Systemic immune-inflammation index is prognostic in testicular germ cell tumors with PD-L1 expressing tumor infiltrating lymphocytes.

Abstract

e16042 Background: Systemic immune-inflammation index (SII) and programmed death-ligand 1 (PD-L1) are prognostic in various types of malignancies. Recently we have shown a prognostic value of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes (TILs) in testicular germ cell tumors (GCT). This study aimed to evaluate prognostic role of SII in a GCT population of patients expressing PD-L1 on TILs. Methods: SII was calculated using platelet (P), neutrophil (N) and lymphocyte (L) counts measured prior to chemotherapy (SII = P x N/L). SII was calculated in our discovery set of 216 patients with GCT treated at National Cancer Institute and St. Elisabeths' Cancer Institute between 1999 and 2015. A model with median obtained from the discovery data was tested in an independent validation set of 181 patients that were included in a retrospective study evaluating PD-L1 on TILs in GCT. PD-L1 on TILs was detected by immunohistochemistry and scored semiquantitatively by weighted histoscore method. SII was dichotomized into low and high categories based on median value. Results: Low SII ( < 1003) was found in 133 patients (73.5%) as opposed to 48 patients (26.5%) with high SII (≥ 1003). Ten (5.5%) and 171 patients (94.5%) from the validaton set had low (HS < 150) and high (HS ≥ 160) expression of PD-L1 on TILs, respectively. Discovery group of patients with high SII had significantly shorter PFS (HR = 4.48, 95% CI 2.44 – 8.23, p = 0.0000) and OS (HR = 6.10 95% CI 3.11 – 11.95, p = 0.0000) opposite to patients with low SII. PFS from validation set confirmed shorter PFS (HR = 3.03, 95% CI 3.86 – 7.46, p = 0.0062) and OS (HR = 6.49 95% CI 2.10 – 20.03, p = 0.0001) in patients with high versus low SII. A combined prognostic value of PD-L1 TILs and SII uncovered three prognostic groups. The best prognosis was observed in patients with low SII and high PD-L1 on TILs, the worst prognosis was seen in patients with high SII and low PD-L1 on TILs. Patients with SII and PD-L1 on TILs both values high or low had intermediate prognosis. Conclusions: SII was prognostic in our patients with GCT independently of international germ cell cancer collaborative group criteria, suggesting involvement of immune mechanisms in the behavior of GCT.