Developments in oligometastatic hormone-sensitive prostate cancer



To review the current understanding and recent developments regarding the concept of oligometastases in hormone-sensitive prostate cancer.


A comprehensive literature search of electronic databases, including PubMed and Embase was conducted for the search term ‘oligometastases’ in combinations with ‘prostate cancer’, ‘hormone sensitive’, ‘genetics’, and ‘molecular’. All articles relating to these search terms have been taken into account.


Prostate cancer remains a major cause of morbidity and mortality worldwide. The majority of these cancer-related deaths result from metastases. Currently, there is a dichotomy in prostate cancer management where it is only deemed curable if it is localized, while any signs of metastasis relegate patients to systemic therapies to delay their inevitable death. A growing body of evidence supports the notion that aggressive treatments during the stable ‘oligometastatic’ state can have significant clinical benefits and potentially ‘reset’ prostate cancer to an earlier time point in cancer progression. This concept of oligometastases has been adopted in other cancer settings such as colorectal and non-small-cell lung cancers.


Multiple clinical and molecular biological studies have been influential in the support of a stable state in metastatic cancer progression coined ‘oligometastases’. As our understanding of oligometastases in hormone-sensitive prostate cancer develops, we will be able to molecularly define the oligometastatic state and develop clinically available diagnostic tests. In doing so, prostate cancer patients will experience significant clinical benefits and the burden of prostate cancer worldwide will likely be reduced.

This is a preview of subscription content, log in to check access.


  1. 1.

    Stewart BW, Wild CP (2014) World Cancer Report 2014. Lyon, France: International Agency for Research on Cancer. World Health Organization 630

  2. 2.

    Langley RR, Fidler IJ (2007) Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr Rev 28:297–321

    CAS  PubMed  Google Scholar 

  3. 3.

    Mottet N, van den Bergh RCN, Briers E et al (2018) EAU Guidelines. Edn. presented at the EAU Annual Congress Copenhagen 2018. EAU Guidelines Office, Arnhem, The Netherlands

  4. 4.

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

    CAS  Google Scholar 

  5. 5.

    Reyes DK, Pienta KJ (2015) The biology and treatment of oligometastatic cancer. Oncotarget 6:8491–8524

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Tosoian JJ, Gorin MA, Ross AE et al (2017) Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol 14:15–25

    CAS  Google Scholar 

  7. 7.

    Gillessen S, Attard G, Beer TM et al (2018) Management of patients with advanced prostate cancer: the Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur Urol 73:178–211

    Google Scholar 

  8. 8.

    Nordlinger B, Quilichini MA, Parc R et al (1987) Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recurrences in 80 patients. Ann Surg 205:256–263

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Hughes KS, Rosenstein RB, Songhorabodi S et al (1988) Resection of the liver for colorectal carcinoma metastases. Dis Colon Rectum 31:1–4

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Gayowski TJ, Iwatsuki S, Madariaga JR et al (1994) Experience in hepatic resection for metastatic colorectal cancer: analysis of clinical and pathologic risk factors. Surgery 116:703–710 (discussion 710–1)

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Scheele J, Stang R, Altendorf-Hofmann A, Paul M (1995) Resection of colorectal liver metastases. World J Surg 19:59–71

    CAS  PubMed  Google Scholar 

  12. 12.

    Fong Y, Cohen AM, Fortner JG et al (1997) Liver resection for colorectal metastases. J Clin Oncol 15:938–946

    CAS  PubMed  Google Scholar 

  13. 13.

    Rougier PH, Milan C, Lazorthes F et al (1995) Prospective study of prognostic factors in patients with unresected hepatic metastases from colorectal cancer. Br J Surg 82:1397–1400

    CAS  PubMed  Google Scholar 

  14. 14.

    Fong Y, Fortner J, Sun RL et al (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230:309–318 (discussion 318–21)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Kanas GP, Taylor A, Primrose JN et al (2012) Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Clin Epidemiol 4:283–301

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Van Cutsem E, Cervantes A, Adam R et al (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422

    PubMed  Google Scholar 

  17. 17.

    Pastorino U, Buyse M, Friedel G et al (1997) Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 113:37–49

    CAS  PubMed  Google Scholar 

  18. 18.

    Pfannschmidt J, Dienemann H (2010) Surgical treatment of oligometastatic non-small cell lung cancer. Lung Cancer 69:251–258

    PubMed  Google Scholar 

  19. 19.

    Peters S, Adjei AA, Gridelli C et al (2012) Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 23(Suppl 7):56–64

    Google Scholar 

  20. 20.

    Richards P, McKISSOCK W (1963) Intracranial metastases. Br Med J 1:15–18

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Gomez DR, Blumenschein GR Jr, Lee JJ et al (2016) Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol 17:1672–1682

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Iyengar P, Wardak Z, Gerber DE et al (2018) Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: a phase 2 randomized clinical trial. JAMA Oncol 4:e173501

    PubMed  Google Scholar 

  23. 23.

    Yao HH, Hong MK, Corcoran NM et al (2014) Advances in local and ablative treatment of oligometastasis in prostate cancer. Asia Pac J Clin Oncol 10:308–321

    PubMed  Google Scholar 

  24. 24.

