Prognostic value of unifocal and multifocal positive surgical margins in a large series of robot-assisted radical prostatectomy for prostate cancer

  • Etienne Xavier Keller
  • Jacqueline Bachofner
  • Anna Jelena Britschgi
  • Karim Saba
  • Ashkan Mortezavi
  • Basil Kaufmann
  • Christian D. Fankhauser
  • Peter Wild
  • Tullio Sulser
  • Thomas Hermanns
  • Daniel Eberli
  • Cédric PoyetEmail author
Original Article



To evaluate the prognostic value of positive surgical margins (PSM) focality for the prediction of biochemical recurrence (BCR) in patients undergoing robotic-assisted radical prostatectomy (RARP) for prostate cancer.


All men with clinically localized prostate cancer undergoing RARP in our tertiary referral centre between May 2005 and August 2016 were retrospectively identified. Patients with neoadjuvant therapy were excluded. Comparisons were made between cases with negative surgical margins (NSM), unifocal PSM (uPSM), and multifocal PSM (mPSM).


From a total of 973 patients available for analysis, 315 (32%) had a PSM. In these patients, 190 had uPSM and 125 had mPSM. Focality of PSM was significantly associated with tumour stage and grade, preoperative PSA, and postoperative PSA persistence (all p < 0.001), but not with nerve sparing (NS) (p = 0.15). PSA persistence was found in 120 (12%) patients, resulting in 853 patients available for survival analyses with a median follow-up of 52 months. Both uPSM and mPSM were found to be independent predictors of BCR, conferring a hazard ratio of 1.9 (95% CI 1.3–3.0; p = 0.002) and 3.4 (95% CI 2.1–5.6; p < 0.001), respectively, when compared to NSM. In subgroup analyses, PSM was particularly predictive for BCR when patients underwent unilateral or bilateral NS (p ≤ 0.003).


Based on a large case series of RARP, we found PSM focality to be an independent predictor of BCR, with a 1.9- and 3.4-fold risk increase for BCR in case of uPSM and mPSM, respectively. PSM seems to be of particular prognostic relevance when NS has been performed.


Prostate cancer Radical prostatectomy Surgical margins Focality Prognosis Biochemical recurrence 


Author contributions

EXK protocol/project development, data collection or management, data analysis, and manuscript writing/editing. JB data collection or management, and manuscript writing/editing. AJB data collection or management, and manuscript writing/editing. KS data collection or management, data analysis, and manuscript writing/editing. AM data collection or management, data analysis, and manuscript writing/editing. BK data collection or management, and manuscript writing/editing. CDF data collection or management, data analysis, and manuscript writing/editing. PW protocol/project development, data analysis, and manuscript writing/editing. TS protocol/project development, data analysis, and manuscript writing/editing. TH protocol/project development, data analysis, and manuscript writing/editing. DE protocol/project development, data analysis, and manuscript writing/editing. CP protocol/project development, data collection or management, data analysis, and manuscript writing/editing.



Compliance with ethical standards

Conflict of interest

The authors disclose no potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Supplementary material

345_2018_2578_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 20 kb)


  1. 1.
    Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, Nordling S, Häggman M, Andersson S-O, Spångberg A, Andrén O, Palmgren J, Steineck G, Adami H-O, Johansson J-E (2014) Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 370:932–942. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ficarra V, Novara G, Artibani W, Cestari A, Galfano A, Graefen M, Guazzoni G, Guillonneau B, Menon M, Montorsi F, Patel V, Rassweiler J, Van Poppel H (2009) Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol 55:1037–1063. CrossRefPubMedGoogle Scholar
  3. 3.
    Sooriakumaran P, Dev HS, Skarecky D, Ahlering TE, Wiklund P (2016) Oncologic outcomes of robotic-assisted radical prostatectomy: the “balancing act” of achieving cancer control and minimizing collateral damage. In: Razdan S (ed) Urinary continence and sexual function after robotic radical prostatectomy. Springer International Publishing, Cham, pp 101–113CrossRefGoogle Scholar
  4. 4.
    Walsh PC, Donker PJ (1982) Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 128:492–497CrossRefPubMedGoogle Scholar
  5. 5.
    Vickers A, Bianco F, Cronin A, Eastham J, Klein E, Kattan M, Scardino P (2010) The learning curve for surgical margins after open radical prostatectomy: implications for margin status as an oncological end point. J Urol 183:1360–1365. CrossRefPubMedGoogle Scholar
  6. 6.
    Yossepowitch O, Briganti A, Eastham JA, Epstein J, Graefen M, Montironi R, Touijer K (2014) Positive surgical margins after radical prostatectomy: a systematic review and contemporary update. Eur Urol 65:303–313. CrossRefPubMedGoogle Scholar
  7. 7.
    Novara G, Ficarra V, Mocellin S, Ahlering TE, Carroll PR, Graefen M, Guazzoni G, Menon M, Patel VR, Shariat SF, Tewari AK, Van Poppel H, Zattoni F, Montorsi F, Mottrie A, Rosen RC, Wilson TG (2012) Systematic review and meta-analysis of studies reporting oncologic outcome after robot-assisted radical prostatectomy. Eur Urol 62:382–404. CrossRefPubMedGoogle Scholar
  8. 8.
    Karakiewicz PI, Eastham JA, Graefen M, Cagiannos I, Stricker PD, Klein E, Cangiano T, Schröder FH, Scardino PT, Kattan MW (2005) Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients. Urology 66:1245–1250. CrossRefPubMedGoogle Scholar
  9. 9.
    Meeks JJ, Eastham JA (2013) Radical prostatectomy: positive surgical margins matter. Urol Oncol 31:974–979. CrossRefPubMedGoogle Scholar
  10. 10.
    Boorjian SA, Karnes RJ, Crispen PL, Carlson RE, Rangel LJ, Bergstralh EJ, Blute ML (2010) The impact of positive surgical margins on mortality following radical prostatectomy during the prostate specific antigen era. J Urol 183:1003–1009. CrossRefPubMedGoogle Scholar
  11. 11.
    Chalfin HJ, Dinizo M, Trock BJ, Feng Z, Partin AW, Walsh PC, Humphreys E, Han M (2012) Impact of surgical margin status on prostate cancer-specific mortality. BJU Int 110:1684–1689. CrossRefPubMedGoogle Scholar
  12. 12.
    Stephenson AJ, Eggener SE, Hernandez AV, Klein EA, Kattan MW, Wood DP, Rabah DM, Eastham JA, Scardino PT (2014) Do margins matter? The influence of positive surgical margins on prostate cancer-specific mortality. Eur Urol 65:675–680. CrossRefGoogle Scholar
  13. 13.
    Wright JL, Dalkin BL, True LD, Ellis WJ, Stanford JL, Lange PH, Lin DW (2010) Positive surgical margins at radical prostatectomy predict prostate cancer specific mortality. J Urol 183:2213–2218. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lee S, Kim KB, Jo JK, Ho JN, Oh JJ, Jeong SJ, Hong SK, Byun SS, Choe G, Lee SE (2016) Prognostic value of focal positive surgical margins after radical prostatectomy. Clin Genitourin Cancer 14(4):e313–e319. CrossRefPubMedGoogle Scholar
  15. 15.
    Somford DM, van Oort IM, Cosyns JP, Witjes JA, Kiemeney LA, Tombal B (2012) Prognostic relevance of number and bilaterality of positive surgical margins after radical prostatectomy. World J Urol 30(1):105–110. CrossRefPubMedGoogle Scholar
  16. 16.
    Umbehr M, Kessler TM, Sulser T, Kristiansen G, Probst N, Steurer J, Bachmann LM (2008) ProCOC: the prostate cancer outcomes cohort study. BMC Urol 8:9. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wettstein MS, Saba K, Umbehr MH, Murtola TJ, Fankhauser CD, Adank JP, Hofmann M, Sulser T, Hermanns T, Moch H, Wild P, Poyet C (2017) Prognostic role of preoperative serum lipid levels in patients undergoing radical prostatectomy for clinically localized prostate cancer. Prostate 77(5):549–556. CrossRefPubMedGoogle Scholar
  18. 18.
    Feicke A, Baumgartner M, Talimi S, Schmid DM, Seifert H-H, Müntener M, Fatzer M, Sulser T, Strebel RT (2009) Robotic-assisted laparoscopic extended pelvic lymph-node dissection for prostate cancer: surgical technique and experience with the first 99 cases. Eur Urol 55:876–883. CrossRefPubMedGoogle Scholar
  19. 19.
    Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, Grading C (2016) The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 40(2):244–252. CrossRefPubMedGoogle Scholar
  20. 20.
    Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA, Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3):428–435. CrossRefPubMedGoogle Scholar
  21. 21.
    Ekici S, Ayhan A, Erkan L, Bakkaloğlu M, Özen H (2003) The role of the pathologist in the evaluation of radical prostatectomy specimens. Scand J Urol Nephrol 37:387–391. CrossRefPubMedGoogle Scholar
  22. 22.
    van der Kwast TH, Collette L, Van Poppel H, Van Cangh P, Vekemans K, DaPozzo L, Bosset JF, Kurth KH, Schroder FH, Bolla M, European Organisation for R, Treatment of Cancer R, Genito-Urinary Cancer G (2006) Impact of pathology review of stage and margin status of radical prostatectomy specimens (EORTC trial 22911). Virchows Arch 449(4):428–434. CrossRefPubMedGoogle Scholar
  23. 23.
    Evans AJ, Henry PC, Van der Kwast TH, Tkachuk DC, Watson K, Lockwood GA, Fleshner NE, Cheung C, Belanger EC, Amin MB, Boccon-Gibod L, Bostwick DG, Egevad L, Epstein JI, Grignon DJ, Jones EC, Montironi R, Moussa M, Sweet JM, Trpkov K, Wheeler TM, Srigley JR (2008) Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens. Am J Surg Pathol 32:1503–1512. CrossRefPubMedGoogle Scholar
  24. 24.
    Mauermann J, Fradet V, Lacombe L, Dujardin T, Tiguert R, Tetu B, Fradet Y (2013) The impact of solitary and multiple positive surgical margins on hard clinical end points in 1712 adjuvant treatment-naive pT2–4 N0 radical prostatectomy patients. Eur Urol 64:19–25. CrossRefPubMedGoogle Scholar
  25. 25.
    Sammon JD, Trinh Q-D, Sukumar S, Ravi P, Friedman A, Sun M, Schmitges J, Jeldres C, Jeong W, Mander N, Peabody JO, Karakiewicz PI, Harris M (2013) Risk factors for biochemical recurrence following radical perineal prostatectomy in a large contemporary series: a detailed assessment of margin extent and location. Urol Oncol 31:1470–1476. CrossRefPubMedGoogle Scholar
  26. 26.
    Stephenson AJ, Wood DP, Kattan MW, Klein EA, Scardino PT, Eastham JA, Carver BS (2009) Location, extent and number of positive surgical margins do not improve accuracy of predicting prostate cancer recurrence after radical prostatectomy. J Urol 182:1357–1363. CrossRefPubMedGoogle Scholar
  27. 27.
    Lee JW, Ryu JH, Kim YB, Yang SO, Lee JK, Jung TY (2013) Do positive surgical margins predict biochemical recurrence in all patients without adjuvant therapy after radical prostatectomy? Korean J Urol 54(8):510–515. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Maxeiner A, Magheli A, Jöhrens K, Kilic E, Braun TL, Kempkensteffen C, Hinz S, Stephan C, Miller K, Busch J (2016) Significant reduction in positive surgical margin rate after laparoscopic radical prostatectomy by application of the modified surgical margin recommendations of the 2009 International Society of Urological Pathology consensus. BJU Int 118:750–757. CrossRefPubMedGoogle Scholar
  29. 29.
