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High-dose radiotherapy with helical tomotherapy and long-term androgen deprivation therapy for prostate cancer: 5-year outcomes

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

We aimed to examine outcomes of high-dose radiotherapy with helical tomotherapy (HT) and long-term androgen deprivation therapy (ADT) for T1–4N0M0 prostate cancer.

Methods

A total of 391 patients treated with HT between June 2006 and December 2013 were included in this retrospective study. All patients received neoadjuvant ADT for a median duration of 10 months followed by HT at a median dose of 78 Gy [interquartile range (IQR) 78–78]. The times of median adjuvant and total ADT were 19 and 27 months (IQR 20–31), respectively. The risk stratification followed the 2015 National Comprehensive Cancer Network criteria. Biochemical disease-free survival (bDFS) followed the Phoenix definition. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale.

Results

Median follow-up from HT start was 60 months (IQR 42–81). Five-year bDFS rates for low-, intermediate-, high-, and very-high-risk groups were 100, 98.2, 97.7, and 87.9 %, respectively. We observed clinical relapse in nine very-high-risk patients and one high-risk patient, resulting in a 5-year clinical relapse-free survival of 100, 100, 99.4, and 91.7 %, respectively, for each risk group. Three patients died of prostate cancer, resulting in a 5-year prostate cancer-specific survival of 99.6 %. The late grade 2 or higher gastrointestinal and genitourinary toxicities were 9.7 and 10.7 %. No cardiovascular fatal events were observed.

Conclusions

This report confirmed the excellent outcomes with acceptable late toxicities with the combination of HT and long-term ADT. Longer follow-up is crucial to further determine the treatment effect and toxicity.

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References

  • Alicikus ZA, Yamada Y, Zhang Z, Pei X, Hunt M, Kollmeier M, Cox B, Zelefsky MJ (2011) Ten-year outcomes of high-dose, intensity-modulated radiotherapy for localized prostate cancer. Cancer 117(7):1429–1437

    Article  PubMed  Google Scholar 

  • Amini A, Rusthoven CG, Jones BL, Armstrong H, Raben D, Kavanagh BD (2016) Survival outcomes of radiotherapy with or without androgen-deprivation therapy for patients with intermediate-risk prostate cancer using the National Cancer Data Base. Urol Oncol 34(4):165.e1–165.e9

    Article  Google Scholar 

  • Berrington de Gonzalez A, Wong J, Kleinerman R, Kim C, Morton L, Bekelman JE (2015) Risk of second cancers according to radiation therapy technique and modality in prostate cancer survivors. Int J Radiat Oncol Biol Phys 91(2):295–302

    Article  PubMed  Google Scholar 

  • Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Pierart M, Mauer ME, Collette L (2009) Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 360(24):2516–2527

    Article  CAS  PubMed  Google Scholar 

  • Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Billiet I, Torecilla JL, Pfeffer R, Cutajar CL, Van der Kwast T, Collette L (2010) External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 11(11):1066–1073

    Article  CAS  PubMed  Google Scholar 

  • Bolla M, Maingon P, Carrie C, Villa S, Kitsios P, Poortmans PM, Sundar S, van der Steen-Banasik EM, Armstrong J, Bosset JF, Herrera FG, Pieters B, Slot A, Bahl A, Ben-Yosef R, Boehmer D, Scrase C, Renard L, Shash E, Coens C, van den Bergh AC, Collette L (2016) Short androgen suppression and radiation dose escalation for intermediate- and high-risk localized prostate cancer: results of EORTC Trial 22991. J Clin Oncol. doi:10.1200/JCO.2015.64.8055

    PubMed  Google Scholar 

  • Brenner DJ, Curtis RE, Hall EJ, Ron E (2000) Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer 88(2):398–406

    Article  CAS  PubMed  Google Scholar 

  • Bria E, Cuppone F, Giannarelli D, Milella M, Ruggeri EM, Sperduti I, Pinnaro P, Terzoli E, Cognetti F, Carlini P (2009) Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer? Meta-analysis of randomized trials. Cancer 115(15):3446–3456

    Article  PubMed  Google Scholar 

  • Cooperberg MR, Broering JM, Carroll PR (2010) Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol 28(7):1117–1123

    Article  PubMed  PubMed Central  Google Scholar 

  • Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31(5):1341–1346

    Article  CAS  PubMed  Google Scholar 

  • D’Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW (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(7):821–827

    Article  PubMed  Google Scholar 

  • Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D’Este C (2011) Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 12(5):451–459

    Article  CAS  PubMed  Google Scholar 

  • Dubray BM, Beckendorf V, Guerif S et al (2011) Does short-term androgen depletion add to high-dose radiotherapy (80 Gy) in localized intermediate-risk prostate cancer? Intermediate analysis of GETUG 14 randomized trial (EU-20503/NCT00104741). Proc Am Soc Clin Oncol 29(suppl):4521 (abstr)

    Google Scholar 

  • Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR (2008) Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02. Eur Urol 54(4):816–823

