Original Study| Volume 21, ISSUE 1, P43-54, February 2023

Download started.


Perioperative Morbidity of Radical Prostatectomy After Intensive Neoadjuvant Androgen Blockade in Men With High-Risk Prostate Cancer: Results of Phase II Trial Compared to a Control Group

Published:October 21, 2022DOI:


      • Intense neoadjuvant therapy doesn't increase the morbidity of radical prostatectomy.
      • Neoadjuvant therapy reduced the rate of positive surgical margins.
      • Neoadjuvant therapy may increase the risk of perioperative thromboembolic events.



      Recent studies about intense neoadjuvant therapy followed by Radical Prostatectomy (RP) lack standardized criteria regarding surgical complications and comparison to a group of patients who underwent RP without the use of neoadjuvant therapy. The aim of this study is to describe and compare the perioperative complication rates.

      Materials and Methods

      This was a prospective, single-center phase II trial in patients with high-risk prostate cancer (HRPCa). The control group included HRPCa patients who underwent RP outside the clinical trial during the same study recruitment period. The interventional group was randomized (1:1) to receive neoadjuvant androgen deprivation therapy plus abiraterone with or without apalutamide followed by RP. Complications observed up to 30 days of surgery were classified based on the Clavien-Dindo classification. Uni- and multivariate analyses were carried out to assess predictive factors associated with perioperative complications.


      In total, 124 patients with HRPCa were underwent to RP between May 27, 2019 and August 6, 2021, including 61 patients in the intervention group and 63 patients in the control group. The general and major complications in the intervention group reached 29.6% and 6.6%, respectively, and 39.7% and 7.9% in the control group, respectively. There was no significant difference between groups. We observed 4.9% of thromboembolic event in the neoadjuvant group.


      There was no significant increase in morbidity rate in RP after intense neoadjuvant therapy. The association of intense androgen deprivation neoadjuvant therapy with RP and extended pelvic lymphadenectomy may increase the risk of a perioperative thromboembolic events.


