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Prostate Cancer Therapy
Tristan R. Lawson, MD; Paige Bennett, MD
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KEY FACTS

  • Terminology

    • Preprocedure

      • Outcomes

        TERMINOLOGY

        • Definitions

          • Prostate cancer therapy
            • Nonmetastatic prostate cancer is treated with prostatectomy, brachytherapy, XRT, hormone therapy, or observation depending on staging and Gleason score
            • Metastatic castration-resistant prostate cancer (mCRPC) is resistant to medical or surgical castration and has limited treatment options
              • Often treated with chemotherapy, including docetaxel and postchemotherapy androgen deprivation therapy with abiraterone acetate and enzalutamide
              • Bone-targeting radionuclides, such as Ra-223 dichloride, can be used to treat bony metastases but do not treat nonosseous metastatic disease
              • Emerging role of prostate-specific membrane antigen (PSMA) ligands coupled with radionuclide, such as Lu-177, as radionuclide therapy
          • Lu-177 PSMA (LuPSMA)
            • PSMA: Cell membrane glycoprotein overexpressed in prostate cancer cells
              • Expressed in normal prostate epithelium as well as normal tissues, including salivary glands, colonic crypts, renal tubular cells, and duodenal mucosa
              • Can be expressed by urothelial, renal, and colonic malignancies and neovasculature of solid tumors
              • No known, naturally occurring ligand; reason for upregulation in prostate cancer is unclear
            • Experimental targeted radioligand therapy for mCRPC consisting of PSMA ligand and Lu-177
            • LuPSMA binds to cell membrane and undergoes endocytosis, concentrating radioactivity within tumor cells
            • Physical t1/2 6.65 days; beta decay
              • Emits beta particles with particle energies of 497 keV (78.6%), 384 keV (9.1%), and 176 keV (12.2%)
              • Mean penetration of beta particles in soft tissues is 670 μm; local radiation to tumor cells
              • Emits low-energy gamma photons of 113 keV (6.6%) and 208 keV (11%)
            • Used as theranostic agent in combination with Ga-68 PSMA PET/CT
            • VISION trial: Current phase 3 clinical trial comparing overall survival in patients with progressive mCRPC receiving standard of care vs. standard of care and LuPSMA therapy
              • Lu-177 PSMA-617 given as IV infusion every 6 weeks for maximum of 6 cycles
          • Ra-223 dichloride
            • Alpha-emitting, bone-seeking compound which can be used in treatment of symptomatic bony metastases in mCRPC
            • ALSYPMCA trial demonstrated overall survival benefit with Ra-223 treatment in patients with mCRPC and bone metastases
          • F-18 fluciclovine PET
            • Novel PET agent approved by FDA for work-up of biochemical recurrence in prostate cancer
              • Decays by positron emission (96.7%), physical t1/2 of 109.7 minutes
              • Normally biodistributes to liver, pancreas, lung, red bone marrow, myocardium, and skeletal muscle
            • Synthetic amino acid that targets amino acid transporters frequently overexpressed in prostate cancer
              • Large neutral amino acid transporters (LAT1, LAT3, LAT4)
              • Alanine-serine-cysteine transporters (ASCT1 and ASCT2)
            • Superior to C-11 choline PET in evaluation of biochemically recurrent prostate cancer
          • Skeletal scintigraphy
            • Tc-99m MDP or Tc-99m HDP skeletal scintigraphy, commonly referred to as "bone scan"
            • t1/2 of 6 hours, primary gamma emission of 140.5 keV (98.6%)
            • Commonly used to evaluate for osseous metastatic disease
          • F-18 NaF PET
            • Bone-seeking PET agent with uptake correlating to areas of bone remodeling and osteoblastic activity
            • FDA approved to evaluate metastatic bony disease and treatment response; does not evaluate soft tissues
            • More costly and less available than traditional scintigraphy
          • F-18 FDG PET
            • Limited role in prostate cancer imaging as most prostate cancers use nonglucose metabolic pathways
            • High-grade cancers (Gleason ≥ 7) are more likely to have increased F-18 FDG uptake
            • Use can be considered in mCRPC when assessing response to therapy of osseous disease

        PREPROCEDURE

        • Indications

          • Contraindications

            • Preprocedure Imaging

              • Getting Started

                PROCEDURE

                • Procedure Steps

                  • Findings and Reporting

                    • Alternative Procedures/Therapies

                      POST PROCEDURE

                      • Expected Outcome

                        • Things To Do

                          • Things To Avoid

                            OUTCOMES

                            • Complications

                              Selected References

                              1. Kratochwil C et al: EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 46(12):2536-44, 2019
                              2. McBean R et al: Lu177-PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution. J Med Imaging Radiat Oncol. 63(4):538-45, 2019
                              3. Parent EE et al: Update on 18F-fluciclovine PET for prostate cancer imaging. J Nucl Med. 59(5):733-9, 2018
                              4. Rahbar K et al: PSMA theranostics: Current status and future directions. Mol Imaging. 17:1536012118776068, 2018
                              5. Emmett L et al: Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 64(1):52-60, 2017
                              6. Dash A et al: Production of (177)Lu for Targeted Radionuclide Therapy: Available Options. Nucl Med Mol Imaging. 49(2):85-107, 2015
                              7. Scher HI et al: End points and outcomes in castration-resistant prostate cancer: from clinical trials to clinical practice. J Clin Oncol. 29(27):3695-704, 2011
                              8. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology
                              Related Anatomy
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                              Related Differential Diagnoses
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                              References
                              Tables

