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What is the ideal combination therapy in de novo, oligometastatic, castration-sensitive prostate cancer?

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Abstract

Purpose

To review current evidence regarding the management of de novo, oligometastatic, castration-sensitive prostate cancer (PCa).

Methods

A literature search was conducted on PubMed/Medline and a narrative synthesis of the evidence was performed in August 2022.

Results

Oligometastatic disease is an intermediate state between localized and aggressive metastatic PCa defined by ≤ 3–5 metastatic lesions, although this definition remains controversial. Conventional imaging has limited accuracy in detecting metastatic lesions, and the implementation of molecular imaging could pave the way for a more personalized treatment strategy. However, oncological data supporting this strategy are needed. Radiotherapy to the primary tumor should be considered standard treatment for oligometastatic PCa (omPCa). However, it remains to be seen whether local therapy still has an additional survival benefit in patients with de novo omPCa when treated with the most modern systemic therapy combinations. There is insufficient evidence to recommend cytoreductive radical prostatectomy as local therapy; or stereotactic body radiotherapy as metastasis-directed therapy in patients with omPCa. Current data support the use of intensified systemic therapy with androgen deprivation therapy (ADT) and next-generation hormone therapies (NHT) for patients with de novo omPCa. Docetaxel has not demonstrated benefit in low volume disease. There are insufficient data to support the use of triple therapy (i.e., ADT + NHT + Docetaxel) in low volume disease.

Conclusion

The present review discusses current data in de novo, omPCa regarding its definition, the increasing role of molecular imaging, the place of local and metastasis-directed therapies, and the intensification of systemic therapies.

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Data are available upon request to the corresponding author.

Code availability

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References

  1. Hellman S, Weichselbaum RR (1995) Oligometastases. J Clin Oncol 13(1):8–10

    Article  CAS  PubMed  Google Scholar 

  2. Ahmed KA, Barney BM, Davis BJ, Park SS, Kwon ED, Olivier KR (2013) Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer. Front Oncol 2:215

    Article  PubMed  PubMed Central  Google Scholar 

  3. Minamimoto R, Loening A, Jamali M et al (2015) Prospective comparison of 99mTc-MDP scintigraphy, combined 18F-NaF and 18F-FDG PET/CT, and whole-body MRI in patients with breast and prostate cancer. J Nucl Med 56(12):1862–1868

    Article  PubMed  Google Scholar 

  4. Hövels AM, Heesakkers RA, Adang EM et al (2008) The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 63(4):387–395

    Article  PubMed  Google Scholar 

  5. Harisinghani MG, Barentsz J, Hahn PF et al (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348(25):2491–2499

    Article  PubMed  Google Scholar 

  6. Gillessen S, Omlin A, Attard G et al (2015) Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann Oncol 26(8):1589–1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Umbehr MH, Müntener M, Hany T, Sulser T, Bachmann LM (2013) The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol 64(1):106–117

    Article  PubMed  Google Scholar 

  8. Hofman MS, Lawrentschuk N, Francis RJ et al (2020) 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 395(10231):1208–1216

    Article  CAS  PubMed  Google Scholar 

  9. Garcia JR, Jorcano S, Soler M et al (2015) 11C-Choline PET/CT in the primary diagnosis of prostate cancer: impact on treatment planning. Q J Nucl Med Mol Imaging 59:342–350

    CAS  PubMed  Google Scholar 

  10. Garcia JR, Compte A, Galan C et al (2021) 18F-choline PET/MRI on initial staging of prostate cancer. Impact on therapy approach. Rev Esp Med Nucl Imagen Mol (Engl Ed) 40:72–81

    CAS  PubMed  Google Scholar 

  11. Kesler M, Kerzhner K, Druckmann I et al (2022) Staging 68 Ga-PSMA PET/CT in 963 consecutive patients with newly diagnosed prostate cancer: incidence and characterization of skeletal involvement. Eur J Nucl Med Mol Imaging 49:2077–2085

