Vol 26, No 4 (2021)
Research paper
Published online: 2021-03-30

open access

Page views 660
Article views/downloads 394
Get Citation

Connect on Social Media

Connect on Social Media

Pathological stage, surgical margin and lymphovascular invasion as prognostic factors after salvage radiotherapy for post-prostatectomy relapsed prostate cancer — outcomes and optimization strategies

Isabel Rodrigues1, Carolina Ferreira12, Joana Gonçalves12, Luísa Carvalho1, Jorge Oliveira2, Carla Castro12, Ângelo Oliveira12
Rep Pract Oncol Radiother 2021;26(4):535-544.


BACKGROUND: Salvage radiotherapy (sRT) is the main potentially curative treatment after biochemical failure/locoregional relapse post-radical prostatectomy (RP).

The aim of the study was to characterize the population who underwent sRT after RP at our Department, to understand the influence of several potential prognosis factors, and to determine possible optimization strategies.

MATERIAL AND METHODS: We retrospectively analyzed patients undergoing sRT at our department between 2012 and 2017, evaluating patient, tumor and treatment characteristics, restaging procedures and clinical outcomes — namely biochemical relapse-free survival (BC-RFS), clinical relapse-free survival (C-RFS), additional hormone therapy-free survival (HT-FS) and overall survival (OS). We assessed potential prognostic factors by univariate and multivariate models (MVA).

RESULTS: We included 277 patients (median age 68 years). Median pre-sRT PSA was > 0.5ng/mL in 54.9%. All underwent prostate bed irradiation. Pelvic lymph nodes were included in 9.7%. Outcome analysis was performed for 264 patients (35.6 months median follow-up).  At 3 years, BC-RFS was 61.4%, C-RFS was 81.3%, HT-FS was 79.9% and OS was 96.6%. Most relapses occurred in regional lymph nodes only (47.9% patients who relapsed). On MVA, lymphovascular invasion, advanced pT-stages and negative margins negatively influenced BC-RFS (p = 0.029, p = 0.002 and p < 0.001) and HT-FS (p = 0.001, p = 0.029 and p = 0.002). C-RFS was worsened by lymphovascular invasion (p = 0.009) and negative margins (p = 0.015). These had no effect on OS. BC-RFS and HT-FS were improved when sRT started while PSA ≤ 0.5 ng/mL (p < 0.05).

CONCLUSION: Lymphovascular invasion, higher pT-stages and negative margins negatively affected prognosis. An early start of sRT (PSA ≤ 0.5 ng/mL) predicted better BC-RFS and HT-FS.

