Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

Background: Actinium-225 (Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world.

Methods: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa.

Comparative Analysis of Morphological and Functional Effects of Ac- and Lu-PSMA Radioligand Therapies (RLTs) on Salivary Glands.

Most Prostate Specific Membrane Antigens (PSMAs) targeting small molecules accumulate in the salivary glands (SGs), raising concerns about SG toxicity, especially after repeated therapies or therapy with Ac-labeled ligands. SG toxicity is assessed clinically by the severity of patient-reported xerostomia, but this parameter can be challenging to objectively quantify. Therefore, we explored the feasibility of using SG volume as a biomarker for toxicity.

Long-Term Nephrotoxicity of Lu-PSMA Radioligand Therapy.

β-emitting Lu targeting prostate-specific membrane antigen (PSMA) is an approved treatment option for metastatic castration-resistant prostate cancer. Data on its long-term nephrotoxicity are sparse. This study aimed to retrospectively evaluate post-Lu-PSMA estimated glomerular filtration rate (eGFR) dynamics for at least 12 mo in a cohort of metastatic castration-resistant prostate cancer patients.

Improved Quality of Life in Metastatic Castration-Resistant Prostate Cancer Patients Receiving Consecutive Cycles of Lu-PSMA I&T.

The aim of this retrospective analysis was to evaluate health-related quality of life (HRQoL) for patients with metastatic castration-resistant prostate cancer (mCRPC) receiving consecutive cycles of Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using the reliable and validated European Organisation for Research and Treatment of Cancer core quality-of-life (QoL) questionnaire. In addition, differences in HRQoL between patients with early discontinuation of treatment because of disease progression and patients who were defined as eligible for treatment continuation were analyzed. In total, 60 mCRPC patients were included in this analysis.

Hsp70-A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers.

Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal tumor biomarker. Since viable, mHsp70-positive tumor cells actively release Hsp70 in lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal tumor biomarker and its potential as an early predictive marker of therapeutic failure.

Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort.

Background: Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy.

Safety and Efficacy of [Lu]-PSMA-I&T Radioligand Therapy in Octogenarians with Metastatic Castration-Resistant Prostate Cancer: Report on 80 Patients over the Age of 80 Years.

Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new treatment option for metastatic castration-resistant prostate cancer (mCRPC). Its low toxicity profile favors use in elderly patients or in patients with critical comorbidities. The purpose of this analysis was to evaluate the efficacy and safety of [Lu]-PSMA RLT in mCRPC patients at least 80 y old.

[New tracers and combinations in radioligand therapy for prostate cancer].

Background: Lutetium radioligand therapy directed against the prostate-specific membrane antigen (PSMA) is a new approved option for the treatment of metastatic, castration-resistant prostate cancer associated with a favorable toxicity profile.

Objectives: What are new or emerging developments in radioligand therapy for prostate cancer?

Materials And Methods: A review of the current literature was performed.

Results: The further development of radioligand therapy for prostate cancer is currently taking place primarily in the following areas: application in earlier stages of the disease, use of alternative isotopes, development and use of new ligands, search for new target structures and combination with other forms of therapy.

The Impact of PSMA PET-Based Eligibility Criteria Used in the Prospective Phase II TheraP Trial in Metastatic Castration-Resistant Prostate Cancer Patients Undergoing Prostate-Specific Membrane Antigen-Targeted Radioligand Therapy.

Prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) has shown encouraging results for treatment of metastatic castration-resistant prostate cancer (mCRPC) in the prospective, multicenter, randomized phase II TheraP study. The inclusion criteria for that study comprised a pretherapeutic Ga-PSMA-11 PET scan showing sufficient tumor uptake using a predefined threshold and the absence of F-FDG-positive, PSMA ligand-negative tumor lesions. However, the prognostic value of these PET-based inclusion criteria remains unclear.

Prognostic Role of Ga-PSMA11 PET-Based Response in Patients with Prostate Cancer Undergoing Taxane-Based Chemotherapy.

This study was performed to assess the prognostic utility of conventional biochemical and imaging response criteria and Ga-PSMA11 PET-adapted or -specific systems regarding overall survival (OS) in men with metastatic hormone-sensitive and castration-resistant prostate cancer (PC) treated with taxane-based chemotherapy. A total of 103 patients (metastatic hormone-sensitive PC, = 57; castration-resistant PC, = 46) underwent taxane-based chemotherapy. All patients had a minimum of 2 prostate-specific membrane antigen (PSMA) PET scans (at baseline and up to 3 mo after treatment).

Prospectively Accelerated T2-Weighted Imaging of the Prostate by Combining Compressed SENSE and Deep Learning in Patients with Histologically Proven Prostate Cancer.

Background: To assess the performance of prospectively accelerated and deep learning (DL) reconstructed T2-weighted (T2w) imaging in volunteers and patients with histologically proven prostate cancer (PCa).

Methods: Prospectively undersampled T2w datasets were acquired with acceleration factors of 1.7 (reference), 3.

Lu-PSMA-I&T for Treatment of Metastatic Castration-Resistant Prostate Cancer: Prognostic Value of Scintigraphic and Clinical Biomarkers.

The aim of this retrospective analysis was to determine prostate-specific antigen (PSA) response, PSA progression-free survival (PFS), and overall survival (OS) in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lu-PSMA-I&T and to identify clinical and scintigraphic prognostic factors for outcome. In total, 301 consecutive mCRPC patients were included in this analysis. Prognostic factors included clinical parameters, routine laboratory parameters, and findings on posttreatment scintigraphy.

