Second-line Pembrolizumab for Metastatic Urothelial Carcinoma: Differences in Treatment Outcomes According to the Primary Site

Naotaka Nishiyama; Yuki Kita; Katsuhiro Ito; Minoru Kato; Shingo Hatakeyama; Yuto Matsushita; Sei Naito; Makito Miyake; Shotaro Nakanishi; Yoichiro Kato; Tadamasa Shibuya; Tetsutaro Hayashi; Hiroaki Yasumoto; Takashi Yoshida; Motohide Uemura; Rikiya Taoka; Hiroyuki Nishiyama; Takashi Kobayashi; Hiroshi Kitamura; Japan Urological Oncology Group

doi:10.21873/anticanres.16703

Second-line Pembrolizumab for Metastatic Urothelial Carcinoma: Differences in Treatment Outcomes According to the Primary Site

Anticancer Res. 2023 Nov;43(11):5041-5050. doi: 10.21873/anticanres.16703.

Authors

Naotaka Nishiyama¹, Yuki Kita², Katsuhiro Ito², Minoru Kato³, Shingo Hatakeyama⁴, Yuto Matsushita⁵, Sei Naito⁶, Makito Miyake⁷, Shotaro Nakanishi⁸, Yoichiro Kato⁹, Tadamasa Shibuya¹⁰, Tetsutaro Hayashi¹¹, Hiroaki Yasumoto¹², Takashi Yoshida¹³, Motohide Uemura¹⁴, Rikiya Taoka¹⁵, Hiroyuki Nishiyama¹⁶, Takashi Kobayashi¹⁷, Hiroshi Kitamura; Japan Urological Oncology Group

Affiliations

¹ Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan.
² Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
³ Department of Urology, Osaka Metropolitan University, Osaka, Japan.
⁴ Department of Urology, Hirosaki University, Aomori, Japan.
⁵ Department of Urology, Hamamatsu University School of Medicine, Shizuoka, Japan.
⁶ Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan.
⁷ Department of Urology, Nara Medical University, Nara, Japan.
⁸ Department of Urology, University of the Ryukyus, Okinawa, Japan.
⁹ Department of Urology, Iwate Medical University, Iwate, Japan.
¹⁰ Department of Urology, Oita University, Oita, Japan.
¹¹ Department of Urology, Hiroshima University, Hiroshima, Japan.
¹² Department of Urology, Shimane University, Shimane, Japan.
¹³ Department of Urology and Andrology, Kansai Medical University, Osaka, Japan.
¹⁴ Department of Urology, Osaka University, Osaka, Japan.
¹⁵ Department of Urology, Kagawa University, Kagawa, Japan.
¹⁶ Department of Urology, University of Tsukuba, Tsukuba, Japan.
¹⁷ Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan; selecao@kuhp.kyoto-u.ac.jp.

PMID: 37909969
DOI: 10.21873/anticanres.16703

Abstract

Background/aim: To evaluate the difference in the clinical efficacy and safety of pembrolizumab between patients with metastatic upper tract urothelial carcinoma (UTUC), which includes renal pelvic urothelial carcinoma (UC) and ureteral UC, and those with metastatic lower tract urothelial carcinoma (LTUC).

Patients and methods: A total of 752 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. We compared progression-free survival (PFS), overall survival (OS) and adverse events (AEs) in patients with renal pelvic UC, ureteral UC, and LTUC.

Results: The median follow-up period was 42.5 [interquartile range (IQR)=35.1-47.4] months. The primary tumor site was in the upper tract in 362 (48.1%) patients [renal pelvis, n=219 (60.5%); ureter, n=143 (39.5%)] and in the lower tract in 390 (51.9%) patients. The estimated glomerular filtration rate before pembrolizumab treatment in the UTUC group was significantly lower than that in the LTUC group (p<0.001). The median PFS in the UTUC and LTUC groups was 3.4 months, respectively (p=0.271). The median OS in the UTUC and LTUC groups was 10.1 months and 11.7 months, respectively (p=0.195). In an analysis of UTUC divided into renal pelvic UC, ureteral UC, and LTUC, patients with renal pelvic UC had a significantly poorer prognosis in comparison to the other two groups (p=0.041). The incidence of any-grade AEs (51.7% vs. 47.9%, p=0.343) and grade ≥3 AEs (12.2% vs. 12.8%, p=0.826) in the two groups was not statistically significantly different.

Conclusion: No significant differences were found between the UTUC and LTUC groups with regard to the oncological outcomes and safety of pembrolizumab. Patients with renal pelvic UC had a significantly poorer prognosis than those with other ureteral UCs and LTUCs.

Keywords: Chemo-resistant urothelial carcinoma; lower tract urothelial carcinoma; pembrolizumab; upper tract urothelial carcinoma.

MeSH terms

Carcinoma, Transitional Cell* / drug therapy
Humans
Kidney Neoplasms* / drug therapy
Retrospective Studies
Treatment Outcome
Ureteral Neoplasms*
Urinary Bladder Neoplasms*

Substances

pembrolizumab