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      Validation of EORTC, CUETO, and EAU risk stratification in prediction of recurrence, progression, and death of patients with initially non–muscle‐invasive bladder cancer (NMIBC): A cohort analysis

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          Abstract

          Brief Description: The results demonstrate that the European Organisation for Research and Treatment of Cancer (EORTC) scale provides the best recurrence and progression prediction in comparison with European Association of Urology (EAU) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk scores among a mixed population of patients with non–muscle‐invasive bladder who were treated with, or without, Bacillus Calmette‐Guerin (BCG) and without any immediate postoperative chemotherapy. The study highlights the role of tumor diameter and extent in transition prediction.

          This retrospective cohort analysis of 322 patients with newly diagnosed non–muscle‐invasive bladder cancer (NMIBC) assesses the concordance and accuracy of predicting recurrence and progression by EAU‐recommended tools (EAU risk groups, EORTC, and CUETO). One‐year and five‐year c‐indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1‐year recurrence risk based on CUETO groups, to 0.82 for 1‐year progression risk based on EAU risk groups. Diameter (HR: 1.91; 95% CI: 1.39‐2.61) and tumor extent (HR: 1.21; 95% CI: 1.01‐1.46 for recurrence; HR: 3.1; 95% CI: 1.40‐6.87 for progression) were shown to be significant predictors in multistate analysis. Lower accuracy of prediction was observed for patients treated with BCG maintenance immunotherapy. The EORTC model (overall c‐index c = 0.64; 95% CI: 0.61‐0.68) was superior to the EAU ( P = .035; .62; 95% CI: 0.59‐0.66) and CUETO ( P < .001; c = 0.53; 95% CI: 0.50‐0.56) models in predicting recurrence. The EORTC model (c = 0.82; 95% CI: 0.77‐0.86) also performed better than CUETO ( P = .008; c = 0.73; 95% CI: 0.66‐0.81) but there was no sufficient evidence that it performed better than EAU ( P = .572; c = 0.81; 95% CI: 0.77‐0.84) for predicting progression. EORTC and CUETO gave similar predictions for progression in BCG‐treated EAU high‐risk patients ( P = .48). We share anonymized individual patient data. In conclusion, despite moderate accuracy, EORTC provided the best recurrence and progression prediction for a mixed population of patients treated with, or without BCG, and without immediate postoperative chemotherapy.

          Abstract

          For mixed population of patients with non–muscle‐invasive bladder who were treated with and without Bacillus Calmette‐Guerin and without any immediate postoperative chemotherapy, we show that European Organisation for Research and Treatment of Cancer scale provides the best recurrence and progression prediction in comparison with European Association of Urology and Club Urologico Espanol de Tratamiento Oncologico risk scores. We highlight the role of diameter and tumor extent in transition prediction.

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          Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials.

          To provide tables that allow urologists to easily calculate a superficial bladder cancer patient's short- and long-term risks of recurrence and progression after transurethral resection. A combined analysis was carried out of individual patient data from 2596 superficial bladder cancer patients included in seven European Organization for Research and Treatment of Cancer trials. A simple scoring system was derived based on six clinical and pathological factors: number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and grade. The probabilities of recurrence and progression at one year ranged from 15% to 61% and from less than 1% to 17%, respectively. At five years, the probabilities of recurrence and progression ranged from 31% to 78% and from less than 1% to 45%. With these probabilities, the urologist can discuss the different options with the patient to determine the most appropriate treatment and frequency of follow-up.
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            Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy.

