A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY)

Kenneth J Pienta, Michael A Gorin, Steven P Rowe, Peter R Carroll, Frédéric Pouliot, Stephan Probst, Lawrence Saperstein, Mark A Preston, Ajjai S Alva, Akash Patnaik, Jeremy C Durack, Nancy Stambler, Tess Lin, Jessica Jensen, Vivien Wong, Barry A Siegel, Michael J Morris, Kenneth J Pienta, Michael A Gorin, Steven P Rowe, Peter R Carroll, Frédéric Pouliot, Stephan Probst, Lawrence Saperstein, Mark A Preston, Ajjai S Alva, Akash Patnaik, Jeremy C Durack, Nancy Stambler, Tess Lin, Jessica Jensen, Vivien Wong, Barry A Siegel, Michael J Morris

Abstract

Purpose: Prostate specific membrane antigen-targeted positron emission tomography/computerized tomography has the potential to improve the detection and localization of prostate cancer. OSPREY was a prospective trial designed to determine the diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography for detecting sites of metastatic prostate cancer.

Materials and methods: Two patient populations underwent 18F-DCFPyL-positron emission tomography/computerized tomography. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. Cohort B enrolled patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Three blinded central readers evaluated the 18F-DCFPyL-positron emission tomography/computerized tomography. Diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography was based on imaging results compared to histopathology. In cohort A, detection of pelvic nodal disease (with specificity and sensitivity as co-primary end points) and of extrapelvic metastases were evaluated. In cohort B, sensitivity and positive predictive value for prostate cancer within biopsied lesions were evaluated.

Results: A total of 385 patients were enrolled. In cohort A (252 evaluable patients), 18F-DCFPyL-positron emission tomography/computerized tomography had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement; median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively. In cohort B (93 evaluable patients, median prostate specific antigen 11.3 ng/ml), median sensitivity and positive predictive value for extraprostatic lesions were 95.8% (87.8%-99.0%) and 81.9% (73.7%-90.2%), respectively.

Conclusions: The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that 18F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of 18F-DCFPyL-positron emission tomography/computerized tomography to stage men with high-risk prostate cancer for nodal or distant metastases, and reliably detect sites of disease in men with suspected metastatic prostate cancer.

Keywords: molecular imaging; neoplasm metastasis; neoplasm staging; prostatic neoplasms.

Conflict of interest statement

Financial interest and/or other relationship with Blue Earth, BK Medical, KOELIS, and OBP Medical and Perineologic.

Financial interest and/or other relationship with Insightec Francis Medical Norcal Lynx Group and Nutcracker Therapeutics.

Financial interest and/or other relationship with Astellas, Tersera and Janssen.

Financial interest and/or other relationship with AstraZeneca, Merck, BMS, Celgene, Prometheus, Arcus Biosciences, Pfizer, EMD Serono, Astellas and Seattle Genetics.

Financial interest and/or other relationship with Adient Medical Scientific and Verix Medical.

Financial interest and/or other relationship with Progenics Pharmaceuticals, Inc.

Financial interest and/or other relationship with Avid Radiopharmaceuticals, ImaginAb Inc., Blue Earth Diagnostics LLC, Capella Imaging LLC, Curium Pharma, General Electric Healthcare, Imaginab Inc., American College of Radiology, and American Medical Foundation for Peer Review and Education.

Financial interest and/or other relationship with ORIC Pharmaceuticals and Curium.

Figures

Figure 1.
Figure 1.
Standards for Reporting of Diagnostic Accuracy flow diagram, cohort A (see supplementary Appendix figure for details, https://www.jurology.com). PLN, pelvic lymph node. Pyl, 18F-DCFPyL.
Figure 2.
Figure 2.
Standards for Reporting of Diagnostic Accuracy flow diagram, cohort B.1 Image-guided biopsy as specified by protocol included CT/MRI or ultrasound-guided biopsy.2 While negative for prostate cancer, 18F-DCFPyL (Pyl) scan correctly identified malignancy, and therefore these rare cases were neither considered to be false-positive for prostate cancer nor true-positive for cancer, but rather as nonevaluable.
Figure 3.
Figure 3.
18F-DCFPyL-PET/CT diagnostic performance (median of 3 independent readers) in high-risk prostate cancer in cohort A.
Figure 4.
Figure 4.
18F-DCFPyL-PET/CT up staged patient with high-risk prostate cancer. This cohort A patient was staged at baseline as T1cN0M0; his PSA was 13.68 ng/ml and his biopsy Gleason score was 4+5. CT (not shown) demonstrated no evidence of metastatic disease. Anterior and posterior bone scintigraphy showed changes of left hip arthroplasty and increased tracer uptake in anterior superior iliac spine (arrow) of uncertain significance, butwas otherwise normal. 18F-DCFPyL-PET/CT showed multifocal osseous lesions involving spine, ribs, pelvis and right clavicle. On subsequent biopsy of transverse process of L3, osseous metastatic (M1b) disease was confirmed.
Figure 5.
Figure 5.
Sensitivity and PPV (median of 3 independent readers, relative to histopathology truth standard) of 18F-DCFPyL-PET/CT in metastatic disease sites (A), by anatomical region (B) and across all PSA ranges in men with recurrent or metastatic prostate cancer (C) in cohort B.

