Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost

Purpose: The focal radiotherapy (RT) boost technique was shown in the FLAME trial to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. The ReIGNITE RT Boost study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. Materials & Methods: 44 radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the FLAME trial protocol. Probability of biochemical failure (BF) was determined using a model from the FLAME trial. The primary metric evaluated was delta BF (ΔBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful. Results: 8 patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. 37% of participant plans were noted to have an absolute increase in BF of 5% or more. Conclusion: Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients. ### Competing Interest Statement AJL reports consulting for MIM Software. AMD is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with GE Healthcare. RRP has an equity interest in CorTech Labs and Curemetrix, serves on the Scientific Advisory Board of Imagine Scientific, and receives research funding from GE Healthcare. MEH reports honoraria from Multimodal Imaging Services Corporation and research funding from GE Healthcare. UAvdH reports research funding from the Dutch Cancer Society and travel support from Elekta AB. XR reports consulting for KM Pharmaceutical Consulting LLC, receives research funding from Varian Medical Systems and Siemens Healthineers, and serves as vice chair of AAPM TG-395. TMS reports honoraria from Varian Medical Systems, WebMD, GE Healthcare, and Janssen; he has an equity interest in CorTechs Labs, Inc. and serves on its Scientific Advisory Board; he receives research funding from GE Healthcare through the University of California San Diego. These companies might potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. ### Funding Statement This work was supported, in part, by the National Institutes of Health (NIH/NIBIB K08 EB026503, NIH/NCI U54CA132384, U54CA132379, UL1TR001442), the American Society for Radiation Oncology (ASTRO), the Prostate Cancer Foundation, the Radiological Society of North America (RSNA), the American College of Radiation Oncology (ACRO), the Grillo-Marxuach Family Fellowship at the Moores Cancer Center of UC San Diego, and the US Department of Defense (CDMRP PC220278). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of UC San Diego gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified data are available to bona fide researchers for non-commercial use upon request.