Early cancer cachexia phenotype predicts survival of advanced urothelial cancer patients treated with pembrolizumab.

AIM We aimed to explore the association between cancer cachexia phenotypes in the early phase of treatment induction and the prognosis of advanced urothelial cancer (aUC) patients receiving pembrolizumab. METHODS This retrospective study included 31 aUC patients treated with pembrolizumab as a second- or later-line therapy. Patients were categorized into three early cancer cachexia phenotypes by changes in skeletal muscle and total adipose indices calculated using computed tomography images taken immediately before and within 3 months after the initiation of pembrolizumab: No Wasting (NW, 11 patients), Fat-Only Wasting (FW, 13), and Muscle and Fat Wasting (MFW, seven). Its association with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS The median follow-up period was 5.7 months. The median number of cycles of pembrolizumab was five. The ORR in NW/FW/MFW was 86%/38%/0%, respectively (p = 0.001). The PFS and OS rates were the best in NW, followed in order by FW and MFW (PFS, 69%/45%/0% at 12 months, p = 0.008; OS, 100%/65%/0% at 12 months, p < 0.001). In multivariate analysis including posttherapeutic cachexia-associated parameters, cancer cachexia phenotype (MFW vs. FW/NW) was an independent predictor of poor OS (hazard ratio 8.59, p < 0.001) along with an increase in neutrophil-lymphocyte ratio (p = 0.028). CONCLUSION Early cancer cachexia phenotypes were significantly associated with the survival of aUC patients treated with pembrolizumab. In contrast to the very early progression and poor prognosis in the MFW group, long-term survival can be expected in the NW/FW groups.