Salvage Radiotherapy After Radical Prostatectomy

  • Alexandros Papachristofilou
  • Pirus Ghadjar
  • Frank Zimmermann
Part of the Medical Radiology book series (MEDRAD)


Salvage radiation therapy is the sole curative treatment for patients experiencing biochemical relapse after radical surgical treatment of prostate cancer. The main dilemma in salvage radiation therapy is, whether or not biochemical relapse represents purely localized recurrent disease in the prostatic fossa or systemic micrometastasis. Initiating salvage radiation therapy at an early time point raises its chances of success, but may lead to overtreatment of patients. Target volume definition and treatment techniques are a matter of current research, with still many questions unanswered. Strategies of treatment escalation either by increasing the treatment dose or combining radiation therapy with androgen deprivation therapy are being addressed in clinical trials.


Prostate Specific Antigen Radical Prostatectomy National Comprehensive Cancer Network Androgen Deprivation Therapy National Comprehensive Cancer Network 


Conflict of Interest Notification

The authors have no actual or potential conflict of interest related to this review. There are no financial disclosures from any author.


  1. A phase III randomized trial of MRI-mapped dose-escalated salvage radiotherapy post-prostatectomy: the MAPS trial. Accessed 26 Nov 2012
  2. Alongi F, Fiorino C, Cozzarini C et al (2009) IMRT significantly reduces acute toxicity of whole-pelvis irradiation in patients treated with post-operative adjuvant or salvage radiotherapy after radical prostatectomy. Radiother Oncol 93(2):207–212PubMedCrossRefGoogle Scholar
  3. Amling CL, Blute ML, Bergstralh EJ et al (2000) Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol 164:101–105PubMedCrossRefGoogle Scholar
  4. Bolla M, van Poppel H, Collette L et al (2005) Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 366:572–578PubMedCrossRefGoogle Scholar
  5. Boorjian SA, Karnes RJ, Crispen PL et al (2009) Radiation therapy after radical prostatectomy: impact on metastasis and survival. J Urol 182(6):2708–2714PubMedCrossRefGoogle Scholar
  6. Buskirk SJ, Pisansky TM, Schild SE et al (2006) Salvage radiotherapy for isolated prostate specific antigen increase after radical prostatectomy: evaluation of prognostic factors and creation of a prognostic scoring system. J Urol 176(3):985–990PubMedCrossRefGoogle Scholar
  7. Cher ML, Bianco FJ Jr, Lam JS et al (1998) Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol 160(4):1387PubMedCrossRefGoogle Scholar
  8. Choo R, Danjoux C, Gardner S et al (2009) Efficacy of salvage radiotherapy plus 2-year androgen suppression for postradical prostatectomy patients with PSA relapse. Int J Radiat Oncol Biol Phys 75(4):983–989PubMedCrossRefGoogle Scholar
  9. Corn BW, Winter K, Pilepich MV (1999) Does androgen suppression enhance the efficacy of postoperative irradiation? A secondary analysis of RTOG 85-31 Radiation Therapy Oncology Group. Urology 54(3):495–502PubMedCrossRefGoogle Scholar
  10. Cotter SE, Chen MH, Moul JW (2011) Salvage radiation in men after prostate-specific antigen failure and the risk of death. Cancer 117(17):3925–3932PubMedCrossRefGoogle Scholar
  11. Da Pozzo LF, Cozzarini C, Briganti A et al (2009) Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur Urol 55(5):1003–1011PubMedCrossRefGoogle Scholar
  12. Dearnaley DP, Khoo VS, Norman AR et al (1999) Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet 353(9149):267–272PubMedCrossRefGoogle Scholar
  13. Digesú C, Cilla S, De Gaetano A et al. (2011) Postoperative intensity modulated radiation therapy in high risk prostate cancer: a dosimetric comparison. Med Dosim 36(3):231–239 (Autumn)Google Scholar
  14. European Urology Association Guidelines on Prostate Cancer (2012). Accessed 26 Nov 2012
  15. Feng M, Hanlon AL, Pisansky TM (2007) Predictive factors for late genitourinary and gastrointestinal toxicity in patients with prostate cancer treated with adjuvant or salvage radiotherapy. Int J Radiat Oncol Biol Phys 68(5):1417–1423PubMedCrossRefGoogle Scholar
