M. Usoz1, A. Ewongwo2, M. Glover3, J. Fang4, Z. Kornberg3, E. Shokylar3, J. Shah3, H. P. Bagshaw4, S. Shah5, and Y. Qian4; 1University of South Carolina, Greenville, SC, 2Department of Radiation Oncology, Stanford University, Stanford, CA, 3Stanford University, Palo Alto, CA, 4Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, 5Stanford Cancer Institute, Palo Alto, CA
Purpose/Objective(s): Bladder preservation with Trimodality therapy is an alternative to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). Multiple retrospective studies have reported similar disease control and overall survival rates with chemoradiation (CRT) compared with RC. The addition of neoadjuvant chemotherapy (NAC) to RC is associated with improved survival. However, the benefit of NAC prior to CRT is not well established. This study reports on the outcomes of NAC prior to CRT for definitive management of MIBC. Materials/
Methods: We performed a retrospective review of 135 adult patients with non-metastatic MIBC who underwent bladder preservation therapy from 2016 to 2022, of which of 38 received NAC. Patients were excluded if they did not receive NAC, underwent RC after NAC, or had less than 1 year follow-up. Overall survival (OS), progression-free survival (PFS), and metastasis-free survival (MFS) were calculated using Kaplan-Meier curves. Differences in survival outcomes by completion of status of NAC were analyzed using log-rank tests. Analyses were performed in SAS version 9.4 and R version 4.3.1. Results: Most patients had high-grade tumors (97%) with urothelial carcinoma being the most common histology (92%). There were 27 patients who completed a full course of NAC (defined as >/= 3 cycles of dose dense methotrexate, vinblastine, doxorubicin, cisplatin or >/= 4 cycles gemcitabine with cisplatin or carboplatin) and 11 patients who did not. In patients treated with RT, 58% had hypofractionated RT (2.2-3.15 Gy/fx) with a median RT dose of 55 Gy, 42% had conventionally fractionated RT (1.8-2.0 Gy/fx) with a median RT dose of 64 Gy. The prescription dose covered an average of 92% of the whole bladder planning target volume (PTV). The 2-year OS, PFS, and MFS were 76% [95% CI 62-92%], 60% [95% CI 46-79%], and 72% [95% CI 58-90%] respectively. Two-year PFS improved in patients who received a full course of NAC (66%, [95% CI 50-87%]) compared to those who did not complete NAC regimen (38%, [95 CI 15-92%]; p=0.042). There was no difference in 2-year OS between patients who completed prescribed course of NAC versus those who did not (Full NAC: 82% [95% 68-98%]; No full NAC: 57% [95% CI 30-100%]; p=0.48). Treatment was overall well tolerated with 26% of grade 2 and 5% of grade 3 toxicity. Conclusion: NAC prior to CRT achieved excellent short term disease-free and survival outcomes in patients with non-metastatic MIBC. Completion of NAC prior to CRT may be associated with lower rates of disease recurrence.
