Significant Improvement of Prognosis After the Advent of Immune Checkpoint Inhibitors in Patients with Advanced, Unresectable, or Metastatic Urothelial Carcinoma: A Propensity Score Matching and Inverse Probability of Treatment Weighting Analysis on Real-

The treatment landscape for advanced, unresectable, or metastatic urothelial carcinoma (aUC) has shifted substantially since the advent of immune checkpoint inhibitors (ICIs). We investigated the extent to which pembrolizumab therapy is superior to conventional chemotherapy as a second-line treatment.

A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 94 patients (21%) who received second-line pembrolizumab and 75 (17%) who received second-line chemotherapy but never received third-line or later ICI therapy were included. We compared overall survival (OS) from the initial date of first-line chemotherapy between two groups by adjusting for prognostic factors through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The IPTW-adjusted hazard ratio and 95% confidence interval were estimated using a multivariate Cox regression analysis. To identify patients who were more likely to benefit from second-line pembrolizumab than from chemotherapy, we performed a subgroup analysis for OS with an IPTW-adjusted model.

The PSM-adjusted comparison showed a significant improvement in the prognosis with second-line pembrolizumab use (P = 0.01). The OS benefit with the advent of pembrolizumab was 8 months (18 months vs 26 months). Multivariable analyses using IPTW adjustment demonstrated that lymph node metastasis (P = 0.001), lung metastasis (P = 0.013), and bone metastasis (P = 0.003) were poor independent prognostic factors, and pembrolizumab use (P = 0.021) was a favorable independent prognostic factor. Subgroup analyses revealed that pembrolizumab was associated with survival benefits over chemotherapy in all subgroups, including young patients (age <70 years), those who received radical surgery, and those without visceral metastasis.

We demonstrated a significant improvement in prognosis after the advent of pembrolizumab for patients with aUC. ICIs should not be restricted based on patient characteristics.

Cancer management and research. 2022 Feb 16*** epublish ***

Makito Miyake, Nobutaka Nishimura, Takuto Shimizu, Mikiko Ohnishi, Masaomi Kuwada, Yoshitaka Itami, Takeshi Inoue, Kenta Ohnishi, Yoshihiro Matsumoto, Takanori Yoshida, Yoshihiro Tatsumi, Masatake Shinohara, Shunta Hori, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Tomomi Fujii, Nobumichi Tanaka, Kiyohide Fujimoto

Department of Urology, Nara Medical University, Kashihara, Nara, 634-8522, Japan., Department of Urology, Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan., Department of Urology, Nara Prefecture General Medical Center, Nara, Japan., Department of Urology, Hoshigaoka Medical Center, Hirakata, Osaka, Japan., Department of Urology, Tane General Hospital, Osaka, Japan., Department of Urology, JCHO Yamato Koriyama Hospital, Koriyama, Nara, Japan., Department of Urology, Osaka Gyoumeikan Hospital, Osaka, Japan., Department of Diagnostic Pathology, Nara Medical University, Kashihara, Nara, 634-8522, Japan.