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Radiotheranostics in advanced prostate cancer: Current and future directions

Prostate Cancer and Prostatic Diseases volume 27, pages 11–21 (2024)Cite this article

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Abstract

The discovery of small molecules that target the extracellular domain of prostate-specific membrane antigen (PSMA) has led to advancements in diagnostic imaging and the development of precision radiopharmaceutical therapies. In this review, we present the available existing data and highlight the key ongoing clinical evaluations of PSMA-based imaging in the management of primary, biochemically recurrent, and metastatic prostate cancer. We also discuss clinical studies that explore the use of PSMA-based radiopharmaceutical therapy (RPT) in metastatic prostate cancer and forthcoming trials that investigate PSMA RPT in earlier disease states. Multidisciplinary collaboration in clinical trial design and therapeutic administration is critical to the continued progress of this evolving radiotheranostics field.

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Fig. 1: Mechanism of action of 177Lu-PSMA radioligand therapy.
Fig. 2: Current treatment landscape for non-metastatic (M0) and metastatic (M1) prostate cancer.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  2. Horoszewicz JS, Kawinski E, Murphy GP. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res. 1987;7:927–35.

    CAS  PubMed  Google Scholar 

  3. Israeli RS, Powell CT, Fair WR, Heston WD. Molecular cloning of a complementary DNA encoding a prostate-specific membrane antigen. Cancer Res. 1993;53:227–30.

    CAS  PubMed  Google Scholar 

  4. Israeli RS, Powell CT, Corr JG, Fair WR, Heston WD. Expression of the prostate-specific membrane antigen. Cancer Res. 1994;54:1807–11.

    CAS  PubMed  Google Scholar 

  5. Troyer JK, Beckett ML, Wright GL Jr. Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int J Cancer. 1995;62:552–8.

    Article  CAS  PubMed  Google Scholar 

  6. Wright GL Jr., Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1:18–28.

    Article  PubMed  Google Scholar 

  7. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.

    CAS  PubMed  Google Scholar 

  8. Sokoloff RL, Norton KC, Gasior CL, Marker KM, Grauer LS. A dual-monoclonal sandwich assay for prostate-specific membrane antigen: levels in tissues, seminal fluid and urine. Prostate. 2000;43:150–7.

    Article  CAS  PubMed  Google Scholar 

  9. Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.

    Article  CAS  PubMed  Google Scholar 

  10. Minner S, Wittmer C, Graefen M, Salomon G, Steuber T, Haese A, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 2011;71:281–8.

    Article  PubMed  Google Scholar 

  11. Haberkorn U, Eder M, Kopka K, Babich JW, Eisenhut M. New Strategies in Prostate Cancer: Prostate-Specific Membrane Antigen (PSMA) Ligands for Diagnosis and Therapy. Clin Cancer Res. 2016;22:9–15.

    Article  CAS  PubMed  Google Scholar 

  12. Jadvar H. Imaging evaluation of prostate cancer with 18F-fluorodeoxyglucose PET/CT: utility and limitations. Eur J Nucl Med Mol Imaging. 2013;40:S5–10.

    Article  PubMed  Google Scholar 

  13. Bednarova S, Lindenberg ML, Vinsensia M, Zuiani C, Choyke PL, Turkbey B. Positron emission tomography (PET) in primary prostate cancer staging and risk assessment. Transl Androl Urol. 2017;6:413–23.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sodee DB, Conant R, Chalfant M, Miron S, Klein E, Bahnson R, et al. Preliminary imaging results using In-111 labeled CYT-356 (Prostascint) in the detection of recurrent prostate cancer. Clin Nucl Med. 1996;21:759–67.

    Article  CAS  PubMed  Google Scholar 

  15. Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V, et al. Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res. 1997;57:3629–34.

    CAS  PubMed  Google Scholar 

  16. Bander NH, Trabulsi EJ, Kostakoglu L, Yao D, Vallabhajosula S, Smith-Jones P, et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J Urol. 2003;170:1717–21.

    Article  CAS  PubMed  Google Scholar 

  17. Alberts IL, Seide SE, Mingels C, Bohn KP, Shi K, Zacho HD, et al. Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis. Eur J Nucl Med Mol imaging. 2021;48:2978–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Calais J, Ceci F, Eiber M, Hope TA, Hofman MS, Rischpler C. et al. 18)F-fluciclovine PET-CT and (68)Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol. 2019;90:1286–94.