    Article  CAS  PubMed  Google Scholar 

  • Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR (2009) Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol 27(1):92–99

    Article  PubMed  Google Scholar 

  • Feng FY, Blas K, Olson K, Stenmark M, Sandler H, Hamstra DA (2013) Retrospective evaluation reveals that long-term androgen deprivation therapy improves cause-specific and overall survival in the setting of dose-escalated radiation for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 86(1):64–71

    Article  PubMed  Google Scholar 

  • Gonzalez BD, Jim HS, Booth-Jones M, Small BJ, Sutton SK, Lin HY, Park JY, Spiess PE, Fishman MN, Jacobsen PB (2015) Course and predictors of cognitive function in patients with prostate cancer receiving androgen-deprivation therapy: a controlled comparison. J Clin Oncol 33(18):2021–2027

    Article  PubMed  Google Scholar 

  • Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU (2008) Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol 26:2497–2504

    Article  CAS  PubMed  Google Scholar 

  • Jao SW, Beart RW Jr, Reiman HM, Gunderson LL, Ilstrup DM (1987) Colon and anorectal cancer after pelvic irradiation. Dis Colon Rectum 30:953–958

    Article  CAS  PubMed  Google Scholar 

  • Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU (2011) Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 365(2):107–118

    Article  CAS  PubMed  Google Scholar 

  • Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458

    Article  CAS  PubMed  Google Scholar 

  • Kapatoes JM, Olivera GH, Ruchala KJ, Smilowitz JB, Reckwerdt PJ, Mackie TR (2001) A feasible method for clinical delivery verification and dose reconstruction in tomotherapy. Med Phys 28(4):528–542

    Article  CAS  PubMed  Google Scholar 

  • Moon K, Stukenborg GJ, Keim J, Theodorescu D (2006) Cancer incidence after localized therapy for prostate cancer. Cancer 107(5):991–998

    Article  PubMed  Google Scholar 

  • Narang AK, Gergis C, Robertson AK, He P, Ram AN, McNutt TR, Griffith E, DeWeese TA, Honig S, Singh H, Song DY, Tran PT, DeWeese TL (2016) Very high-risk localized prostate cancer: outcomes following definitive radiation. Int J Radiat Oncol Biol Phys 94(2):254–262

    Article  PubMed  Google Scholar 

  • National Comprehensive Cancer Network (2015) NCCN clinical practice guidelines in oncology: prostate cancer V1 2015. http://www.nccn.org/. Accessed 10 April 2015

  • Nead KT, Gaskin G, Chester C, Swisher-McClure S, Dudley JT, Leeper NJ, Shah NH (2016) Androgen deprivation therapy and future Alzheimer’s disease risk. J Clin Oncol 34(6):566–571

    Article  CAS  PubMed  Google Scholar 

  • Neugut AI, Ahsan H, Robinson E, Ennis RD (1997) Bladder carcinoma and other second malignancies after radiotherapy for prostate carcinoma. Cancer 79(8):1600–1604

    Article  CAS  PubMed  Google Scholar 

  • Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, Beckman JA, Choueiri TK (2011) Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA 306(21):2359–2366

    Article  CAS  PubMed  Google Scholar 

  • Onozawa M, Hinotsu S, Tsukamoto T, Oya M, Ogawa O, Kitamura T, Suzuki K, Naito S, Namiki M, Nishimura K, Hirao Y, Akaza H (2014) Recent trends in the initial therapy for newly diagnosed prostate cancer in Japan. Jpn J Clin Oncol 44(10):969–981

    Article  PubMed  Google Scholar 

  • Pickles T, Phillips N (2002) The risk of second malignancy in men with prostate cancer treated with or without radiation in British Columbia, 1984–2000. Radiother Oncol 65:145–151

    Article  PubMed  Google Scholar 

  • Pollack A, Abramowitz MC (2016) Weighing the addition of androgen suppression therapy to radiotherapy dose escalation for intermediate-risk prostate cancer. J Clin Oncol. doi:10.1200/JCO.2015.66.2320

    PubMed  Google Scholar 

  • Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H (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(4):965–974

    Article  PubMed  Google Scholar 

  • Roach M 3rd, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, Lawton C, Valicenti R, Grignon D, Pilepich MV (2008) Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 26(4):585–591

    Article  PubMed  Google Scholar 

  • Schmidt-Hansen M, Hoskin P, Kirkbride P, Hasler E, Bromham N (2014) Hormone and radiotherapy versus hormone or radiotherapy alone for non-metastatic prostate cancer: a systematic review with meta-analyses. Clin Oncol (R Coll Radiol) 26(10):e21–e46

    Article  CAS  Google Scholar 

  • Sharma NK, Li T, Chen DY, Pollack A, Horwitz EM, Buyyounouski MK (2011) Intensity-modulated radiotherapy reduces gastrointestinal toxicity in patients treated with androgen deprivation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 80(2):437–444