Article available in PDF format

View PDF Download PDF file


  1. Fersino S, Tebano U, Mazzola R, et al. Moderate Hypofractionated Postprostatectomy Volumetric Modulated Arc Therapy With Daily Image Guidance (VMAT-IGRT): A Mono-institutional Report on Feasibility and Acute Toxicity. Clin Genitourin Cancer. 2017; 15(4): e667–e673.
  2. Cozzarini C, Fiorino C, Briganti A, et al. Higher-than-expected severe (Grade 3-4) late urinary toxicity after postprostatectomy hypofractionated radiotherapy: a single-institution analysis of 1176 patients. Eur Urol. 2014; 66(6): 1024–1030.
  3. Parker CC, Clarke NW, Cook AD, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020; 396(10260): 1413–1421.
  4. Kneebone A, Fraser-Browne C, Delprado W, et al. A Phase III Multi-Centre Randomised Trial comparing adjuvant versus early salvage Radiotherapy following a Radical Prostatectomy: Results of the TROG 08.03 and ANZUP “RAVES” Trial. Int J Radiat Oncol Biol Phys. 2019; 105(1): S37–S38.
  5. Sargos P, Chabaud S, Latorzeff I, et al. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020; 21(10): 1341–1352.
  6. Tourinho-Barbosa R, Srougi V, Nunes-Silva I, et al. Biochemical recurrence after radical prostatectomy: what does it mean? Int Braz J Urol. 2018; 44(1): 14–21.
  7. Jackson WC, Suresh K, Tumati V, et al. Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality: Competition Between Age and Time to Biochemical Failure. Eur Urol Oncol. 2018; 1(4): 276–282.
  8. Do T, Parker RG, Do C, et al. Salvage radiotherapy for biochemical and clinical failures following radical prostatectomy. Cancer J Sci Am. 1998; 4(5): 324–330.
  9. Mottet N, Cornford P, van den Bergh RCN et al. EAU Prostate Cancer Guidelines. https://uroweb.org/guideline/prostate-cancer/ (9 June 2020).
  10. Couñago F, Sancho G, Catalá V, et al. Magnetic resonance imaging for prostate cancer before radical and salvage radiotherapy: What radiation oncologists need to know. World J Clin Oncol. 2017; 8(4): 305–319.
  11. Panje C, Zilli T, Dal Pra A, et al. Radiotherapy for pelvic nodal recurrences after radical prostatectomy: patient selection in clinical practice. Radiat Oncol. 2019; 14(1): 177.
  12. Goldstein J, Even-Sapir E, Ben-Haim S, et al. Does Choline PET/CT Change the Management of Prostate Cancer Patients With Biochemical Failure? Am J Clin Oncol. 2017; 40(3): 256–259.
  13. Huang SM, Yin L, Yue JL, et al. Direct comparison of choline PET/CT and MRI in the diagnosis of lymph node metastases in patients with prostate cancer. Medicine (Baltimore). 2018; 97(50): e13344.
  14. Luiting HB, van Leeuwen PJ, Busstra MB, et al. Use of gallium-68 prostate-specific membrane antigen positron-emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature. BJU Int. 2020; 125(2): 206–214.
  15. Emmett L, van Leeuwen PJ, Nandurkar R, et al. Treatment Outcomes from Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET. J Nucl Med. 2017; 58(12): 1972–1976.
  16. Sharma V, Nehra A, Colicchia M, et al. Multiparametric Magnetic Resonance Imaging Is an Independent Predictor of Salvage Radiotherapy Outcomes After Radical Prostatectomy. Eur Urol. 2018; 73(6): 879–887.
  17. De Bari B, Mazzola R, Aiello D, et al. (Ga)-PSMA-PET/CT for the detection of postoperative prostate cancer recurrence: Possible implications on treatment volumes for radiation therapy. Cancer Radiother. 2019; 23(3): 194–200.
  18. De Bari B, Mazzola R, Aiello D, et al. Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series. Radiol Med. 2018; 123(9): 719–725.
  19. Alongi F, Fersino S, Giaj Levra N, et al. Impact of 18F-Choline PET/CT in the Decision-Making Strategy of Treatment Volumes in Definitive Prostate Cancer Volumetric Modulated Radiation Therapy. Clin Nucl Med. 2015; 40(11): e496–e500.
  20. Couñago F, Díaz Gavela AA, Sancho G, et al. Multiparametric magnetic resonance imaging-guided salvage radiotherapy in prostate cancer. Rep Pract Oncol Radiother. 2019; 24(5): 472–480.
  21. Mazzola R, Francolini G, Triggiani L, et al. Metastasis-directed Therapy (SBRT) Guided by PET-CT F-CHOLINE Versus PET-CT Ga-PSMA in Castration-sensitive Oligorecurrent Prostate Cancer: A Comparative Analysis of Effectiveness. Clin Genitourin Cancer. 2020 [Epub ahead of print].
  22. Baumgarten L, Borchert A, Sood A, et al. Impact of timing on salvage radiation therapy adverse events following radical prostatectomy: A secondary analysis of the RTOG 9601 cohort. Urol Oncol. 2020; 38(2): 38.e17–38.e22.
  23. Carrie C, Magné N, Burban-Provost P, et al. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial. Lancet Oncol. 2019; 20(12): 1740–1749.
  24. Pisansky TM, Thompson IM, Valicenti RK, et al. Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline Amendment 2018-2019. J Urol. 2019; 202(3): 533–538.
  25. Bianchi L, Gandaglia G, Fossati N, et al. Adjuvant Radiotherapy in Prostate Cancer Patients Treated with Surgery: The Impact of Age and Tumor Characteristics. Eur Urol Focus. 2015; 1(2): 191–199.
  26. Brand DH, Parker JI, Dearnaley DP, et al. Patterns of recurrence after prostate bed radiotherapy. Radiother Oncol. 2019; 141: 174–180.
  27. Zhang L, Wu B, Zha Z, et al. Surgical margin status and its impact on prostate cancer prognosis after radical prostatectomy: a meta-analysis. World J Urol. 2018; 36(11): 1803–1815.
  28. Kvåle R, Myklebust TÅ, Fosså SD, et al. Impact of positive surgical margins on secondary treatment, palliative radiotherapy and prostate cancer-specific mortality. A population-based study of 13 198 patients. Prostate. 2019; 79(16): 1852–1860.
  29. Jackson W, Hamstra DA, Johnson S, et al. Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy. Cancer. 2013; 119(18): 3287–3294.
  30. Ervandian M, Høyer M, Petersen SE, et al. Salvage radiation therapy following radical prostatectomy. A national Danish study. Acta Oncol. 2016; 55(5): 598–603.
  31. Fossati N, Karnes RJ, Cozzarini C, et al. Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy. Eur Urol. 2016; 69(4): 728–733.
  32. Goenka A, Magsanoc JM, Pei X, et al. Long-term outcomes after high-dose postprostatectomy salvage radiation treatment. Int J Radiat Oncol Biol Phys. 2012; 84(1): 112–118.
  33. Jeong JU, Nam TK, Song JY, et al. Prognostic significance of lymphovascular invasion in patients with prostate cancer treated with postoperative radiotherapy. Radiat Oncol J. 2019; 37(3): 215–223.
  34. Stish BJ, Pisansky TM, Harmsen WS, et al. Improved Metastasis-Free and Survival Outcomes With Early Salvage Radiotherapy in Men With Detectable Prostate-Specific Antigen After Prostatectomy for Prostate Cancer. J Clin Oncol. 2016; 34(32): 3864–3871.

Reports of Practical Oncology and Radiotherapy