Mizuki Kobayashi1, Shintaro Narita1, Yoshiyuki Matsui2, Souhei Kanda1, Yu Hidaka3, Hiroyasu Abe3, Toyonori Tsuzuki4, Katsuhiro Ito5, Takahiro Kojima6, Minoru Kato7, Shingo Hatakeyama8, Yuto Matsushita9, Sei Naito10, Masanobu Shiga6, Makito Miyake11, Yusuke Muro12, Shotaro Nakanishi13, Yoichiro Kato14, Tadamasa Shibuya15, Tetsutaro Hayashi16, Hiroaki Yasumoto17, Takashi Yoshida18, Motohide Uemura19, Rikiya Taoka20, Manabu Kamiyama21, Satoshi Morita3, Tomonori Habuchi1, Osamu Ogawa22, Hiroyuki Nishiyama6, Hiroshi Kitamura23, Takashi Kobayashi22. 1. Department of Urology, Akita University Graduate School of Medicine, Akita, Japan. 2. Department of Urology, National Cancer Center Hospital, Tokyo, Japan. 3. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 4. Department of Surgical Pathology, Aichi Medical University, Nagoya, Japan. 5. Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan. 6. Department of Urology, University of Tsukuba, Japan. 7. Department of Urology, Osaka City University, Osaka, Japan. 8. Department of Urology, Hirosaki University, Hirosaki, Japan. 9. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 10. Department of Urology, Faculty of Medicine, Yamagata University, Yamagata, Japan. 11. Department of Urology, Nara Medical University, Kashihara, Japan. 12. Department of Urology, Shizuoka General Hospital, Shizuoka, Japan. 13. Department of Urology, University of the Ryukyus, Nishihara, Japan. 14. Department of Urology, Iwate Medical University, Morioka, Japan. 15. Department of Urology, Oita University, Yufu, Japan. 16. Department of Urology, Hiroshima University, Hiroshima, Japan. 17. Department of Urology, Shimane University, Izumo, Japan. 18. Department of Urology, Kansai Medical University, Hirakata, Japan. 19. Department of Urology, Osaka University, Suita, Japan. 20. Department of Urology, Kagawa University, Kita, Japan. 21. Department of Urology, University of Yamanashi, Chuo, Japan. 22. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 23. Department of Urology, University of Toyama, Toyama, Japan.
Abstract
OBJECTIVES: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo-resistant urothelial carcinoma (UC). PATIENTS AND METHODS: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68-1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15-0.90; P = 0.023) compared to patients with PUC. CONCLUSIONS: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo-resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.
OBJECTIVES: To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemo-resistant urothelial carcinoma (UC). PATIENTS AND METHODS: The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR) and overall survival (OS) were compared between the groups using a propensity score matching (PSM). RESULTS: Overall, 147 (19.5%) patients harboured any histological variant UC (VUC). After PSM, there were no significant differences in the objective response rate (ORR, 24.5% vs 17.3%, P = 0.098) or disease control rate (DCR, 36.7% vs 30.2%, P = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, was associated with a similar risk of death (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.68-1.20; P = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had a comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, P = 0.031), DCR (52.6%, P = 0.032), and OS (HR 0.37, 95% CI 0.15-0.90; P = 0.023) compared to patients with PUC. CONCLUSIONS: The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemo-resistant UC. The patients with sarcomatoid VUC achieved favourable responses and survival rates compared to PUC.