Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Integrating systemic therapy and metastasis-directed therapy in oligometastatic hormone-sensitive prostate cancer

Prostate Cancer and Prostatic Diseases (2025)Cite this article

Subjects

Abstract

Background

Oligometastatic hormone-sensitive prostate cancer (omHSPC) represents a favorable and potentially curable disease state in which metastasis-directed therapy (MDT) improves outcomes. The combination of MDT and systemic treatment is the next frontier of omHSPC.

Objective

To review and synthesize current evidence from prospective trials evaluating MDT alone or combined with systemic therapy in synchronous and metachronous omHSPC, and to highlight the evolving role of advanced imaging, genomics, and ongoing efforts in refining treatment strategies.

Methods

This review synthesizes data from prospective trials, meta-analyses, and ongoing studies assessing MDT in omHSPC. Key trials include STOMP, ORIOLE, EXTEND, RADIOSA, and the X-MET meta-analysis, with emphasis on clinical outcomes and biomarkers

Results

In metachronous omHSPC, STOMP and ORIOLE phase II trials demonstrated that MDT significantly improves progression-free survival (PFS) and delays androgen deprivation therapy (ADT) compared to observation. The EXTEND and RADIOSA trials suggest combining MDT with short-term ADT further improves outcomes. The X-MET meta-analysis confirmed benefits in PFS, radiographic PFS, and castration-resistance-free survival with MDT. No randomized trial has yet evaluated MDT with current standard of care ADT + androgen receptor pathway inhibitor (ARPI) therapy, though EXTEND did include a limited subset of patients receiving ARPI. Advanced imaging, especially PSMA-PET, is transforming MDT planning by enabling more accurate lesion detection than conventional imaging. In synchronous omHSPC, the role of MDT remains under investigation in ongoing trials such as TERPS, STAMPEDE2 and START-MET.

Conclusions

MDT offers clinical benefit in metachronous omHSPC, particularly when combined with systemic therapy. Advanced imaging and genomic profiling are critical tools for refining patient selection. Most data stem from phase II studies without ADT + ARPI control groups; larger randomized trials are needed to define the role of MDT in standard practice and optimize personalized care strategies.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Hall ME, Huelster HL, Luckenbaugh AN, Laviana AA, Keegan KA, Klaassen Z, et al. Metastatic hormone-sensitive prostate cancer: current perspective on the evolving therapeutic landscape. Onco Targets Ther. 2020;13:3571–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37:2974–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.

    Article  CAS  PubMed  Google Scholar 

  5. Saad F, Vjaters E, Shore N, Olmos D, Xing N, Pereira de Santana Gomes AJ, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024;42:4271–81.

    Article  CAS  PubMed  Google Scholar 

  6. Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389:1453–65.

    Article  CAS  PubMed  Google Scholar 

  7. Hussain M, Fizazi K, Shore ND, Heidegger I, Smith MR, Tombal B, et al. Metastatic hormone-sensitive prostate cancer and combination treatment outcomes: a review. JAMA Oncol. 2024;10:807–20.

    Article  PubMed  Google Scholar 

  8. Ryan CJ, Ke X, Lafeuille MH, Romdhani H, Kinkead F, Lefebvre P, et al. Management of patients with metastatic castration-sensitive prostate cancer in the real-world setting in the United States. J Urol. 2021;206:1420–9.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Grisay G, Lavaud P, Fizazi K. Current systemic therapy in men with metastatic castration-sensitive prostate cancer. Curr Oncol Rep. 2024;26:488–95.

    Article  CAS  PubMed  Google Scholar 

  10. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13:8–10.

    Article  CAS  PubMed  Google Scholar 

  11. Lehrer EJ, Singh R, Wang M, Chinchilli VM, Trifiletti DM, Ost P, et al. Safety and survival rates associated with ablative stereotactic radiotherapy for patients with oligometastatic cancer: a systematic review and meta-analysis. JAMA Oncol. 2021;7:92–106.

    Article  PubMed  Google Scholar 

  12. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393:2051–8.

    Article  PubMed  Google Scholar 

  13. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, Bruycker AD, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): five-year results of a randomized phase II trial. J Clin Oncol. 2020;38:10.