            This review focuses on the prediction of recurrence and progression in non-muscle invasive bladder cancer (NMIBC) and the treatments advocated for this disease. To review the current status of epidemiology, recurrence, and progression of NMIBC and the state-of-the art treatment for this disease. A literature search in English was performed using PubMed and the guidelines of the European Association of Urology and the American Urological Association. Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Special attention was given to fluorescent cystoscopy, the new World Health Organisation 2004 classification system for grade, and the role of substaging of T1 NMIBC. In NMIBC, approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of cancer in western society and the most expensive cancer per patient. Recurrence (in < or = 80% of patients) is the main problem for pTa NMIBC patients, whereas progression (in < or = 45% of patients) is the main threat in pT1 and CIS NMIBC. In a recent European Organisation for Research and Treatment of Cancer analysis, multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Tumour grade, stage, and CIS are the most important variables for progression. Treatment ranges from transurethral resection (TUR) followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes, re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients to early cystectomy for treatment-refractory high-risk NMIBC. NMIBC is a heterogeneous disease with varying therapies, follow-up strategies, and oncologic outcomes for an individual patient.
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              High Oct4 expression: implications in the pathogenesis of neuroblastic tumours

              Background Neuroblastic tumours (NBTs) are paediatric solid tumours derived from embryonic neural crest cells which harbour their own cancer stem cells (CSC). There is evidence indicating that CSC may be responsible for tumour progression, chemotherapy resistance and recurrence in NBTs. Oct4 is a transcription factor which plays a key role in mammal embryonic development and stem cell fate regulation. The aim of the study is to elucidate the clinical significance of Oct4 in NBTs. Methods We studied Oct4 expression in 563 primary NBTs using digital image quantification. Chi-square test was applied to analyse the correlation between histopathology and the Oct4+ cell percentage. Survival analysis was carried out with Kaplan-Meier curves and log-rank test. Additionally, a multivariate Cox regression analysis with the stepwise backwards (Wald) method was undertaken to calculate the impact of Oct4 expression level on survival. Results We found that tumours with a high proportion of cells expressing Oct4 correlated statistically with undifferentiated and poorly differentiated neuroblastoma / nodular ganglioneuroblastoma, and that Oct4 expression was not present in ganglioneuroma (p < 0.05). Statistical analysis also indicated a relationship between high Oct4 expression levels, high-risk patients according to the International Neuroblastoma Risk Group pre-treatment classification parameters, larger blood vessels and low survival rates. Conclusions These results suggest that the Oct4 gene may regulate NBT pathogenic differentiation pathways, and should thus be considered as a target for knockdown when developing novel therapies for high-risk NBT patients.
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                Author and article information

                Contributors
                konrad@konsta.com.pl
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                26 March 2020
                June 2020
                : 9
                : 11 ( doiID: 10.1002/cam4.v9.11 )
                : 4014-4025
                Affiliations
                [ 1 ] Department of Urology Copernicus Memorial Hospital Medical University of Lodz Lodz Poland
                [ 2 ] Department of Urology The Hospital Ministry of the Interior and Administration Lodz Poland
                [ 3 ] Department of Biostatistics and Translational Medicine Medical University of Lodz Lodz Poland
                [ 4 ] Department of Radiation Oncology Dana‐Farber Cancer Institute Harvard Medical School Boston MA USA
                Author notes
                [*] [* ] Correspondence

                Konrad Stawiski, Department of Biostatistics and Translational Research, Medical University of Lodz, Mazowiecka 15, Lodz 92‐215, Poland.

                Email: konrad@ 123456konsta.com.pl

                Author information
                https://orcid.org/0000-0001-8615-5940
                https://orcid.org/0000-0002-6550-3384
                https://orcid.org/0000-0002-5083-9168
                Article
                CAM43007
                10.1002/cam4.3007
                7286464
                32216043
                1ab4b8b7-bd97-48b0-984a-9ba1863c2f63
                © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 October 2019
                : 25 February 2020
                : 01 March 2020
                Page count
                Figures: 2, Tables: 5, Pages: 12, Words: 8648
                Funding
                Funded by: Narodowe Centrum Nauki , open-funder-registry 10.13039/501100004281;
                Award ID: 2018/29/N/NZ5/02422
                Categories
                Original Research
                Cancer Prevention
                Original Research
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:10.06.2020

                Oncology & Radiotherapy
                bladder cancer,non–muscle‐invasive bladder cancer,prediction,risk stratification,systematic review

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