    Article  Google Scholar 

  19. Sonni I, Felker ER, Lenis AT, Sisk AE, Bahri S, Allen-Auerbach M, et al. Head-to-Head Comparison of (68)Ga-PSMA-11 PET/CT and mpMRI with a Histopathology Gold Standard in the Detection, Intraprostatic Localization, and Determination of Local Extension of Primary Prostate Cancer: Results from a Prospective Single-Center Imaging Trial. J Nucl Med. 2022;63:847–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tosoian JJ, Gorin MA, Rowe SP, Andreas D, Szabo Z, Pienta KJ, et al. Correlation of PSMA-targeted 18F-DCFPyL PET/CT findings with immunohistochemical and genomic data in a patient with metastatic neuroendocrine prostate cancer. Clin Genitourin Cancer. 2017;15:e65–8.

    Article  PubMed  Google Scholar 

  21. Bertagna F, Albano D, Cerudelli E, Gazzilli M, Giubbini R, Treglia G. Potential of radiolabeled PSMA PET/CT or PET/MRI diagnostic procedures in gliomas/glioblastomas. Curr Radiopharmaceuticals. 2020;13:94–98.

    Article  Google Scholar 

  22. Bilgin R, Ergül N, Çermik TF. Incidental meningioma mimicking metastasis of prostate adenocarcinoma in 68Ga-labeled PSMA ligand PET/CT. Clin Nucl Med. 2016;41:956–8.

    Article  PubMed  Google Scholar 

  23. Hermann RM, Djannatian M, Czech N, Nitsche M. Prostate-specific membrane antigen PET/CT: False-positive results due to sarcoidosis. Case Rep. Oncol. 2016;9:457–63.

    Article  PubMed  PubMed Central  Google Scholar 

  24. de Galiza Barbosa F, Queiroz MA, Nunes RF, Costa LB, Zaniboni EC, Marin JFG, et al. Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings. Cancer Imaging. 2020;20:23.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Rauscher I, Krönke M, König M, Gafita A, Maurer T, Horn T, et al. Matched-pair comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med. 2020;61:51–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sasikumar A, Joy A, Nanabala R, Pillai M, Hari T. 68Ga-PSMA PET/CT false-positive tracer uptake in Paget disease. Clin Nucl Med. 2016;41:e454–5.

    Article  PubMed  Google Scholar 

  27. Ribeiro AMB, Lima ENP, Rocha MM. Fibrous dysplasia as a possible false-positive finding in 68Ga-labeled prostate-specific membrane antigen positron emission tomography/computed tomography study in the follow-up of prostate cancer. World J Nucl Med. 2019;18:409–12.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rowe SP, Pienta KJ, Pomper MG, Gorin MA. PSMA-RADS version 1.0: A step towards standardizing the interpretation and reporting of PSMA-targeted PET imaging studies. Eur Urol. 2018;73:485.

    Article  PubMed  Google Scholar 

  29. Fanti S, Minozzi S, Morigi JJ, Giesel F, Ceci F, Uprimny C, et al. Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions. Eur J Nucl Med Mol Imaging. 2017;44:1622–35.

    Article  CAS  PubMed  Google Scholar 

  30. Eiber M, Herrmann K, Calais J, Hadaschik B, Giesel FL, Hartenbach M, et al. Prostate cancer molecular imaging standardized evaluation (PROMISE): proposed miTNM classification for the interpretation of PSMA-ligand PET/CT. J Nucl Med. 2018;59:469–78.

    Article  PubMed  Google Scholar 

  31. Toriihara A, Nobashi T, Baratto L, Park S, Hatami N, Duan H, et al. Comparison of three interpretation criteria of 68Ga-PSMA PET based on inter-and intra-reader agreement. Soc Nuclear Med. 2020;61:533–9.

  32. Ceci F, Oprea-Lager DE, Emmett L, Adam JA, Bomanji J, Czernin J, et al. E-PSMA: The EANM standardized reporting guidelines v1.0 for PSMA-PET. Eur J Nucl Med Mol Imaging. 2021;48:1626–38.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Emmett L, Buteau J, Papa N, Moon D, Thompson J, Roberts MJ, et al. The additive diagnostic value of prostate-specific membrane antigen positron emission tomography computed tomography to multiparametric magnetic resonance imaging triage in the diagnosis of prostate cancer (PRIMARY): a prospective multicentre study. Eur Urol. 2021;80:682–9.

