Prediction of survival in patients with muscle-invasive bladder cancer (MIBC) by neutrophil (NTP) infiltration in benign lymph nodes (LNs).

Abstract

273 Background: In preclinical models, NTPs appear to establish a pre−metastatic niche that fosters the invasion of metastases (Kowanetz et al PNAS 2010). This observation still requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15, a NTP marker, was performed for the entire cohort. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), vascular endothelial growth factor receptor−1 (VEGFR1), and CD68 (a macrophage marker) were further assessed in an initial cohort (detailed subsequently) via IHC. Positively staining cells were counted and averaged over 8 high power fields (hpfs). Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan−Meier method and log−rank test. Results: In an initial cohort of 19 pts who had received no neoadjuvant chemotherapy (NC), a median CD15 count of 284/hpf was noted. Median OS was higher in those pts with low CD15 as compared to high CD15 (158.7 mos v 36.9 mos, P=0.02). Median OS was also improved in those with high pSTAT3 v low pSTAT3 (not reached v 106.4 mos, P=0.04), but no difference was noted in OS in groups stratified by clinical stage, VEGFR1 staining, or CD68 staining. To determine if the prognostic value of CD15 staining was retained in pts with exposure to NC, the cohort was expanded to include an additional 36 pts who had received either preoperative GC (n=17) or MVAC (n=19) chemotherapy. In this group, no significant difference in OS was noted based using the previously applied CD15 cutoff. Conclusions: NTP recruitment to benign LNs may be prognostic of OS in pts with MIBC who have not received NC. pSTAT3, a putative mediator of NTP recruitment, may play a role in this phenomenon. VEGFR1 and CD68, which may mediate pre−metastatic niche through a different mechanism, do not predict OS in our dataset (Kaplan et al Nature 2005). Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.