Nuttaphon Aleenajitpong, Rory L Cochran, Sarah Mercaldo, Harleen Kaur, Nabih Nakrour, Isabela C S Lima, Mukesh G Harisinghani
Routine quantitative MRI and PSMA PET intensity metrics did not independently predict PFS or improve discrimination beyond clinical variables in grade group 3 or higher prostate cancer. Given the event count, this is a failure to detect incremental value rather than evidence of its absence. The PI-RADS 5 association was imprecisely estimated and is hypothesis-generating.
BACKGROUND: Multiparametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) PET are increasingly used for pretreatment staging of prostate cancer, but their incremental prognostic value for progression-free survival (PFS) beyond clinical variables remains uncertain.
OBJECTIVE: To evaluate whether mpMRI and PSMA PET features independently predict PFS in grade group 3 or higher prostate cancer and add value beyond clinical variables.
METHODS: This single-center retrospective study included patients with biopsy-proven grade group 3 or higher prostate adenocarcinoma who underwent mpMRI followed by 18F-piflufolastat PET/CT within 90 days in 2022, with follow-up through March 2026. The primary analysis comprised 101 patients without distant organ metastasis; the full cohort of 127 patients served as a secondary analysis. Clinical, MRI, and PSMA PET variables were evaluated in nested Cox models compared by C-index and likelihood ratio tests.
RESULTS: In the primary cohort, 22 of 101 patients (22%) progressed (median follow-up, 3.2 years). Univariably, lower minimum and mean tumor ADC were associated with progression (P = 0.026 and 0.029). In the predefined reduced multivariable model, PI-RADS 5 retained an independent association with worse PFS (HR 5.69, 95% CI 1.13 to 28.65; P = .035; Firth HR 4.44, P = .026), whereas normalized ADC and intensity-based PSMA PET metrics did not. Adding imaging to clinical variables improved neither model fit (likelihood ratio P = .457) nor discrimination (optimism-corrected C-index, 0.77 clinical-only versus 0.73 clinical-plus-imaging). PRIMARY 5 versus 1-4 was not associated with PFS (HR 1.09, 0.45 to 2.60; P = 0.852).
CONCLUSION: Routine quantitative MRI and PSMA PET intensity metrics did not independently predict PFS or improve discrimination beyond clinical variables in grade group 3 or higher prostate cancer. Given the event count, this is a failure to detect incremental value rather than evidence of its absence. The PI-RADS 5 association was imprecisely estimated and is hypothesis-generating.