Publications by authors named "Sartor O"

Introduction: SPLASH (NCT04647526) is a multicenter phase III trial evaluating the efficacy and safety of [Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). This study leveraged a lead-in phase to assess tissue dosimetry and evaluate preliminary safety and efficacy, prior to expansion into a randomized phase. Here we report those results.

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Purpose: Two randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong ADT-free survival or progression-free survival (PFS) in patients with metachronous oligometastatic prostate cancer (omCSPC) patients. While most omCSPC patients have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating PSMA-positive extracellular vesicles (PSMA+EV) and prostate specific antigen (PSA) in a biomarker correlative study using blood samples from three independent patient cohorts.

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Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

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  • This study focused on the diverse types of FOXA1 genetic alterations found in prostate cancer and their implications for clinical management.
  • Researchers classified FOXA1 mutations into four distinct classes, each with specific characteristics and prognostic significance based on survival outcomes.
  • Results indicated that certain FOXA1 alterations, particularly class 1A, were linked to improved survival rates, while other classes, especially class 2 and amplified versions, were associated with poorer outcomes and higher risks in treatment response.
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  • The importance of germline genetic testing (GGT) for prostate cancer patients has grown, as it helps tailor treatment plans and manage the disease more effectively.
  • GGT is now considered a standard practice not just for prostate cancer, but also for other cancers like breast and ovarian, emphasizing the need for all patients to have equitable access to this testing.
  • Offering comprehensive GGT allows for better decision-making between patients and doctors, aids in detecting potential future cancers, and facilitates testing for family members who may be at risk.
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Current US clinical practice guidelines for advanced prostate cancer management contain recommendations based on high-level evidence from randomized controlled trials; however, these guidelines do not address the nuanced clinical questions that are unanswered by prospective trials but nonetheless encountered in day-to-day practice. To address these practical questions, the 2024 US Prostate Cancer Conference (USPCC 2024) was created to generate US-focused expert clinical decision-making guidance for circumstances in which level 1 evidence is lacking. At the second annual USPCC meeting (USPCC 2024), a multidisciplinary panel of experts convened to discuss ongoing clinical challenges related to 5 topic areas: biochemical recurrence; metastatic, castration-sensitive prostate cancer; poly [ADP-ribose] polymerase inhibitors; prostate-specific membrane antigen radioligand therapy; and metastatic, castration-resistant prostate cancer.

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  • * In a study conducted at Mayo Clinic, 273 patients were analyzed, revealing that those with liver metastasis received an average of 3 treatment cycles and had a lower response rate in prostate-specific antigen (PSA) reduction compared to patients without liver metastasis (30.23% vs. 49.77%).
  • * The research utilized real-world clinical data and statistical methods to compare patient outcomes based on the presence of liver metastasis, highlighting disparities in treatment responses and survival rates.
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Radioligand therapies such as [Lu] Lu-PSMA-617 have gained significant momentum in cancer treatment after clinical trials and multicenter studies demonstrated their safety and efficacy. As these innovative treatments become more widespread, rare and unique clinical manifestations are expected to be observed. In this report, we describe a case with metastatic castration-resistant prostate cancer (mCRPC) and peripancreatic lymph node metastases who developed acute pancreatitis following [Lu] Lu-PSMA-617 therapy.

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Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) prolonged life in patients with metastatic castration-resistant prostate cancer (mCRPC) in VISION (NCT03511664). However, distinguishing between patients likely and unlikely to respond remains a clinical challenge. We present the first multivariable models of outcomes with Lu-PSMA-617 built using data from VISION, a large prospective phase 3 clinical trial powered for overall survival.

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Background And Objective: This review aims to provide an overview of novel diagnostic and therapeutic radiopharmaceuticals tested recently or used currently in genitourinary cancers within prospective phase 1-2 clinical trials, summarizing progresses and future directions.

Methods: A systematic search was conducted using the PubMed/MEDLINE and ClinicalTrials.gov databases for original prospective research studies following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