    Article  CAS  PubMed  Google Scholar 

  34. Hope TA, Goodman JZ, Allen IE, Calais J, Fendler WP, Carroll PR. Metaanalysis of (68)Ga-PSMA-11 PET Accuracy for the Detection of Prostate Cancer Validated by Histopathology. J Nucl Med. 2019;60:786–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang LL, Li WC, Xu Z, Jiang N, Zang SM, Xu LW. et al.(68)Ga-PSMA PET/CT targeted biopsy for the diagnosis of clinically significant prostate cancer compared with transrectal ultrasound guided biopsy: A prospective randomized single-centre study. Eur J Nucl Med Mol Imaging. 2021;48:483–92.

    Article  CAS  PubMed  Google Scholar 

  36. Raveenthiran S, Yaxley WJ, Franklin T, Coughlin G, Roberts M, Gianduzzo T, et al. Findings in 1,123 Men with Preoperative (68)Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography and Multiparametric Magnetic Resonance Imaging Compared to Totally Embedded Radical Prostatectomy Histopathology: Implications for the Diagnosis and Management of Prostate Cancer. J Urol. 2022;207:573–80.

    Article  CAS  PubMed  Google Scholar 

  37. Roberts MJ, Morton A, Donato P, Kyle S, Pattison DA, Thomas P, et al. 68Ga-PSMA PET/CT tumour intensity pre-operatively predicts adverse pathological outcomes and progression-free survival in localised prostate cancer. Eur J Nucl Med Mol imaging. 2021;48:477–82.

    Article  CAS  PubMed  Google Scholar 

  38. Roberts MJ, Morton A, Papa N, Franklin A, Raveenthiran S, Yaxley WJ, et al. Primary tumour PSMA intensity is an independent prognostic biomarker for biochemical recurrence-free survival following radical prostatectomy. Eur J Nucl Med Mol Imaging. 2022;49:3289–94.

  39. Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, 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, multicentre study. Lancet. 2020;395:1208–16.

    Article  CAS  PubMed  Google Scholar 

  40. Pienta KJ, Gorin MA, Rowe SP, Carroll PR, Pouliot F, Probst S, et al. A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with (18)F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol. 2021;206:52–61.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Jansen BHE, Bodar YJL, Zwezerijnen GJC, Meijer D, van der Voorn JP, Nieuwenhuijzen JA, et al. Pelvic lymph-node staging with (18)F-DCFPyL PET/CT prior to extended pelvic lymph-node dissection in primary prostate cancer - the SALT trial. Eur J Nucl Med Mol Imaging. 2021;48:509–20.

    Article  CAS  PubMed  Google Scholar 

  42. van Kalmthout LWM, van Melick HHE, Lavalaye J, Meijer RP, Kooistra A, de Klerk JMH, et al. Prospective Validation of Gallium-68 Prostate Specific Membrane Antigen-Positron Emission Tomography/Computerized Tomography for Primary Staging of Prostate Cancer. J Urol. 2020;203:537–45.

    Article  PubMed  Google Scholar 

  43. Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. JAMA Oncol. 2019;5:856–63.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Fendler WP, Weber M, Iravani A, Hofman MS, Calais J, Czernin J, et al. Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancerdisease burden by PSMA-PET in nmCRPC. Clin Cancer Res. 2019;25:7448–54.

    Article  CAS  PubMed  Google Scholar 

  45. Schöder H, Hope TA, Knopp M, Kelly WK, Michalski JM, Lerner SP, et al. Considerations on integrating prostate-specific membrane antigen positron emission tomography imaging into clinical prostate cancer trials by national clinical trials network cooperative groups. J Clin Oncol. 2022;40:1500–5.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Dietlein F, Kobe C, Hohberg M, Zlatopolskiy BD, Krapf P, Endepols H, et al. Intraindividual comparison of 18F-PSMA-1007 with renally excreted PSMA ligands for PSMA PET imaging in patients with relapsed prostate cancer. J Nucl Med. 2020;61:729–34.

    Article  CAS  PubMed  Google Scholar 

  47. Langbein T, Wang H, Rauscher I, Kroenke M, Knorr K, Wurzer A, et al. Utility of 18F-rhPSMA-7.3 PET for imaging of primary prostate cancer and preoperative efficacy in N-staging of unfavorable intermediate-to very high-risk patients validated by histopathology. J Nucl Med. 2022;63:1334–42.