    Article  CAS  PubMed  Google Scholar 

  12. Gupta SK, Watson T, Denham J et al (2017) Prostate-specific membrane antigen positron emission tomography-computed tomography for prostate cancer: distribution of disease and implications for radiation therapy planning. Int J Radiat Oncol Biol Phys 99:701–709

    Article  PubMed  Google Scholar 

  13. Erdoğan M, Özkan EE, Öztürk SA, Yıldız M, Şengül SS (2020) The role of Ga-68 PSMA PET/CT scan on differentiating of oligometastatic and high risk prostate cancer. Mol Imaging Radionucl Ther 29:98–104

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hofman MS, Lawrentschuk N, Francis RJ et al (2020) 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. The Lancet 395:1208–1216

    Article  CAS  Google Scholar 

  15. Boevé LMS, Hulshof MCCM, Vis AN et al (2019) 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 75(3):410–418

    Article  PubMed  Google Scholar 

  16. Parker CC, James ND, Brawley CD et al (2018) Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet 392(10162):2353–2366

    Article  PubMed  PubMed Central  Google Scholar 

  17. Parker CC, James ND, Brawley CD et al (2022) 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 19(6):e1003998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Burdett S, Boevé LM, Ingleby FC et al (2019) Prostate radiotherapy for metastatic hormone-sensitive prostate cancer: a STOPCAP systematic review and meta-analysis. Eur Urol 76(1):115–124

    Article  PubMed  PubMed Central  Google Scholar 

  19. Culp SH, Schellhammer PF, Williams MB (2014) Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol 65(6):1058–1066

    Article  PubMed  Google Scholar 

  20. Sooriakumaran P, Karnes J, Stief C et al (2016) A multi-institutional analysis of perioperative outcomes in 106 men who underwent radical prostatectomy for distant metastatic prostate cancer at presentation. Eur Urol 69(5):788–794

    Article  PubMed  Google Scholar 

  21. Lumen N, De Bleser E, Buelens S et al (2021) The role of cytoreductive radical prostatectomy in the treatment of newly diagnosed low-volume metastatic prostate cancer. Results from the local treatment of metastatic prostate cancer (LoMP) registry. Eur Urol Open Sci 29:68–76

    Article  PubMed  PubMed Central  Google Scholar 

  22. Dai B, Zhang S, Wan FN et al (2022) Combination of androgen deprivation therapy with radical local therapy versus androgen deprivation therapy alone for newly diagnosed oligometastatic prostate cancer: a phase II randomized controlled trial. Eur Urol Oncol 5(5):519–525

    Article  PubMed  Google Scholar 

  23. Francini E, Gray KP, Xie W et al (2018) Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate 78(12):889–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Katipally RR, Pitroda SP, Juloori A, Chmura SJ, Weichselbaum RR (2022) The oligometastatic spectrum in the era of improved detection and modern systemic therapy. Nat Rev Clin Oncol 19(9):585–599

    Article  PubMed  Google Scholar 

  25. Palma DA, Olson R, Harrow S et al (2020) Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol 38(25):2830–2838

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ost P, Reynders D, Decaestecker K et al (2018) Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol 36(5):446–453

    Article  CAS  PubMed  Google Scholar 

  27. Phillips R, Shi WY, Deek M et al (2020) Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. JAMA Oncol 6(5):650–659

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bowden P, See AW, Frydenberg M et al (2020) Fractionated stereotactic body radiotherapy for up to five prostate cancer oligometastases: interim outcomes of a prospective clinical trial. Int J Cancer 146(1):161–168

    Article  CAS  PubMed  Google Scholar 

  29. Reverberi C, Massaro M, Osti MF et al (2020) Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer. Sci Rep 10(1):17471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Deantoni CL, Fodor A, Cozzarini C et al (2020) Prostate cancer with low burden skeletal disease at diagnosis: outcome of concomitant radiotherapy on primary tumor and metastases. Br J Radiol 93(1108):20190353

    Article  PubMed  PubMed Central  Google Scholar 

  31. Reyes DK, Rowe SP, Schaeffer EM et al (2020) Multidisciplinary total eradication therapy (TET) in men with newly diagnosed oligometastatic prostate cancer. Med Oncol 37(7):60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kyriakopoulos CE, Chen YH, Carducci MA et al (2018) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 36(11):1080–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gravis G, Boher JM, Joly F et al (2016) Androgen Deprivation Therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol 70(2):256–262

    Article  CAS  PubMed  Google Scholar 

  34. Clarke NW, Ali A, Ingleby FC et al (2019) Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol 30(12):1992–2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fizazi K, Tran N, Fein L et al (2019) Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol 20(5):686–700

    Article  CAS  PubMed  Google Scholar 

  36. James ND, Clarke NW, Cook A et al (2022) Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476). Int J Cancer 151(3):422–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Armstrong AJ, Azad AA, Iguchi T et al (2022) Improved survival with enzalutamide in patients with metastatic hormone-sensitive prostate cancer. J Clin Oncol 40(15):1616–1622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chi KN, Chowdhury S, Bjartell A et al (2021) Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol 39(20):2294–2303

    Article  CAS  PubMed  Google Scholar 

  39. Davis ID, Martin AJ, Zielinski RR et al (2022) Updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). J Clin Oncol 40(17_suppl):LBA5004

    Article  Google Scholar 

  40. Fizazi K, Foulon S, Carles J et al (2022) 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 × 2 factorial design. Lancet 399(10336):1695–1707

    Article  CAS  PubMed  Google Scholar 

  41. Smith MR, Hussain M, Saad F et al (2022) Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med 386(12):1132–1142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vale CL, Fisher D, Godolphin P et al (2022) Defining more precisely the effects of docetaxel plus ADT for men with mHSPC: meta-analysis of individual participant data from randomized trials. J Clin Oncol 40(16_suppl):5070

    Article  Google Scholar 

  43. Menges D, Yebyo HG, Sivec-Muniz S (2022) Treatments for metastatic hormone-sensitive prostate cancer: systematic review, network meta-analysis, and benefit-harm assessment. Eur Urol Oncol 11(22):S2588–93. https://doi.org/10.1016/j.euo.2022.04.007

    Article  Google Scholar 

  44. Gillessen S, Armstrong A, Attard G et al (2022) Management of patients with advanced prostate cancer: report from the advanced prostate cancer consensus conference 2021. Eur Urol 82(1):115–141

    Article  CAS  PubMed  Google Scholar 

  45. Hussain M, Carducci MA, Clarke N (2022) Evolving role of prostate-specific membrane antigen-positron emission tomography in metastatic hormone-sensitive prostate cancer: more questions than answers? J Clin Onco l40(26):3011–3014. https://doi.org/10.1200/JCO.22.00208

    Article  Google Scholar 

  46. Baciarello G, Özgüroğlu M, Mundle S et al (2022) Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: a post-hoc exploratory analysis of the LATITUDE study. Eur J Cancer 162:56–64

    Article  CAS  PubMed  Google Scholar 

  47. Harshman LC, Chen YH, Liu G et al (2018) Seven-month prostate-specific antigen is prognostic in metastatic hormone-sensitive prostate cancer treated with androgen deprivation with or without docetaxel. J Clin Oncol 36(4):376–382

    Article  CAS  PubMed  Google Scholar 

  48. Saad F, Hussain MHA, Tombal BF et al (2022) Association of prostate-specific antigen (PSA) response and overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 3 ARASENS trial. J Clin Oncol 40(16_suppl):5078

    Article  Google Scholar 

  49. Cattrini C, España R, Mennitto A et al (2021) Optimal sequencing and predictive biomarkers in patients with advanced prostate cancer. Cancers (Basel) 13(18):4522

    Article  CAS  PubMed  Google Scholar 

  50. Hamid AA, Huang HC, Wang V et al (2021) Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial. Ann Oncol 32(9):1157–1166

    Article  CAS  PubMed  Google Scholar 

  51. Castro E, Romero-Laorden N, Del Pozo A et al (2019) PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol 37(6):490–503

    Article  CAS  PubMed  Google Scholar 

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Funding

The study was not funded.