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


        • Siegel RL
        • Miller KD
        • Jemal A.
        Cancer statistics, 2020.
        CA Cancer J Clin. 2020; 70: 7-30
        • Cooperberg MR
        • Broering JM
        • Carroll PR.
        Time trends and local variation in primary treatment of localized prostate cancer.
        J Clin Oncol. 2010; 28: 1117-1123
        • Yossepowitch O
        • Eggener SE
        • Jr Bianco FJ
        • et al.
        Radical prostatectomy for clinically localized, high risk prostate cancer: critical analysis of risk assessment methods.
        J Urol. 2007; 178: 493-499
        • Mottet N
        • van den Bergh RCN
        • Briers E
        • et al.
        EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: screening, diagnosis, and local treatment with curative intent.
        Eur Urol. 2021; 79: 243-262
        • Stephenson AJ
        • Kattan MW
        • Eastham JA
        • et al.
        Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era.
        J Clin Oncol. 2009; 27: 4300-4305
        • Yuh B
        • Artibani W
        • Heidenreich A
        • et al.
        The role of robot-assisted radical prostatectomy and pelvic lymph node dissection in the management of high-risk prostate cancer: a systematic review.
        Eur Urol. 2014; 65: 918-927
        • McKay RR
        • Choueiri TK
        • Taplin ME.
        Rationale for and review of neoadjuvant therapy prior to radical prostatectomy for patients with high-risk prostate cancer.
        Drugs. 2013; 73: 1417-1430
        • Shelley MD
        • Kumar S
        • Wilt T
        • Staffurth J
        • Coles B
        • Mason MD.
        A systematic review and meta-analysis of randomised trials of neo-adjuvant hormone therapy for localised and locally advanced prostate carcinoma.
        Cancer Treat Rev. 2009; 35: 9-17
        • Beer TM
        • Armstrong AJ
        • Rathkopf DE
        • et al.
        Enzalutamide in metastatic prostate cancer before chemotherapy.
        N Engl J Med. 2014; 371: 424-433
        • de Bono JS
        • Logothetis CJ
        • Molina A
        • et al.
        Abiraterone and increased survival in metastatic prostate cancer.
        N Engl J Med. 2011; 364: 1995-2005
        • Ryan ST
        • Patel DN
        • Parsons JK
        • McKay RR.
        Neoadjuvant approaches prior to radical prostatectomy.
        Cancer J. 2020; 26: 2-12
        • Williams SB
        • Davis JW
        • Wang X
        • et al.
        Neoadjuvant systemic therapy before radical prostatectomy in high-risk prostate cancer does not increase surgical morbidity: contemporary results using the clavien system.
        Clin Genitourin Cancer. 2016; 14: 130-138
        • Mohler JL
        • Kantoff PW
        • Armstrong AJ
        • et al.
        Prostate cancer, version 2.2014.
        J Natl Compr Canc Netw. 2014; 12: 686-718
        • Walsh PC.
        Anatomic radical prostatectomy: evolution of the surgical technique.
        J Urol. 1998; 160: 2418-2424
        • Freire MP
        • Choi WW
        • Lei Y
        • Carvas F
        • Hu JC.
        Overcoming the learning curve for robotic-assisted laparoscopic radical prostatectomy.
        Urol Clin North Am. 2010; 37: 37-47
        • Van Velthoven RF
        • Ahlering TE
        • Peltier A
        • Skarecky DW
        • Clayman RV.
        Technique for laparoscopic running urethrovesical anastomosis: the single knot method.
        Urology. 2003; 61: 699-702
        • Dindo D
        • Demartines N
        • Clavien PA.
        Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.
        Ann Surg. 2004; 240: 205-213
        • Bhindi B
        • Karnes RJ
        • Rangel LJ
        • et al.
        Independent Validation of the American Joint Committee on Cancer 8th Edition Prostate Cancer Staging Classification.
        J Urol. 2017; 198: 1286-1294
        • Taplin ME
        • Montgomery B
        • Logothetis CJ
        • et al.
        Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study.
        J Clin Oncol. 2014; 32: 3705-3715
        • Montgomery B
        • Tretiakova MS
        • Joshua AM
        • et al.
        Neoadjuvant enzalutamide prior to prostatectomy.
        Clin Cancer Res. 2017; 23: 2169-2176
        • McKay RR
        • Ye H
        • Xie W
        • et al.
        Evaluation of intense androgen deprivation before prostatectomy: a randomized phase II trial of enzalutamide and leuprolide with or without abiraterone.
        J Clin Oncol. 2019; 37: 923-931
        • Efstathiou E
        • Davis JW
        • Pisters L
        • et al.
        Clinical and biological characterisation of localised high-risk prostate cancer: results of a randomised preoperative study of a luteinising hormone-releasing hormone agonist with or without abiraterone acetate plus prednisone.
        Eur Urol. 2019; 76: 418-424
        • McKay RR
        • Xie W
        • Ye H
        • et al.
        Results of a randomized phase ii trial of intense androgen deprivation therapy prior to radical prostatectomy in men with high-risk localized prostate cancer.
        J Urol. 2021; 206: 80-87
        • Martin RC
        • Brennan MF
        • Jaques DP
        Quality of complication reporting in the surgical literature.
        Ann Surg. 2002; 235: 803-813
        • Berglund RK
        • Tangen CM
        • Powell IJ
        • et al.
        Ten-year follow-up of neoadjuvant therapy with goserelin acetate and flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study 9109.
        Urology. 2012; 79: 633-637
        • Bullock MJ
        • Srigley JR
        • Klotz LH
        • Goldenberg SL.
        Pathologic effects of neoadjuvant cyproterone acetate on non-neoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma: a detailed analysis of radical prostatectomy specimens from a randomized trial.
        Am J Surg Pathol. 2002; 26: 1400-1413
        • Froehner M
        • Propping S
        • Koch R
        • et al.
        Is the post-radical prostatectomy gleason score a valid predictor of mortality after neoadjuvant hormonal treatment?.
        Urol Int. 2016; 96: 302-308
        • Goldenberg SL
        • Klotz LH
        • Srigley J
        • et al.
        Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer.
        Can Urol Oncol Group J Urol. 1996; 156: 873-877
        • Novara G
        • Ficarra V
        • Mocellin S
        • et al.
        Systematic review and meta-analysis of studies reporting oncologic outcome after robot-assisted radical prostatectomy.
        Eur Urol. 2012; 62: 382-404
        • Tan WS
        • Krimphove MJ
        • Cole AP
        • et al.
        Variation in positive surgical margin status after radical prostatectomy for pT2 prostate cancer.
        Clin Genitourin Cancer. 2019; 17: e1060-e1068
        • Briganti A
        • Larcher A
        • Abdollah F
        • et al.
        Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores.
        Eur Urol. 2012; 61: 480-487
        • Lestingi JFP
        • Guglielmetti GB
        • Trinh QD
        • et al.
        Extended versus limited pelvic lymph node dissection during radical prostatectomy for intermediate- and high-risk prostate cancer: early oncological outcomes from a randomized phase 3 trial.
        Eur Urol. 2021; 79: 595-604
        • Briganti A
        • Karakiewicz PI
        • Chun FK
        • et al.
        Percentage of positive biopsy cores can improve the ability to predict lymph node invasion in patients undergoing radical prostatectomy and extended pelvic lymph node dissection.
        Eur Urol. 2007; 51: 1573-1581
        • Cacciamani GE
        • Maas M
        • Nassiri N
        • et al.
        Impact of pelvic lymph node dissection and its extent on perioperative morbidity in patients undergoing radical prostatectomy for prostate cancer: a comprehensive systematic review and meta-analysis.
        Eur Urol Oncol. 2021; 4: 134-149
        • Regenbogen SE
        • Ehrenfeld JM
        • Lipsitz SR
        • Greenberg CC
        • Hutter MM
        • Gawande AA.
        Utility of the surgical apgar score: validation in 4119 patients.
        Arch Surg. 2009; 144: 30-37
        • Pompe RS
        • Beyer B
        • Haese A
        • et al.
        Postoperative complications of contemporary open and robot-assisted laparoscopic radical prostatectomy using standardised reporting systems.
        BJU Int. 2018; 122: 801-807
        • Knipper S
        • Mazzone E
        • Mistretta FA
        • et al.
        Impact of obesity on perioperative outcomes at robotic-assisted and open radical prostatectomy: results from the National Inpatient Sample.
        Urology. 2019; 133: 135-144
        • Igel TC
        • Barrett DM
        • Segura JW
        • Benson RC
        • Rife CC.
        Perioperative and postoperative complications from bilateral pelvic lymphadenectomy and radical retropubic prostatectomy.
        J Urol. 1987; 137: 1189-1191
        • Patel HD
        • Faisal FA
        • Trock BJ
        • et al.
        Effect of pharmacologic prophylaxis on venous thromboembolism after radical prostatectomy: the PREVENTER randomized clinical trial.
        Eur Urol. 2020; 78: 360-368
      1. Tikkinen KAO, Cartwright R, Gould MK, et al. EAU guidelines on thromboprophylaxis in urological surgery. Presented at the EAU Annual Congress Barcelona; Arnhem, The Netherlands: EAU Guidelines Office; 2019 ISBN 978-94-92671-04-2 (accessed in January 10, 2022).