  16. Geinitz H, Riegel MG, Thamm R et al (2012) Outcome after conformal salvage radiotherapy in patients with rising prostate-specific antigen levels after radical prostatectomy. Int J Radiat Oncol Biol Phys 82(5):1930–1937PubMedCrossRefGoogle Scholar
  17. Giannarini G, Nguyen DP, Thalmann GN et al (2012) Diffusion-weighted magnetic resonance imaging detects local recurrence after radical prostatectomy: initial experience. Eur Urol 61(3):616–620PubMedCrossRefGoogle Scholar
  18. Goenka A, Magsanoc JM, Pei X et al (2011) Improved toxicity profile following high-dose post prostatectomy salvage radiation therapy with intensity-modulated radiation therapy. Eur Urol 60(6):1142–1148PubMedCrossRefGoogle Scholar
  19. Graute V, Jansen N, Ubleis C et al (2012) Relationship between PSA kinetics and (18F) fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy. Eur J Nucl Med Mol Imag 39(2):271–282CrossRefGoogle Scholar
  20. Han M, Partin AW, Zahurak M et al (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 169:517–523PubMedCrossRefGoogle Scholar
  21. Huch Böni RA, Meyenberger C, Pok Lundquist J et al. (1996) Value of endorectal coil versus body coil MRI for diagnosis of recurrent pelvic malignancies. Abdom Imag 21(4):345–352Google Scholar
  22. Katz MS, Zelefsky MJ, Venkatraman ES et al (2003) Predictors of biochemical outcome with salvage conformal radiotherapy after radical prostatectomy for prostate cancer. J Clin Oncol 21(3):483–489PubMedCrossRefGoogle Scholar
  23. King CR (2012) The timing of salvage radiotherapy after radical prostatectomy: a systematic review. Int J Radiat Oncol Biol Phys 84(1):104–111PubMedCrossRefGoogle Scholar
  24. King CR, Kapp DS (2008) Radiotherapy after prostatectomy: is the evidence for dose escalation out there? Int J Radiat Oncol Biol Phys 71:346–350PubMedCrossRefGoogle Scholar
  25. King CR, Spiotto MT (2008) Improved outcomes with higher doses for salvage radiotherapy after prostatectomy. Int J Radiat Oncol Biol Phys 71:23–27PubMedCrossRefGoogle Scholar
  26. King CR, Presti JC Jr, Gill H et al (2004) Radiotherapy after radical prostatectomy: does transient androgen suppression improve outcomes? Int J Radiat Oncol Biol Phys 59(2):341–347PubMedCrossRefGoogle Scholar
  27. Kupelian PA, Katcher J, Levin HS, Klein EA (1997) Stage T1-prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy. Int J Radiat Oncol Biol Phys 37:1043–1052PubMedCrossRefGoogle Scholar
  28. Lawton CA, DeSilvio M, Roach M 3rd et al (2007) An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 69(3):646–655PubMedCentralPubMedCrossRefGoogle Scholar
  29. Liauw SL, Pitroda SP, Eggener SE et al. (2012) Evaluation of the prostate bed for local recurrence after radical prostatectomy using endorectal magnetic resonance imaging. Int J Radiat Oncol Biol Phys 85:378–384Google Scholar
  30. Macdonald OK, D’Amico AV, Sadetsky N et al. (2008) Predicting PSA failure following salvage radiotherapy for a rising PSA post-prostatectomy: from the CaPSURE database. Urol Oncol 26(3):271–275Google Scholar
  31. Meerleer GD, Fonteyne V, Meersshout S et al (2008) Salvage intensity-modulated radiotherapy for rising PSA after radical prostatectomy. Radiother Oncol 89:205–213PubMedCrossRefGoogle Scholar
  32. Meng MV, Shinohara K, Grossfeld GD, Carroll PR (2002) Local therapy for recurrent prostate cancer. In: Kantoff PW, Carroll PR, D’Amico AV (eds) Prostate cancer: principles and practice, pp 307–316. Lippincott Williams and Wilkins, Philadelphia Google Scholar
  33. Michalski J, Lawton C, El Naqa I et al (2010) Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 76(2):361–368PubMedCentralPubMedCrossRefGoogle Scholar
  34. Nath SK, Sandhu AP, Rose BS et al (2010) Toxicity analysis of postoperative image-guided intensity-modulated radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 78(2):435–441PubMedCrossRefGoogle Scholar
  35. NCCN (2012) Clinical practice guidelines in oncology: prostate cancer version 3.2012. Accessed on 26 Nov 2012
  36. Neuhof D, Hentschel T, Bischof M et al (2007) Long-term results and predictive factors of three-dimensional conformal salvage radiotherapy for biochemical relapse after prostatectomy. Int J Radiat Oncol Biol Phys 67:1411–1417PubMedCrossRefGoogle Scholar
  37. Nguyen PL, Je Y, Schutz FA et al (2011) Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA 306(21):2359–2366PubMedCrossRefGoogle Scholar
