The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study


      To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era.

      Methods and Materials

      The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons.


      A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT.


      In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. American Cancer Society. Cancer facts & figures 2013. Available at: http://www.Cancer.Org/research/cancerfactsstatistics/cancerfactsfigures2013/index. Accessed June 5, 2013.

      2. Surveillance, Epidemiology and End Results: Cancer stat fact sheet (prostate). Available at: Accessed June 6, 2013.

        • Heidenreich A.
        • Ohlmann C.H.
        • Polyakov S.
        Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy.
        Eur Urol. 2007; 52: 29-37
        • Ji J.
        • Yuan H.
        • Wang L.
        • et al.
        Is the impact of the extent of lymphadenectomy in radical prostatectomy related to the disease risk? A single center prospective study.
        J Surg Res. 2012; 178: 779-784
        • Warde P.
        • Mason M.
        • Ding K.
        • et al.
        Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: A randomised, phase 3 trial.
        Lancet. 2011; 378: 2104-2111
        • Widmark A.
        • Klepp O.
        • Solberg A.
        • et al.
        Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): An open randomised phase III trial.
        Lancet. 2009; 373: 301-308
        • Boorjian S.A.
        • Thompson R.H.
        • Siddiqui S.
        • et al.
        Long-term outcome after radical prostatectomy for patients with lymph node positive prostate cancer in the prostate specific antigen era.
        J Urol. 2007; 178 (discussion 870-871): 864-870
        • Da Pozzo L.F.
        • Cozzarini C.
        • Briganti A.
        • et al.
        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. 2009; 55: 1003-1011
        • Ghavamian R.
        • Bergstralh E.J.
        • Blute M.L.
        • et al.
        Radical retropubic prostatectomy plus orchiectomy versus orchiectomy alone for pTxN+ prostate cancer: A matched comparison.
        J Urol. 1999; 161 (discussion 1227-1228): 1223-1227
        • Robnett T.J.
        • Whittington R.
        • Malkowicz S.B.
        • et al.
        Long-term use of combined radiation therapy and hormonal therapy in the management of stage D1 prostate cancer.
        Int J Radiat Oncol Biol Phys. 2002; 53: 1146-1151
        • Zagars G.K.
        • Pollack A.
        • von Eschenbach A.C.
        Addition of radiation therapy to androgen ablation improves outcome for subclinically node-positive prostate cancer.
        Urology. 2001; 58: 233-239
        • Lawton C.A.
        • Winter K.
        • Grignon D.
        • et al.
        Androgen suppression plus radiation versus radiation alone for patients with stage D1/pathologic node-positive adenocarcinoma of the prostate: Updated results based on national prospective randomized trial radiation therapy oncology group 85-31.
        J Clin Oncol. 2005; 23: 800-807
        • Schroder F.H.
        • Kurth K.H.
        • Fossa S.D.
        • et al.
        Early versus delayed endocrine treatment of T2-3 pN1-3 M0 prostate cancer without local treatment of the primary tumour: Final results of European Organisation for the Research and Treatment of Cancer protocol 30846 after 13 years of follow-up (a randomised controlled trial).
        Eur Urol. 2009; 55: 14-22
        • Cheng L.
        • Zincke H.
        • Blute M.L.
        • et al.
        Risk of prostate carcinoma death in patients with lymph node metastasis.
        Cancer. 2001; 91: 66-73
        • Daneshmand S.
        • Quek M.
        • Stein J.
        • et al.
        Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: Long-term results.
        J Urol. 2004; 172: 2252-2255
        • Joslyn S.A.
        • Konety B.R.
        Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer.
        Urology. 2006; 68: 121-125
        • Jagsi R.
        • Abrahamse P.
        • Hawley S.T.
        • et al.
        Underascertainment of radiotherapy receipt in Surveillance, Epidemiology, and End Results registry data.
        Cancer. 2012; 118: 333-341
        • Walker G.V.
        • Giordano S.H.
        • Williams M.
        • et al.
        Muddy water? Variation in reporting receipt of breast cancer radiation therapy by population-based tumor registries.
