Abstract 3893: Enhanced detection of molecular subtypes in prostate cancer using saturation biopsy: Insights into tumor heterogeneity and racial disparities

Abstract Prostate cancer is characterized by remarkable molecular heterogeneity associated with disease progression and clinical outcomes. We have identified distinct molecular subtypes between CA and AA in biomarker expression associated with altered clinical outcomes. This study compares the effectiveness of standard 12-core biopsy and saturation biopsy in identifying molecular subtypes of prostate cancer and evaluating biomarker expression patterns across racial groups. We analyzed 104 cases that underwent saturation biopsies (median min, max 23 [14, 27], cores with cancer (median 11 [5, 25] and compared them with 130 cases with standard 12-core biopsies (median min, max 12 [12, 16]; cores with cancer median min, max 4 [1, 16] using ERG, ETV1, ETV4 and SPINK1 by combined multiplex IHC and RNA ISH. Saturation biopsy demonstrated superior detection of molecular subtypes, identifying higher rates of SPINK1- and ETV4-positive tumor foci than standard biopsy (p <.001). It also reduced the frequency of negative cases for all four biomarkers, indicating a higher prevalence of ETS gene fusions in prostate cancer (94%) than was reported previously. Caucasian American (CA) patients exhibited higher frequencies of ERG- and ETV1-positive tumor foci, while African American (AA) patients showed higher frequencies of SPINK1- and ETV4-positive foci and presented with higher Gleason Grade Groups at the time of biopsy. ERG positivity was associated with lower Gleason Grade Groups in both racial groups (CA p=.004; AA p <.001), and ETV1 positivity was linked to higher Gleason Grade Groups (CA p<.001; AA p<.001). These findings concord with our previous observations on the association of ETV1 And ETV4 with worse recurrence-free survival in CA and AA, respectively, underscoring significant racial variations in prostate cancer biology and the prognostic implications of biomarker expression. Saturation biopsy identified 16 distinct molecular subtypes with one or more than one ETS gene fusion, compared with 13 detected by standard 12-core biopsy. By uncovering a greater diversity of tumor subtypes, saturation biopsy highlights the extent of complex tumor heterogeneity and prostate cancer biology. It reveals fewer cases classified as ETS fusions compared with standard biopsies. This study demonstrates that saturation biopsy is a more effective diagnostic tool for detecting molecular subtypes and evaluating tumor heterogeneity in prostate cancer. The enhanced detection of subtype diversity and its ability to identify biomarker expression patterns associated with racial disparities underscores the potential of saturation biopsy in guiding precision oncology. These findings have profound implications for improving diagnostic accuracy, addressing racial inequality, and informing tailored treatment strategies for prostate cancer patients. Citation Format: Wei Zhao, Pin Li, Shannon Carskadon, Jessica Ryba, Hristina Trpevski, Vishnav Ramesh, Dhananjay Chitale, Firas Abdollah, Wooju Jeong, Craig Rogers, Daniel Isaac, Nilesh Gupta, Nallasivam Palanisamy. Enhanced detection of molecular subtypes in prostate cancer using saturation biopsy: Insights into tumor heterogeneity and racial disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3893.