Author information

Authors and Affiliations

  1. Department of Urology, APHM, North Academic Hospital, Marseille, France

    Michael Baboudjian

  2. Department of Urology, APHM, La Conception Hospital, Marseille, France

    Michael Baboudjian

  3. Department of Urology, Fundació Puigvert, Autonoma University of Barcelona, Barcelona, Spain

    Michael Baboudjian

  4. Department of Urology, La Croix du Sud Hôpital, Quint Fonsegrives, France

    Michael Baboudjian, Jean-Baptiste Beauval & Guillaume Ploussard

  5. Department of Medical Oncology, Institut Bergonié, 33000, Bordeaux, France

    Guilhem Roubaud

  6. Department of Pathology, CHRU Tours, Tours, France

    Gaëlle Fromont

  7. Department of Nuclear Medicine, Scintep–Institut Daniel Hollard, Grenoble, France

    Mathieu Gauthé

  8. Department of Urology, Institut Mutualiste Montsouris, Paris, France

    Eric Barret

  9. Department of Urology, CHU de Pointe-à-Pitre, University of Antilles, University of Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, 97110, Pointe-à-Pitre, France

    Laurent Brureau

  10. Department of Radiotherapy, Institut Curie, Paris, France

    Gilles Créhange

  11. Department of Urology, Hôpital Européen Georges-Pompidou, APHP, Paris–Paris University–U1151 Inserm-INEM, Necker, Paris, France

    Charles Dariane

  12. Department of Urology, Grenoble Alpes University Hospital, Université Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG, Grenoble, France

    Gaëlle Fiard

  13. Department of Urology, CHU Rennes, Rennes, France

    Romain Mathieu

  14. Service d’urologie Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France

    Alain Ruffion

  15. Equipe 2-Centre d’Innovation en Cancérologie de Lyon (EA 3738 CICLY)-Faculté de Médecine Lyon Sud-Université Lyon 1, Lyon, France

    Alain Ruffion

  16. Sorbonne University, GRC 5 Predictive Onco-Uro, AP-HP, Urology, Pitie-Salpetriere Hospital, 75013, Paris, France

    Morgan Rouprêt

  17. Sorbonne University, AP-HP, Radiology, Pitie-Salpetriere Hospital, 75013, Paris, France

    Raphaële Renard-Penna

  18. Department of Radiotherapy, Institut Bergonié, 33000, Bordeaux, France

    Paul Sargos

  19. Department of Urology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France

    Guillaume Ploussard

Authors
  1. Michael Baboudjian
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  2. Guilhem Roubaud
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  3. Gaëlle Fromont
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  14. Raphaële Renard-Penna
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  16. Guillaume Ploussard
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Consortia

the Prostate Cancer Committee of the French Association of Urology

Contributions

Study concept and design: GP. Acquisition of data: All authors. Analysis and interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: None.

Corresponding author

Correspondence to Michael Baboudjian.

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The authors report no conflict of interest.

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For this study design (i.e., review), ethical approval is not required.

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Topic Issue WJU: Invited review from Dr. Rajwa/Dr. Tsaur.

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Baboudjian, M., Roubaud, G., Fromont, G. et al. What is the ideal combination therapy in de novo, oligometastatic, castration-sensitive prostate cancer?. World J Urol 41, 2033–2041 (2023). https://doi.org/10.1007/s00345-022-04239-1

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