Extensive Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy-like Picture.

Lutetium-177 prostate-specific membrane antigen (Lu-PSMA) radioligand therapy is an option that is increasingly being used for treatment of metastatic castration-resistant prostate cancer. This delivers β-radiation to cells expressing PSMA and high accumulation of the radiopharmaceutical occurs in the kidneys. Here we report three cases of radiation nephropathy with severe chronic kidney disease induced by renal thrombotic microangiopathy following extensive treatment with Lu-PSMA radioligand therapy.

Novel Framework for Treatment Response Evaluation Using PSMA PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0): An International Multicenter Study.

Our objective was to develop version 1.0 of a novel framework for response evaluation criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) and a composite response classification that combines responses by prostate-specific antigen (PSA) measurements and by RECIP 1.0 (PSA + RECIP).

[Update on systemic treatment of urothelial cancer: therapy in transition].

The systemic treatment of locally advanced and metastatic urothelial carcinoma has been changing at a breathtaking pace for a few years. However, platinum-based chemotherapy continues to be the central component of perioperative therapies and first-line treatment in the metastatic stage. Immunotherapies with immune checkpoint inhibitors are now an integral part of therapy algorithms.

Cytoreductive radical prostatectomy after chemohormonal therapy in patients with primary metastatic prostate cancer.

Objective: Cytoreductive radical prostatectomy (cRP) has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer (mHSPC) to prevent local complications and potentially improve oncological outcomes. In this study, we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment, postoperative complication rates, as well as early postoperative continence.

Methods: In this retrospective study, 38 patients with mHSPC underwent cRP after primary chemohormonal therapy (3-monthly luteinising hormone-releasing hormone-analogue + six cycles 3-weekly docetaxel 75 mg/m) at two centers between September 2015 and December 2018.

Narrative review: prostate-specific membrane antigen-radioligand therapy in metastatic castration-resistant prostate cancer.

Radioactive-labelled ligands targeting the prostate-specific membrane antigen (PSMA), a transmembrane protein overexpressed in prostate cancer (PC), have shown promising activity in treatment of metastatic castration-resistant prostate cancer (mCRPC). PSMA-617 and PSMA-I&T (imaging and therapy), both labeled to the beta-emitter lutetium-177 (Lu177), are most frequently used in clinical routine and have shown a favorable side-effect profile. Common side effects are transient xerostomia.

Pretherapeutic Comparative Dosimetry of Lu-rhPSMA-7.3 and Lu-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer.

Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands allow for labeling with F and radiometals for endoradiotherapy. rhPSMA-7.3 has been designated as a lead compound with promising preclinical data for Lu-rhPSMA-7.

Nomograms to predict outcomes after Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study.

Background: Lutetium-177 (Lu) prostate-specific membrane antigen (Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after Lu-PSMA in patients with mCRPC.

[Advanced prostate cancer: sequence of androgen receptor-targeted substances and chemotherapy determines long-term survival].

The treatment of advanced prostate cancer is changing. New study data and the resulting new therapeutic options have led to increasingly differentiated treatment decisions. Despite the changing therapy landscape, taxane-based chemotherapy-being a life-prolonging treatment-remains an indispensable therapeutic component for chemotherapy-fit patients in the metastatic setting.

Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-resistant Prostate Cancer After Failure of Lutetium-177-PSMA.

Background: Beta-emitting Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new option for metastatic castration-resistant prostate cancer (mCRPC), but its antitumor effect can decrease over time.

Objective: To report the safety and activity of alpha-emitting Ac-225-PSMA-617 RLT in mCRPC that has progressed after Lu-177-PSMA.

Design, Setting, And Participants: Twenty-six patients were treated under a compassionate use protocol.

First Experience Using F-Flubrobenguane PET Imaging in Patients with Suspected Pheochromocytoma or Paraganglioma.

Pheochromocytomas and paragangliomas are a rare tumor entity originating from adrenomedullary chromaffin cells in the adrenal medulla or in sympathetic, paravertebral ganglia outside the medulla. Small lesions are especially difficult to detect by conventional CT or MRI and even by SPECT with the currently available radiotracers (e.g.

Efficacy and Safety of Lu-labeled Prostate-specific Membrane Antigen Radionuclide Treatment in Patients with Diffuse Bone Marrow Involvement: A Multicenter Retrospective Study.

The Lu-labeled prostate-specific membrane antigen (LuPSMA) radionuclide therapy for metastatic castration-resistant prostate cancer is under investigation in a phase III trial (VISION: NCT03511664). However, patients with diffuse bone involvement, diagnosed with a "superscan" by bone scintigraphy at baseline, were excluded due to a lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted positron emission tomography.

PSMA-PET/CT-based Lymph Node Atlas for Prostate Cancer Patients Recurring After Primary Treatment: Clinical Implications for Salvage Radiation Therapy.

Background: Many patients experience recurrence of prostate cancer after radical prostatectomy.

Objective: The aim of this study was to visually analyze typical patterns of lymph node (LN) involvement for prostate cancer (PC) patients with biochemical recurrence after radical prostatectomy and lymphadenectomy by creating a color-coded heat map using gallium-68 prostate-specific membrane antigen positron emission tomography (Ga-PSMA-PET) imaging. Further, we evaluated which LNs were covered by the Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) contouring guidelines.