Skip to main content
SpringerLink
Log in

Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

Ergebnisse der lokoregionalen Strahlentherapie bei metastatischen kastrationsresistenten und mit Abirateronacetat behandelten Prostakarzinompatienten

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone.

Materials and methods

The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed.

Resultsn

Median follow-up time was 14.2 months (range: 2.3–54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

Conclusions

Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

Zusammenfassung

Ziel

Bewertung des potenziellen Nutzens der kurativen Strahlentherapie (RT) für den Primärtumor bei Patienten mit metastasiertem kastrationsresistentem Prostatakrebs (mCRPC), die mit Abirateron behandelt werden.

Material und Methoden

Die klinischen Parameter von 106 mit Abirateron behandelten mCRPC-Patienten wurden retrospektiv bewertet. Die Patienten waren bei der Diagnose entweder oligometastatisch (≤5 Metastasen) oder wurden nach Analyse der systemischen Behandlung oligometastatisch. Eine lokale RT für Primärtumor und Beckenlymphknoten bekamen 44 Patienten (41%), 62 Patienten (59%) hatten keine RT des Primärtumors. Nach der Propensity-Match-Analyse wurden insgesamt 92 Patienten analysiert.

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 14,2 Monate (Spanne 2,3–54,9 Monate). Das mediane Gesamtüberleben (OS) war bei den mit lokaler RT behandelten Patienten gegenüber dem Primärtumor höher als bei denjenigen ohne lokale RT, mit grenzwertiger Signifikanz (24,1 vs. 21,4 Monate; p = 0,08). Die lokale RT für die Prostata- und Beckenlymphatika verringerte signifikant die lokale Rezidivrate (16 Patienten, 31% vs. 2 Patienten, 5%; p = 0,003). In der multivariaten Analyse war die 3 Wochen nach Abiraterontherapie ermittelte PSA-Antwort ≥50 des Ausgangswerts der einzige signifikante Prognosefaktor für ein besseres OS und progressionsfreies Überleben (PFS). Patienten, die mit primärer Prostata-RT behandelt wurden, zeigten eine signifikant geringere Progression unter Abirateron und eine längere Abirateron-Periode als Patienten ohne lokale Prostata-RT.

Schlussfolgerung

Die lokale Prostata-RT verbesserte das OS und die lokale Kontrolle bei mit Abirateron behandelten mCRPC-Patienten signifikant. Die mit primärer RT behandelten Patienten hatten unter Abirateron eine deutlich geringere Progression und eine längere Abirateron-Periode als Patienten, die ohne lokale Prostata-RT behandelt wurden.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer Statistics, 2017. CA Cancer J Clin 67(1):7–30. https://doi.org/10.3322/caac.21387

    Article  PubMed  Google Scholar 

  2. Crawford ED, Higano CS, Shore ND, Hussain M, Petrylak DP (2015) Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol 194(6):1537–1547. https://doi.org/10.1016/j.juro.2015.06.106

    Article  PubMed  Google Scholar 

  3. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr., Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI, COU-AA-301 Investigators (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364(21):1995–2005. https://doi.org/10.1056/NEJMoa1014618

    Article  PubMed  PubMed Central  Google Scholar 

  4. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS, AFFIRM Investigators (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367(13):1187–1197. https://doi.org/10.1056/NEJMoa1207506

    Article  CAS  PubMed  Google Scholar 

  5. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO, TROPIC Investigators (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376(9747):1147–1154. https://doi.org/10.1016/S0140-6736(10)61389-X

    Article  CAS  PubMed  Google Scholar 

  6. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF, IMPACT Study Investigators (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422. https://doi.org/10.1056/NEJMoa1001294

    Article  CAS  PubMed  Google Scholar 

  7. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall’Oglio M, Franzen L, Coleman R, Vogelzang NJ, O’Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland OS, Sartor O, ALSYMPCA Investigators (2013) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369(3):213–223. https://doi.org/10.1056/NEJMoa1213755

    Article  CAS  PubMed  Google Scholar 

  8. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B, PREVAIL Investigators (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371(5):424–433. https://doi.org/10.1056/NEJMoa1405095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE, COU-AA-302 Investigators (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 1(4):152–160. https://doi.org/10.1016/S1470-2045

    Article  Google Scholar 

  10. Dy SM, Asch SM, Naeim A, Sanati H, Walling A, Lorenz KA (2008) Evidence-based standards for cancer pain management. J Clin Oncol 26(23):3879–3885. https://doi.org/10.1200/JCO.2007.15.9517

    Article  PubMed  Google Scholar 

  11. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R, European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group (2001) Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 358(9286):966–970

