Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy

Thang, Sue Ping; Violet, John; Sandhu, Shahneen; Iravani, Amir; Akhurst, Tim; Kong, Grace; Kumar, Aravind Ravi; Murphy, Declan; Williams, Scott; Hicks, Rodney J.; Hofman, Michael S

doi:10.1016/j.euo.2018.11.007

Cited by 152 publications

(133 citation statements)

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“…High PSMA expression is associated with defective DNA damage repair and PTEN loss, whereas patients with low 68 Ga-PSMA expression have poor survival (29)(30)(31). Since bone biopsies in this study were not obtained from metastases with low 68 Ga-PSMA uptake, these sites are underrepresented in the current study.…”

Section: Discussionmentioning

confidence: 99%

⁶⁸Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

et al. 2020

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For individual treatment decisions in patients with metastatic prostate cancer (mPC), molecular diagnostics are increasingly used. Bone metastases are frequently the only source for obtaining metastatic tumor tissue. However, the success rate of computed tomography (CT)-guided bone biopsies for molecular analyses in mPC patients is only ~40%. Positron emission tomography (PET) using Gallium-68 prostate specific membrane antigen (68 Ga-PSMA) is a promising tool to improve the harvest rate of bone biopsies for molecular analyses. Aim of this study was to determine the success rate of 68 Ga-PSMA guided bone biopsies for molecular diagnostics in mPC patients. Methods: Within a prospective multicenter whole-genome sequencing trial (NCT01855477), 69 mPC patients underwent 68 Ga-PSMA PET/CT prior to bone biopsy. Primary endpoint was success rate (tumor percentage ≥30%) of 68 Ga-PSMA guided bone biopsies. At biopsy sites, 68 Ga-PSMA uptake was quantified using rigid body image registration of 68 Ga-PSMA PET/CT and interventional CT. Actionable somatic alterations were identified. Results: Success rate of 68 Ga-PSMA guided biopsies for molecular analyses was 70%. At biopsy sites categorized as positive, inconclusive, or negative for 68 Ga-PSMA uptake, 70%, 64%, and 36% of biopsies were tumor positive (≥30%), respectively (p=0.0610). In tumor positive biopsies, 68 Ga-PSMA uptake was significantly higher (p=0.008), whereas radiodensity was significantly lower (p=0.006). With an area under the curve of 0.84 and 0.70, both 68 Ga-PSMA uptake (maximum standardized uptake value) and radiodensity (mean Hounsfield Units) were strong predictors for a positive biopsy. Actionable somatic alterations were detected in 73% of the sequenced biopsies. Conclusion: In patients with mPC, 68 Ga-PSMA PET/CT improves the success rate of CT-guided bone biopsies for by on November 5, 2020. For personal use only. jnm.snmjournals.org Downloaded from 4 molecular analyses, thereby identifying actionable somatic alterations in more patients. Therefore, 68 Ga-PSMA PET/CT may be considered for guidance of bone biopsies in both clinical practice and clinical trials.

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Section: Discussionmentioning

confidence: 99%

⁶⁸Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

et al. 2020

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“…Additionally, patients who have been excluded from the study on the basis of low PSMA avidity or discordant FDG‐avid disease on screening 68 Ga‐PSMA‐11 and 18 F‐FDG PET/CT, respectively, will also have their treatment and outcomes assessed .…”

Section: Introductionmentioning

confidence: 99%

TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

et al. 2019

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ObjectiveTo assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177 Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Results and Conclusions177 Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177 Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

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“…85,[92][93][94][95] In contrast, PSMA ligand-based RNT results in on-target, off-tumor radiation exposure to salivary glands and the digestive tract and possible late renal toxicity. [63][64][65]82,[84][85][86][87] Beta particle-emitting 90 Y-and 177 Lu-labeled J591 agents have demonstrated promise as theranostic agents in clinical studies. 85,[92][93][94][95][96][97] In SPECT imaging, 90 Y-(using 111 Indium imaging) and 177 111,112 The FDA has not allowed PSA changes to be considered as an indicator of clinical benefit in prostate cancer trials.…”

Section: Recent Developments In Psma-pet Imagingmentioning

confidence: 99%

“…Biopsy studies are being initiated at Peter MacCallum Cancer Center to investigate the biology and clinical impact of tumor heterogeneity based on PSMA and FDG PET imaging. The median OS of months) 65. Imaging and blood biomarkers from patients on this trial were evaluated to identify any with potential prognostic value.FDG volume and PSMA intensity were identified as most prognostic of OS, followed by lactate dehydrogenase, alkaline phosphatase (ALP), and bone scan index 84.…”

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Meeting report from the Prostate Cancer Foundation PSMA theranostics state of the science meeting

et al. 2020

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Introduction The Prostate Cancer Foundation (PCF) convened a PCF prostate‐specific membrane antigen (PSMA) Theranostics State of the Science Meeting on 18 November 2019, at Weill Cornell Medicine, New York, NY. Methods The meeting was attended by 22 basic, translational, and clinical researchers from around the globe, with expertise in PSMA biology, development and use of PSMA theranostics agents, and clinical trials. The goal of this meeting was to discuss the current state of knowledge, the most important biological and clinical questions, and critical next steps for the clinical development of PSMA positron emission tomography (PET) imaging agents and PSMA‐targeted radionuclide agents for patients with prostate cancer. Results Several major topic areas were discussed including the biology of PSMA, the role of PSMA‐targeted PET imaging in prostate cancer, the physics and performance of different PSMA‐targeted PET imaging agents, the current state of clinical development of PSMA‐targeted radionuclide therapy (RNT) agents, the role of dosimetry in PSMA RNT treatment planning, barriers and challenges in PSMA RNT clinical development, optimization of patient selection for PSMA RNT trials, and promising combination treatment approaches with PSMA RNT. Discussion This article summarizes the presentations from the meeting for the purpose of globally disseminating this knowledge to advance the use of PSMA‐targeted theranostic agents for imaging and treatment of patients with prostate cancer.

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Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy

Cited by 152 publications

References 31 publications

⁶⁸Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

⁶⁸Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

Meeting report from the Prostate Cancer Foundation PSMA theranostics state of the science meeting

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Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy

Cited by 152 publications

References 31 publications

68Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

68Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

TheraP: a randomized phase 2 trial of 177Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)

Meeting report from the Prostate Cancer Foundation PSMA theranostics state of the science meeting

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⁶⁸Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

⁶⁸Ga-PSMA–Guided Bone Biopsies for Molecular Diagnostics in Patients with Metastatic Prostate Cancer

TheraP: a randomized phase 2 trial of ¹⁷⁷Lu‐PSMA‐617 theranostic treatment vs cabazitaxel in progressive metastatic castration‐resistant prostate cancer (Clinical Trial Protocol ANZUP 1603)