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Background <p>This study evaluated the real-world effectiveness and prognostic factors of platinum rechallenge therapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC), with particular attention to DNA damage response (DDR) pathway gene alterations.</p> Methods <p>We retrospectively analyzed 78 patients with la/mUC who received platinum rechallenge therapy across three tertiary referral hospitals in Korea. Clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were assessed. Prognostic factors were identified using univariate and multivariate analyses. The impact of DDR pathway gene alterations on treatment response was also evaluated in patients with available data.</p> Results <p>The ORR of platinum rechallenge was 42.3%, with median PFS and OS of 4.7 and 9.0&#xa0;months, respectively. ORR was numerically higher in ECOG 0–1 versus ≥ 2 (48.2% vs. 27.3%), and in patients without versus with liver metastasis (45.2% vs. 31.2%). Multivariable Cox regression analysis identified ECOG performance status ≥ 2 and liver metastasis as independent adverse prognostic factors. DDR pathway alterations were present in approximately 30% of patients but showed no correlation with ORR, PFS, or OS.</p> Conclusion <p>Platinum rechallenge demonstrated meaningful clinical activity in selected patients with la/mUC. Clinical factors such as performance status and liver metastasis may help identify patients most likely to benefit. Although DDR pathway alterations were common, they were not associated with treatment outcomes.</p>

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Real-world effectiveness and prognostic factors of platinum rechallenge in advanced urothelial cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Eo Jin Kim,
  • Jwa Hoon Kim,
  • Jinah Chu,
  • Yun-Gyoo Lee,
  • Hyeon-Su Im

摘要

Background

This study evaluated the real-world effectiveness and prognostic factors of platinum rechallenge therapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC), with particular attention to DNA damage response (DDR) pathway gene alterations.

Methods

We retrospectively analyzed 78 patients with la/mUC who received platinum rechallenge therapy across three tertiary referral hospitals in Korea. Clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were assessed. Prognostic factors were identified using univariate and multivariate analyses. The impact of DDR pathway gene alterations on treatment response was also evaluated in patients with available data.

Results

The ORR of platinum rechallenge was 42.3%, with median PFS and OS of 4.7 and 9.0 months, respectively. ORR was numerically higher in ECOG 0–1 versus ≥ 2 (48.2% vs. 27.3%), and in patients without versus with liver metastasis (45.2% vs. 31.2%). Multivariable Cox regression analysis identified ECOG performance status ≥ 2 and liver metastasis as independent adverse prognostic factors. DDR pathway alterations were present in approximately 30% of patients but showed no correlation with ORR, PFS, or OS.

Conclusion

Platinum rechallenge demonstrated meaningful clinical activity in selected patients with la/mUC. Clinical factors such as performance status and liver metastasis may help identify patients most likely to benefit. Although DDR pathway alterations were common, they were not associated with treatment outcomes.