    Article  PubMed  Google Scholar 

  • Tabata N, Ohno Y, Matsui R, Sugiyama H, Ito Y, Tsukuma H, Oshima A (2008) Partial cancer prevalence in Japan up to 2020: estimates based on incidence and survival data from population-based cancer registries. Jpn J Clin Oncol 38(2):146–157

    Article  PubMed  Google Scholar 

  • Tendulkar RD, Reddy CA, Stephans KL, Ciezki JP, Klein EA, Mahadevan A, Kupelian PA (2012) Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Int J Radiat Oncol Biol Phys 82(4):1397–1404

    Article  PubMed  Google Scholar 

  • Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S, Sugimoto S, Ikeda T, Terasaki M, Izumi S et al (1994) Cancer incidence in atomic bomb survivors. Part II: solid tumors, 1958–1987. Radiat Res 137(2 Suppl):S17–S67

    Article  CAS  PubMed  Google Scholar 

  • Tomita N, Kodaira T, Tachibana H, Nakamura T, Tomoda T, Nakahara R, Inokuchi H, Hayashi N, Fuwa N (2009) Dynamic conformal arc radiotherapy with rectum hollow-out technique for localized prostate cancer. Radiother Oncol 90(3):346–352

    Article  PubMed  Google Scholar 

  • Tomita N, Soga N, Ogura Y, Hayashi N, Shimizu H, Kubota T, Ito J, Hirata K, Ohshima Y, Tachibana H, Kodaira T (2012) Preliminary results of intensity-modulated radiation therapy with helical tomotherapy for prostate cancer. J Cancer Res Clin Oncol 138(11):1931–1936

    Article  CAS  PubMed  Google Scholar 

  • Tomita N, Kodaira T, Teshima T, Ogawa K, Kumazaki Y, Yamauchi C, Toita T, Uno T, Sumi M, Onishi H, Kenjo M, Nakamura K (2014) Japanese structure survey of high-precision radiotherapy in 2012 based on institutional questionnaire about the patterns of care. Jpn J Clin Oncol 44(6):579–586

    Article  PubMed  Google Scholar 

  • Ueshima H (2007) Explanation for the Japanese paradox: prevention of increase in coronary heart disease and reduction in stroke. J Atheroscler Thromb 14:278–286

    Article  PubMed  Google Scholar 

  • Ueshima H, Sekikawa A, Miura K, Turin TC, Takashima N, Kita Y, Watanabe M, Kadota A, Okuda N, Kadowaki T, Nakamura Y, Okamura T (2008) Cardiovascular disease and risk factors in Asia: a selected review. Circulation 118:2702–2709

    Article  PubMed  PubMed Central  Google Scholar 

  • Viani GA, Stefano EJ, Afonso SL (2009) Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys 74:1405–1418

    Article  PubMed  Google Scholar 

  • Wong WW, Vora SA, Schild SE, Ezzell GA, Andrews PE, Ferrigni RG, Swanson SK (2009) Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy. Cancer 115(23):5596–5606

    Article  CAS  PubMed  Google Scholar 

  • Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodriguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villa S, Perez de la Haza A, Calvo FA (2015) High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol 16(3):320–327

    Article  CAS  PubMed  Google Scholar 

  • Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, Amols HI (2008a) Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 70(4):1124–1129

    Article  PubMed  Google Scholar 

  • Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O, Park J, Shippy A (2008b) Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation on biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 71(4):1028–1033

    Article  PubMed  Google Scholar 

  • Zumsteg ZS, Zelefsky MJ (2012) Short-term androgen deprivation therapy for patients with intermediate-risk prostate cancer undergoing dose-escalated radiotherapy: the standard of care? Lancet Oncol 13(6):e259–e269. doi:10.1016/S1470-2045(12)70084-0

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusaku, Nagoya, 464-8681, Japan

    Natsuo Tomita, Makoto Ito, Yutaro Koide, Maiko Yoshida, Kana Kimura, Chiyoko Makita, Hiroyuki Tachibana & Takeshi Kodaira

  2. Department of Urology, Aichi Cancer Center Hospital, Nagoya, Japan

    Norihito Soga, Yuji Ogura, Norio Hayashi & Takumi Kageyama

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  1. Natsuo Tomita
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  2. Norihito Soga
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  3. Yuji Ogura
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  4. Norio Hayashi
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  5. Takumi Kageyama
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  6. Makoto Ito
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  7. Yutaro Koide
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  8. Maiko Yoshida
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  9. Kana Kimura
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  10. Chiyoko Makita
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  11. Hiroyuki Tachibana
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  12. Takeshi Kodaira
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Correspondence to Natsuo Tomita.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or similar ethical standards.

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Informed consent was obtained from all patients included in the study.

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Tomita, N., Soga, N., Ogura, Y. et al. High-dose radiotherapy with helical tomotherapy and long-term androgen deprivation therapy for prostate cancer: 5-year outcomes. J Cancer Res Clin Oncol 142, 1609–1619 (2016). https://doi.org/10.1007/s00432-016-2173-9

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  • DOI: https://doi.org/10.1007/s00432-016-2173-9

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