Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE.

Lutathera® is the first EMA- and FDA-approved radiopharmaceutical for radioligand therapy (RLT). Currently, on the legacy of the NETTER1 trial, only adult patients with progressive unresectable somatostatin receptor (SSTR) positive gastroenteropancreatic (GEP) neuroendocrine neoplasms (NET) can be treated with Lutathera®. Conversely, patients with SSTR-positive disease arising from outside the gastroenteric region do not currently have access to Lutathera® treatment despite several papers in the literature reporting the effectiveness and safety of RLT in these settings. Moreover, patients with well-differentiated G3 GEP-NET are also still "Lutathera orphans", and retreatment with RLT in patients with disease relapse is currently not approved. The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera® outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera® will be considered and discussed to provide an updated picture of future investigations.

Detection rate of 18F-Choline positron emission tomography/computed tomography in patients with non-metastatic hormone sensitive and castrate resistant prostate cancer.

BACKGROUND: To assess the detection rate of 18F-choline PET/CT in non-metastatic hormone-sensitive prostate cancer (hsPCa) and non-metastatic castrate resistant prostate cancer (CRPCa), based on the criteria proposed in the phase III SPARTAN trial and with high Gleason Score (GS). METHODS: Between October 2008 and September 2019, data from a retrospective multicenter study (N.=4 centers), involving patients undergoing 18F-choline PET/CT scans for a biochemical recurrence of PCa, were collected. The following inclusion criteria were used: 1) histologically proven PCa; 2) a non-metastatic disease in accordance with conventional imaging findings; 3) a PSA doubling time (PSAdt) <10 months; 4) a GS>8; and 5) no pelvic node>2 cm. The group of hsPCa and CRPCa patients, were compared by using a non-parametric statistical analysis. Moreover, a logistic regression analysis and ROC curves were used. RESULTS: One hundred forty patients were included. Of these, 82 patients were affected by hsPCa, and 58 had a CRPCa. Overall, 18F-Choline PET/CT was positive in 99/140 (70.7%). It was positive in 55/82 (67.1%) hsPCa patients and in 44/58 (75.9%) CRPCa subjects, respectively. The site of recurrence at 18F-Choline PET/CT were: 16 (27.6%) and 20 (24.4%) in prostatic bed, 25 (43.1%) and 24 (29.3%) in loco-regional lymph nodes and in 27 (46.6%) and 28 (34.1%) in distant organs, respectively for CRPCa and hsPCa patients. The optimal cut-off values for PSA at the time of PET/CT for the prediction or recurrence were 0.5 vs. 2.5 ng/mL for all site of recurrence (AUC: 0.70 vs. 0.72), 0.48 vs. 3.4 ng/mL for prostatic bed (AUC: 0.60 vs. 0.59), 0.5 vs. 1.5 for loco-regional lymph nodes (AUC: 0.62 vs. 0.57) and 2.2 vs. 2.8 ng/mL for distant metastasis (AUC: 0.74 vs. 0.71), respectively in CRPCa and hsPCa (all P=NS). Sensitivities and specificities of 18F-Choline PET/CT for the identification of recurrence disease in all patient population, in hsPCa and CRPCa were 83.7% and 87.5%, 78.9% and 88.9%, 91.4% and 85.7%, respectively. CONCLUSIONS: The rate of positive 18F-Choline PET/CT is similar in patients with a hsPCa and CRPCa, in case of low PSAdt and high GS. Therefore, non-metastatic PCa patients should be assessed by molecular imaging, in order to adapt the most appropriate therapeutic approach.

18F-Choline PET/CT or PET/MR and the evaluation of response to systemic therapy in prostate cancer: are we ready?

Purpose: During the last decade, [18F]F-choline positron emission tomography (PET) had a rising role in prostate cancer (PCa) imaging. However, despite auspicious premises, [18F]F-choline PET is not currently recommended for the evaluation of response to therapy assessment in PCa, mainly due to the lack of large-scale prospective trials. Methods: We report the cases of seven patients affected by PCa, in which [18F]F-choline PET (either with computed tomography-CT or magnetic resonance imaging-MR) contributed significantly in the systemic therapy response evaluation. Results and conclusion: [18F]F-choline PET/CT or PET/MR demonstrated to be a useful imaging modality in the assessment of response to systemic therapy in metastatic PCa patients, irrespective of the stage of disease (either in hormone sensitive and in castrate resistant condition) and the kind of systemic treatment. In most cases, PSA serum values and [18F]F-choline PET showed a synchronous disease evolution after systemic therapy. ADT can alter [18F]F-choline uptake, therefore the time of scan should be correctly planned. Finally, PET/CT with [18F]F-choline is a useful tool for reinforcing the identification of metastatic disease in case of a switch from metastatic castration sensitive to castration resistant PCa.

PET/MRI in prostate cancer: a systematic review and meta-analysis.

AIM: In recent years, the clinical availability of scanners for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) has enabled the practical potential of multimodal, combined metabolic-receptor, anatomical, and functional imaging to be explored. The present systematic review and meta-analysis summarize the diagnostic information provided by PET/MRI in patients with prostate cancer (PCa). MATERIALS AND METHODS: A literature search was conducted in three different databases. The terms used were "choline" or "prostate-specific membrane antigen - PSMA" AND "prostate cancer" or "prostate" AND "PET/MRI" or "PET MRI" or "PET-MRI" or "positron emission tomography/magnetic resonance imaging." All relevant records identified were combined, and the full texts were retrieved. Reports were excluded if (1) they did not consider hybrid PET/MRI; or (2) the sample size was < 10 patients; or (3) the raw data were not enough to enable the completion of a 2 × 2 contingency table. RESULTS: Fifty articles were eligible for systematic review, and 23 for meta-analysis. The pooled data concerned 2104 patients. Initial disease staging was the main indication for PET/MRI in 24 studies. Radiolabeled PSMA was the tracer most frequently used. In primary tumors, the pooled sensitivity for the patient-based analysis was 94.9%. At restaging, the pooled detection rate was 80.9% and was higher for radiolabeled PSMA than for choline (81.8% and 77.3%, respectively). CONCLUSIONS: PET/MRI proved highly sensitive in detecting primary PCa, with a high detection rate for recurrent disease, particularly when radiolabeled PSMA was used.