  38. Ohri N, Dicker AP, Trabulsi EJ et al (2012a) Can early implementation of salvage radiotherapy for prostate cancer improve the therapeutic ratio? A systematic review and regression meta-analysis with radiobiological modelling. Eur J Cancer 48(6):837–844PubMedCrossRefGoogle Scholar
  39. Ohri N, Dicker AP, Trabulsi EJ et al (2012b) Can early implementation of salvage radiotherapy for prostate cancer improve the therapeutic ratio? A systematic review and regression meta-analysis with radiobiological modelling. Eur J Cancer 48(6):837–844PubMedCrossRefGoogle Scholar
  40. Paul R, Hoppmann M, van Randenborgh H et al (2004) Residual benign prostatic glands at the urethrovesical anastomosis after radical retropubic prostatectomy: prediction and impact on disease outcome. Eur Urol 46(3):321–326PubMedCrossRefGoogle Scholar
  41. Pazona JF, Han M, Hawkins SA et al (2005) Salvage radiation therapy for prostate specific antigen progression following radical prostatectomy: 10-year outcome estimates. J Urol 174(4 Pt 1):1282–1286PubMedCrossRefGoogle Scholar
  42. Pearse M, Choo R, Danjoux C et al (2008) Prospective assessment of gastrointestinal and genitourinary toxicity of salvage radiotherapy for patients with prostate-specific antigen relapse or local recurrence after radical prostatectomy. Int J Radiat Oncol Biol Phys 72(3):792–798PubMedCrossRefGoogle Scholar
  43. Picchio M, Briganti A, Fanti S et al (2011) The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol 59(1):51–60PubMedCrossRefGoogle Scholar
  44. Pisansky TM, Kozelsky TF, Myers RP et al (2000) Radiotherapy for isolated serum prostate specific antigen elevation after prostatectomy for prostate cancer. J Urol 163(3):845–850PubMedCrossRefGoogle Scholar
  45. Pommier P, Chabaud S, Lagrange JL et al (2007) Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol 25(34):5366–5373PubMedCrossRefGoogle Scholar
  46. Poortmans P, Bossi A, Vandeputte K et al (2007) Guidelines for target volume definition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC Radiation Oncology Group. Radiother Oncol 84(2):121–127PubMedCrossRefGoogle Scholar
  47. Pound CR, Partin AW, Eisenberger MA et al (1999) Natural history of progression after PSA elevation following radical prostatectomy. JAMA 281:1591–1597PubMedCrossRefGoogle Scholar
  48. Prostate radiation therapy or short-term androgen deprivation therapy and pelvic lymph node radiation therapy with or without prostate radiation therapy in treating patients with a rising PSA after surgery for prostate cancer. Accessed 26 Nov 2012
  49. Radiation therapy and androgen deprivation therapy in treating patients who have undergone surgery for prostate cancer (RADICALS). Accessed 26 Nov 2012
  50. Radiation therapy in treating patients with relapsed prostate cancer after surgery. Accessed 26 Nov 2012
  51. Radiation therapy with or without Goserelin in treating patients who have undergone surgery for recurrent or refractory prostate cancer. Accessed 26 Nov 2012
  52. Radiation therapy with or without hormone therapy in treating patients who have undergone surgery for stage I, stage II, or stage III prostate cancer. Accessed 26 Nov 2012
  53. Radiotherapy—Adjuvant Versus Early Salvage (RAVES). Accessed 26 Nov 2012
  54. Riou O, Laliberte B, Azria D et al. (2012) Implementing intensity modulated radiotherapy to the prostate bed: dosimetric study and early clinical results. Med Dosim pii: S0958-3947 (12) 00167-7Google Scholar
  55. RTOG (2012) Pelvic lymph node volumes for prostate cancer atlas. Accessed 26 Nov 2012
  56. Schild SE, Wong WW, Novicki DE et al (1996) Detection of residual prostate cancer after radical prostatectomy with the Abbott IMx PSA assay. Urology 47(6):878–881PubMedCrossRefGoogle Scholar
  57. Sciarra A, Panebianco V, Salciccia S et al (2008) Role of dynamic contrast-enhanced magnetic resonance (MR) imaging and proton MR spectroscopic imaging in the detection of local recurrence after radical prostatectomy for prostate cancer. Eur Urol 54(3):589–600PubMedCrossRefGoogle Scholar
  58. Sciarra A, Panebianco V, Ciccariello M et al (2010) Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy. Clin Cancer Res 16(6):1875–1883PubMedCrossRefGoogle Scholar
