Site versus central read discrepancy rates in PCWG3 evaluation for progression.

5067 Background: Prostate Cancer Working Group-3 Criteria (PCWG3) is the standard for determining radiographic response assessments in Prostate Cancer (PC) Clinical Trials. PCWG3 accounts for soft tissue and bone responses by following RECIST and evaluation of metastatic bone disease, respectively. In PC, the determination of progressive disease (PD) by bone metastases is often challenging due to increased osteoblastic activity during drug treatment known as flare phenomenon. To account for this, PCWG3 uses the 2+2 rule during the flare window and requires persistence of bone lesions over a specified period. Protocols often require blinded independent central review (BICR) verification of PD (VOP) where sites request BICR confirm site suspected radiographic PD (rPD). This is often a challenge as BICR radiologists are required to follow the strict PCWG3 requirements for PD. Previous studies have shown a 32% site vs. central discordance in RECIST trials, yet there is limited data for PCWG3. Due to the complexity of PCWG3, we hypothesized that site vs central discordance is greater than that of RECIST. Thus, we aimed to examine site vs central discordance for PD by PCWG3 by analyzing archived data on site requested radiographic VOP. Methods: Aggregate data from metastatic PC trials requiring BICR VOP by PCWG3 was collected and retrospectively analyzed. Of the 6537 patient data reviewed, 3685 patients had at least one site requested VOP. For these patients with site suspected progression, a comparison between site submitted VOP requests and the BICR outcome of PD or non-PD was used for determination of discordance. The data was further categorized based on the number of times the site submitted a request and when BICR verified PD. Results: Analyses showed 50.91% of patients had BICR verified PD at the time of initial site request. The remaining 49.09% of patients had at least one instance of non-PD before PD was determined by BICR. For 33.3% of patients, central PD was never verified by BICR. In the remaining patients with VOP requests, 11.78% had verified PD following one Non-PD result, 4.03% had verified PD following two or more non-PD results. Conclusions: BICR verified rPD serves as an important endpoint in PC trials yet our analysis shows almost half of initial patient VOP requests from the site were not verified centrally. This is greater than the established discordance in RECIST trials and warrants further investigation. For over 15% of patients who did not have verified PD by BICR on the first request, PD was verified in a subsequent request. We postulate that these discrepancies are due site misinterpretation of PCWG3 or sites requesting VOP when insufficient time has passed to meet the persistence requirements. In addition, PCWG3s requirement for lesion persistence may differ from clinical practice in the assessment of PD. This preliminary analysis provides vital insight into site vs central discordance in BICR confirmation of PD in PC trials.