    Dev HS, Wiklund P, Patel V, Parashar D, Palmer K, Nyberg T, Skarecky D, Neal DE, Ahlering T, Sooriakumaran P (2015) Surgical margin length and location affect recurrence rates after robotic prostatectomy. Urol Oncol 33:109.e107–109.e113. CrossRefGoogle Scholar
  30. 30.
    Sooriakumaran P, Ploumidis A, Nyberg T, Olsson M, Akre O, Haendler L, Egevad L, Nilsson A, Carlsson S, Jonsson M, Adding C, Hosseini A, Steineck G, Wiklund P (2015) The impact of length and location of positive margins in predicting biochemical recurrence after robot-assisted radical prostatectomy with a minimum follow-up of 5 years. BJU Int 115(1):106–113. CrossRefPubMedGoogle Scholar
  31. 31.
    Kordan Y, Salem S, Chang SS, Clark PE, Cookson MS, Davis R, Herrell SD, Baumgartner R, Phillips S, Smith JA Jr, Barocas DA (2009) Impact of positive apical surgical margins on likelihood of biochemical recurrence after radical prostatectomy. J Urol 182(6):2695–2701. CrossRefPubMedGoogle Scholar
  32. 32.
    Pfitzenmaier J, Pahernik S, Tremmel T, Haferkamp A, Buse S, Hohenfellner M (2008) Positive surgical margins after radical prostatectomy: do they have an impact on biochemical or clinical progression? BJU Int 102(10):1413–1418. CrossRefPubMedGoogle Scholar
  33. 33.
    Godoy G, Tareen BU, Lepor H (2009) Site of positive surgical margins influences biochemical recurrence after radical prostatectomy. BJU Int 104(11):1610–1614. CrossRefPubMedGoogle Scholar
  34. 34.
    Shikanov S, Song J, Royce C, Al-Ahmadie H, Zorn K, Steinberg G, Zagaja G, Shalhav A, Eggener S (2009) Length of positive surgical margin after radical prostatectomy as a predictor of biochemical recurrence. J Urol 182(1):139–144. CrossRefPubMedGoogle Scholar
  35. 35.
    Psutka SP, Feldman AS, Rodin D, Olumi AF, Wu C-L, McDougal WS (2011) Men with organ-confined prostate cancer and positive surgical margins develop biochemical failure at a similar rate to men with extracapsular extension. Urology 78:121–125. CrossRefPubMedGoogle Scholar
  36. 36.
    Hsu M, Chang SL, Ferrari M, Nolley R, Presti JC Jr, Brooks JD (2011) Length of site-specific positive surgical margins as a risk factor for biochemical recurrence following radical prostatectomy. Int J Urol 18(4):272–279. CrossRefPubMedGoogle Scholar
  37. 37.
    O’Neil LM, Walsh S, Cohen RJ, Lee S (2015) Prostate carcinoma with positive margins at radical prostatectomy: role of tumour zonal origin in biochemical recurrence. BJU Int 116(Suppl 3):42–48. CrossRefPubMedGoogle Scholar
  38. 38.
    Preston MA, Breau RH, Lantz AG, Morash C, Gerridzen RG, Doucette S, Mallick R, Eastham JA, Cagiannos I (2015) The association between nerve sparing and a positive surgical margin during radical prostatectomy. Urol Oncol 33:18.e11–18.e16. CrossRefGoogle Scholar
  39. 39.
    Boehm K, Graefen M (2015) Prostate cancer: nerve-sparing surgery and risk of positive surgical margins. Nat Rev Urol 12:131–132. CrossRefPubMedGoogle Scholar
  40. 40.
    Lo SK, Li IT, Tsou TS, See L (1995) Non-significant in univariate but significant in multivariate analysis: a discussion with examples. Changgeng Yi Xue Za Zhi 18(2):95–101PubMedGoogle Scholar
  41. 41.
    Mortezavi A, Keller EX, Poyet C, Hermanns T, Saba K, Randazzo M, Fankhauser CD, Wild PJ, Moch H, Sulser T, Eberli D (2016) Clinical impact of prostate biopsy undergrading in an academic and community setting. World J Urol. CrossRefPubMedGoogle Scholar
  42. 42.
    von Bodman C, Brock M, Roghmann F, Byers A, Löppenberg B, Braun K, Pastor J, Sommerer F, Noldus J, Palisaar RJ (2013) Intraoperative frozen section of the prostate decreases positive margin rate while ensuring nerve sparing procedure during radical prostatectomy. J Urol 190:515–520. CrossRefGoogle Scholar
  43. 43.
    Beyer B, Schlomm T, Tennstedt P, Boehm K, Adam M, Schiffmann J, Sauter G, Wittmer C, Steuber T, Graefen M, Huland H, Haese A (2014) A feasible and time-efficient adaptation of NeuroSAFE for da Vinci robot-assisted radical prostatectomy. Eur Urol 66:138–144. CrossRefPubMedGoogle Scholar
  44. 44.
    Bianchi R, Cozzi G, Petralia G, