International Journal of Clinical Oncology

, Volume 23, Issue 6, pp 1148–1159 | Cite as

Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS): first analysis on survival

  • Kazuto ItoEmail author
  • Shiro Saito
  • Atsunori Yorozu
  • Shinsuke Kojima
  • Takashi Kikuchi
  • Satoshi Higashide
  • Manabu Aoki
  • Hirofumi Koga
  • Takefumi Satoh
  • Toshio Ohashi
  • Katsumasa Nakamura
  • Norihisa Katayama
  • Nobumichi Tanaka
  • Masahiro Nakano
  • Naoyuki Shigematsu
  • Takushi Dokiya
  • Masanori Fukushima
  • For the J-POPS Investigators
Original Article



Investigating oncological outcomes in patients registered in the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) in terms of biochemical relapse-free survival (bRFS) by the Phoenix and the newly developed J-POPS definitions, exploration of predictive factors for bRFS, and preliminary verification of pitfalls of prostate-specific antigen (PSA) failure definitions.


Between July 2005 and June 2007, 2316 clinically localized patients underwent permanent seed implantation. The primary endpoint was bRFS. One of the secondary endpoints was overall survival (OS).


The median age was 69 and performance status was 0 in 99.1% of participants. The median biologically effective dose (BED) was about 180 Gy2. During a median follow-up of 60.0 months, 8.4 and 5.9% had PSA failure by the Phoenix and the J-POPS definitions, respectively. The 5-year bRFSs based on the Phoenix and the J-POPS definitions were 89.1 and 91.6%, respectively. The 5-year OS was 97.3%. According to multivariate analyses, only age affected bRFS based on the Phoenix definition, whereas the risk group and BED independently affected bRFS based on the J-POPS definition. A spontaneous PSA decrease was seen in 91.1% of participants after PSA failure based on the Phoenix definition alone, but in only 22.2% after PSA failure based on the J-POPS definition alone.


The world’s largest registration study, J-POPS, consisted of patients with longevity, and a highly quality-controlled BED resulted in excellent bRFS and OS. The high likelihood of PSA bounce by the Phoenix definition should be taken into account, especially in younger patients.

Clinical trial information



Prostate cancer Brachytherapy External beam radiation therapy Iodine-125 



Thanks to all of the investigators who contributed to the cohort 1 in the J-POPS (see list of the J-POPS Investigators). This research was supported by the Foundation for Biomedical Research and Innovation (Kobe, Japan; This work was supported in part by a Health Labor Sciences Research Grant from the Japanese Ministry of Health, Labor and Welfare (H29-ICT-Ippan-002).

Compliance with ethical standards

Conflict of interest

Kazuto Ito received honoraria from Takeda Pharmaceutical Company Limited, AstraZeneca and Astellas. Shiro Saito received honoraria from Takeda Pharmaceutical Company Limited, AstraZeneca, and Astellas and received grant support from Takeda Pharmaceutical Company Limited, AstraZeneca, and Astellas. None of the remaining authors has conflicts of interest that could be perceived as prejudicing the impartiality of the research reported and none has any financial support from industrial companies that are related with this research.

Supplementary material

10147_2018_1309_MOESM1_ESM.doc (50 kb)
Supplementary material 1 (DOC 49 KB)
10147_2018_1309_MOESM2_ESM.pdf (191 kb)
Supplementary material 2 (PDF 190 KB)
10147_2018_1309_MOESM3_ESM.pdf (312 kb)
Figure S1. Study flow diagram in the J-POPS (cohort 1) (PDF 311 KB)
10147_2018_1309_MOESM4_ESM.pdf (338 kb)
Figure S2. Biochemical relapse-free rate (bRFR) based on the Phoenix and the J-POPS definitions (PDF 338 KB)


