progression risk (with 7-13 scores) (p <0.002 and p<0.05, correspondingly), but recurrent noninvasive urothelial bladder cancer with progression − belonging to the group of high risk progression (with 14-23 scores) (p <0.006). The issue concerning specification of the recurrence prognostic criteria and progression of non-invasive urothelial bladder cancer remains relevant, which stipulates the use of such diagnostic methods as immunohistochemical examination with molecular biomarkers for detection of aggressive clinical behavior of tumors.