Beyond PSMA: The essential complementary role of MRI in staging prostate cancer with Low-PSMA expression phenotypes

While prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a highly sensitive modality for staging prostate cancer, a notable subset of patients presents with negative findings, leading to potential under-diagnosis. The incremental diagnostic value of multiparametric magnetic resonance imaging (mpMRI) in this specific cohort remains poorly defined. This study aimed to evaluate the added value of mpMRI in newly diagnosed prostate cancer patients with negative PSMA PET/CT results and to identify patient characteristics that predict this benefit.

This retrospective study included 200 patients with newly diagnosed, treatment-naïve prostate cancer who underwent both ⁶⁸ Ga-PSMA-11 PET/CT and pelvic mpMRI between June 2018 and September 2021. We identified patients with negative ⁶⁸ Ga-PSMA-11 PET/CT findings but positive mpMRI results (PSMA-/MRI +). The clinicopathological characteristics, including Prostate-Specific Antigen (PSA) levels and Gleason scores, of the PSMA-/MRI + group were compared with the rest of the cohort. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of PSMA-/MRI + status.

Of the 200 patients, 18 presented with negative ⁶⁸ Ga-PSMA-11 PET/CT findings. Among 18 patients with negative ⁶⁸ Ga-PSMA-11 PET/CT scans, mpMRI successfully detected lesions in 17 (94.4%). These PSMA-/MRI + findings were validated as true positives by histopathology, follow-up imaging, or PSA response to therapy. Patients in the PSMA-/MRI + group exhibited significantly lower PSA levels (mean, 22.6 vs. 60.0 ng/mL; P = 0.002) and lower Gleason scores (median, 7 [6, 9] vs. 7 [7, 9]; P = 0.013). Multivariate analysis confirmed that both a lower PSA level (OR, 0.117; 95% CI, 0.024-0.566; P = 0.008) and a lower Gleason score (OR, 0.218; 95% CI, 0.060-0.787; P = 0.020) were independent predictors of PSMA-/MRI + findings. Patients with both low PSA (< 24.05 ng/mL) and low Gleason score (< 7) had the highest detection rate of PSMA-/MRI + lesions (37.5%, P < 0.001).

Multiparametric MRI provides significant added diagnostic value in detecting prostate cancer in newly diagnosed patients with negative ⁶⁸ Ga-PSMA-11 PET/CT results. This complementary role is particularly pronounced in patients with lower PSA levels and Gleason scores. Integrating mpMRI into the diagnostic pathway for this subgroup can mitigate the risk of under-staging and improve clinical decision-making.