    Article  CAS  PubMed  Google Scholar 

  48. Wurzer A, Di Carlo D, Schmidt A, Beck R, Eiber M, Schwaiger M, et al. Radiohybrid ligands: A novel tracer concept exemplified by 18F-or 68Ga-labeled rhPSMA inhibitors. J Nucl Med. 2020;61:735–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Calais J, Fendler WP, Eiber M, Gartmann J, Chu FI, Nickols NG, et al. Impact of (68)Ga-PSMA-11 PET/CT on the management of prostate cancer patients with biochemical recurrence. J Nucl Med. 2018;59:434–41.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wu SY, Boreta L, Shinohara K, Nguyen H, Gottschalk AR, Hsu I-C, et al. Impact of staging 68Ga-PSMA-11 PET scans on radiation treatment plansin patients with prostate cancer. Urology. 2019;125:154–62.

    Article  PubMed  Google Scholar 

  51. Morris MJ, Rowe SP, Gorin MA, Saperstein L, Pouliot F, Josephson D, et al. Diagnostic Performance of (18)F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study. Clin Cancer Res. 2021;27:3674–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Boreta L, Gadzinski AJ, Wu SY, Xu M, Greene K, Quanstrom K, et al. Location of Recurrence by Gallium-68 PSMA-11 PET scan in prostate cancer patients eligible for salvage radiotherapy. Urology. 2019;129:165–71.

    Article  PubMed  Google Scholar 

  53. Fendler WP, Ferdinandus J, Czernin J, Eiber M, Flavell RR, Behr SC, et al. Impact of (68)Ga-PSMA-11 PET on the Management of Recurrent Prostate Cancer in a Prospective Single-Arm Clinical Trial. J Nucl Med. 2020;61:1793–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. 68Ga-PSMA-11 PET/CT mapping of prostate cancer biochemical recurrence after radical prostatectomy in 270 patients with a PSA level of less than 1.0 ng/mL: impact on salvage radiotherapy planning. J Nucl Med. 2018;59:230–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Menard C, Delouya G, Wong P, Beauchemin M, Barkati M, Taussky D, et al. Randomized controlled trial of PSMA PET/CT guided intensification of radiotherapy for prostate cancer: Detection rates and impact on radiotherapeutic management. Int J Radiat Oncol, Biol, Phys. 2020;108:S18.

    Article  Google Scholar 

  56. Glicksman RM, Metser U, Vines D, Valliant J, Liu Z, Chung PW, et al. Curative-intent metastasis-directed therapies for molecularly-defined oligorecurrent prostate cancer: A prospective phase II trial testing the oligometastasis hypothesis. Eur Urol. 2021;80:374–82.

    Article  CAS  PubMed  Google Scholar 

  57. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36:446–53.

    Article  CAS  PubMed  Google Scholar 

  58. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): Five-year results of a randomized phase II trial. Am Soc Clin Oncol. 2020;38:6_suppl, 10–10.

  59. Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020;6:650–9.

  60. Deek MP, Van der Eecken K, Sutera P, Deek RA, Fonteyne V, Mendes AA, et al. Long-term outcomes and genetic predictors of response to metastasis-directed therapy versus observation in oligometastatic prostate cancer: analysis of STOMP and ORIOLE trials. J Clin Oncol. 2022;40:3377–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Narayan V, Gladney W, Plesa G, Vapiwala N, Carpenter E, Maude SL, et al. A phase I clinical trial of PSMA-directed/TGFβ-insensitive CAR-T cells in metastatic castration-resistant prostate cancer. Am Soc Clin Oncol. 2019;37:7_suppl, TPS347.

  62. Hofman MS, Sandhu S, Eu P, Price J, Akhurst T, Iravani A, et al. Lutetium-177 PSMA (LuPSMA) theranostics phase II trial: Efficacy, safety and QoL in patients with castrate-resistant prostate cancer treated with LuPSMA. Ann Oncol. 2017;28:v270.

  63. Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. [(177)Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397:797–804.

    Article  CAS  PubMed  Google Scholar 

  64. Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. TheraP: 177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel—Overall survival after median follow-up of 3 years (ANZUP 1603). Am Soc Clin Oncol. 2022;40:16_suppl:5000.

  65. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N. Engl J Med. 2021;385:1091–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Advanced Accelerator Applications. PLUVICTO. U.S. Food and Drug Administration.

  67. Weineisen M, Schottelius M, Simecek J, Baum RP, Yildiz A, Beykan S, et al. 68Ga-and 177Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med. 2015;56:1169–76.

    Article  CAS  PubMed  Google Scholar 

  68. Golan S, Frumer M, Zohar Y, Rosenbaum E, Yakimov M, Kedar D, et al. Neoadjuvant 177Lu-PSMA-I&T radionuclide treatment in patients with high-risk prostate cancer before radical prostatectomy: A single-arm Phase 1 trial. Eur Urol Oncol. 2022;7:S2588-9311(22)00165-1.

