Prostate-Specific Membrane Antigen PET/CT Complements MRI for Focal Therapy Selection in Prostate Cancer: A Whole-Mount Histopathologic Study
- 1Department of Urology, Cedars-Sinai Medical Center, Los Angeles, California, USA; Department of Urology, David Geffen School of Medicine, University of Californ
Abstract
BackgroundThe incremental value of PSMA PET/CT over multiparametric MRI (mpMRI) for selecting patients for prostate cancer focal therapy is undefined. Unlike lesion-detection studies, we evaluated whether PSMA PET/CT, mpMRI, and their combination correctly determine focal therapy eligibility when validated against whole-mount histopathology (WMHP).
MethodsWe retrospectively analyzed patients undergoing radical prostatectomy (RP) at UCLA (2017-2024) with preoperative PSMA PET/CT and mpMRI, biopsy grade group (GG) [≤]3, unilateral disease, and prostate-specific antigen <20 ng/mL. Two blinded readers per modality assessed extraprostatic extension (EPE), seminal vesicle invasion (SVI), bilateral disease, and multifocality; a third adjudicated discordances. Eligibility required absence of all four. On WMHP, ineligibility was EPE, SVI, multifocal or bilateral disease with a contralateral or secondary GG[≥]2 nodule, or any GG>3 focus at RP. Modalities were compared by McNemar tests.
ResultsOf 112 patients, 77 (69%) were ineligible on WMHP, including 19 (17%) with a GG>3 focus at RP. Sensitivity and specificity were 53% and 54% for PET and 70% and 49% for mpMRI. Combined imaging improved sensitivity to 83% (P<0.001 vs PET; P=0.002 vs MRI) but reduced specificity to 26%. Per 100 patients at this prevalence, this would correctly identify approximately 9 additional ineligible patients while falsely excluding approximately 7 true candidates. mpMRI was more sensitive than PET for EPE (77% vs 32%, P<0.001), whereas PET was more specific (90% vs 58%, P<0.001). Combined imaging improved detection of multifocal (44% vs 23%, P=0.001) and bilateral disease (45% vs 23%, P=0.002) versus MRI alone.
ConclusionsAdding PSMA PET/CT to mpMRI significantly improves sensitivity for exclusionary features, reflecting complementary molecular and anatomic information. However, combined imaging still misses a substantial proportion of adverse pathology, so imaging alone should not determine eligibility.
O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/26362553v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): [email protected]@3bce70org.highwire.dtl.DTLVardef@6e56aeorg.highwire.dtl.DTLVardef@1fcbac1_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract
C_FIG
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BibTeX
@misc{sonni2026prostatespecific,
title = {{Prostate-Specific Membrane Antigen PET/CT Complements MRI for Focal Therapy Selection in Prostate Cancer: A Whole-Mount Histopathologic Study}},
author = {I. Sonni and Z. Mohammadigoldar and G. Furey and K. Kimura and P. C. Movva and A. Holzgreve and S. Bahri and T. Sevco and A. Chung and A. Sisk and T. Grogan and J. Czernin and K. Sung and J. Calais and S. E. Eggener and W. Brisbane and R. E. Reiter and S. Raman and A. B. Weiner},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.26362553},
url = {https://www.medrxiv.org/content/10.64898/2026.09.09.26362553v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Prostate-Specific Membrane Antigen PET/CT Complements MRI for Focal Therapy Selection in Prostate Cancer: A Whole-Mount Histopathologic Study
AU - I. Sonni
AU - Z. Mohammadigoldar
AU - G. Furey
AU - K. Kimura
AU - P. C. Movva
AU - A. Holzgreve
AU - S. Bahri
AU - T. Sevco
AU - A. Chung
AU - A. Sisk
AU - T. Grogan
AU - J. Czernin
AU - K. Sung
AU - J. Calais
AU - S. E. Eggener
AU - W. Brisbane
AU - R. E. Reiter
AU - S. Raman
AU - A. B. Weiner
PY - 2026
DA - 2026/09/09
PB - medRxiv
DO - 10.64898/2026.09.09.26362553
UR - https://www.medrxiv.org/content/10.64898/2026.09.09.26362553v1
AB - BackgroundThe incremental value of PSMA PET/CT over multiparametric MRI (mpMRI) for selecting patients for prostate cancer focal therapy is undefined. Unlike lesion-detection studies, we evaluated whether PSMA PET/CT, mpMRI, and their combination correctly determine focal therapy eligibility when validated against whole-mount histopathology (WMHP). MethodsWe retrospectively analyzed patients undergoing radical prostatectomy (RP) at UCLA (2017-2024) with preoperative PSMA PET/CT and mpMRI, biopsy grade group (GG) [≤]3, unilateral disease, and prostate-specific antigen <20 ng/mL. Two blinded readers per modality assessed extraprostatic extension (EPE), seminal vesicle invasion (SVI), bilateral disease, and multifocality; a third adjudicated discordances. Eligibility required absence of all four. On WMHP, ineligibility was EPE, SVI, multifocal or bilateral disease with a contralateral or secondary GG[≥]2 nodule, or any GG>3 focus at RP. Modalities were compared by McNemar tests. ResultsOf 112 patients, 77 (69%) were ineligible on WMHP, including 19 (17%) with a GG>3 focus at RP. Sensitivity and specificity were 53% and 54% for PET and 70% and 49% for mpMRI. Combined imaging improved sensitivity to 83% (P<0.001 vs PET; P=0.002 vs MRI) but reduced specificity to 26%. Per 100 patients at this prevalence, this would correctly identify approximately 9 additional ineligible patients while falsely excluding approximately 7 true candidates. mpMRI was more sensitive than PET for EPE (77% vs 32%, P<0.001), whereas PET was more specific (90% vs 58%, P<0.001). Combined imaging improved detection of multifocal (44% vs 23%, P=0.001) and bilateral disease (45% vs 23%, P=0.002) versus MRI alone. ConclusionsAdding PSMA PET/CT to mpMRI significantly improves sensitivity for exclusionary features, reflecting complementary molecular and anatomic information. However, combined imaging still misses a substantial proportion of adverse pathology, so imaging alone should not determine eligibility. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/26362553v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): [email protected]@3bce70org.highwire.dtl.DTLVardef@6e56aeorg.highwire.dtl.DTLVardef@1fcbac1_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG
ER -