References

    1. Shinohara K, Wheeler TM and Scardino PT: The appearance of prostate cancer on transrectal ultrasonography: correlation of imaging and pathological examinations. J Urol 1989; 142: 76.
    1. Hricak H, Dooms GC, Jeffrey RB et al. Prostatic carcinoma: staging by clinical assessment, CT, and MR imaging. Radiology 1987; 162: 331.
    1. Scheidler J, Hricak H, Vigneron DB et al. Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging—-clinicopathologic study. Radiology 1999; 213: 473.
    1. Blomqvist L, Carlsson S, Gjertsson P et al. Limited evidence for the use of imaging to detect prostate cancer: a systematic review. Eur J Radiol 2014; 83: 1601.
    1. Höovels AM, Heesakkers RAM, Adang EM et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 2008; 63: 387.
    1. Turpin A, Girard E, Baillet C et al. Imaging for metastasis in prostate cancer: a review of the literature. Front Oncol 2020; 10: 55.
    1. Evans JD, Jethwa KR, Ost P et al. Prostate cancer-specific PET radiotracers: a review on the clinical utility in recurrent disease. Pract Radiat Oncol 2018; 8: 28.
    1. U.S. Food and Drug Administration: FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer. December 1, 2020. press release. Available at .
    1. Chang SS: Overview of prostate-specific membrane antigen. Rev Urol, suppl., 2004; 6: S13.
    1. Wright GL Jr,Haley C, Beckett ML et al. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol 1995; 1: 18.
    1. Silver DA, Pellicer I, Fair WR et al. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997; 3: 81.
    1. Hofman MS, Hicks RJ, Maurer T et al. Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics 2017; 37: 1512.
    1. Maurer T, Gschwend JE, Rauscher I et al. Diagnostic efficacy of 68Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016; 195: 1436.
    1. Gorin MA, Rowe SP, Patel HD et al. Prostate specific membrane antigen targeted 18F-DCFPyL positron emission tomography/computerized tomography for the preoperative staging of high risk prostate cancer: results of a prospective, phase II, single center study. J Urol 2018; 199: 126.
    1. Dietlein M, Kobe C, Kuhnert G et al. Comparison of [18F]DCFPyL and [68Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol 2015; 17: 575.
    1. Rowe SP, Campbell SP, Mana-Ay M et al. Prospective evaluation of PSMA-targeted 18F-DCFPyL PET/CT in men with biochemical failure after radical prostatectomy for prostate cancer. J Nucl Med 2020; 61: 58.
    1. Chen Y, Pullambhatla M, Foss CA et al. 2-(3-{1-Carboxy-5-[(6-[18F] fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res 2011; 17: 7645.
    1. Recent Updates to National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Available at . Accessed July 12, 2016.
    1. Crippa F, Leutner M, Belli F et al. Which kinds of lymph node metastases can FDG PET detect? A clinical study in melanoma. J Nucl Med 2000; 41: 1491.
    1. Scher HI, Morris MJ, Stadler WM et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group (PCWG3). J Clin Oncol 2016; 34: 1402.
    1. Kucharczyk MJ, So J, Gravis G et al. A combined biological and clinical rationale for evaluating metastasis directed therapy in the management of oligometastatic prostate cancer. Radiother Oncol 2020; 152: 80.
    1. Trabulsi EJ, Rumble BR, Jadvar H et al. Optimum imaging strategies for advanced prostate cancer: ASCO Guideline. J Clin Oncol 2020; 38: 1.
    1. Guckenberger M, Lievens Y, Bouma AB et al. Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for research and treatment of cancer consensus recommendation. Lancet Oncol 2020; 21: e18.
    1. Fendler WP, Weber M and Iravani A: Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res 2019; 25: 7448.
    1. Bostwick DG, Pacelli A, Blute M et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma—a study of 184 cases. Cancer 1998; 82: 2256.
    1. Bouchelouche K, Choyke PL and Capala J: Prostate specific membrane antigen—a target for imaging and therapy with radionuclides. Discov Med 2010; 9: 55.
    1. Hofman MS, Lawrentschuk N, Francis RJ et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicenter study. Lancet 2020; 395: 1208.
    1. Hope TA, Armstrong WR, Murthy V et al. Accuracy of 68Ga-PSMA-11 for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: a multicenter prospective phase III imaging study. J Clin Oncol, suppl., 2020; 38: 5502.

Source: PubMed

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