  69. Dhiantravan N, Violet J, Eapen R, Alghazo O, Scalzo M, Jackson P, et al. Clinical trial protocol for LuTectomy: A Single-arm study of the dosimetry, safety, and potential benefit of 177Lu-PSMA-617 prior to prostatectomy. Eur Urol Focus. 2021;7:234–7.

    Article  PubMed  Google Scholar 

  70. Violet J, Jackson P, Ferdinandus J, Sandhu S, Akhurst T, Iravani A, et al. Dosimetry of (177)Lu-PSMA-617 in metastatic castration-resistant prostate cancer: Correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes. J Nucl Med. 2019;60:517–23.

    Article  CAS  PubMed  Google Scholar 

  71. Buteau JP, Martin AJ, Emmett L, Iravani A, Sandhu S, Joshua AM, et al. PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu] Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): A biomarker analysis from a randomised, open-label, phase 2 trial. Lancet Oncol. 2022;23:1389–97.

    Article  CAS  PubMed  Google Scholar 

  72. Kuo P, Hesterman J, Rahbar K, Kendi AT, Wei XX, Fang B, et al. [68Ga] Ga-PSMA-11 PET baseline imaging as a prognostic tool for clinical outcomes to [177Lu] Lu-PSMA-617 in patients with mCRPC: A VISION substudy. Am Soc Clin Oncol. 2022;40:6_suppl, 5002.

  73. Calais J, Czernin J, Thin P, Gartmann J, Nguyen K, Armstrong WR, et al. Safety of PSMA-targeted molecular radioligand therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). J Nucl Med. 2021;62:1447–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gafita A, Calais J, Grogan TR, Hadaschik B, Wang H, Weber M, et al. Nomograms to predict outcomes after (177)Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: An international, multicentre, retrospective study. Lancet Oncol. 2021;22:1115–25.

    Article  CAS  PubMed  Google Scholar 

  75. Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375:443–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161:1215–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl J Med. 2015;373:1697–708.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Velho PI, Qazi F, Hassan S, Carducci MA, Denmeade SR, Markowski MC, et al. Efficacy of radium-223 in bone-metastatic castration-resistant prostate cancer with and without homologous repair gene defects. Eur Urol. 2019;76:170–6.

    Article  Google Scholar 

  79. Sonpavde G, Pond GR, Berry WR, de Wit R, Armstrong AJ, Eisenberger MA, et al. Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy. Urologic Oncol.: Seminars Original Investig. 2012;30:607–13.

  80. van der Doelen MJ, Velho PI, Slootbeek PH, Naga SP, Bormann M, van Helvert S, et al. Impact of DNA damage repair defects on response to radium-223 and overall survival in metastatic castration-resistant prostate cancer. Eur J Cancer. 2020;136:16–24.

    Article  PubMed  Google Scholar 

  81. Castro E, Mejorada RL, Saez M, De Giorgi U, Aragón I, Laorden NR, et al. Impact of germline mutations in homologous recombination (HR) genes on the response to Radium-223 for metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2019;30:v343–v4.

    Article  Google Scholar 

  82. Crumbaker M, Emmett L, Horvath LG, Joshua AM. Exceptional response to 177Lutetium prostate-specific membrane antigen in prostate cancer harboring DNA repair defects. JCO Precis Oncol. 2019;3:1–5.

    Article  PubMed  Google Scholar 

  83. Privé BM, Slootbeek PH, Laarhuis BI, Naga SP, van Der Doelen MJ, van Kalmthout LW, et al. Impact of DNA damage repair defects on response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer. Prostate cancer Prostatic Dis. 2022;25:71–78.

    Article  PubMed  Google Scholar 

  84. Sutera P, Deek MP, Van der Eecken K, Wyatt AW, Kishan AU, Molitoris JK, et al. Genomic biomarkers to guide precision radiotherapy in prostate cancer. Prostate. 2022;82:S73–S85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): A single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33.

    Article  CAS  PubMed  Google Scholar 

  86. Dosimetry for optimized, personalized radiopharmaceutical therapy. Seminars in Radiation Oncology, 2021.

  87. Dawson LA, Kavanagh BD, Paulino AC, Das SK, Miften M, Li XA, et al. Radiation-associated kidney injury. Int J Radiat Oncol* Biol* Phys. 2010;76:S108–S115.