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  • Novel therapies for metastatic castration-resistant prostate cancer (mCRPC) have improved outcomes, but optimal treatment selection remains unclear.
  • A comprehensive review of clinical trials and guidelines was conducted, identifying key factors for treatment selection like personal history, symptoms, and genetic testing.
  • The article discusses the current mCRPC treatment landscape, including recommended options and ongoing trials, while offering recommendations for treatment sequencing based on patient-specific factors.
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  • Innovations in advanced prostate cancer have improved outcomes, but there's still a lack of high-level evidence in clinical management, prompting the 2024 Advanced Prostate Cancer Consensus Conference to survey experts for insights.
  • A panel of 120 international experts developed and voted on 183 consensus questions through a web-based survey prior to the conference, defining consensus as ≥75% agreement.
  • The voting results highlight areas of agreement and disagreement that can guide clinical decisions and future research, with a focus on individualizing treatment based on patient characteristics and encouraging participation in clinical trials.
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  • The clinical trial PROpel investigated the combination of olaparib and abiraterone for treating first-line metastatic castration-resistant prostate cancer (mCRPC) and found it improved progression-free survival (rPFS) compared to a placebo with abiraterone.
  • In post hoc analyses, asymptomatic/mildly symptomatic patients experienced a significant rPFS benefit (27.6 months vs. 19.1 months) with the treatment, whereas symptomatic patients showed no meaningful improvement (14.1 vs. 13.8 months).
  • The study concluded that olaparib plus abiraterone demonstrates efficacy in asymptomatic/mildly symptomatic mCRPC patients, while results for symptomatic
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  • - Optimal management of metastatic castration-resistant prostate cancer (mCRPC) is complicated by new treatments like [Lu]Lu-PSMA-617, requiring careful monitoring of adverse events (AEs) and adherence to radiation safety protocols.
  • - The authors emphasize the importance of educating healthcare professionals on AEs (e.g., fatigue, dry mouth) and radiation safety to improve patient management during PSMA-targeted radiopharmaceutical therapy (RPT).
  • - Effective patient counseling and multidisciplinary collaboration among oncologists and nuclear medicine teams are crucial for safe treatment delivery and addressing challenges like urinary incontinence.
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The phase 3 VISION trial demonstrated that [Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]-positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSIs). The U.S.

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Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer.

Methods: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling).

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  • The gastrin-releasing peptide receptor (GRPr) is being studied as a potential diagnostic and therapeutic target for various cancers, particularly in detecting intra-prostatic prostate cancer (PCa) lesions using [Ga] Ga-GRPr PET imaging.
  • A systematic review analyzed data from 9 studies with 291 patients, finding that [Ga] Ga-GRPr PET imaging had detection rates of 87.09% for overall patients and 89.01% for those with Gleason scores of 7 or higher, while per-lesion detection rates were 78.54%.
  • The detection rate for multiparametric MRI (mpMRI) was slightly higher at 91.85%, but the difference compared to [Ga
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Background And Objective: The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [Lu]Lu-PSMA-617 (Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving Lu-PSMA-617.

Methods: Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to Lu-PSMA-617 plus protocol-permitted standard of care (SoC).

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  • The study focuses on metastatic castration-resistant prostate cancer (mCRPC) that is resistant to androgen receptor signaling inhibitors, which is often lethal, and aims to investigate liquid biopsy biomarkers related to this disease.
  • Researchers analyzed cell-free DNA and methylation from 126 mCRPC patients and developed a "stem-like" signature through RNA sequencing from both single cells and bulk samples.
  • Findings indicated that specific alterations in cell-free DNA correlated with poorer patient outcomes, and an increase in stemness-associated traits in lethal mCRPC patients suggests a reprogramming mechanism that contributes to the aggressiveness of the cancer.
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  • Lutetium 177 (Lu-PSMA-617) is a targeted therapy for metastatic castration-resistant prostate cancer (mCRPC), and baseline Ga-PSMA-11 PET/CT parameters may help determine treatment effectiveness.
  • The analysis used data from the VISION trial, where participants received either Lu-PSMA-617 plus standard care or standard care alone, focusing on how various PET parameters related to treatment outcomes like survival and response rates.
  • Results showed that higher whole-body tumor standardized uptake value (SUV) was linked to better treatment outcomes; for every 1-unit increase in SUV, the risk of radiographic progression and death decreased, indicating Lu-PS
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  • * A consensus among medical professionals led to the creation of a standardized PSMA PET/CT reporting template, aimed at streamlining communication between radiologists and referring physicians.
  • * The proposed template includes essential details like treatment history, tumor uptake information, and incidental findings, which are intended to improve the clarity and utility of imaging reports in patient management.
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Treatment with Lu-prostate-specific membrane antigen (PSMA)-617 (Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing Lu-PSMA-617 therapy.

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Background: Many patients use artificial intelligence (AI) chatbots as a rapid source of health information. This raises important questions about the reliability and effectiveness of AI chatbots in delivering accurate and understandable information.

Purpose: To evaluate and compare the accuracy, conciseness, and readability of responses from OpenAI ChatGPT-4 and Google Bard to patient inquiries concerning the novel Lu-PSMA-617 therapy for prostate cancer.

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Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) plus protocol-permitted standard of care (SOC) prolonged overall survival (OS) and radiographic progression-free survival (rPFS) versus SOC in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 VISION study, in addition to beneficial effects on symptomatic skeletal events (SSEs) and health-related quality of life (HRQOL).

Methods: Post hoc analyses used the full analysis set from the VISION study (N = 831) overall and by randomized treatment arm (Lu-PSMA-617 plus SOC, n = 551; SOC, n = 280). Correlations were determined between OS and rPFS and between rPFS or OS and time to SSE or to worsening HRQOL (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and 5-level EQ-5D [EQ-5D-5L]).

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Background: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.

Objective: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT.

Design, Setting, And Participants: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel.

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