    Article  Google Scholar 

  14. Gomez DR, Tang C, Zhang J, Blumenschein GR Jr., Hernandez M, Lee JJ, et al. Local consolidative therapy vs. maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol. 2019;37:1558–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Palma DA, Olson R, Harrow S, Correa RJM, Schneiders F, Haasbeek CJA, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 4–10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019;19:816.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol. 2018;4:e173501.

    Article  PubMed  Google Scholar 

  17. Ruers T, Van Coevorden F, Punt CJ, Pierie JE, Borel-Rinkes I, Ledermann JA, et al. Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. J Natl Cancer Inst. 2017;109:djx015.

  18. Sutera P, Phillips RM, Deek M, Ozyigit G, Onal C, Tran PT. The promise of metastasis-directed therapy for oligometastatic prostate cancer: going beneath the surface with molecular Imaging. J Nucl Med. 2022;63:339–41.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fossati N, Scarcella S, Gandaglia G, Suardi N, Robesti D, Boeri L, et al. Underestimation of positron emission tomography/computerized tomography in assessing tumor burden in prostate cancer nodal recurrence: head-to-head comparison of (68)Ga-PSMA and (11)C-choline in a large, multi-institutional series of extended salvage lymph node dissections. J Urol. 2020;204:296–302.

    Article  PubMed  Google Scholar 

  20. Gore EM, Hu C, Sun AY, Grimm DF, Ramalingam SS, Dunlap NE, et al. Randomized phase II study comparing prophylactic cranial irradiation alone to prophylactic cranial irradiation and consolidative extracranial irradiation for extensive-disease small cell lung cancer (ED SCLC): NRG Oncology RTOG 0937. J Thorac Oncol. 2017;12:1561–70.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chmura SJ, Winter KA, Woodward WA, Borges VF, Salama JK, Al-Hallaq HA, et al. NRG-BR002: a phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). J Clin Oncol. 2022;40:1007–1007

  22. Reddy JP, Sherry AD, Fellman B, Liu S, Bathala T, Haymaker C, et al. Adding metastasis-directed therapy to standard-of-care systemic therapy for oligometastatic breast cancer (EXTEND): a multicenter, randomized phase 2 trial. Int J Radiat Oncol Biol Phys. 2025;121:885–93.

    Article  PubMed  Google Scholar 

  23. 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 

  24. Sutera P, Van Der Eecken K, Kishan AU, Hamid A, Grist E, Attard G, et al. Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics. Prostate Cancer Prostatic Dis. 2022;25:713–19.

  25. Sutera P, Song Y, Shetty AC, English K, Van der Eecken K, Guler OC, et al. Genomic determinants associated with modes of progression and patterns of failure in metachronous oligometastatic castration-sensitive prostate cancer. Eur Urol Oncol. 2025;8:111–8.

    Article  PubMed  Google Scholar 

  26. Deek MP, Van der Eecken K, Phillips R, Parikh NR, Isaacsson Velho P, Lotan TL, et al. The mutational landscape of metastatic castration-sensitive prostate cancer: the spectrum theory revisited. Eur Urol. 2021;80:632–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hamid AA, Gray KP, Shaw G, MacConaill LE, Evan C, Bernard B, et al. Compound genomic alterations of TP53, PTEN, and RB1 tumor suppressors in localized and metastatic prostate cancer. Eur Urol. 2019;76:89–97.

    Article  CAS  PubMed  Google Scholar 

  28. Gillespie EF, Yang JC, Mathis NJ, Marine CB, White C, Zhang Z, et al. Prophylactic radiation therapy versus standard of care for patients with high-risk asymptomatic bone metastases: a multicenter, randomized phase II clinical trial. J Clin Oncol. 2024;42:38–46.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wang JH, Sherry AD, Bazyar S, Sutera P, Radwan N, Phillips RM, et al. Outcomes of radium-223 and stereotactic ablative radiotherapy versus stereotactic ablative radiotherapy for oligometastatic prostate cancers: The RAVENS phase II randomized trial. J Clin Oncol. 2025;43:2059–68.