    Article  CAS  Google Scholar 

  12. Temple LK, Hsieh L, Wong WD, Saltz L, Schrag D (2004) Use of surgery among elderly patients with stage IV colorectal cancer. J Clin Oncol 22(17):3475–3484. https://doi.org/10.1200/JCO.2004.10.218

    Article  PubMed  Google Scholar 

  13. 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. https://doi.org/10.1002/cncr.25467

    Article  PubMed  Google Scholar 

  14. Culp SH, Karam JA, Wood CG (2014) Population-based analysis of factors associated with survival in patients undergoing cytoreductive nephrectomy in the targeted therapy era. Urol Oncol 32(5):561–568. https://doi.org/10.1016/j.urolonc.2013.12.003

    Article  PubMed  Google Scholar 

  15. Fossati N, Trinh QD, Sammon J, Sood A, Larcher A, Sun M, Karakiewicz P, Guazzoni G, Montorsi F, Briganti A, Menon M, Abdollah F (2015) Identifying optimal candidates for local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: a SEER-based study. Eur Urol 67(1):3–6. https://doi.org/10.1016/j.eururo.2014.08.056

    Article  PubMed  Google Scholar 

  16. Satkunasivam R, Kim AE, Desai M, Nguyen MM, Quinn DI, Ballas L, Lewinger JP, Stern MC, Hamilton AS, Aron M, Gill IS (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(2):378–385. https://doi.org/10.1016/j.juro.2015.02.084

    Article  PubMed  PubMed Central  Google Scholar 

  17. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M, Prostate Cancer Clinical Trials Working Group (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26(7):1148–1159. https://doi.org/10.1200/JCO.2007.12.4487

    Article  PubMed  PubMed Central  Google Scholar 

  18. Aizawa R, Takayama K, Nakamura K, Inoue T, Kobayashi T, Akamatsu S, Yamasaki T, Ogawa O, Mizowaki T (2018) Long-term outcomes of definitive external-beam radiotherapy for non-metastatic castration-resistant prostate cancer. Int J Clin Oncol. https://doi.org/10.1007/s10147-018-1265-8

    Article  PubMed  Google Scholar 

  19. Lankford SP, Pollack A, Zagars GK (1995) Radiotherapy for regionally localized hormone refractory prostate cancer. Int J Radiat Oncol Biol Phys 33(4):907–912. https://doi.org/10.1016/0360-3016(95)02005-0

    Article  CAS  PubMed  Google Scholar 

  20. Botticella A, Guarneri A, Filippi AR, Levra NG, Munoz F, Ragona R, Gontero P, Ricardi U (2013) May non-metastatic clinically localized castration-resistant prostate cancer after primary androgen ablation benefit from salvage prostate radiotherapy? J Cancer Res Clin Oncol 139(11):1955–1960. https://doi.org/10.1007/s00432-013-1520-3

    Article  PubMed  Google Scholar 

  21. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA, TAX 327 Investigators (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351(15):1502–1512. https://doi.org/10.1056/NEJMoa040720

    Article  CAS  PubMed  Google Scholar 

  22. Fidler IJ, Poste G (2008) The “seed and soil” hypothesis revisited. Lancet Oncol 9(8):808. https://doi.org/10.1016/S1470-2045(08)70201-8

    Article  PubMed  Google Scholar 

  23. Kaplan RN, Rafii S, Lyden D (2006) Preparing the “soil”: the premetastatic niche. Cancer Res 66(23):11089–11093. https://doi.org/10.1158/0008-5472.CAN-06-2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L, Massague J (2009) Tumor self-seeding by circulating cancer cells. Cell 139(7):1315–1326. https://doi.org/10.1016/j.cell.2009.11.025

    Article  PubMed  PubMed Central  Google Scholar 

  25. Resel Folkersma L, San Jose Manso L, Galante Romo I, Moreno Sierra J, Olivier Gomez C (2012) Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer. Urology 80(6):1328–1332. https://doi.org/10.1016/j.urology.2012.09.001

    Article  PubMed  Google Scholar 

  26. Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr., Munshi N, Crawford ED (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 345(23):1655–1659. https://doi.org/10.1056/NEJMoa003013

    Article  CAS  PubMed  Google Scholar 

  27. Rusthoven CG, Jones BL, Flaig TW, Crawford ED, Koshy M, Sher DJ, Mahmood U, Chen RC, Chapin BF, Kavanagh BD, Pugh TJ (2016) Improved survival with prostate radiation in addition to androgen deprivation therapy for men with newly diagnosed metastatic prostate cancer. J Clin Oncol 34(24):2835–2842. https://doi.org/10.1200/jco.2016.67.4788