        Int J Radiat Oncol Biol Phys. 2013; 86: 686-693
        • Messing E.
        • Manola J.
        • Yao J.
        • et al.
        Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy.
        Lancet Oncol. 2006; 7: 472-479
        • Bill-Axelson A.
        • Holmberg L.
        • Filen F.
        • et al.
        Radical prostatectomy versus watchful waiting in localized prostate cancer: The Scandinavian Prostate Cancer Group-4 randomized trial.
        J Natl Cancer Inst. 2008; 100: 1144-1154
        • Swanson G.P.
        • Thompson I.M.
        • Basler J.
        Current status of lymph node-positive prostate cancer: Incidence and predictors of outcome.
        Cancer. 2006; 107: 439-450
        • Cadeddu J.A.
        • Partin A.W.
        • Epstein J.I.
        • et al.
        Stage D1 (T1-3, N1-3, M0) prostate cancer: A case-controlled comparison of conservative treatment versus radical prostatectomy.
        Urology. 1997; 50: 251-255
        • Cheng C.W.
        • Bergstralh E.J.
        • Zincke H.
        Stage D1 prostate cancer. A nonrandomized comparison of conservative treatment options versus radical prostatectomy.
        Cancer. 1993; 71: 996-1004
        • Engel J.
        • Bastian P.J.
        • Baur H.
        • et al.
        Survival benefit of radical prostatectomy in lymph node-positive patients with prostate cancer.
        Eur Urol. 2010; 57: 754-761
        • Steuber T.
        • Budaus L.
        • Walz J.
        • et al.
        Radical prostatectomy improves progression-free and cancer-specific survival in men with lymph node positive prostate cancer in the prostate-specific antigen era: A confirmatory study.
        BJU Int. 2011; 107: 1755-1761
        • Thompson I.M.
        • Tangen C.
        • Basler J.
        • et al.
        Impact of previous local treatment for prostate cancer on subsequent metastatic disease.
        J Urol. 2002; 168: 1008-1012
        • Buskirk S.J.
        • Pisansky T.M.
        • Atkinson E.J.
        • et al.
        Lymph node-positive prostate cancer: Evaluation of the results of the combination of androgen deprivation therapy and radiation therapy.
        Mayo Clin Proc. 2001; 76: 702-706
        • Whittington R.
        • Malkowicz S.B.
        • Machtay M.
        • et al.
        The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer.
        Int J Radiat Oncol Biol Phys. 1997; 39: 673-680
        • Kuefer R.
        • Volkmer B.G.
        • Loeffler M.
        • et al.
        Comparison of external radiation therapy vs. radical prostatectomy in lymph node positive prostate cancer patients.
        Prostate Cancer Prostatic Dis. 2004; 7: 343-349
        • Briganti A.
        • Karnes R.J.
        • Da Pozzo L.F.
        • et al.
        Combination of adjuvant hormonal and radiation therapy significantly prolongs survival of patients with pT2-4 pN+ prostate cancer: Results of a matched analysis.
        Eur Urol. 2011; 59: 832-840
        • Johnstone P.A.
        • Assikis V.
        • Goodman M.
        • et al.
        Lack of survival benefit of post-operative radiation therapy in prostate cancer patients with positive lymph nodes.
        Prostate Cancer Prostatic Dis. 2007; 10: 185-188
        • Kaplan J.R.
        • Kowalczyk K.J.
        • Borza T.
        • et al.
        Patterns of care and outcomes of radiotherapy for lymph node positivity after radical prostatectomy.
        BJU Int. 2013; 111: 1208-1214
        • Thompson I.M.
        • Tangen C.M.
        • Paradelo J.
        • et al.
        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. 2009; 181: 956-962
        • Bolla M.
        • van Poppel H.
        • Tombal B.
        • et al.
        Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: Long-term results of a randomised controlled trial (EORTC trial 22911).
        Lancet. 2012; 380: 2018-2027
        • Wiegel T.
        • Bottke D.
        • Steiner U.
        • et al.
        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. 2009; 27: 2924-2930
        • Briganti A.
        • Blute M.L.
        • Eastham J.H.
        • et al.
        Pelvic lymph node dissection in prostate cancer.
        Eur Urol. 2009; 55: 1251-1265
        • Gofrit O.N.
        • Zorn K.C.
        • Steinberg G.D.
        • et al.
        The Will Rogers phenomenon in urological oncology.
        J Urol. 2008; 179: 28-33


      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.