  1. 1.
    International Agency for Research on Cancer (IARC) (2012) Prostate cancer. Estimated incidence, mortality and prevalence worldwide in 2012. Globocan 2012. Available via DIALOG. Accessed April 2016
  2. 2.
    Ito K (2014) Prostate cancer in Asian men. Nat Rev Urol 11:197–212CrossRefGoogle Scholar
  3. 3.
    Grimm P, Billiet I, Bostwick D et al (2012) 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 109(Suppl 1):22–29CrossRefGoogle Scholar
  4. 4.
    Peinemann F, Grouven U, Bartel C et al (2011) Permanent interstitial low-dose-rate brachytherapy for patients with localised prostate cancer: a systematic review of randomised and nonrandomised controlled clinical trials. Eur Urol 60:881–893CrossRefGoogle Scholar
  5. 5.
    Stone NN, Stock RG (2007) Long-term urinary, sexual, and rectal morbidity in patients treated with iodine-125 prostate brachytherapy followed up for a minimum of 5 years. Urology 69:338–342CrossRefGoogle Scholar
  6. 6.
    Waterman FM, Dicker AP (2003) Probability of late rectal morbidity in 125I prostate brachytherapy. Int J Radiat Oncol Biol Phys 55:342–353CrossRefGoogle Scholar
  7. 7.
    Saito S, Ito K, Yorozu A et al (2015) Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). Int J Clin Oncol 20:375–385CrossRefGoogle Scholar
  8. 8.
    Stock RG, Stone NN, Cesaretti JA et al (2006) Rosenstein BS. Biologically effective dose values for prostate brachytherapy: effects on PSA failure and posttreatment biopsy results. Int J Radiat Oncol Biol Phys 64:527–533CrossRefGoogle Scholar
  9. 9.
    Roach M III, Hanks G, Thames H Jr et al (2006) Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65:965–974CrossRefGoogle Scholar
  10. 10.
    Thames H, Kuban D, Levy L et al (2003) Comparison of alternative biochemical failure definitions based on clinical outcome in 4839 prostate cancer patients treated by external beam radiotherapy between 1986 and 1995. Int J Radiat Oncol Biol Phys 57:929–943CrossRefGoogle Scholar
  11. 11.
    Crook J, Gillan C, Yeung I et al (2007) PSA kinetics and PSA bounce following permanent seed prostate brachytherapy. Int J Radiat Oncol Biol Phys 69:426–433CrossRefGoogle Scholar
  12. 12.
    Mazeron R, Bajard A, Montbarbon X et al (2012) Permanent 125I-seed prostate brachytherapy: early prostate specific antigen value as a predictor of PSA bounce occurrence. Radiat Oncol 7:46CrossRefGoogle Scholar
  13. 13.
    Zwahlen DR, Smith R, Andrianopoulos N et al (2011) Prostate-specific antigen bounce after permanent iodine-125 prostate brachytherapy—an Australian analysis. Int J Radiat Oncol Biol Phys 79:179–187CrossRefGoogle Scholar
  14. 14.
    Satoh T, Ishiyama H, Matsumoto K et al (2009) Prostate-specific antigen ‘bounce’ after permanent 125I-implant brachytherapy in Japanese men: a multi-institutional pooled analysis. BJU Int 103:1064–1068CrossRefGoogle Scholar
  15. 15.
    McGrath SD, Antonucci JV, Fitch DL et al (2010) PSA bounce after prostate brachytherapy with or without neoadjuvant androgen deprivation. Brachytherapy 9:137–144CrossRefGoogle Scholar
  16. 16.
    Thompson A, Keyes M, Pickles T et al (2010) Evaluating the Phoenix definition of biochemical failure after (125)I prostate brachytherapy: Can PSA kinetics distinguish PSA failures from PSA bounces? Int J Radiat Oncol Biol Phys 78:415–421CrossRefGoogle Scholar
  17. 17.
    D’Amico AV, Manola J, Loffredo M et al (2004) 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 292:821–827CrossRefGoogle Scholar
  18. 18.
    D’Amico AV1, Chen MH, Renshaw AA et al (2008) Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 299:289–295CrossRefGoogle Scholar
  19. 19.
    Critz FA, Levinson AK, Williams WH et al (1997) The PSA nadir that indicates potential cure after radiotherapy for prostate cancer. Urology 49:668–672CrossRefGoogle Scholar
  20. 20.
    Pickles T, Kim-Sing C, Morris WJ et al (2003) Evaluation of the Houston biochemical relapse definition in men treated with prolonged neoadjuvant and adjuvant androgen ablation and assessment of follow-up lead-time bias. Int J Radiat Oncol Biol Phys 57:11–18CrossRefGoogle Scholar
  21. 21.
    Stone NN, Stock RG, Cesaretti JA et al (2010) Local control following permanent prostate brachytherapy: effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys 76:355–360CrossRefGoogle Scholar
  22. 22.
    Ho AY, Burri RJ, Cesaretti JA et al (2009) Radiation dose predicts for biochemical control in intermediate-risk prostate cancer patients treated with low-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 75:16–22CrossRefGoogle Scholar
  23. 23.
    Stone NN, Potters L, Davis BJ et al (2009) Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7–10 prostate cancer treated with permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 73:341–346CrossRefGoogle Scholar
  24. 24.
    Ohashi T, Yorozu A, Saito S et al (2015) Urinary and rectal toxicity profiles after permanent iodine-125 implant brachytherapy in Japanese men: nationwide J-POPS multi-institutional prospective cohort study. Int J Radiat Oncol Biol Phys 93:141–149CrossRefGoogle Scholar
  25. 25.
    Nakano M, Yorozu A, Saito S et al (2015) Seed migration after transperineal interstitial prostate brachytherapy by using loose seeds: Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) multi-institutional cohort study. Radiat Oncol 10:228. CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Miki K, Kiba T, Sasaki H et al (2010) Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial. BMC Cancer 10:572CrossRefGoogle Scholar
  27. 27.
    Konaka H, Egawa S, Saito S et al (2012) Tri-modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial. BMC Cancer 12:110CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2018

