Prediction model for recurrence probabilities after intravesical chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer, including external validation

Abstract

PurposeTo develop a model to predict recurrence for patients with intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) treated with intravesical chemotherapy which can be challenging because of the heterogeneous characteristics of these patients.MethodsData from three Dutch trials were combined. Patients treated with intravesical chemotherapy with characteristics according to the IR definition of the EAU guideline 2013 were included. Uni- and multivariable Cox regression with selection methods were used to identify predictors of recurrence at 1, 2, and 5 years. An easy-readable table for recurrence probabilities was developed. An external validation was done using data from Spanish patients.ResultsA total of 724 patients were available for analyses, of which 305 were primary patients. Recurrences occurred in 413 patients (57 %). History of recurrences, history of intravesical treatment, grade 2, multiple tumors, and adjuvant treatment with epirubicin were relevant predictors for recurrence-free survival with hazard ratios of 1.48, 1.38, 1.22, 1.56, and 1.27, respectively. A table for recurrence probabilities was developed using these five predictors. Based on the probability of recurrence, three risk groups were identified. Patients in each of the separate risk groups should be scheduled for less or more aggressive treatment. The model showed sufficient discrimination and good predictive accuracy. External validation showed good validity.ConclusionIn our model, we identified five relevant predictors for recurrence-free survival in IR-NMIBC patients treated with intravesical chemotherapy. These recurrence predictors allow the urologists to stratify patients in risk groups for recurrence that could help in deciding for an individualized treatment approach.Electronic supplementary materialThe online version of this article (doi:10.1007/s00345-015-1598-0) contains supplementary material, which is available to authorized users.

Selected protein expression in a new prognostic model for patients with non-muscle-invasive bladder cancer

“…Attempts have been made by many researchers to improve the algorithms developed by the EORTC. Some authors have focused on the preparation of prognostic models for specific groups of patients, while others have attempted to determine the probability of tumor recurrence by evaluating gene polymorphisms, inflammation, or the presence of tumor markers in urine (Ieda et al 2016;Kim et al 2016;Maturana et al 2016;Chen et al 2012;Cui et al 2017;Todenhöfer et al 2014;Lammers et al 2016). The possibility of improving the accuracy of these algorithms by means of immunohistochemistry was also analyzed (Ding et al 2014;Passoni et al 2016).…”

What is new in non-muscle-invasive bladder cancer in 2016?

“…Intermediate Risk (IR)-NMIBC has a critical threshold when urologists choose intravesical chemotherapy protocol, either SI or maintanance therapy. Lammers et al [28] reported a risk tablefor IR-NMIBC patients treated with intravesical chemotherapy including five relevant predictors of reccurence-free survival: history of recurrences, history of intravesical treatment, grade 2, multiple tumors and adjuvant treatment with epi-rubicin. These individual predictors were used to subdivide IR patients into three risk groups, which is related to recurrence outcome.…”

“…The urologist together with the patient can choose for an individualized treatment approach. [28] However, further chemotherapy instillations after SI improved recurrence-free survival in intermediate-risk patients. [29] The available evidence does not support treatment longer than one year of intravesical chemotherapy (LE: 3).…”

Urinary laminin‐γ2 is a novel biomarker of non‐muscle invasive urothelial carcinoma

“…However, the sensitivities of NMP22 and BTA are 32-92% and 53-89%, respectively, and their specificities are 51-94% and 53-89%, respectively. (2,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) Furthermore, BTA and NMP22 yield a high pseudopositive ratio for hematuria, urinary infections, and urolithiasis patients; therefore, these tests are not used routinely for diagnosis of NMIUC. (2,11) Thus, development of new tumor markers for UC that can also replace cystoscopy for routine monitoring examination is desirable.Ln-c2, a component of (17) is an interesting candidate tumor biomarker, as it is expressed in cancerous tissues.…”