World Journal of Urology

, Volume 37, Issue 12, pp 2597–2606 | Cite as

Treatment of the primary tumor in metastatic prostate cancer

  • Ye Yuan
  • Amar U. Kishan
  • Nicholas G. NickolsEmail author
Topic Paper


The cornerstone of treatment for metastatic prostate cancer patients has been conventional androgen deprivation therapy, with additional systemic therapy initiated only after castration resistance, and local therapy reserved for palliation. Compelling results from modern trials challenge this paradigm, arguing for initiating escalated hormone therapy and/or chemotherapy during the castration-sensitive disease state for many patients. Furthermore, modern radiotherapy techniques allow for local control of disease with low risk of toxicity. Finally, new PET probes with enhanced sensitivity and accuracy are likely to become a part of routine staging and will lead to an increased incidence of patients with metastatic disease at presentation, with a shift toward identification of patients with limited metastatic disease. As such, the landscape is primed for investigations aimed to explore the role of primary tumor therapy for patients with metastatic prostate cancer. We review the existing data evaluating primary tumor therapy for patients with metastatic prostate cancer and describe ongoing clinical trials testing the hypothesis that primary tumor therapy may benefit patients with metastatic prostate cancer.


Prostate cancer Oligometastatic Radiotherapy Hormone-sensitive metastatic 


Authors’ contributions

YY: data collection, data analysis, manuscript writing. AUK: data collection, data analysis, manuscript writing. NGN: data collection, data analysis, manuscript writing.

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest to disclose. As this is a review article, there was no research involving human participants or animals, nor informed consent needed.


