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.

Conventional radical versus focal treatment for localised prostate cancer: a propensity score weighted comparison of 6-year tumour control

Abstract

Background

For localised prostate cancer, focal therapy offers an organ-sparing alternative to radical treatments (radiotherapy or prostatectomy). Currently, there is no randomised comparative effectiveness data evaluating cancer control of both strategies.

Methods

Following the eligibility criteria PSA < 20 ng/mL, Gleason score ≤ 7 and T-stage ≤ T2c, we included 830 radical (440 radiotherapy, 390 prostatectomy) and 530 focal therapy (cryotherapy, high-intensity focused ultrasound or high-dose-rate brachytherapy) patients treated between 2005 and 2018 from multicentre registries in the Netherlands and the UK. A propensity score weighted (PSW) analysis was performed to compare failure-free survival (FFS), with failure defined as salvage treatment, metastatic disease, systemic treatment (androgen deprivation therapy or chemotherapy), or progression to watchful waiting. The secondary outcome was overall survival (OS). Median (IQR) follow-up in each cohort was 55 (28–83) and 62 (42–83) months, respectively.

Results

At baseline, radical patients had higher PSA (10.3 versus 7.9) and higher-grade disease (31% ISUP 3 versus 11%) compared to focal patients. After PSW, all covariates were balanced (SMD < 0.1). 6-year weighted FFS was higher after radical therapy (80.3%, 95% CI 73.9–87.3) than after focal therapy (72.8%, 95% CI 66.8–79.8) although not statistically significant (p = 0.1). 6-year weighted OS was significantly lower after radical therapy (93.4%, 95% CI 90.1–95.2 versus 97.5%, 95% CI 94–99.9; p = 0.02). When compared in a three-way analysis, focal and LRP patients had a higher risk of treatment failure than EBRT patients (p < 0.001), but EBRT patients had a higher risk of mortality than focal patients (p = 0.008).

Conclusions

Within the limitations of a cohort-based analysis in which residual confounders are likely to exist, we found no clinically relevant difference in cancer control conferred by focal therapy compared to radical therapy at 6 years.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Two-way propensity weighted failure-free survival (FFS) and overall survival (OS).
Fig. 2: Three-way propensity weighted failure-free survival (FFS) and overall survival (OS).

Data availability

De-identified participant data that underlie the results reported in this article are stored in an institutional repository and may be shared upon request to the corresponding author.

References

  1. 1.

    Tamada S, Ninomiya N, Kitamoto K, Kato M, Yamasaki T, Iguchi T, et al. Comparative effectiveness of radical prostatectomy and curative radiotherapy in localized prostate cancer: long-term follow-up. J Radiat Res. 2017;58:552–8.

    CAS  PubMed  Google Scholar 

  2. 2.

    Grimm P, Billiet I, Bostwick D, Dicker AP, Frank S, Immerzeel J, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int. 2012;109(Suppl 1):22–29.

    Article  Google Scholar 

  3. 3.

    Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415–24.

    Article  Google Scholar 

  4. 4.

    Sooriakumaran P, Nyberg T, Akre O, Haendler L, Heus I, Olsson M, et al. Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes. BMJ 2014;348:g1502.

    Article  Google Scholar 

  5. 5.

    Taguchi S, Fukuhara H, Shiraishi K, Nakagawa K, Morikawa T, Kakutani S, et al. Radical Prostatectomy versus external beam radiotherapy for ct1-4n0m0 prostate cancer: comparison of patient outcomes including mortality. PLoS ONE. 2015;10:e0141123.

    Article  Google Scholar 

  6. 6.

    Vernooij RWM, Cremers R, Jansen H, Somford DM, Kiemeney LA, van Andel G, et al. Urinary incontinence and erectile dysfunction in patients with localized or locally advanced prostate cancer: a nationwide observational study. Urol Oncol. 2020;38:735.e17–25.

  7. 7.

    Donovan JL, Hamdy FC, Lane JA, Mason M, Metcalfe C, Walsh E, et al. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med. 2016;375:1425–37.

    CAS  Article  Google Scholar 

  8. 8.

    Lardas M, Liew M, van den Bergh RC, De Santis M, Bellmunt J, Van den Broeck T, et al. Quality of life outcomes after primary treatment for clinically localised prostate cancer: a systematic review. Eur Urol. 2017;72:869–85.

    Article  Google Scholar 

  9. 9.

    Lam TBL, MacLennan S, Willemse PM, Mason MD, Plass K, Shepherd R, et al. EAU-EANM-ESTRO-ESUR-SIOG prostate cancer guideline panel consensus statements for Deferred Treatment With Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETECTIVE Study). Eur Urol. 2019;76:790–813.

    Article  Google Scholar 

  10. 10.

    McClure TD, Margolis DJ, Hu JC. Partial gland ablation in the management of prostate cancer: a review. Curr Opin Urol. 2017;27:156–60.

    Article  Google Scholar 

  11. 11.

    Valerio M, Cerantola Y, Eggener SE, Lepor H, Polascik TJ, Villers A, et al. New and established technology in focal ablation of the prostate: a systematic review. Eur Urol. 2017;71:17–34.

    Article  Google Scholar 

  12. 12.

    Stabile A, Orczyk C, Hosking-Jervis F, Giganti F, Arya M, Hindley RG, et al. Medium-term oncological outcomes in a large cohort of men treated with either focal or hemi-ablation using high-intensity focused ultrasonography for primary localized prostate cancer. BJU Int. 2019;124:431–40.

    Article  Google Scholar 

  13. 13.

    Guillaumier S, Peters M, Arya M, Afzal N, Charman S, Dudderidge T, et al. A multicentre study of 5-year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer. Eur Urol. 2018;74:422–9.

    Article  Google Scholar 

  14. 14.

    Shah TT, Peters M, Eldred-Evans D, Miah S, Yap T, Faure-Walker NA, et al. Early-medium-term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multicentre registry. Eur Urol. 2019;76:98–105.

    Article  Google Scholar 

  15. 15.

    Barqawi A, Pessoa RR, Al-Musawi M, MacDermott T, O’Donnell CI. The impact of performing a 3d mapping biopsy prior to primary cryotherapy for the treatment of prostate cancer. Urology 2020;144:171–6.

    Article  Google Scholar 

  16. 16.

    Tourinho-Barbosa RR, Sanchez-Salas R, Claros OR, Collura-Merlier S, Bakavicius A, Carneiro A, et al. Focal therapy for localized prostate cancer with either high intensity focused ultrasound or cryoablation: a single institution experience. J Urol. 2020;203:320–30.

    Article  Google Scholar 

  17. 17.

    Oishi M, Gill IS, Tafuri A, Shakir A, Cacciamani GE, Iwata T, et al. Hemigland cryoablation of localized low, intermediate and high risk prostate cancer: oncologic and functional outcomes at 5 years. J Urol. 2019;202:1188–98.

    Article  Google Scholar 

  18. 18.

    Hamdy FC, Elliott D, le Conte S, Davies LC, Burns RM, Thomson C, et al. Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT. Health Technol Assess. 2018;22:1–96.

    Article  Google Scholar 

  19. 19.

    Ahmed HU, Berge V, Bottomley D, Cross W, Heer R, Kaplan R, et al. Can we deliver randomized trials of focal therapy in prostate cancer? Nat Rev Clin Oncol. 2014;11:482–91.

    CAS  Article  Google Scholar 

  20. 20.

    Reddy D, Shah TT, Dudderidge T, McCracken S, Arya M, Dobbs C, et al. Comparative Healthcare Research Outcomes of Novel Surgery in prostate cancer (IP4-CHRONOS): A prospective, multi-centre therapeutic phase II parallel Randomised Control Trial. Contemp Clin Trials. 2020;93:105999.

  21. 21.

    Shah TT, Reddy D, Peters M, Ball D, Kim NH, Gomez EG, et al. Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study. Prostate Cancer Prostatic Dis. 2021. https://doi.org/10.1038/s41391-020-00315-y.

  22. 22.

    Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. 2007;4:e297.

    Article  Google Scholar 

  23. 23.

    Diaz A, Roach M 3rd, Marquez C, Coleman L, Pickett B, Wolfe JS, et al. Indications for and the significance of seminal vesicle irradiation during 3D conformal radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 1994;30:323–9.

    CAS  Article  Google Scholar 

  24. 24.

    Peters M, van Son MJ, Moerland MA, Kerkmeijer LGW, Eppinga WSC, Meijer RP, et al. MRI-Guided ultrafocal HDR brachytherapy for localized prostate cancer: median 4-year results of a feasibility study. Int J Radiat Oncol Biol Phys. 2019;104:1045–53.

    Article  Google Scholar 

  25. 25.

    Li L, Greene T. A weighting analogue to pair matching in propensity score analysis. Int J Biostat. 2013;9:215–34.

    Article  Google Scholar 

  26. 26.

    Yoshida K, Hernandez-Diaz S, Solomon DH, Jackson JW, Gagne JJ, Glynn RJ, et al. Matching weights to simultaneously compare three treatment groups: comparison to three-way matching. Epidemiology 2017;28:387–95.

    Article  Google Scholar 

  27. 27.

    Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res. 2011;46:399–424.

    Article  Google Scholar 

  28. 28.

    Simopoulos DN, Sisk AE Jr, Priester A, Felker ER, Kwan L, Delfin MK, et al. Cancer core length from targeted biopsy: an index of prostate cancer volume and pathological stage. BJU Int. 2019;124:275–81.

    Article  Google Scholar 

  29. 29.

    Nascimento B, Miranda EP, Jenkins LC, Benfante N, Schofield EA, Mulhall JP. Testosterone recovery profiles after cessation of androgen deprivation therapy for prostate cancer. J Sex Med. 2019;16:872–9.

    Article  Google Scholar 

  30. 30.

    Nam W, Choi SY, Yoo SJ, Ryu J, Lee J, Kyung YS, et al. Factors associated with testosterone recovery after androgen deprivation therapy in patients with prostate cancer. Investig Clin Urol. 2018;59:18–24.

    Article  Google Scholar 

  31. 31.

    Akakura K, Suzuki H, Ichikawa T, Fujimoto H, Maeda O, Usami M, et al. A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months. Jpn J Clin Oncol. 2006;36:789–93.

    Article  Google Scholar 

  32. 32.

    Taguchi S, Shiraishi K, Fukuhara H. Updated evidence on oncological outcomes of surgery versus external beam radiotherapy for localized prostate cancer. Jpn J Clin Oncol. 2020;50:963–9.

    Article  Google Scholar 

  33. 33.

    Mohler JL, Antonarakis ES, Armstrong AJ, D’Amico AV, Davis BJ, Dorff T, et al. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2019;17:479–505.

    CAS  Article  Google Scholar 

  34. 34.

    Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29.

    Article  Google Scholar 

  35. 35.

    Dasgupta P, Davis J, Hughes S. NICE guidelines on prostate cancer 2019. BJU Int. 2019;124:1.

    Article  Google Scholar 

  36. 36.

    Komisarenko M, Martin LJ, Finelli A. Active surveillance review: contemporary selection criteria, follow-up, compliance and outcomes. Transl Androl Urol. 2018;7:243–55.

    Article  Google Scholar 

  37. 37.

    Gill IS, Azzouzi AR, Emberton M, Coleman JA, Coeytaux E, Scherz A, et al. Randomized trial of partial gland ablation with vascular targeted phototherapy versus active surveillance for low risk prostate cancer: extended followup and analyses of effectiveness. J Urol. 2018;200:786–93.

    Article  Google Scholar 

  38. 38.

    Tay KJ, Amin MB, Ghai S, Jimenez RE, Kench JG, Klotz L, et al. Surveillance after prostate focal therapy. World J Urol. 2019;37:397–407.

    Article  Google Scholar 

  39. 39.

    Lennernas B, Majumder K, Damber JE, Albertsson P, Holmberg E, Brandberg Y, et al. Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes. Acta Oncol. 2015;54:875–81.

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

M.J.v.S. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: M.J.v.S., M.P., D.R., T.T.S., H.U.A. and A.F. Drafting of the manuscript: M.J.v.S. Critical revision of the manuscript for important intellectual content: M.P., D.R., T.T.S., J.J.W.L., S.M., T.D., S.M., R.G.H., A.E., R.N., R.P., J.V., H.L., C.M., C.O., M.E., M.A., H.U.A., J.R.N.v.d.V.v.Z., M.W. and A.F. Statistical analysis: M.J.v.S. and M.P. Obtaining funding: not applicable. Administrative, technical, or material support: S.R., F.H.-J. Supervision: H.U.A., J.R.N.v.d.V.v.Z., M.W. and A.F.

Corresponding author

Correspondence to Marieke J. van Son.

Ethics declarations

Conflict of interest

Dr Peters and Dr van der Voort van Zyp received a research grant from the Dutch Cancer Society. Dr Reddy received a research grant from Prostate Cancer UK and received travel grants from Imperial Health Charity and Sonacare. Dr Shah received funding from Prostate Cancer UK and the St Peters Trust and has received funding in the past for conference attendance from Astellas, Ferring and Galil Medical. Professor Moore receives funding from the National Institute for Health Research, The European Association of Urology Research Foundation, MRC, Cancer Research UK, Prostate Cancer UK, Movember and the Cancer Vaccine Institute for clinical prostate cancer research. She has received advisory board fees for Genomic Health. Professor Emberton’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre. He was awarded NIHR Senior Investigator in 2015. He receives funding from NIHR-i4i, MRC (UK), Cancer Research UK, Sonacare Inc., Trod Medical, Cancer Vaccine Institute and Sophiris Biocorp for trials in prostate cancer. He is a medical consultant to Sonacare Inc., Sophiris Biocorp, Steba Biotech, Exact Imaging and Profound Medical. Professor Ahmed’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre. He currently receives funding from the Wellcome Trust, Medical Research Council (UK), Prostate Cancer UK, Cancer Research UK, The BMA Foundation, The Urology Foundation, The Imperial Health Charity, Sonacare Inc., Trod Medical and Sophiris Biocorp for trials and studies in prostate cancer. He was a paid medical consultant for Sophiris Biocorp and is still a paid proctor for HIFU, cryotherapy and Rezum water vapour therapy. Dr Winkler received a travel grant and a loan of device from Zicom Biobot. The remaining authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

van Son, M.J., Peters, M., Reddy, D. et al. Conventional radical versus focal treatment for localised prostate cancer: a propensity score weighted comparison of 6-year tumour control. Prostate Cancer Prostatic Dis 24, 1120–1128 (2021). https://doi.org/10.1038/s41391-021-00369-6

Download citation

Further reading

Search

Quick links