    Article  PubMed  Google Scholar 

  31. Nabrinsky E, Macklis J, Bitran J. A review of the abscopal effect in the era of immunotherapy. Cureus. 2022;14:e29620.

    PubMed  PubMed Central  Google Scholar 

  32. Tang C, Sherry AD, Haymaker C, Bathala T, Liu S, Fellman B, et al. Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer: the EXTEND phase 2 randomized clinical trial. JAMA Oncol. 2023;9:825–34.

  33. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36:1080–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.

    Article  CAS  PubMed  Google Scholar 

  36. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381:121–31.

    Article  CAS  PubMed  Google Scholar 

  38. Armstrong AJ, Petrylak DP, Shore ND, Szmulewitz RZ, Holzbeierlein J, Villers A, et al. ARCHES: 5-year follow-up overall survival (OS) analysis of enzalutamide (ENZA) plus androgen-deprivation therapy (ADT) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). J Clin Oncol. 2025;43:5005.

    Article  Google Scholar 

  39. Hoyle AP, Ali A, James ND, Cook A, Parker CC, de Bono JS, et al. Abiraterone in “high-“ and “low-risk” metastatic hormone-sensitive prostate cancer. Eur Urol. 2019;76:719–28.

    Article  CAS  PubMed  Google Scholar 

  40. Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Overall survival of men with metachronous metastatic hormone-sensitive prostate cancer treated with enzalutamide and androgen deprivation therapy. Eur Urol. 2021;80:275–9.

    Article  CAS  PubMed  Google Scholar 

  41. Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, et al. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24:323–34.

    Article  CAS  PubMed  Google Scholar 

  42. Armstrong AJ, Iguchi T, Azad AA, Villers A, Alekseev B, Petrylak DP, et al. The Efficacy of enzalutamide plus androgen deprivation therapy in oligometastatic hormone-sensitive prostate cancer: a post hoc analysis of ARCHES. Eur Urol. 2023;84:229–41.

    Article  CAS  PubMed  Google Scholar 

  43. Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Flechon A, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. 2022;399:1695–707.

    Article  CAS  PubMed  Google Scholar 

  44. Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386:1132–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Gillessen S, Turco F, Davis ID, Efstathiou JA, Fizazi K, James ND, et al. Management of patients with advanced prostate cancer. Report from the 2024 advanced prostate cancer consensus conference (APCCC). Eur Urol. 2025;87:157–216.

    Article  PubMed  Google Scholar 

  46. Sutera PA, Shetty AC, Hakansson A, Van der Eecken K, Song Y, Liu Y, et al. Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer. Ann Oncol. 2023;34:605–14.

    Article  CAS  PubMed  Google Scholar 

  47. National Comprehensive Cancer Network. 2025. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Prostate Cancer, Version 2.2025. Accessed September 7, 2025.

  48. Ingrosso G, Lancia A, Bardoscia L, Becherini C, Bottero M, Bertini N, et al. Current diagnostic and therapeutic options in de novo low-volume metastatic hormone-sensitive prostate cancer. Expert Rev Anticancer Ther. 2025;25:741–54.

    Article  CAS  PubMed  Google Scholar 

  49. Boeve LMS, Hulshof M, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD trial. Eur Urol. 2019;75:410–8.

    Article  PubMed  Google Scholar 

  50. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Parker CC, James ND, Brawley CD, Clarke NW, Ali A, Amos CL, et al. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: long-term results from the STAMPEDE randomised controlled trial. PLoS Med. 2022;19:e1003998.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Burdett S, Boeve LM, Ingleby FC, Fisher DJ, Rydzewska LH, Vale CL, et al. Prostate radiotherapy for metastatic hormone-sensitive prostate cancer: a STOPCAP systematic review and meta-analysis. Eur Urol. 2019;76:115–24.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bossi A, Foulon S, Maldonado X, Sargos P, MacDermott R, Kelly P, et al. Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. 2024;404:2065–76.

    Article  PubMed  Google Scholar 

  54. EAU Guidelines. Edn. presented at the EAU Annual Congress Madrid 2025. ISBN 978-94-92671-29-5.

  55. Bryce AH, Agarwal N, Beltran H, Hussain MH, Sartor O, Shore N, et al. Implementing evidence-based strategies for men with biochemically recurrent and advanced prostate cancer: consensus recommendations from the US prostate cancer conference 2024. Cancer. 2025;131:e35612.