  1. 1.
    Mohler JL, Lee RJ, Antonarakis ES et al (2018) National Comprehensive Cancer Network. Prostate Cancer (Version 4.2018). Accessed 16 July 2018
  2. 2.
    Huggins C, Hodges CV (2002) Studies on prostatic cancer. J Urol 167:948–951. CrossRefPubMedGoogle Scholar
  3. 3.
    Schally AV, Arimura A, Kastin AJ et al (1971) Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science 173:1036–1038CrossRefGoogle Scholar
  4. 4.
    James ND, Spears MR, Clarke NW et al (2015) Survival with newly diagnosed metastatic prostate cancer in the “Docetaxel Era”: data from 917 patients in the control arm of the STAMPEDE trial (MRC PR08, CRUK/06/019). Eur Urol 67:1028–1038. CrossRefGoogle Scholar
  5. 5.
    Nguyen PL, Alibhai SMH, Basaria S et al (2015) Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol 67:825–836. CrossRefPubMedGoogle Scholar
  6. 6.
    Fizazi K, Tran N, Fein L et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377:352–360. CrossRefGoogle Scholar
  7. 7.
    James ND, de Bono JS, Spears MR et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377:338–351. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kim M-Y, Oskarsson T, Acharyya S et al (2009) Tumor self-seeding by circulating cancer cells. Cell 139:1315–1326. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gundem G, Van Loo P, Kremeyer B et al (2015) The evolutionary history of lethal metastatic prostate cancer. Nature 520:353–357. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kaplan RN, Rafii S, Lyden D (2006) Preparing the “soil”: the premetastatic niche. Cancer Res 66:11089–11093. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Cai C, Balk SP (2011) Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy. Endocr Relat Cancer 18:R175–R182. CrossRefPubMedGoogle Scholar
  12. 12.
    Heidenreich A, Pfister D, Porres D (2015) Cytoreductive radical prostatectomy in patients with prostate cancer and low volume skeletal metastases: results of a feasibility and case-control study. J Urol 193:832–838. CrossRefPubMedGoogle Scholar
  13. 13.
    Won ACM, Gurney H, Marx G et al (2013) Primary treatment of the prostate improves local palliation in men who ultimately develop castrate-resistant prostate cancer. BJU Int 112:E250–E255. CrossRefPubMedGoogle Scholar
  14. 14.
    Steinberg GD, Epstein JI, Piantadosi S, Walsh PC (1990) Management of stage D1 adenocarcinoma of the prostate: the Johns Hopkins experience 1974 to 1987. J Urol 144:1425–1432CrossRefGoogle Scholar
  15. 15.
    Flanigan RC, Salmon SE, Blumenstein BA et al (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345:1655–1659. CrossRefGoogle Scholar
  16. 16.
    Mickisch GH, Garin A, van Poppel H et al (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358:966–970CrossRefGoogle Scholar
  17. 17.
    Méjean A, Ravaud A, Thezenas S et al (2018) Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med 379:417–427. CrossRefPubMedGoogle Scholar
  18. 18.
    Bristow RE, Tomacruz RS, Armstrong DK et al (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248–1259. CrossRefGoogle Scholar
  19. 19.
    Fader AN, Rose PG (2007) Role of surgery in ovarian carcinoma. J Clin Oncol 25:2873–2883. CrossRefPubMedGoogle Scholar
  20. 20.
    du Bois A, Reuss A, Pujade-Lauraine E et al (2009) Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer 115:1234–1244. CrossRefPubMedGoogle Scholar
  21. 21.
    Choti MA, Sitzmann JV, Tiburi MF et al (2002) Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 235:759–766CrossRefGoogle Scholar
  22. 22.
    Pawlik TM, Scoggins CR, Zorzi D et al (2005) Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 241: 715–722:discussion 722–724Google Scholar
  23. 23.
    Pitroda SP, Khodarev NN, Huang L et al (2018) Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. Nat Commun. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. PubMed NCBI. Accessed 2 Oct 2018
  25. 25.
    Harris E, Barry M, Kell MR (2013) Meta-analysis to determine if surgical resection of the primary tumour in the setting of stage IV breast cancer impacts on survival. Ann Surg Oncol 20:2828–2834. CrossRefPubMedGoogle Scholar
  26. 26.
    Badwe R, Hawaldar R, Nair N et al (2015) Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 16:1380–1388. CrossRefPubMedGoogle Scholar
  27. 27.
    DallEra MA, Lo MJ, Chen J et al (2018) Nine-year prostate cancer survival differences between aggressive versus conservative therapy in men with advanced and metastatic prostate cancer: local therapy in advanced prostate cancer. Cancer 124:1921–1928. CrossRefGoogle Scholar
  28. 28.
    Kelly SP, Anderson WF, Rosenberg PS, Cook MB (2018) Past, current, and future incidence rates and burden of metastatic prostate cancer in the United States. Eur Urol Focus 4:121–127. CrossRefPubMedGoogle Scholar
  29. 29.
    Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM (2016) Increasing incidence of metastatic prostate cancer in the United States (2004–2013). Prostate Cancer Prostatic Dis 19:395–397. CrossRefPubMedGoogle Scholar
  30. 30.
    Calais J, Cao M, Nickols NG (2018) The utility of PET/CT in the planning of external radiation therapy for prostate cancer. J Nucl Med 59:557–567. CrossRefPubMedGoogle Scholar
  31. 31.
    Widmark A, Klepp O, Solberg A et al (2009) Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 373:8CrossRefGoogle Scholar
  32. 32.
    Warde P, Mason M, Ding K et al (2011) Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet 378:2104–2111. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    James ND, Spears MR, Clarke NW et al (2014) Impact of node status and radiotherapy on failure-free survival in patients with newly-diagnosed non-metastatic prostate cancer: data from > 690 patients in the control arm of the STAMPEDE trial. Int J Radiat Oncol Biol Phys 90:S13. CrossRefGoogle Scholar
  34. 34.
    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 65:1058–1066. CrossRefPubMedGoogle Scholar
  35. 35.
    Antwi S, Everson TM (2014) Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: a population-based, propensity score analysis. Cancer Epidemiol 38:435–441. CrossRefPubMedGoogle Scholar
  36. 36.
    Satkunasivam R, Kim AE, Desai M et al (2015) Radical prostatectomy or external beam radiation therapy vs no local therapy for survival benefit in metastatic prostate cancer: a SEER-medicare analysis. J Urol 194:378–385. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Parikh RR, Byun J, Goyal S, Kim IY (2017) Local therapy improves overall survival in patients with newly diagnosed metastatic prostate cancer. Prostate 77:559–572. CrossRefPubMedGoogle Scholar
  38. 38.
    Löppenberg B, Dalela D, Karabon P et al (2017) The impact of local treatment on overall survival in patients with metastatic prostate cancer on diagnosis: a national cancer data base analysis. Eur Urol 72:14–19. CrossRefPubMedGoogle Scholar
  39. 39.
    Leyh-Bannurah S-R, Gazdovich S, Budäus L et al (2017) Local therapy improves survival in metastatic prostate cancer. Eur Urol 72:118–124. CrossRefPubMedGoogle Scholar
  40. 40.
    Steuber T, Berg KD, Røder MA et al (2017) Does cytoreductive prostatectomy really have an impact on prognosis in prostate cancer patients with low-volume bone metastasis? Results from a prospective case-control study. Eur Urol Focus 3:646–649. CrossRefPubMedGoogle Scholar
  41. 41.
    Cho Y, Chang JS, Rha KH et al (2016) Does radiotherapy for the primary tumor benefit prostate cancer patients with distant metastasis at initial diagnosis? PLoS One 11:e0147191. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Rusthoven CG, Jones BL, Flaig TW et al (2016) Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer. J Clin Oncol 34:2835–2842. CrossRefPubMedGoogle Scholar
  43. 43.
    Gratzke C, Engel J, Stief CG (2014) Role of radical prostatectomy in metastatic prostate cancer: data from the munich cancer registry. Eur Urol 66:602–603. CrossRefPubMedGoogle Scholar
  44. 44.
    Boevé LMS, Hulshof MCCM, Vis AN et al (2018) 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. CrossRefPubMedGoogle Scholar
  45. 45.
    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. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Sweeney CJ, Chen Y-H, Carducci M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373:737–746. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    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 36:446–453. CrossRefGoogle Scholar
  48. 48.
    O’Shaughnessy MJ, McBride SM, Vargas HA et al (2017) A Pilot study of a multimodal treatment paradigm to accelerate drug evaluations in early-stage metastatic prostate cancer. Urology 102:164–172. CrossRefPubMedGoogle Scholar
  49. 49.
    Hellman S, Weichselbaum RR (1995) Oligometastases. J Clin Oncol 13:8–10. CrossRefGoogle Scholar
  50. 50.
    Soloway MS, Hardeman SW, Hickey D et al (1988) Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 61:195–202CrossRefGoogle Scholar
  51. 51.
    Singh D, Yi WS, Brasacchio RA et al (2004) Is there a favorable subset of patients with prostate cancer who develop oligometastases? Int J Radiat Oncol Biol Phys 58:3–10. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ye Yuan
    • 1
  • Amar U. Kishan
    • 1
  • Nicholas G. Nickols
    • 1
    • 2
    Email author
  1. 1.Department of Radiation OncologyUCLALos AngelesUSA
  2. 2.Department of Radiation OncologyVA Greater Los Angeles Healthcare SystemLos AngelesUSA

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