    Koo KC, Dasgupta P (2018) Treatment of oligometastatic hormone-sensitive prostate cancer: a comprehensive review. Yonsei Med J 59:567–579

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    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

    PubMed  Google Scholar 

  26. 26.

    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

    PubMed  Google Scholar 

  27. 27.

    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

    PubMed  Google Scholar 

  28. 28.

    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

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    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

    CAS  Google Scholar 

  30. 30.

    Tree AC, Khoo VS, Eeles RA et al (2013) Stereotactic body radiotherapy for oligometastases. Lancet Oncol 14:e28–e37

    PubMed  Google Scholar 

  31. 31.

    Campbell PJ, Yachida S, Mudie LJ et al (2010) The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467:1109–1113

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Yachida S, Jones S, Bozic I et al (2010) Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467:1114–1117

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Wuttig D, Baier B, Fuessel S et al (2009) Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient. Int J Cancer 125:474–482

    CAS  Google Scholar 

  35. 35.

    Pitroda SP, Khodarev NN, Huang L et al (2018) Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. Nat Commun 9:1793

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Lussier YA, Khodarev NN, Regan K et al (2012) Oligo- and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs. PLoS One 7:e50141

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Wong AC, Watson SP, Pitroda SP et al (2016) Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). Cancer 122:2242–2250

    CAS  PubMed  Google Scholar 

  38. 38.

    Uppal A, Ferguson MK, Posner MC et al (2014) Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs. Clin Exp Metastasis 31:735–748

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Zhang H-W, Wang E-W, Li L-X et al (2016) A regulatory loop involving miR-29c and Sp1 elevates the TGF-β1 mediated epithelial-to-mesenchymal transition in lung cancer. Oncotarget 7:85905–85916

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Harazono Y, Muramatsu T, Endo H et al (2013) miR-655 Is an EMT-suppressive microRNA targeting ZEB1 and TGFBR2. PLoS One 8:e62757

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Huang B, Luo W, Sun L et al (2013) MiRNA-125a-3p is a negative regulator of the RhoA-actomyosin pathway in A549 cells. Int J Oncol 42:1734–1742

    CAS  PubMed  Google Scholar 

  42. 42.

    Anaya-Ruiz M, Bandala C, Perez-Santos JLM (2013) miR-485 acts as a tumor suppressor by inhibiting cell growth and migration in breast carcinoma T47D cells. Asian Pac J Cancer Prev 14:3757–3760

    PubMed  Google Scholar 

  43. 43.

    Vaira V, Faversani A, Dohi T et al (2012) miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression. Oncogene 31:27–38

    CAS  PubMed  Google Scholar 

  44. 44.

    Dykxhoorn DM, Wu Y, Xie H et al (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One 4:e7181

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Korpal M, Ell BJ, Buffa FM et al (2011) Direct targeting of Sec23a by miR-200 s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17:1101–1108

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Sapre N, Hong MKH, Macintyre G et al (2014) Curated microRNAs in urine and blood fail to validate as predictive biomarkers for high-risk prostate cancer. PLoS One 9:e91729

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Hong MKH, Macintyre G, Wedge DC et al (2015) Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat Commun 6:6605

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Shah RB, Mehra R, Chinnaiyan AM et al (2004) Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res 64:9209–9216

    CAS  PubMed  Google Scholar 

  49. 49.

    Yuhas JM, Tarleton AE (1978) Dormancy and spontaneous recurrence of human breast cancer in vitro. Cancer Res 38:3584–3589

    CAS  PubMed  Google Scholar 

  50. 50.

    Braun S, Vogl FD, Naume B et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802

    CAS  PubMed  Google Scholar 

  51. 51.

    Kobayashi A, Okuda H, Xing F et al (2011) Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med 208(13):2641–2655

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Zhou Y, Zhang G-J, Wang J et al (2017) Current status of lymph node micrometastasis in gastric cancer. Oncotarget 8:51963–51969

    PubMed  PubMed Central  Google Scholar 

Download references


The Australian Prostate Cancer Centre Epworth is supported by the Australian Government as represented by the Department of Health and Ageing. KC is supported by a Postgraduate Medical Research Scholarship from the Prostate Cancer Research Fund, and the Research Training Program Scholarship from the Australian Commonwealth Government. NMC is supported by a Movember—Distinguished Gentleman’s Ride Clinician Scientist Award through Prostate Cancer Foundation of Australia’s Research Program.


The work had no specific source of funding.

Author information




Chow: Project development, data collection and analysis, manuscript writing/editing. McCoy: Data collection and analysis, manuscript writing/editing. Stuchbery: Data analysis, manuscript writing/editing. Corcoran: Project development, manuscript writing/editing. Hovens: Project development, data analysis, manuscript writing/editing.

Corresponding author

Correspondence to Christopher M. Hovens.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This review does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Informed consent was not solicited as it was not applicable in this review.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chow, K., McCoy, P., Stuchbery, R. et al. Developments in oligometastatic hormone-sensitive prostate cancer. World J Urol 37, 2549–2555 (2019).

Download citation


  • Oligometastases
  • Metastasis
  • Prostate cancer
  • Hormone sensitive
  • Genetics
  • Review