Advertisement

Nomograms for Metastasis-Free and Overall Survival for Pathologically Node Positive Prostate Cancer Patients Treated With or Without Radiation Therapy Plus Short-Term ADT

  • Ryan Hutten
    Affiliations
    Leader, HCI Genitourinary Cancers Center, Rudolph P. and Edna S. Reese Endowed Research Professor, Professor of Radiation Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah
    Search for articles by this author
  • Jonathan D. Tward
    Correspondence
    Address for correspondence: Jonathan D. Tward, M.D., Ph.D, Leader, HCI Genitourinary Cancers Center, Rudolph P. and Edna S. Reese Endowed Research Professor, Professor of Radiation Oncology, Huntsman Cancer Institute at the University of Utah
    Affiliations
    Leader, HCI Genitourinary Cancers Center, Rudolph P. and Edna S. Reese Endowed Research Professor, Professor of Radiation Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah
    Search for articles by this author
Published:February 07, 2022DOI:https://doi.org/10.1016/j.clgc.2022.01.018

      Abstract

      Purpose/Objectives

      We aimed to develop nomograms to predict the risk reduction for metastasis and death in pathologically node-positive (pN +) prostate cancer patients treated with or without radiation therapy (RT).

      Materials/Methods

      From a prospectively gathered institutional database, we identified patients with pN + M0 prostate cancer after surgery. We evaluated several regression models of known or suspected clinical-pathologic covariates and selected the model with the highest Harrell's concordance-index (c-index) and clinical utility to prognosticate metastasis for inclusion in a nomogram. Covariates in the final, competing-risk adjusted, metastasis model included PSA nadir after surgery, pathologic T-stage, margin status, Gleason score (GS), number of positive lymph nodes, and use of postoperative radiotherapy combined with androgen deprivation therapy (RT + ADT). The overall survival model also included Charlson comorbidity score and age.

      Results

      336 pN + men with a mean age of 64.9 years and a median follow-up of 4.1 years who had a radical prostatectomy were included in the analysis. 83 men were recommended RT + ADT, of whom 4% refused the ADT and received RT alone. C-index was 0.85 and 0.71 for the MFS and OS models, respectively. On multivariable analysis (MVA) adjusted for competing risks, RT + ADT significantly improved MFS (HR=0.70 P = < .01) with number of nodes positive, GS 8-10, PSA nadir > 1 ng/mL, and pT3b prognostic for metastasis. MVA for OS demonstrates RT+ADT improves survival (HR=0.40, P = .02), with GS8-10 and PSA nadir > 1.0 prognostic for death.

      Conclusion

      We developed predictive nomograms for patients with pN+ prostate cancer following radical prostatectomy. These models can discretely quantify an individual's risk of metastasis or death with and without post-prostatectomy radiotherapy.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

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

      References

      1. NCCN Clinical Practice Guidelines in Oncology – Prostate Cancer, version 1.2020, 2020. Accessed 4/21/2020, https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.