    Article  PubMed  Google Scholar 

  88. Emami B, Lyman J, Brown A, Cola L, Goitein M, Munzenrider J, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol* Biol* Phys. 1991;21:109–22.

    Article  CAS  PubMed  Google Scholar 

  89. Bodei L, Kidd M, Paganelli G, Grana CM, Drozdov I, Cremonesi M, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015;42:5–19.

    Article  CAS  PubMed  Google Scholar 

  90. Bergsma H, Konijnenberg MW, van der Zwan WA, Kam BL, Teunissen JJ, Kooij PP, et al. Nephrotoxicity after PRRT with 177Lu-DOTA-octreotate. Eur J Nucl Med Mol Imaging. 2016;43:1802–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Schäfer H, Mayr S, Büttner-Herold M, Knorr K, Steinhelfer L, Böger CA, et al. Extensive 177Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy–like Picture. Eur Urol. 2022;7:S0302-2838(22)02401-0.

  92. Radiopharmaceuticals for bone metastases. Seminars in Radiation Oncology, 2021.

  93. Bayer HealthCare Pharmaceuticals. Xofigo. U.S. Food and Drug Administration.

  94. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  PubMed  Google Scholar 

  95. Spratt DE, Osborne JR, Zumsteg ZS, Rebeiz K, Leeman J, Rivera A, et al. Radium-223 outcomes after multiple lines of metastatic castration-resistant prostate cancer therapy in clinical practice: implication of pre-treatment spinal epidural disease. Prostate Cancer Prostatic Dis. 2016;19:271–6.

    Article  CAS  PubMed  Google Scholar 

  96. Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:408–19.

    Article  CAS  PubMed  Google Scholar 

  97. Gillessen S, Choudhury A, Rodriguez-Vida A, Nole F, Gallardo Diaz E, Roumeguere TA, et al. Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis. Wolters Kluwer Health, 2021.

  98. Morris MJ, Corey E, Guise TA, Gulley JL, Kevin Kelly W, Quinn DI, et al. Radium-223 mechanism of action: implications for use in treatment combinations. Nat Rev Urol. 2019;16:745–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Den RB, George D, Pieczonka C, McNamara M. Ra-223 treatment for bone metastases in castrate-resistant prostate cancer: Practical management issues for patient selection. Am J Clin Oncol. 2019;42:399–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Satapathy S, Sood A, Das CK, Mittal BR. Evolving role of 225Ac-PSMA radioligand therapy in metastatic castration-resistant prostate cancer—A systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2021;24:880–90.

    Article  CAS  PubMed  Google Scholar 

  101. Hammer S, Hagemann UB, Zitzmann-Kolbe S, Larsen A, Ellingsen C, Geraudie S, et al. Preclinical efficacy of a Psma-targeted thorium-227 conjugate (Psma-Ttc), a targeted alpha therapy for prostate cancerpreclinical efficacy of Psma-Ttc in prostate cancer. Clin Cancer Res. 2020;26:1985–96.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    Angela Y. Jia

  2. Department of Radiation Oncology, Johns Hopkins University, Baltimore, MD, USA

    Ana P. Kiess

  3. Department of Nuclear Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    Qiubai Li

  4. University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA

    Emmanuel S. Antonarakis

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  1. Angela Y. Jia
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  2. Ana P. Kiess
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  3. Qiubai Li
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  4. Emmanuel S. Antonarakis
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Contributions

AYJ – study design, draft, manuscript preparation and revision; APK – study design, manuscript revision; QL – manuscript revision; ESA – conceptualization, supervision, study design, manuscript revision. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Angela Y. Jia.

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Competing interests

AYJ was a paid consultant for Myovant. A.P.K has served as an unpaid consultant for Novartis and has received research support (to institution) from Merck, Bayer, Novartis and POINT. ESA has served as a paid consultant for Janssen, Astellas, Sanofi, Bayer, Bristol Myers Squibb, Amgen, Constellation, Blue Earth, Exact Sciences, Invitae, Curium, Pfizer, Merck, AstraZeneca, Clovis, and Eli Lilly; and has received research support (to his institution) from Janssen, Johnson & Johnson, Sanofi, Bristol Myers Squibb, Pfizer, AstraZeneca, Novartis, Curium, Constellation, Celgene, Merck, Bayer, Clovis, and Orion.

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Jia, A.Y., Kiess, A.P., Li, Q. et al. Radiotheranostics in advanced prostate cancer: Current and future directions. Prostate Cancer Prostatic Dis 27, 11–21 (2024). https://doi.org/10.1038/s41391-023-00670-6

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