Authors and Affiliations

  • Kazuto Ito
    • 1
    • 2
    Email author
  • Shiro Saito
    • 3
  • Atsunori Yorozu
    • 4
  • Shinsuke Kojima
    • 5
  • Takashi Kikuchi
    • 5
  • Satoshi Higashide
    • 5
  • Manabu Aoki
    • 6
  • Hirofumi Koga
    • 7
  • Takefumi Satoh
    • 8
    • 9
  • Toshio Ohashi
    • 10
  • Katsumasa Nakamura
    • 11
  • Norihisa Katayama
    • 12
  • Nobumichi Tanaka
    • 13
  • Masahiro Nakano
    • 14
  • Naoyuki Shigematsu
    • 10
  • Takushi Dokiya
    • 15
  • Masanori Fukushima
    • 5
  • For the J-POPS Investigators
  1. 1.Department of UrologyGunma UniversityGunmaJapan
  2. 2.Institute for Preventive MedicineKurosawa HospitalTakasakiJapan
  3. 3.Department of UrologyNational Hospital Organization Tokyo Medical CenterTokyoJapan
  4. 4.Department of Radiation OncologyNational Hospital Organization Tokyo Medical CenterTokyoJapan
  5. 5.Translational Research Informatics CenterFoundation for Biomedical Research and InnovationHyogoJapan
  6. 6.Department of Radiation OncologyJikei University School of MedicineTokyoJapan
  7. 7.Seisyukai ClinicFukuokaJapan
  8. 8.Department of UrologyKitasato University School of MedicineKanagawaJapan
  9. 9.Takefumi Satoh Prostate ClinicTokyoJapan
  10. 10.Department of Radiation OncologyKeio University School of MedicineTokyoJapan
  11. 11.Department of Radiation OncologyHamamatsu University School of MedicineShizuokaJapan
  12. 12.Department of Radiation OncologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  13. 13.Department of UrologyNara Medical University HospitalNaraJapan
  14. 14.Department of UrologyGifu University Graduate School of MedicineGifuJapan
  15. 15.Department of Radiation OncologySaitama Medical CollegeSaitamaJapan

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