AUA 2019: Pretreatment Neutrophil-to-lymphocyte Ratio is a Novel Biomarker for Predicting Worse Clinical Outcome in Chemo-resistant Urothelial Carcinoma Patients Treated with Pembrolizumab

Chicago, IL USA ( Several studies have reported prognostic value of neutrophil to lymphocyte ratio in urothelial carcinoma, with higher pre-treatment values being associated with significantly poorer outcomes in cancer-specific mortality and response to neoadjuvant chemo. In 2017, pembrolizumab was approved in the United States and Japan as the second line for metastatic urothelial carcinoma which has progressed following cisplatin chemotherapy.

At Moderated Poster Session #26 (Invasive Bladder Cancer #1) at the 2019 annual meeting of the American Urological Association, Dr. Koichiro Ogihara presented “Pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting worse clinical outcome in chemo-resistant urothelial carcinoma patients treated with pembrolizumab” a retrospective analysis of 50 patients from his institution with a median follow up of 4.3 months. Using a ROC curve analysis a neutrophil-to-lymphocyte ratio of 3.90 was used as a cutoff for Neutrophil-to-lymphocyte (NLR) high and NLR low disease. Abdominal imaging was performed before and after 2-3 cycles of pembrolizumab and clinical response was evaluated using RECIST v1.1 criteria.

13 of the 45 cases with a visible disease on pre-pembrolizumab imaging were classified as NLR high. The baseline characteristics between the NLR high and NLR low groups were similar, except the NLR high group had a higher rate of liver metastases. Median progression free survival was approximately 1.5 months in the NLR high group and 3.0 months in the NLR group. Median cancer specific survival was approximately 6 months in the NLR high group and was not reached in the low NLR group.  On multivariate analysis, these patients had significantly higher rates of progression (HR 3.29 95% 1.04-10.3) and 6 month cancer-specific death (HR 6.06 95% CI 1.06-34.5). NLR was the only significant predictor of these outcomes in this multivariate analysis, acknowledging that performance status was not included in the model. Patients with progressive disease by RECIST criteria on initial post-pembrolizumab imaging had significant higher NLRs relative to responders pooled with those with stable disease (2.63 vs 3.86, p=0.037). The fact that the NLR increased in 59% of patients after administration of pembrolizumab was not discussed during the presentation but is noted in the abstract. The implications of this change are currently unclear.

During his presentation, Dr. Ogihara declined to speculate as to a mechanism to explain this effect, and given that NLR has been shown to portend a number of different poor outcomes in a number of different states of urothelial carcinoma, it is unlikely to relate to the mechanism of pembrolizumab specifically. Instead, this paper serves to validate NLR as a powerful prognostic marker in even this very advanced state in the progression of urothelial carcinoma.

Presented by: Koichiro Ogihara. Department of Urology, Keio University, Tokyo, Japan

Written by: Marshall Strother, MD, Chief Resident, Division of Urology, University of Pennsylvania, Philadelphia PA at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois