Non-muscle-invasive Bladder Cancer Part 2

Non-muscle-invasive Bladder Cancer Part 2 Comprehensive Review Article Prof. Dr. Semir. A. Salim. Al Samarrai PREDICTING DISEASE RECURRENCE AND PROGRESSION: TaT1 tumours Treatment should take into account a patient’s prognosis. In order to predict the risk of disease recurrence and/ or progression, several prognostic models for specified patient populations have been introduced. Scoring models using the WHO 1973 classification system The 2006 European Organisation for Research and Treatment of Cancer (EORTC) scoring model to be able to predict both the short- and long-term risks of disease recurrence and progression in individual patients, the EORTC Genito-Urinary Cancer Group (GUCG) published a scoring system and risk tables based on the WHO 1973 classification in 2006 [1]. The scoring system is based on the 6 most significant clinical and pathological factors in patients mainly treated by intravesical chemotherapy: • Number of tumours; • Tumour diameter; • Prior recurrence rate; • T category; • Concurrent CIS; • WHO 1973 tumour grade. Using the 2006 EORTC scoring model, individual probabilities of recurrence and progression at 1 and 5 years may be calculated (https://www.omnicalculator.com/health/eortc-bladder-cancer). The model for patients with Ta G1/G2 (WHO 1973) tumours treated with chemotherapy Patients with Ta G1/G2 tumours receiving chemotherapy were stratified into 3 risk groups for recurrence, taking into account the history of recurrences, history of intravesical treatment, tumour grade (WHO 1973), number of tumours and adjuvant chemotherapy [2]. Club Urologico Español de Tratamiento Oncologico (CUETO) scoring model for BCG-treated patients A model that predicts the risk of recurrence and progression, based on 12 doses of intravesical BCG over a 5 to 6 months period following TURB, has been published by the CUETO (Spanish Urological Oncology Group). It is based on an analysis of 1,062 patients from 4 CUETO trials that compared different intravesical BCG treatments. No immediate post-operative instillation or second TURB was performed in these patients. The scoring system is based on the evaluation of seven prognostic factors: • gender; • age; • prior recurrence status; • number of tumours; • T category; • associated CIS; • WHO 1973 tumour grade. Using this model, the calculated risk of recurrence is lower than that obtained by the EORTC tables. For progression, probability is lower only in high-risk patients [3]. The lower risks in the CUETO tables may be attributed to the use of BCG in this study. The prognostic value of the EORTC scoring system has been confirmed by data from the CUETO patients treated with BCG and by long-term follow-up in an independent patient population [4, 5]. The 2016 EORTC scoring model for patients treated with maintenance BCG In 1,812 intermediate- and high-risk patients without CIS treated with 1 to 3 years of maintenance BCG, the EORTC found that the prior disease-recurrence rate and number of tumours were the most important prognostic factors for disease recurrence, stage and WHO 1973 grade for disease progression and diseasespecific survival, while age and WHO 1973 grade were the most important prognostic factors for OS. T1 G3 patients did poorly, with 1- and 5-year disease-progression rates of 11.4% and 19.8%, respectively. Using these data, EORTC risk groups and nomograms for BCG-treated patients were developed [6]. Scoring model using the WHO 2004/2016 and WHO 1973 classification systems EAU NMIBC 2021 scoring model To update the risk of disease progression and create new prognostic factor risk groups using both the WHO 1973 and WHO 2004/2016 classification systems (without central pathology review), individual patient data from 3,401 primary patients treated from 1990 to 2018 were used [7]. Only patients treated with TURB ± intravesical chemotherapy were included, those treated with adjuvant intravesical BCG were excluded because BCG may reduce the risk of disease progression. From the multivariate analysis, tumour stage, WHO 1973 grade, WHO 2004/2016 grade, concomitant CIS, number of tumours, tumour size and age were independent predictors of disease progression [7]. Further prognostic factors Further prognostic factors have been described in selected patient populations: • In T1G3 tumours, important prognostic factors were female sex, CIS in the prostatic urethra in men treated with an induction course of BCG, and age, tumour size and concurrent CIS in BCG-treated patients (62% with an induction course only) [8, 9]. • Attention must be given to patients with T1G3 tumours in bladder (pseudo) diverticulum because of the absence of muscle layer in the diverticular wall [10]. • In patients with T1 tumours, the finding of residual T1 disease at second TURB is an unfavourable prognostic factor [11-13]. In patients with T1G2 tumours treated with TURB, recurrence at 3 months was the most important predictor of progression [14]. • The prognostic value of pathological factors has been discussed elsewhere. More research is needed to determine the role of molecular markers in improving the predictive accuracy of currently available risk tables [4, 15]. • Pre-operative neutrophil-to-lymphocyte ratio may have prognostic value in NMIBC. This data, however, needs further validation [16]. Carcinoma in situ Without any treatment, approximately 54% of patients with CIS progress to muscle-invasive disease [17]. There are no reliable prognostic factors, but some studies, however, have reported a worse prognosis in concurrent CIS and T1 tumours compared to primary CIS [18,19], in extended CIS [20] and in CIS in the prostatic urethra [8]. The response to intravesical treatment with BCG or chemotherapy is an important prognostic factor for subsequent progression and death caused by BC [3–5, 14]. Approximately 10 to 20% of complete responders eventually progress to muscle-invasive disease, compared with 66% of non-responders [21, 22]. Patient stratification into risk groups To be able to facilitate treatment recommendations, the Guidelines Panel recommends the stratification of patients into risk groups based on their probability of progression to muscle-invasive disease. The new risk group definitions provided in these EAU Guidelines are based on an IPD analysis in primary patients and the calculation of their progression scores (2021 EAU NMIBC scoring model) [7]. For calculation of the risk group in individual patients, either one, or both, of the WHO 1973 and WHO 2004/2016 classification systems may be used. The probability of