LAUSR

Bladder cancer is the sixth leading cause of cancer in the EU with 124,000 people diagnosed and over 40,000 people dying from the disease each year. The estimated total cost of bladder cancer across EU in 2012 was 4.9 billion of Euros [1]. By 2030, the annual incidence is projected to be almost duplicated (219,000); so epidemiologic efforts as well as improvements in cost-effective treatments and diagnosis are required. Bacillus Calmette Guerin (BCG) is the first line treatment for the NMIBC to prevent recurrence and progression. Despite treatment, 30–50% of patients fail to respond and 15% experience progression to MIBC; so predicting patients who might not benefit from BCG treatment is necessary, so other therapies such as chemohyperthermia or radical cystectomy could be performed. Identification of the BCG response markers that are clinically significant, disease relevant, reproductible and easily accessible in the clinical settings is challenging up to date. In this paper, Aydin et al. [2]. even despite an adequate statistical analysis, a large sample and a considerable followup, did not find statistical relation between PD-L1 expression and response to BCG treatment. As they cited in this paper, our experience agrees with their findings [3]; so, how to explain the wide variability of results reports by differents groups? Devil is on details, and this heterogeneity of results could be explained by the strain and dose of BCG used, the inclusion or not in the study of patients with carcinoma in situ, the immunohistochemical staining method used as well as the determination of the place of PD-L1 (inflammatory or neoplastic cells). Intravesical administration of BCG is hypothesized to act as a localized Th1-polarizing immunomodulator that induces massive influx of inflammatory cells. As Rentsch et al. reported, BCG Connaught appears to be a stronger inducer of a Th1 polarized response compared with BCG Tice, and it was significantly more effective in terms of recurrence-free survival [4]. Kamer et al. [5] presented a promising tool to predict recurrences with an 80% accuracy. However, we have to consider the high variability of production, liberation and detection of such cytokines, which could be difficult in the clinical application of that cytokine panel. We have also to consider if the assay is feasible to perform at a hospitalbased laboratory, as well as the involved costs. The search of prognostic factors goes on, and Aydin et al. open other paths to get the wished prognosis tool. Probably the solution will be to combine clinical pathology, cellular, genetic, epigenetic and molecular markers.