Anatomic and Functional Prostate Cancer Imaging

HomeRadiologyVol. 301, No. 2 PreviousNext Reviews and CommentaryFree AccessEditorialAnatomic and Functional Prostate Cancer ImagingHadyn T. Williams , T. Lane EstesHadyn T. Williams , T. Lane EstesAuthor AffiliationsFrom the Department of Radiology and Imaging, Sections of Nuclear Medicine (H.T.W.) and Abdominal Imaging (T.L.E.), Medical College of Georgia, Augusta University, 1120 15th St, Augusta, GA 30912.Address correspondence to H.T.W. (e-mail: [email protected]).Hadyn T. Williams T. Lane EstesPublished Online:Aug 31 2021https://doi.org/10.1148/radiol.2021211837MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In An earlier incorrect version appeared online. This article was corrected on September 7, 2021.See also the article by Margel and Bernstine et al in this issue.Hadyn T. Williams, MD, Department of Radiology and Imaging, Nuclear Medicine Section, professor, Medical College of Georgia, Augusta University, is a fellow and past president of the American College of Nuclear Medicine and a fellow of the American College of Radiology and has organized, moderated, and participated in research council section sessions at national/international society meetings, with research interests and numerous publications in Nuclear Medicine and PET.Download as PowerPointOpen in Image Viewer T. Lane Estes, MD, Department of Radiology and Imaging, Abdominal Imaging Section chief, associate professor, Medical College of Georgia, Augusta University, has extensive expertise in multiparametric MRI and has received Certificate of Merit from the Radiological Society of North America (RSNA) and has provided RSNA/American Association of Physicists in Medicine physics module.Download as PowerPointOpen in Image Viewer Anatomic and functional imaging endeavor to depict cancer with high sensitivity and help characterize cancer with high specificity. These tools provide more accurate diagnosis and help to guide optimal treatment. Prostate cancer, diagnosed by image-guided biopsy, uses a combination of histopathologic, laboratory, clinical, and imaging findings to provide risk stratification and treatment guidance.Multiparametric MRI combines T1- and T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging to depict intraprostatic tumors with high sensitivity. It also depicts extracapsular extension and seminal vesicle invasion to guide appropriate therapy, which includes nerve-sparing surgical procedure options. Multiparametric MRI is equivalent to CT for pelvic lymph node staging (1).Lower glucose utilization by prostate cancers means that fluorine 18 (18F) fluorodeoxyglucose PET has lower efficacy in detecting prostate cancers. Higher lipid utilization with use of the tracers carbon 11 (11C) choline (U.S. Food and Drug Administration [FDA] approved) and the tracer 11C-acetate (not FDA approved) provides higher efficacy in detecting prostate cancer and metastatic disease. But each requires an onsite cyclotron for production because of the short 11C half-life of 20 minutes, severely limiting its use (2).The amino acid analog transporter PET tracer, 18F-fluciclovine (Axumin), was approved by the FDA on May 27, 2016, and is now widely available from regional cyclotrons (the 18F half-life is 110 minutes). This tracer changes management in 64% of men with prostate-specific antigen biochemically recurrent prostate cancer after primary treatment. 18F-fluciclovine is recognized by the National Comprehensive Cancer Network as an appropriate next evaluation in detecting intraprostatic and extraprostatic sites of disease. However, high amino acid analog transporter use is not specific for prostate cancer. Increased 18F-fluciclovine PET tracer avidity is also observed in primary and metastatic brain cancer and other cancers and in inflammatory and other lesions with higher amino acid utilization (3).In this issue of Radiology, Margel and Bernstine et al (4) evaluated the more specific gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET agent and its contribution to multiparametric MRI in prostate cancer detection. PET examinations with PSMA tracer-avid lesions and multiparametric MRI lesions with findings that were equivocal, likely, or highly likely for significant intraprostatic cancer were