A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy

Abstract Purpose: We conducted a prospective pilot study to evaluate safety and feasibility of TraceIT®, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiotherapy (RT). Materials and Methods: Patients with muscle invasive bladder cancer (MIBC) receiving definitive RT were eligible. TraceIT® was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor (TURBT). The primary endpoint was the difference between radiation treatment planning margin on daily cone-beam CT based on alignment to TraceIT® vs standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume (PTV) margin. TraceIT® visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by CTCAE v4.03. Results: The trial was fully accrued and fifteen patients were analyzed. TraceIT® was injected in 4 sites/patient (range 4-6). Overall, 94% (95% CI 90-98%) of injection sites were radiographically visible at RT initiation vs. 71% (95% CI 62-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat TURBT followed by bladder tumor bed boost fields and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced PTV margins (0.67cm vs 1.56cm) for the initial phase of RT, but not for the boost (1.01cm vs 0.96cm). This allowed for improved target coverage (D95% 80-83% to 91-94%) for two patients retrospectively planned with both VMAT and 3DCRT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT® placement occurred. No patients required salvage cystectomy. Conclusions: TraceIT® intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized MIBC. Improved image-guided treatment may facilitate strategies to improve local control and minimize toxicity.