  59. Shah O, Melamed J, Lepor H (2001) Analysis of apical soft tissue margins during radical retropubic prostatectomy. J Urol 165(6 Pt 1):1943–1948PubMedCrossRefGoogle Scholar
  60. Sheets NC, Goldin GH, Meyer AM et al (2012) Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA 307(15):1611–1620PubMedCentralPubMedCrossRefGoogle Scholar
  61. Shipley WU, Hunt D, Lukka HR et al. (2011) Initial report of RTOG 9601, a phase III trial in prostate cancer: effect of anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) on freedom from progression and incidence of metastatic disease in patients following radical prostatectomy (RP) with pT2-3, N0 disease and elevated PSA levels. J Clin Oncol 29 (suppl 7; abstr 1) Google Scholar
  62. Slovin SF, Wilton AS, Heller G, Scher HI (2005) Time to detectable metastatic disease in patients with rising prostate-specific antigen values following surgery or radiation therapy. Clin Cancer Res 11:8669–8673PubMedCrossRefGoogle Scholar
  63. Spiotto MT, Hancock SL, King CR (2007) Radiotherapy after prostatectomy: improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients. Int J Radiat Oncol Biol Phys 69(1):54–61PubMedCrossRefGoogle Scholar
  64. Stephenson AJ, Shariat SF, Zelefsky MJ et al (2004) Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA 291:1325–1332PubMedCrossRefGoogle Scholar
  65. Stephenson AJ, Scardino PT, Kattan MW et al (2007) Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 25:2035–2041PubMedCentralPubMedCrossRefGoogle Scholar
  66. Taylor N, Kelly JF, Kuban DA et al (2003) Adjuvant and salvage radiotherapy after radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys 56(3):755–763PubMedCrossRefGoogle Scholar
  67. Thompson IM Jr, Tangen CM, Paradelo J et al (2006) Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 296:2329–2335PubMedCrossRefGoogle Scholar
  68. Thompson IM, Tangen CM, Paradelo J et al (2009) Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 181:956–962PubMedCentralPubMedCrossRefGoogle Scholar
  69. Tiguert R, Rigaud J, Lacombe L et al (2003) Neoadjuvant hormone therapy before salvage radiotherapy for an increasing post-radical prostatectomy serum prostate specific antigen level. J Urol 170(2 Pt 1):447–450PubMedCrossRefGoogle Scholar
  70. Tongco WP, Wehner MS, Basler JW (2001) Does urethral-sparing prostatectomy risk residual prostate cancer? Urology 57(3):495–498PubMedCrossRefGoogle Scholar
  71. Trial to evaluate radiotherapy followed by endocrine therapy vs endocrine therapy alone for PSA failure after radical prostatectomy. Accessed on 26 Nov 2012
  72. Trock BJ, Han M, Freedland SJ et al (2008) Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 299(23):2760–2769PubMedCentralPubMedCrossRefGoogle Scholar
  73. 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 74:1405–1418PubMedCrossRefGoogle Scholar
  74. Ward JF, Moul JW (2005) Rising prostate-specific antigen after primary prostate cancer therapy. Nat Clin Pract Urol 2:174–182PubMedCrossRefGoogle Scholar
  75. Ward JF, Zincke H, Bergstralh EJ et al (2004) Prostate specific antigen doubling time subsequent to radical prostatectomy as a prognosticator of outcome following salvage radiotherapy. J Urol 172(6 Pt 1):2244–2248PubMedCrossRefGoogle Scholar
  76. Wiegel T, Bottke D, Bandlow P et al (2002) The value of PSA measurements at 30 Gy, 50 Gy and 60 Gy for dose limitation in patients with radiotherapy for PSA increase after radical prostatectomy. Strahlenther Onkol 178(8):422–425PubMedCrossRefGoogle Scholar
  77. Wiegel T, Bottke D, Steiner U et al (2009a) Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 27:2924–2930PubMedCrossRefGoogle Scholar
  78. Wiegel T, Lohm G, Bottke D et al (2009b) Achieving an undetectable PSA after radiotherapy for biochemical progression after radical prostatectomy is an independent predictor of biochemical outcome–results of a retrospective study. Int J Radiat Oncol Biol Phys 73(4):1009–1016PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Alexandros Papachristofilou
    • 1
  • Pirus Ghadjar
    • 2
  • Frank Zimmermann
    • 1
  1. 1.Department of Radiation OncologyUniversity Hospital BaselBaselSwitzerland
  2. 2.Department of Radiation OncologyInselspital, Bern University HospitalBernSwitzerland

Personalised recommendations