The objective of this study was to compare ¹⁸F-PSMA-1007 PET/CT and ¹⁸F-fluorocholine PET/CT for the localization of prostate cancer (PCa) biochemical recurrence. Methods: This prospective, open-label, randomized, crossover multicenter study included PCa patients with prior definitive therapy and suspected PCa recurrence. All men underwent both ¹⁸F-PSMA-1007 PET/CT and ¹⁸F-fluorocholine PET/CT (102 received ¹⁸F-PSMA-1007 PET/CT first and 88 received ¹⁸F-fluorocholine PET/CT first). All images were assessed independently by 3 readers masked to all clinical information using a 3-point qualitative scale (0 = no recurrence, 1 = undetermined, and 2 = recurrence). Patients were monitored for approximately 6 mo. An independent panel with a urologist, radiologist, and nuclear physician reviewed all clinical data, including imaging and response to therapy, but were masked regarding PET/CT information; acting in consensus, they determined a patient-based and region-based composite standard of truth for PCa lesions. The “correct detection rates” for PCa lesions on a patient basis for each radiopharmaceutical were compared for the 3 readers individually and for the “average reader.” Secondary objectives included determining whether PET/CT findings affected diagnostic thinking (impact of a test result on posttest vs. pretest probability of a correct diagnosis), therapeutic decision making (description and quantification of impact of diagnostic information gained with both radiopharmaceuticals on patient management), and adequacy of management changes. Results: A total of 190 patients were included. The primary endpoint was met. The overall correct detection rates were 0.82 for ¹⁸F-PSMA-1007 and 0.65 for ¹⁸F-fluorocholine (P < 0.0001) when undetermined findings were considered positive for malignancy and 0.77 and 0.57, respectively (P < 0.0001), when undetermined findings were considered negative for malignancy. A change in diagnostic thinking due to PET/CT was reported in 149 patients; ¹⁸F-PSMA-1007 contributed more than ¹⁸F-fluorocholine in 93 of these patients. In 122 patients, PET/CT led to an adequate diagnosis that benefited the patient; ¹⁸F-PSMA-1007 contributed more than ¹⁸F-fluorocholine in 88 of these patients. Conclusion:¹⁸F-PSMA-1007 PET/CT is superior to ¹⁸F-fluorocholine PET/CT for the localization of PCa recurrence. Decision making was more beneficial when based on ¹⁸F-PSMA-1007 PET/CT results. Visual Abstract

We aimed to evaluate the impact of prostate-specific membrane antigen ligand labelled with gallium-68 (PSMA-11) PET/CT in restaging patients with castration-resistant nonmetastatic prostate cancer (PCa). Thirty patients were included. At least one malignant focus was found in 27/30 patients (90%). The PSMA-11 PET/CT positivity rate in patients whose prostate-specific antigen serum level (PSA) was greater than 2 ng/ml was 100% (20/20), significantly superior to that of patients whose PSA was less than 2 ng/ml (7/10 = 70%). Six patients (20%) were categorized as oligometastatic (≤3 metastatic foci). Based on the 17 patients for whom a standard of truth was feasible, the overall sensitivity and specificity of PSMA-11 PET/CT in detecting residual disease in castration-resistant PCa patients were 87% and 100% respectively. PSMA-11 PET/CT impacted patients’ disease management in 70% of cases, 60% of case when PSA was less than 2 ng/ml. This management was considered as adequate in 91% of patients. PSMA-11 PET/CT appeared to be effective in restaging patients with castration-resistant nonmetastatic PCa. PSMA-11 PET/CT should be considered as a replacement for bone scans under these conditions.

Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.

Active surveillance (AS) in prostate cancer (PCa) represents a curative alternative for men with localised low-risk PCa. Continuous improvement of AS patient’s selection and surveillance modalities aims at reducing misclassification, simplifying modalities of surveillance and decreasing need for invasive procedures such repeated biopsies. Biomarkers represent interesting tools to evaluate PCa diagnosis and prognosis, of which many are readily available or under evaluation. The aim of this review is to investigate the biomarker performance for AS selection and patient outcome prediction. Blood, urinary and tissue biomarkers were studied and a brief description of use was proposed along with a summary of major findings. Biomarkers represent promising tools which could be part of a more tailored risk AS strategy aiming to offer personalized medicine and to individualize the treatment and monitoring of each patient. The usefulness of biomarkers has mainly been suggested for AS selection, whereas few studies have investigated their role during the monitoring phase. Randomized prospective studies dealing with imaging are needed as well as larger prospective studies with long-term follow-up and strong oncologic endpoints.