compared with multiparametric MRI lesions alone. This adds pretest selection bias for patients with greater likelihood of disease, which may inflate specificity. Addition of the results at PSMA PET to multiparametric MRI improved specificity for disease detection from 49% to 76% with similar sensitivities. PSMA PET sensitivity was 88% and multiparametric MRI was 92%, and the greatest benefit of PSMA PET was seen in patients with lesions equivocal for prostate cancer at multiparametric MRI. This study shows that functional imaging better evaluates true cancer extent than does anatomic imaging alone, positively impacting prostate cancer diagnosis and potentially leading to more effective treatment options.The FDA approved 68Ga-PSMA-11 on December 1, 2020, for PET imaging of PSMA-positive prostate cancer lesions in men with suspected metastasis who are candidates for initial definitive therapy and with suspected recurrence based on elevated serum prostate-specific antigen level (5). It was shown that 68Ga-PSMA-11 PET had better diagnostic accuracy in dominant and nondominant tumor depiction and in upgrading and helping to determine adverse pathologic results in prostate cancers, whereas multiparametric MRI helped to better predict extracapsular extension and seminal vesicle invasion than 68Ga-PSMA-11 PET, illustrating their strengths and additive use.Production of 68Ga-PSMA-11 (Illumet, Cardinal Health and Telix) requires a germanium 68 (68Ge)/68Ga generator or cyclotron for production at a radiopharmacy and use within a 2-hour delivery range because of the 68-minute half-life of 68Ga.Approval from the FDA does not equate to reimbursement from Centers for Medicare and Medicaid Services or insurance for the examination performed. Like 18F-fluciclovine and other FDA-approved PET radiotracers, approved 68Ga-PSMA-11 had level II codes from the Healthcare Common Procedure Coding System assigned to enable billing submissions to Centers for Medicare and Medicaid Services, effective July 1, 2021 (6,7).On May 27, 2021, the FDA approved 18F-piflufolastat (Pylarify) PSMA-targeted radiotracer for PET in prostate cancer lesions in men suspected of having metastasis who are candidates for initial definitive therapy and with suspected recurrence on the basis of elevated serum prostate-specific antigen level. These are the same indications for which 68Ga-PSMA was approved, but it has not yet been assigned a Healthcare Common Procedure Coding System A-code for billing attempts. In patients with biochemical-recurrent prostate cancer with none localized on baseline imaging, 18F-piflufolastat has demonstrated high correct localization and detection rates, including in patients with low prostate-specific antigen values (median prostate-specific antigen, 0.8 ng/mL). Developed by Lantheus, it has a 110-minute half-life and should have wide availability from a cyclotron and radiopharmacy network system (8).PSMA-targeted radiotracers were compared with the widely used 18F-fluciclovine amino acid analog radiotracer for detection of prostate cancer biochemical recurrence after definitive therapy. The meta-analysis (9) revealed a significantly higher detection rate of 80% with 68Ga-PSMA or 18F-PSMA PET/CT than with 18F-fluciclovine PET/CT (detection rate, 62%) but not significantly different when prostate-specific antigen was less than 1.0 ng/mL.Lutetium 177 (177Lu) PSMA-R2, 177Lu-PSMA-617, and anti-PSMA ligand 177Lu-CTT-140 are systemically delivered radiopharmaceuticals currently in clinical trials. These radiopharmaceuticals provide specific PSMA-targeted β-particle radiation therapy to prostate cancer sites. Combined with PSMA-PET imaging, these radiopharmaceuticals fulfill the National Institutes of Health/National Cancer Institute goals of matching companion diagnostic radiopharmaceutical imaging to the same specific agent linked to a therapeutic radiopharmaceutical, which would provide precision theranostic services (10).Functional and anatomic imaging provide complementary and additive efficacy for accurate assessment of cancer extent. Combining diagnostic accuracy in guiding therapy with specific companion precision treatment holds the promise of more effective diagnosis and treatment of cancers.Disclosures of Conflicts of Interest: H.T.W. disclosed no relevant relationships. T.L.E. disclosed no relevant relationships.References1. Stabile A, Giganti F, Rosenkrantz AB, et al. Multiparametric MRI for prostate cancer diagnosis: current status and future directions. Nat Rev Urol 2020;17(1):41–61. Crossref, Medline, Google Scholar2. Schaeffer E, Srinivas S, Antonarakis ES, et al. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 2.2021. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Published February 17, 2021. Accessed July 18, 2021. Google Scholar3. Barsky AR, Ahn GS, Pantel AA, Vapiwala N. Non-prostate cancer malignancies detected by 18F-Fluciclovine PET/CT. J Clin Oncol 2020;38(6_suppl):28. Crossref, Google Scholar4. Margel D, Bernstine H, Groshar D, et al. Diagnostic performance of 68Ga prostate-specific membrane antigen PET/MRI compared with multiparametric MRI for detecting clinically significant prostate cancer. Radiology 2021.https://doi.org/10.1148/radiol.2021204093. Published online August 31, 2021. Link, Google Scholar5. Koseoglu E, Kordan Y, Kilic M, et al. Diagnostic ability of Ga-68 PSMA PET to detect dominant and non-dominant tumors, upgrading and adverse pathology in patients with PIRADS 4-5 index lesions undergoing radical prostatectomy. Prostate Cancer Prostatic Dis 2021;24(1):202–209. Crossref, Medline, Google Scholar6. Prescribing information for Gallium Ga 68 PSMA-11 Injection, for intravenous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212642s000lbl.pdf. Accessed July 18, 2021. Google Scholar7. Centers for Medicare & Medicaid Services (CMS) Healthcare Common Procedure CodingSystem. (HCPCS) Application Summaries and Coding Decisions. First Quarter 2021 Coding Cycle for Drug and Biological Products. https://www.cms.gov/files/document/2021-hcpcs-application-summary-quarter-1-2021-drugs-and-biologics-updated-05262021.pdf. Accessed July 18, 2021. Google Scholar8. Prescribing information for PYLARIFY (piflufolastat F 18) injection, for intravenous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214793s000lbl.pdf. Accessed July 18, 2021. Google Scholar9. Tan N, Oyoyo U, Bavadian N, et al. PSMA-targeted Radiotracers versus 18F Fluciclovine for the Detection of Prostate Cancer Biochemical Recurrence after Definitive Therapy: A Systematic Review and Meta-Analysis. Radiology 2020;296(1):44–55. Link, Google Scholar10. Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 2020;19(9):589–60.[Published correction appears in Nat Rev Drug Discov 2020;19(11):819.]. Crossref, Medline, Google ScholarArticle HistoryReceived: July 19 2021Revision requested: Aug 4 2021Revision received: Aug 5 2021Accepted: Aug 9 2021Published online: Aug 31 2021Published in print: Nov 2021 FiguresReferencesRelatedDetailsAccompanying This ArticleDiagnostic Performance of 68Ga Prostate-specific Membrane Antigen PET/MRI Compared with Multiparametric MRI for Detecting Clinically Significant Prostate CancerAug 31 2021RadiologyAnatomic and Functional Prostate Cancer ImagingOct 25 2021RadiologyRecommended Articles 18F-DCFPyL PET/CT in Men with Prostate CancerRadiology2022Volume: 305Issue: 2pp. 429-430Competitive Advantage of PSMA Theranostics in Prostate CancerRadiology2021Volume: 299Issue: 2pp. 261-263Diagnostic Accuracy of Multiparametric MRI versus 68Ga-PSMA-11 PET/MRI for Extracapsular Extension and Seminal Vesicle Invasion in Patients with Prostate CancerRadiology2019Volume: 293Issue: 2pp. 350-358Diagnostic Accuracy of 68Ga-PSMA-11 PET/MRI Compared with Multiparametric MRI in the Detection of Prostate CancerRadiology2018Volume: 289Issue: 3pp. 730-737Clinical PET Imaging in Prostate CancerRadioGraphics2017Volume: 37Issue: 5pp. 1512-1536See More RSNA Education Exhibits Prostate MRI in Stereotactic Body Radiation Therapy (SBRT) Treatment Planning and Delivery for Localized Prostate CancerDigital Posters2020DCE MRI: A Superhero Or Villain In Prostate MRI?Digital Posters2022Hybrid PSMA Imaging of The Prostate: A Guide For the Beginner- A Reference For the ExpertDigital Posters2022 RSNA Case Collection Anterior transition zone prostate adenocarcinomaRSNA Case Collection2020Peripheral Zone Prostate Cancer with PseudocapsuleRSNA Case Collection2022Locally advanced, metastatic prostate adenocarcinomaRSNA Case Collection2020 Vol. 301, No. 2 Metrics Altmetric Score PDF download