        • Hackman G
        • Taari K
        • Tammela TL
        • et al.
        Randomized trial of adjuvant radiotherapy following radical prostatectomy versus radical prostatectomy alone in prostate cancer patients with positive margins or extracapsular extension.
        Eur Urol. 2019; 76: 586-595https://doi.org/10.1016/j.eururo.2019.07.001
        • Thompson IM
        • Tangen CM
        • 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: 956-962https://doi.org/10.1016/j.juro.2008.11.032
        • Wiegel T
        • Bartkowiak D
        • Bottke D
        • et al.
        Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial.
        Eur Urol. 2014; 66: 243-250https://doi.org/10.1016/j.eururo.2014.03.011
        • 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 (London, England). 2012; 380: 2018-2027https://doi.org/10.1016/s0140-6736(12)61253-7
        • 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: 1740-1749https://doi.org/10.1016/s1470-2045(19)30486-3
        • Shipley WU
        • Seiferheld W
        • Lukka HR
        • et al.
        Radiation with or without antiandrogen therapy in recurrent prostate cancer.
        N Engl J Med. 2017; 376: 417-428https://doi.org/10.1056/NEJMoa1607529
        • Pollack A
        • Karrison TG
        • Balogh AG
        • et al.
        Short term androgen deprivation therapy without or with pelvic lymph node treatment added to prostate bed only salvage radiotherapy: The NRG Oncology/RTOG 0534 SPPORT Trial.
        Int J Radiat Oncol*Biol*Phys. 2018; 102: 1605https://doi.org/10.1016/j.ijrobp.2018.08.052
        • Abdollah F
        • Karnes RJ
        • Suardi N
        • et al.
        Impact of adjuvant radiotherapy on survival of patients with node-positive prostate cancer.
        J Clin Oncol. 2014; 32: 3939-3947https://doi.org/10.1200/JCO.2013.54.7893
        • Da Pozzo LF
        • 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: 1003-1011https://doi.org/10.1016/j.eururo.2009.01.046
        • Briganti A
        • Karnes RJ
        • Da Pozzo LF
        • 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: 832-840https://doi.org/10.1016/j.eururo.2011.02.024
        • Lin CC
        • Gray PJ
        • Jemal A
        • Efstathiou JA.
        Androgen deprivation with or without radiation therapy for clinically node-positive prostate cancer.
        J Natl Cancer Inst. 2015; 107https://doi.org/10.1093/jnci/djv119
        • Jegadeesh N
        • Liu Y
        • Zhang C
        • et al.
        The role of adjuvant radiotherapy in pathologically lymph node-positive prostate cancer.
        Cancer. 2017; 123: 512-520
        • Messing EM
        • 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: 472-479https://doi.org/10.1016/s1470-2045(06)70700-8
      2. Granfors T, Modig H, Damber J-E, Tomic R. Long-term followup of a randomized study of locally advanced prostate cancer treated with combined orchiectomy and external radiotherapy versus radiotherapy alone. 2006;176:544-547. doi:10.1016/j.juro.2006.03.092w.