    Article  PubMed  Google Scholar 

  56. Sutera P, Shetty AC, Song Y, Hodges T, Hoang T, Rana Z, et al. Identification of a predictive genomic biomarker for prostate-directed therapy in synchronous low-volume metastatic castration-sensitive prostate cancer. Eur Urol Oncol. 2024;7:241–7.

    Article  PubMed  Google Scholar 

  57. Reyes DK, Trock BJ, Tran PT, Pavlovich CP, Deville C, Allaf ME, et al. Interim analysis of companion, prospective, phase II, clinical trials assessing the efficacy and safety of multi-modal total eradication therapy in men with synchronous oligometastatic prostate cancer. Med Oncol. 2022;39:63.

    Article  CAS  PubMed  Google Scholar 

  58. Reyes DK, Rowe SP, Schaeffer EM, Allaf ME, Ross AE, Pavlovich CP, et al. Multidisciplinary total eradication therapy (TET) in men with newly diagnosed oligometastatic prostate cancer. Med Oncol. 2020;37:60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nickols NG, Tsai S, Kane N, Tran S, Ghayouri L, Diaz-Perez S, et al. Systemic and tumor-directed therapy for oligometastatic prostate cancer: the SOLAR phase 2 trial in de novo oligometastatic prostate cancer. Eur Urol. 2024;86:190–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Chang Y, Zhao X, Xiao Y, Yan S, Xu W, Wang Y, et al. Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial. Front Med. 2023;17:231–9.

    Article  PubMed  Google Scholar 

  61. Reverberi C, Massaro M, Osti MF, Anzellini D, Marinelli L, Montalto A, et al. Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer. Sci Rep. 2020;10:17471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hao C, Ladbury C, Lyou Y, Manoukian S, Ruel C, Frankel P, et al. Long-term outcomes of patients on a phase II prospective trial of oligometastatic hormone-sensitive prostate cancer treated with androgen deprivation and external beam radiation. Int J Radiat Oncol Biol Phys. 2022;114:705–10.

    Article  PubMed  Google Scholar 

  63. Deek MP, Sutera P, Jing Y, Gao R, Rothman E, Day H, et al. Multi-institutional analysis of metastasis-directed therapy with or without androgen deprivation therapy in oligometastatic castration-sensitive prostate cancer. Eur Urol Oncol. 2024;7:1403–10.

  64. Sánchez-Iglesias ÁL, Morillo-Macías V, Santafé-Jiménez A, Ferrer-Albiach C. Bone-only oligometastatic prostate cancer: can SABR improve outcomes? A single-center experience. Radiat Oncol J. 2022;40:192–9.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Rogowski P, Trapp C, von Bestenbostel R, Schmidt-Hegemann NS, Shi R, Ilhan H, et al. Outcomes of metastasis-directed therapy of bone oligometastatic prostate cancer. Radiat Oncol. 2021;16:125.

    Article  PubMed  PubMed Central  Google Scholar 

  66. 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 

  67. 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.

  68. Wang JH, Sherry AD, Bazyar S, Sutera P, Radwan N, Phillips RM, et al. Outcomes of radium-223 and stereotactic ablative radiotherapy versus stereotactic ablative radiotherapy for oligometastatic prostate cancers: the RAVENS phase II randomized trial. J Clin Oncol. 2025;43:2059–68

  69. Sherry AD, Haymaker CL, Fellman BM, Bathala TK, Medina-Rosales MN, Liu S, et al. Metastasis-directed therapy (MDT) plus androgen deprivation therapy (ADT) for oligometastatic prostate cancer (omPC): primary results of the EXTEND continuous ADT (cADT) basket plus combined analysis with the updated intermittent ADT (iADT) basket and immune correlatives. J Clin Oncol. 2025;43:140–140

  70. Marvaso G, Corrao G, Zaffaroni M, Vincini MG, Lorubbio C, Gandini S, et al. ADT with SBRT versus SBRT alone for hormone-sensitive oligorecurrent prostate cancer (RADIOSA): a randomised, open-label, phase 2 clinical trial. Lancet Oncol. 2025;26:300–11.

    Article  CAS  PubMed  Google Scholar 

  71. Ost P, Siva S, Brabrand S, Dirix P, Liefhooghe N, Otte FX, et al. Salvage metastasis-directed therapy versus elective nodal radiotherapy for oligorecurrent nodal prostate cancer metastases (PEACE V-STORM): a phase 2, open-label, randomised controlled trial. Lancet Oncol. 2025;26:695–706.

    Article  CAS  PubMed  Google Scholar 

  72. Francolini G, Allegra AG, Detti B, Cataldo VD, Caini S, Bruni A, et al. Stereotactic body radiation therapy and abiraterone acetate for patients affected by oligometastatic castrate-resistant prostate cancer: a randomized phase II trial (ARTO). J Clin Oncol. 2023;41:5561–8.

    Article  CAS  PubMed  Google Scholar 

  73. Niazi T, Saad F, Koul R, Thibault I, Chung PWM, Wakil G, et al. Metastases-directed therapy in addition to standard systemic therapy in oligometastatic castration resistant prostate cancer: a randomized phase II trial (GROUQ-PCS 9). J Clin Oncol. 2025;43:22.

    Article  Google Scholar 

  74. Tang C, Sherry AD, Hwang H, Francolini G, Livi L, Tran PT, et al. World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): an analysis from the X-MET collaboration. J Clin Oncol. 2025;43:15.

    Article  Google Scholar 

  75. Tang C, Sherry AD, Hwang H, Francolini G, Livi L, Tran PT, et al. World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): an analysis from the X-MET collaboration. J Clin Oncol. 2025;43:15–15.

  76. Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, et al. Salvage therapy for prostate cancer: AUA/ASTRO/SUO guideline part III: salvage therapy after radiotherapy or focal therapy, pelvic nodal recurrence and oligometastasis, and future directions. J Urol. 2024;211:526–32.

    Article  PubMed  Google Scholar 

  77. Zilli T, Achard V, Dal Pra A, Schmidt-Hegemann N, Jereczek-Fossa BA, Lancia A, et al. Recommendations for radiation therapy in oligometastatic prostate cancer: an ESTRO-ACROP Delphi consensus. Radiother Oncol. 2022;176:199–207.

    Article  PubMed  Google Scholar 

  78. 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 

  79. 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;20:1286–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Jani AB, Schreibmann E, Goyal S, Halkar R, Hershatter B, Rossi PJ, et al. (18)F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial. Lancet. 2021;397:1895–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Deijen CL, Vrijenhoek GL, Schaake EE, Vogel WV, Moonen LMF, Pos FJ, et al. PSMA-11-PET/CT versus choline-PET/CT to guide stereotactic ablative radiotherapy for androgen deprivation therapy deferral in patients with oligometastatic prostate cancer. Clin Transl Radiat Oncol. 2021;30:1–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Mazzola R, Francolini G, Triggiani L, Napoli G, Cuccia F, Nicosia L, et al. Metastasis-directed therapy (SBRT) guided by PET-CT (18)F-CHOLINE versus PET-CT (68)Ga-PSMA in castration-sensitive oligorecurrent prostate cancer: a comparative analysis of effectiveness. Clin Genitourin Cancer. 2021;19:230–6.

    Article  PubMed  Google Scholar 

  83. Wang R, Shen G, Huang M, Tian R. The diagnostic role of (18)F-choline, (18)F-fluciclovine and (18)F-PSMA PET/CT in the detection of prostate cancer with biochemical recurrence: a meta-analysis. Front Oncol. 2021;11:684629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sutera P, Song Y, Van der Eecken K, Shetty AC, English K, Hodges T, et al. Clinical and genomic differences between advanced molecular imaging-detected and conventional imaging-detected metachronous oligometastatic castration-sensitive prostate cancer. Eur Urol. 2023;84:531–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Holzgreve A, Armstrong WR, Clark KJ, Benz MR, Smith CP, Djaileb L, et al. PSMA-PET/CT findings in patients with high-risk biochemically recurrent prostate cancer with no metastatic disease by conventional imaging. JAMA Netw Open. 2025;8:e2452971.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Rana ZH, Helie N, Eggleston C, Baker K, Molitoris JK, Ferris MJ, et al. Phase 2 randomized total eradication of metastatic lesions following definitive radiation to the prostate in de novo oligometastatic prostate cancer (TERPs) trial. J Clin Oncol. 2023;41:TPS275–TPS.

    Article  Google Scholar 

  87. Abdel-Aty H, O’Shea L, Amos C, Brown LC, Grist E, Attard G, et al. The STAMPEDE2 trial: a site survey of current patterns of care, access to imaging and treatment of metastatic prostate cancer. Clin Oncol (R Coll Radiol). 2023;35:e628–e35.

    Article  CAS  PubMed  Google Scholar 

  88. Bsteh D, Buckley J, Mitchell S, Ostrow D, Parmentier J-H, Jahan S, et al. Combined genomic profiling of cell-free DNA (cfDNA) and circulating tumor cell DNA (ctcDNA) in S1802, a prospective phase 3 trial for metastatic prostate cancer (mHSPC). J Clin Oncol. 2025;43:e17111–e.

    Article  Google Scholar 

  89. Koontz BF, Karrison T, Pisansky TM, Posadas EM, Ballas LK, Berlin A, et al. NRG-GU011: a phase II double-blinded, placebo-controlled trial of prostate oligometastatic radiotherapy with or without androgen deprivation therapy in oligometastatic prostate cancer (NRG PROMETHEAN). J Clin Oncol. 2023;41:TPS283–TPS.

    Article  Google Scholar 

  90. Francolini G, Cataldo VD, Garlatti P, Caini S, Bruni A, Simoni N, et al. PERSIAN trial: early results from a randomized phase II trial testing apalutamide and stereotactic body radiation therapy for low-burden, metastatic, hormone-sensitive prostate cancer. J Clin Oncol. 2025;43:160.

    Article  Google Scholar 

  91. Deek MP, Shi X, Radwan N, Eggleston C, Baker K, Rana ZH, et al. Phase 2 randomized study of high-risk metachronous oligometastatic prostate cancer with high-risk mutations treated with metastasis-directed therapy and niraparib/abiraterone acetate plus prednisone (KNIGHTS) trial. J Clin Oncol. 2025;43:TPS283–TPS.

    Article  Google Scholar 

  92. Sartor AO, Kiess AP, Feng FY, Hadaschik BA, Herrmann K, Iagaru A, et al. PSMA-delay castration (DC): an open-label, multicenter, randomized phase 3 study of [177Lu]Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer (OMPC). J Clin Oncol. 2025;43:TPS5127–TPS.

    Article  Google Scholar 

  93. Sherry AD, et al. Peripheral T-cell priming and micrometastatic disease control with metastasis-directed therapy: multidimensional immunogenomic profiling of oligometastatic prostate cancer in the EXTEND trial. Int J Radiat Oncol Biol Phys. 2023;117:S33–4.

Download references

Acknowledgements

PTT is funded by an anonymous donor, Movember Foundation-Distinguished Gentlemen’s Ride-Prostate Cancer Foundation, and the National Institutes of Health and National Cancer Institute (1R01CA271540 and U54CA273956) and Department of Defense (W81XWH-21-1-0296). XS is supported by the NIH/NCI T32 Training Grant in Cancer Biology (T32CA154274). PS is supported by the Prostate Cancer Foundation. AJA is funded by NIH 5R01CA233585–05.

Author information

Authors and Affiliations

  1. Department of Hematology Oncology, University of Maryland Medical Center, Baltimore, MD, USA

    Xiaolei Shi

  2. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jarey H. Wang

  3. Department of Urology, MD Anderson, Houston, TX, USA

    Brian F. Chapin

  4. Department of Genitourinary Medical Oncology, University of Texas MD Anderson, Houston, TX, USA

    Ana Aparicio & Sumit K. Subudhi

  5. Department of Radiation Oncology, University of Maryland, Baltimore, MD, USA

    Phuoc T. Tran

  6. Department of Genitourinary Radiation Oncology, University of Texas MD Anderson, Houston, TX, USA

    Ryan J. Park & Chad Tang

  7. Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA

    Matthew P. Deek

  8. Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, USA

    Hong Zhang, Kevin C. Bylund, Micheal Cummings & Philip Sutera

  9. Duke Cancer Institute Center for Prostate and Urologic Cancers, Departments of Medicine, Surgery, Pharmacology and Cancer Biology, Duke University, Durham, NC, USA

    Andrew J. Armstrong

Authors
  1. Xiaolei Shi
    View author publications

    Search author on:PubMed Google Scholar

  2. Jarey H. Wang
    View author publications

    Search author on:PubMed Google Scholar

  3. Brian F. Chapin
    View author publications

    Search author on:PubMed Google Scholar

  4. Ana Aparicio
    View author publications

    Search author on:PubMed Google Scholar

  5. Sumit K. Subudhi
    View author publications

    Search author on:PubMed Google Scholar

  6. Phuoc T. Tran
    View author publications

    Search author on:PubMed Google Scholar

  7. Ryan J. Park
    View author publications

    Search author on:PubMed Google Scholar

  8. Matthew P. Deek
    View author publications

    Search author on:PubMed Google Scholar

  9. Hong Zhang
    View author publications

    Search author on:PubMed Google Scholar

  10. Kevin C. Bylund
    View author publications

    Search author on:PubMed Google Scholar

  11. Micheal Cummings
    View author publications

    Search author on:PubMed Google Scholar

  12. Andrew J. Armstrong
    View author publications

    Search author on:PubMed Google Scholar

  13. Chad Tang
    View author publications

    Search author on:PubMed Google Scholar

  14. Philip Sutera
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Conceptualization: XS, PS, and PT. Literature search: XS and PS. Drafting of manuscript: XS and PS. Critical review of manuscript: XS, JHW, BC, AA, SKS, PT, RJP, MPD, HZ, KB, MC, AJA, CT, and PS.

Corresponding author

Correspondence to Philip Sutera.

Ethics declarations

Competing interests

PTT disclosures: Consulting/advisory role and Patent with Natsar Pharmaceuticals (Compounds and methods of use in ablative radiotherapy. Patent filed 3/9/2012. PCT/US2012/028475. PCT/WO/2012/122471) licensed with royalties to Natsar Pharmaceuticals. Consulting/advisory role and research funding with Astellas Pharma, Reflexion Medical, Bayer Health. Consulting/advisory role with Bayer, Regeneron, Pfizer, Janssen, AstraZeneca, Lantheus, and Novartis. SKS reports grants from AstraZeneca, Johnson and Johnson, and Regeneron; consulting/advisory roles for Apricity Health LLC, Arcus Biosciences, Baird, Bayer, Boxer Capital, Breaking Data, Bristol Myers Squibb, Dava Oncology, Dendreon, Hervolution, Johnson & Johnson, Kahr Medical Ltd, Kiniksa Pharmaceuticals, Macrogenics, Merck, NoeticInsight, Novartis, OncLive (owned by Intellisphere, LLC), Pfizer, Portage, Regeneron, Rondo Therapeutics, The Clinical Comms Group, and Vicero. CT disclosure: drug support for trial from Merck, drug and financial support from Noxopharm; Assay and financial support from Myriad Genetics; Royalties and licenses with Wolter Kluwer, Stanford Office of Technology and Licensing; Participation on a data safety monitoring board or advisory board with Bayer, Lantheus, Telix, Molli Surgical, Siemen Healthineer; other support from Elekta, Vision RT. AJA disclosure: Research support (to Duke) from the NIH/NCI, PCF/Movember, DOD, Astellas, Pfizer, Bayer, Janssen, BMS, AstraZeneca, Merck, Pathos, Amgen, Novartis; Consulting or advising relationships with Astellas, Pfizer, Bayer, Janssen, BMS, AstraZeneca, Merck, Forma, Celgene, Myovant, Exelixis, GoodRx, Novartis, Medscape, MJH, Z Alpha, Telix.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, X., Wang, J.H., Chapin, B.F. et al. Integrating systemic therapy and metastasis-directed therapy in oligometastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis (2025). https://doi.org/10.1038/s41391-025-01041-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41391-025-01041-z

Search

Advanced search

Quick links