                              Tables

                              KEY FACTS

                              • Terminology

                                • Preprocedure

                                  • Outcomes

                                    TERMINOLOGY

                                    • Definitions

                                      • Prostate cancer therapy
                                        • Nonmetastatic prostate cancer is treated with prostatectomy, brachytherapy, XRT, hormone therapy, or observation depending on staging and Gleason score
                                        • Metastatic castration-resistant prostate cancer (mCRPC) is resistant to medical or surgical castration and has limited treatment options
                                          • Often treated with chemotherapy, including docetaxel and postchemotherapy androgen deprivation therapy with abiraterone acetate and enzalutamide
                                          • Bone-targeting radionuclides, such as Ra-223 dichloride, can be used to treat bony metastases but do not treat nonosseous metastatic disease
                                          • Emerging role of prostate-specific membrane antigen (PSMA) ligands coupled with radionuclide, such as Lu-177, as radionuclide therapy
                                      • Lu-177 PSMA (LuPSMA)
                                        • PSMA: Cell membrane glycoprotein overexpressed in prostate cancer cells
                                          • Expressed in normal prostate epithelium as well as normal tissues, including salivary glands, colonic crypts, renal tubular cells, and duodenal mucosa
                                          • Can be expressed by urothelial, renal, and colonic malignancies and neovasculature of solid tumors
                                          • No known, naturally occurring ligand; reason for upregulation in prostate cancer is unclear
                                        • Experimental targeted radioligand therapy for mCRPC consisting of PSMA ligand and Lu-177
                                        • LuPSMA binds to cell membrane and undergoes endocytosis, concentrating radioactivity within tumor cells
                                        • Physical t1/2 6.65 days; beta decay
                                          • Emits beta particles with particle energies of 497 keV (78.6%), 384 keV (9.1%), and 176 keV (12.2%)
                                          • Mean penetration of beta particles in soft tissues is 670 μm; local radiation to tumor cells
                                          • Emits low-energy gamma photons of 113 keV (6.6%) and 208 keV (11%)
                                        • Used as theranostic agent in combination with Ga-68 PSMA PET/CT
                                        • VISION trial: Current phase 3 clinical trial comparing overall survival in patients with progressive mCRPC receiving standard of care vs. standard of care and LuPSMA therapy
                                          • Lu-177 PSMA-617 given as IV infusion every 6 weeks for maximum of 6 cycles
                                      • Ra-223 dichloride
                                        • Alpha-emitting, bone-seeking compound which can be used in treatment of symptomatic bony metastases in mCRPC
                                        • ALSYPMCA trial demonstrated overall survival benefit with Ra-223 treatment in patients with mCRPC and bone metastases
                                      • F-18 fluciclovine PET
                                        • Novel PET agent approved by FDA for work-up of biochemical recurrence in prostate cancer
                                          • Decays by positron emission (96.7%), physical t1/2 of 109.7 minutes
                                          • Normally biodistributes to liver, pancreas, lung, red bone marrow, myocardium, and skeletal muscle
                                        • Synthetic amino acid that targets amino acid transporters frequently overexpressed in prostate cancer
                                          • Large neutral amino acid transporters (LAT1, LAT3, LAT4)
                                          • Alanine-serine-cysteine transporters (ASCT1 and ASCT2)
                                        • Superior to C-11 choline PET in evaluation of biochemically recurrent prostate cancer
                                      • Skeletal scintigraphy
                                        • Tc-99m MDP or Tc-99m HDP skeletal scintigraphy, commonly referred to as "bone scan"
                                        • t1/2 of 6 hours, primary gamma emission of 140.5 keV (98.6%)
                                        • Commonly used to evaluate for osseous metastatic disease
                                      • F-18 NaF PET
                                        • Bone-seeking PET agent with uptake correlating to areas of bone remodeling and osteoblastic activity
                                        • FDA approved to evaluate metastatic bony disease and treatment response; does not evaluate soft tissues
                                        • More costly and less available than traditional scintigraphy
                                      • F-18 FDG PET
                                        • Limited role in prostate cancer imaging as most prostate cancers use nonglucose metabolic pathways
                                        • High-grade cancers (Gleason ≥ 7) are more likely to have increased F-18 FDG uptake
                                        • Use can be considered in mCRPC when assessing response to therapy of osseous disease

                                    PREPROCEDURE

                                    • Indications

                                      • Contraindications

                                        • Preprocedure Imaging

                                          • Getting Started

                                            PROCEDURE

                                            • Procedure Steps

                                              • Findings and Reporting

                                                • Alternative Procedures/Therapies

                                                  POST PROCEDURE

                                                  • Expected Outcome

                                                    • Things To Do

                                                      • Things To Avoid

                                                        OUTCOMES

                                                        • Complications

                                                          Selected References

                                                          1. Kratochwil C et al: EANM procedure guidelines for radionuclide therapy with 177Lu-labelled PSMA-ligands (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 46(12):2536-44, 2019
                                                          2. McBean R et al: Lu177-PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution. J Med Imaging Radiat Oncol. 63(4):538-45, 2019
                                                          3. Parent EE et al: Update on 18F-fluciclovine PET for prostate cancer imaging. J Nucl Med. 59(5):733-9, 2018
                                                          4. Rahbar K et al: PSMA theranostics: Current status and future directions. Mol Imaging. 17:1536012118776068, 2018
                                                          5. Emmett L et al: Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 64(1):52-60, 2017
                                                          6. Dash A et al: Production of (177)Lu for Targeted Radionuclide Therapy: Available Options. Nucl Med Mol Imaging. 49(2):85-107, 2015
                                                          7. Scher HI et al: End points and outcomes in castration-resistant prostate cancer: from clinical trials to clinical practice. J Clin Oncol. 29(27):3695-704, 2011
                                                          8. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology