M. A. Whitmill1, B. M. Anderson1, M. C. Repka1, S. Sud1, H. J. Tan2, M. A. Bjurlin2, M. Milowsky3, W. Y. Kim3, T. L. Rose3, and N. A. Wijetunga4; 1Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, 2Department of Urology, University of North Carolina, Chapel Hill, NC, 3Division of Oncology, University of North Carolina, Chapel Hill, NC, 4Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Purpose/Objective(s):Trimodality therapy (TMT) for muscle invasive bladder cancer (MIBC) is an alternative to radical cystectomy with comparable rates of local control and overall survival (OS). Recurrences are common after therapy, prompting a need to better understand failure patterns and contributing factors. Given the inherent variation in treating a dynamic bladder adjacent to dose-limiting organs-at-risk (OARs), a study of spatial and dosimetric aspects of treatment is warranted. We evaluated patients treated with definitive TMT for MIBC, with a specific focus on spatial and dosimetric factors that may underlie failure patterns.Materials/
Methods: We analyzed a database of TMT patients treated at a single institution from September 2014 to January 2023, conducting a retrospective review of treatment, radiographic, and clinical factors. Detailed radiation planning and dosimetric information, including dose to targets and OARs relative to prescription. Pre-treatment disease and local recurrences were mapped to six bladder wall regions defined by EAU endoscopy guidelines. Results: We identified 43 patients with MIBC who underwent curative intent TMT, with 88% (39) having at least one available biopsy. Prescription dose varied between 45 and 64.8 Gy delivered in 1.80 to 2.75 Gy fractions. Three and five year OS were 62% and 36%, with 24 patients alive by the study end. 51% (22) of patients were treated with 3D-CRT, 44% (19) were treated with IMRT, and 5% (2) with a hybrid approach. Concurrent chemotherapies were mostly 5-fluorouracil / Mitomycin-C (53%) or gemcitabine (35%). 47% (22) of patients had repeat TURBT prior to chemoRT. The posterior (37%) and lateral (51% right, 35% left) walls were the most common sites of involvement, while the dome (23%) and trigone (21%) were least common. 11 patients failed locally with median time to failure (TTF) of 11.6 months. 13 patients failed distantly with median TTF of 11.3 months. 23% (10) of patients had a history of non-bladder cancer and 21% (9) had prior non-MIBC. 60% of patients were current or former tobacco users with a median of 30 pack-years. Of 11 local failures, 82% (9) had at least partial regional overlap to the treated primary. Dosimetric analysis of patients with local failure shows a median GTV D95% of 99.6% (96.8-100.7%), CTV D95% of 97.7% (93.6-102.0%), and PTV D95% of 98.2% (84.3-101.2%). The median D1% of the rectum was 99.9% (62.5-104.6%), the sigmoid 101% (95.9-104.5%), and the small bowel was 80.9% (5.2-104.4%). Conclusion: Local failure after TMT is common, with a significant proportion of recurrences occurring at or near the site of pre-treatment disease. As we observed a large range in target and OAR dose, further investigation is warranted to determine whether superior local control may be achieved through altered spatial and dosimetric considerations without additional toxicity. Additionally, identifying molecular correlates of failure patterns may also provide valuable insights into the response to TMT and guide personalized treatment strategies.
