Primary staging of prostate cancer relies on modalities, which are limited. We evaluate simultaneous [Ga]Ga-PSMA-11 PET (PSMA-PET)/MRI as a new diagnostic method for primary tumor-node-metastasis staging compared with histology and its impact on therapeutic decisions. We investigated 122 patients with PSMA-PET/MRI prior to planned radical prostatectomy (RP). Primary endpoint was the accuracy of PSMA-PET/MRI in tumor staging as compared with staging-relevant histology. In addition, a multidisciplinary team reassessed the initial therapeutic approach to evaluate its impact on the therapeutic management. PSMA-PET/MRI correctly identified prostate cancer in 119 of 122 patients (97.5%). Eighty-one patients were treated with RP and pelvic lymphadenectomy. The accuracy for T staging was 82.5% [95% confidence interval (CI), 73-90; < 0.001], for T2 stage was 85% (95% CI, 71-94; < 0.001), for T3a stage was 79% (95% CI, 43-85; < 0.001), for T3b stage was 94% (95% CI, 73-100; < 0.001), and for N1 stage was 93% (95% CI, 84-98; < 0.001). PSMA-PET/MRI changed the therapeutic strategy in 28.7% of the patients with either the onset of systemic therapy/radiotherapy ( = 16) or active surveillance ( = 19). PSMA-PET/MRI can provide an accurate staging of newly diagnosed prostate cancer. In addition, treatment strategies were changed in almost a third of the patients due to the information of this hybrid imaging technique.

Purpose Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. Methods Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. Results The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. Conclusion Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

Purpose: The pretherapeutic assessment of prostate cancer is challenging and still holds the risk of overor undertreatment. This prospective trial investigates positron emission tomography (PET) with [ 18 F]fluoroethylcholine (FEC) combined with endorectal magnetic resonance imaging (MRI) for the assessment of primary prostate cancer.Experimental design: Patients with prostate cancer based on needle biopsy findings, scheduled for radical prostatectomy, were assessed by FEC-PET and MRI in identical positioning. After prostatectomy, imaging results were compared with histologic whole-mount sections, and the PET/MRI lesion-based semiquantitative FEC uptake was compared with biopsy Gleason scores and postoperative histology.Results: PET/MRI showed a patient-based sensitivity of 95% (36/38; 95% confidence interval (CI), 82%-99%). The analysis of 128 prostate lesions demonstrated a sensitivity/specificity/positive predictive value/ negative predictive value/accuracy of 67%/35%/59%/44%/54% (P ¼ 0.8295) for MRI and 85%/45%/68%/ 69%/68% (P ¼ 0.0021) for PET, which increased to 84%/80%/85%/78%/82% (P < 0.0001) by combined FEC-PET/MRI in lesions >5 mm (n ¼ 98). For lesions in patients with Gleason >6 tumors (n ¼ 43), MRI and PET achieved 73%/31%/71%/33%/60% (P ¼ 1.0000) and 90%/62%/84%/73%/81% (P ¼ 0.0010), which were improved to 87%/92%/96%/75%/88% (P < 0.0001) by combined PET/MRI. Applying semiquantitative PET analysis, carcinomas with Gleason scores >6 were distinguished from those with Gleason 6 with a specificity of 90% and a positive predictive value of 83% (P ¼ 0.0011; needle biopsy 71%/60%, P ¼ 0.1071).Conclusions: In a prospective diagnostic trial setting, combined FEC-PET/MRI achieved very high sensitivity in the detection of the dominant malignant lesion of the prostate, and markedly improved upon PET or MRI alone. Noninvasive Gleason score assessment was more precise than needle biopsy in this patient cohort. Hence, FEC-PET/MRI merits further investigation in trials of randomized, multiarm design.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3′‐triiodo‐L‐thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ‐Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage‐specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3‐ and androgen‐mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

The aim of this study was to evaluate 18 F-fluoroethylcholine PET/CT as a metabolic imaging technique for the assessment of treatment response to 90 Y radioembolization in patients with locally advanced hepatocellular carcinoma (HCC). Methods: Thirty-four HCC patients undergoing 78 18 F-fluoroethylcholine PET/CT scans were identified for this study. Patients with initial or follow-up metastastic disease (n 5 9) were excluded at the time point of the metastatic occurrence as well as patients with negative α-fetoprotein (AFP; n 5 1), resulting in 24 patients and 57 scans that were eligible. All patients were scheduled for radioembolization and underwent 1 pretherapeutic and at least 1 posttherapeutic 18 F-fluoroethylcholine PET/CT scan. Volume-of-interest analysis and volume-of-interest subtractions were performed. Maximum, mean, and peak standardized uptake value (SUV) analysis was performed, and the total intrahepatic 18 F-fluoroethylcholine positive tumor volume (FEC-PTV) and tumorto-background ratio were assessed. Statistical analysis was performed using a decreasing AFP of at least 20% as a standard of reference for therapy response including receiver-operatingcharacteristic analyses as well as descriptive and correlation analyses and multiple logistic regression. Results: Fourteen follow-up examinations were categorized as responder and 19 follow-up examinations as nonresponder. Absolute AFP values did not correlate with SUV parameters (P 5 0.055). In receiver-operating-characteristic analyses, the initial mean SUV, Dmaximum SUV, and Dtumor-tobackground ratio demonstrated the highest area under the curve, 0.84 (P 5 0.009), 0.83 (P 5 0.011), and 0.83 (P 5 0.012), respectively, resulting in a positive prediction of 82%, 83%, and 91% at the respective cutoff points. When multiple logistic regression analysis was applied, this resulted in an area under the curve of 0.90 (P 5 0.001), with a positive prediction of 94% and a sensitivity of 94%. The FEC-PTV did not reach significance in the presented dataset. Conclusion: 18 F-fluoroethylcholine PET/CT demonstrates a high potential for follow-up assessment in the context of radioembolization in patients with locally advanced, but nonmetastatic, HCC and initially elevated AFP, possibly enabling early therapy monitoring independent of morphology.