Pre-therapeutic lymphocytopenia: a new prognostic factor for failure of endovesical BCG-immunotherapy in non-muscle invasive bladder cancer

Abstract

Abstract Background Inflammation plays a key role in the initiation and development of cancers. The prognostic value of inflammation biomarkers is proven in several urological and non-urological cancers. Knowing that the mechanism of action of endovesical BCG-immunotherapy in the treatment of non-muscle-invasive bladder cancer (NMIBC) is based on inflammation; lymphocytes have a key role in this reaction, particularly in the cytotoxic phase and can be predictive biomarkers of the response to BCG-therapy. The main objective of our work is therefore to study the impact of the number of lymphocytes on the response to endovesical BCG-immunotherapy, and more specifically lymphocytopenia (Lp) as a prognostic factor for BCG-failure. Methods Our study is a monocentric retrospective cohort carried for prognostic purposes, including 200 patients neodiagnosed with non-muscle-invasive bladder cancer (Ta -T1 stages), who required adjuvant treatment to TURB by BCG-immunotherapy, over a period of 5 years from January 2012 to December 2016. The cutoff value chosen was 1.67 × 109/L using maximized Log-Rank test. Survival analysis was studied using a Kaplan–Meier model. The comparison between the thresholds (L ≤ Vs > 1.67 × 109/L) concerning the recurrence and progression rates was carried out using the Log-Rank test. The association between lymphocytopenia and BCG-therapy failure was assessed in univariate and multivariate analysis by the Cox model. Statistical analysis was performed using Jamovi statistical software. Results One hundred and eight patients had a lymphocyte count > 1.67 × 109/L while 92 had a lymphocyte count ≤ 1.67 × 109/L. The median lymphocyte value was 1.64 (1.19; 2.4). The median survival without failure of BCG treatment was significantly better in the high lymphocyte-count group, with median of 22 months in the > 1.67 × 109/L group versus 11 months until failure in the ≤ 1.67 × 109/L group. A lymphocyte count ≤ 1.67 × 109/L was associated with failure of BCG-therapy in univariate (HR = 4.80, P ≤ 0.001) and multivariate (HR = 1.88, P = 0.025) studies. Other factors associated in the univariate study were found: T1 stage (P = 0.001), high-grade urothelial carcinoma (P = 0.001), multifocal tumor (P = 0.001), tumor size > 3 cm (P = 0.001), concomitant carcinoma in situ (Cis) (P = 0.001) and vascular emboli (P = 0.001). Multivariate study showed significant factors that are, in addition to lymphocytopenia, the presence of T1 stage (P = 0.011) and vascular emboli (P = 0.013). Conclusion Our study has shown an association between lymphocytes count and NMIBC progression. Patients with lymphocytopenia carry an increased risk of endovesical BCG-immunotherapy failure. These results should be further validated.

Keywords

• Lymphocytopenia
• BCG-immunotherapy
• Recurrence
• Progression