        • Kaplan EL
        • Meier P.
        Nonparametric estimation from incomplete observations.
        J Am Statist Assoc. 1958; 53: 457-481https://doi.org/10.2307/2281868
        • Tward JD
        • O'Neil B
        • Boucher K
        • et al.
        Metastasis, mortality, and quality of life for men with NCCN high and very high risk localized prostate cancer following surgical and/or combined modality radiation therapies.
        Clin Genitourin Cancer. 2020; https://doi.org/10.1016/j.clgc.2019.11.023
        • Harrell Jr., FE
        • Lee KL
        • Mark DB
        Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors.
        Stat Med. 1996; 15: 361-387https://doi.org/10.1002/(sici)1097-0258(19960229)15:4<361::Aid-sim168>3.0.Co;2-4
        • Fine JP
        • Gray RJ.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Statist Assoc. 1999; 94: 496-509
        • Cox DR.
        Regression models and life-tables.
        J Royal Statist Soc Series B (Methodological). 1972; 34: 187-220
        • Spratt DE
        • Tward JD.
        Absolute versus relative benefit of androgen deprivation therapy for prostate cancer: moving beyond the hazard ratio to personalize therapy.
        Int J Radiat Oncol Biol Phys. 2020; 108: 899-902https://doi.org/10.1016/j.ijrobp.2020.06.011
        • Nini A
        • Gandaglia G
        • Fossati N
        • et al.
        Patterns of clinical recurrence of node-positive prostate cancer and impact on long-term survival.
        Eur Urol. 2015; 68: 777-784https://doi.org/10.1016/j.eururo.2015.04.035
        • Hutten RJ
        • Parsons MW
        • Weil CR
        • et al.
        Temporal trends and predictors in diagnosing pathologic node-positive prostate cancer in clinically node-negative patients.
        Clin Genitourin Cancer. 2021; https://doi.org/10.1016/j.clgc.2021.05.003
        • Abdollah F
        • Suardi N
        • Cozzarini C
        • et al.
        Selecting the optimal candidate for adjuvant radiotherapy after radical prostatectomy for prostate cancer: a long-term survival analysis.
        Eur Urol. 2013; 63: 998-1008https://doi.org/10.1016/j.eururo.2012.10.036
        • Zagars GK
        • Pollack A
        • von Eschenbach AC.
        Addition of radiation therapy to androgen ablation improves outcome for subclinically node-positive prostate cancer.
        Urology. 2001; 58: 233-239https://doi.org/10.1016/s0090-4295(01)01168-2
        • Abdollah F
        • Karnes RJ
        • Suardi N
        • et al.
        Predicting survival of patients with node-positive prostate cancer following multimodal treatment.
        Eur Urol. 2014; 65: 554-562https://doi.org/10.1016/j.eururo.2013.09.025
        • Karnes Robert J.
        • Passoni Niccolo
        • et al.
        • Touijer K. Reply to Pim J. van Leeuwen and Henk G. van der Poel's Letter to the Editor re: Karim A. Touijer
        Survival outcomes of men with lymph node-positive prostate cancer after radical prostatectomy: a comparative analysis of different postoperative management strategies.
        Eur Urol. 2018; 73 (Eur Urol. Jul 2018;74(1):e18-e19): 890-896https://doi.org/10.1016/j.eururo.2018.04.002
        • Kaplan JR
        • Kowalczyk KJ
        • Borza T
        • et al.
        Patterns of care and outcomes of radiotherapy for lymph node positivity after radical prostatectomy.
        BJU Int. 2013; 111: 1208-1214https://doi.org/10.1111/bju.12079
        • Bianchi L
        • Nini A
        • Bianchi M
        • et al.
        The role of prostate-specific antigen persistence after radical prostatectomy for the prediction of clinical progression and cancer-specific mortality in node-positive prostate cancer patients.
        Eur Urol. 2016; 69: 1142-1148https://doi.org/10.1016/j.eururo.2015.12.010
        • Boorjian SA
        • Thompson RH
        • 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 870-1): 864-870https://doi.org/10.1016/j.juro.2007.05.048
        • Briganti A
        • Karnes JR
        • Da Pozzo LF
        • et al.
        Two positive nodes represent a significant cut-off value for cancer specific survival in patients with node positive prostate cancer. A new proposal based on a two-institution experience on 703 consecutive N+ patients treated with radical prostatectomy, extended pelvic lymph node dissection and adjuvant therapy.
        Eur Urol. 2009; 55: 261-270https://doi.org/10.1016/j.eururo.2008.09.043
        • Daneshmand S
        • Quek ML
        • Stein JP
        • et al.
        Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results.
        J Urol. 2004; 172: 2252-2255https://doi.org/10.1097/01.ju.0000143448.04161.cc
        • Kim JK
        • Jeong CW
        • Ku JH
        • Kim HH
        • Kwak C.
        Prostate specific antigen (PSA) persistence 6 weeks after radical prostatectomy and pelvic lymph node dissection as predictive factor of radiographic progression in node-positive prostate cancer patients.
        J Cancer. 2019; 10: 2237-2242https://doi.org/10.7150/jca.29714
        • Kim YJ
        • Song C
        • Eom KY
        • Kim IA
        • Kim JS.
        Lymph node ratio determines the benefit of adjuvant radiotherapy in pathologically 3 or less lymph node-positive prostate cancer after radical prostatectomy: a population-based analysis with propensity-score matching.
        Oncotarget. 2017; 8: 110625-110634https://doi.org/10.18632/oncotarget.22610
        • Stephenson AJ
        • Scardino PT
        • Kattan MW
        • et al.
        Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy.
        J Clin Oncol. 2007; 25: 2035-2041https://doi.org/10.1200/JCO.2006.08.9607
        • Tendulkar RD
        • Agrawal S
        • Gao T
        • et al.
        Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy.
        J Clin Oncol. 2016; 34: 3648-3654https://doi.org/10.1200/JCO.2016.67.9647
      3. Testing the Addition of the Drugs, Apalutamide and Abiraterone Acetate With Prednisone, to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer.