Introduction & Objectives: Capecitabine, an oral 5-fluourouracil (5-FU) prodrug, could serve as a suitable alternative for 5-FU as a radiosensitizer in concurrent chemoradiotherapy (CCRT). Avoiding the necessity of indwelling central venous infusional devices, capecitabine is associated with increased convenience for both patients and healthcare professionals. Since large comparative studies are lacking, we aimed to compare toxicity, health-related quality of life (HRQoL) and survival after CCRT with 5-FU versus capecitabine.

Materials & Methods: Patients with non-metastatic urothelial MIBC (cT2-T4a, N0-2, M0), diagnosed between November 2017 and November 2019 and treated with CCRT with mitomycin C and either capecitabine or 5-FU were identified from the Netherlands Cancer Registry. Patient, tumor and treatment characteristics, and toxicity were compared between groups using ANOVA and Chi-square or Fisher-exact tests. HRQoL per treatment group was evaluated over time using the EORTC-QLQ-C30 questionnaire. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan Meier analyses with inverse probability treatment weights to adjust for baseline differences.

Results: Of the 266 patients included, 120 (45%) were treated with 5-FU and 146 (55%) with capecitabine. Compared to 5-FU, more patients in the capecitabine group completed a curative CCRT protocol according to treatment plan (60 vs 75%, p=0.01). Adverse events rates were equal in both groups (22 versus 18%, p=0.44). Two-year overall survival was significantly in favor of capecitabine (76% vs 62%, p=0.01). Two-year DFS was not significantly different (63% vs 51%, p=0.16). Reported HRQoL was similar for both treatment groups and showed a temporary decrease in several functioning or symptom scores at 6 or 12 months after diagnosis, but restored again to pre-treatment levels two years after diagnosis.

Conclusions: Concurrent chemoradiotherapy treatment with capecitabine and MMC is associated with a similar toxicity profile and health-related quality of life compared to 5-FU plus MMC. Also survival appears to be similar or even slightly better. As capecitabine is more patient-friendly compared to 5-FU, our data are in favor of replacement of 5-FU by capecitabine in CCRT of MIBC.

**Introduction & Objectives**: Capecitabine, an oral 5-fluourouracil (5-FU) prodrug, could serve as a suitable alternative for 5-FU as a radiosensitizer in concurrent chemoradiotherapy (CCRT). Avoiding the necessity of indwelling central venous infusional devices, capecitabine is associated with increased convenience for both patients and healthcare professionals. Since large comparative studies are lacking, we aimed to compare toxicity, health-related quality of life (HRQoL) and survival after CCRT with 5-FU versus capecitabine.

**Materials & Methods**: Patients with non-metastatic urothelial MIBC (cT2-T4a, N0-2, M0), diagnosed between November 2017 and November 2019 and treated with CCRT with mitomycin C and either capecitabine or 5-FU were identified from the Netherlands Cancer Registry. Patient, tumor and treatment characteristics, and toxicity were compared between groups using ANOVA and Chi-square or Fisher-exact tests. HRQoL per treatment group was evaluated over time using the EORTC-QLQ-C30 questionnaire. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan Meier analyses with inverse probability treatment weights to adjust for baseline differences.

**Results**: Of the 266 patients included, 120 (45%) were treated with 5-FU and 146 (55%) with capecitabine. Compared to 5-FU, more patients in the capecitabine group completed a curative CCRT protocol according to treatment plan (60 vs 75%, p=0.01). Adverse events rates were equal in both groups (22 versus 18%, p=0.44). Two-year overall survival was significantly in favor of capecitabine (76% vs 62%, p=0.01). Two-year DFS was not significantly different (63% vs 51%, p=0.16). Reported HRQoL was similar for both treatment groups and showed a temporary decrease in several functioning or symptom scores at 6 or 12 months after diagnosis, but restored again to pre-treatment levels two years after diagnosis.

**Conclusions**: Concurrent chemoradiotherapy treatment with capecitabine and MMC is associated with a similar toxicity profile and health-related quality of life compared to 5-FU plus MMC. Also survival appears to be similar or even slightly better. As capecitabine is more patient-friendly compared to 5-FU, our data are in favor of replacement of 5-FU by capecitabine in CCRT of MIBC.

Concurrent chemoradiation for muscle-invasive bladder cancer using 5-fluorouracil versus capecitabine