    Article  CAS  PubMed  Google Scholar 

  28. Kirby M, Hirst C, Crawford ED (2011) Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 65(11):1180–1192. https://doi.org/10.1111/j.1742-1241.2011.02799.x

    Article  CAS  PubMed  Google Scholar 

  29. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE, COU-AA-302 Investigators (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368(2):138–148. https://doi.org/10.1056/NEJMoa1209096

    Article  CAS  PubMed  Google Scholar 

  30. O’Donnell A, Judson I, Dowsett M, Raynaud F, Dearnaley D, Mason M, Harland S, Robbins A, Halbert G, Nutley B, Jarman M (2004) Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 90(12):2317–2325. https://doi.org/10.1038/sj.bjc.6601879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Luu-The V, Belanger A, Labrie F (2008) Androgen biosynthetic pathways in the human prostate. Best Pract Res Clin Endocrinol Metab 22(2):207–221. https://doi.org/10.1016/j.beem.2008.01.008

    Article  CAS  PubMed  Google Scholar 

  32. Mostaghel EA, Cho E, Zhang A, Alyamani M, Kaipainen A, Green S, Marck BT, Sharifi N, Wright JL, Gulati R, True LD, Loda M, Matsumoto AM, Tamae D, Penning TN, Balk SP, Kantoff PW, Nelson PS, Taplin ME, Montgomery RB (2017) Association of tissue Abiraterone levels and SLCO genotype with Intraprostatic steroids and pathologic response in men with high-risk localized prostate cancer. Clin Cancer Res 23(16):4592–4601. https://doi.org/10.1158/1078-0432.CCR-16-2245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Rescigno P, Lorente D, Bianchini D, Ferraldeschi R, Kolinsky MP, Sideris S, Zafeiriou Z, Sumanasuriya S, Smith AD, Mehra N, Jayaram A, Perez-Lopez R, Mateo J, Parker C, Dearnaley DP, Tunariu N, Reid A, Attard G, de Bono JS (2016) Prostate-specific antigen decline after 4 weeks of treatment with abiraterone acetate and overall survival in patients with metastatic castration-resistant prostate cancer. Eur Urol 70(5):724–731. https://doi.org/10.1016/j.eururo.2016.02.055

    Article  CAS  PubMed  Google Scholar 

  34. Sridhara R, Eisenberger MA, Sinibaldi VJ, Reyno LM, Egorin MJ (1995) Evaluation of prostate-specific antigen as a surrogate marker for response of hormone-refractory prostate cancer to suramin therapy. J Clin Oncol 13(12):2944–2953. https://doi.org/10.1200/JCO.1995.13.12.2944

    Article  CAS  PubMed  Google Scholar 

  35. Kelly WK, Scher HI, Mazumdar M, Vlamis V, Schwartz M, Fossa SD (1993) Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer. J Clin Oncol 11(4):607–615. https://doi.org/10.1200/JCO.1993.11.4.607

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Faculty of Medicine, Adana Dr. Turgut Noyan Research and Treatment Centre, Baskent University, 01120, Adana, Turkey

    Berna Akkus Yildirim MD, Cem Onal MD & Ozan Cem Guler MD

  2. Division of Medical Oncology, Faculty of Medicine, Baskent University, 01120, Adana, Turkey

    Fatih Kose MD, Ali Ayberk Besen MD, Ahmet Taner Sumbul MD & Huseyin Mertsoylu MD

  3. Division of Radiation Oncology, Iskenderun Gelisim Hospital, Hatay, Turkey

    Ezgi Oymak MD

  4. Division of Medical Oncology, Adana City Hospital, Adana, Turkey

    Ali Murat Sedef MD

  5. Division of Medical Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Sercan Aksoy MD

  6. Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Sadık Muallaoglu MD & Gokhan Ozyigit MD

Authors
  1. Berna Akkus Yildirim MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cem Onal MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatih Kose MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ezgi Oymak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali Murat Sedef MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ali Ayberk Besen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sercan Aksoy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ozan Cem Guler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ahmet Taner Sumbul MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sadık Muallaoglu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Huseyin Mertsoylu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gokhan Ozyigit MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cem Onal MD.

Ethics declarations

Conflict of interest

B.A. Yildirim, C. Onal, F. Kose, E. Oymak, A.M. Sedef, A.A. Besen, S. Aksoy, O.C. Guler, A.T. Sumbul, S. Muallaoglu, H. Mertsoylu, and G. Ozyigit declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yildirim, B.A., Onal, C., Kose, F. et al. Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate. Strahlenther Onkol 195, 872–881 (2019). https://doi.org/10.1007/s00066-019-01429-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-019-01429-6

Keywords

Schlüsselwörter

Search

Navigation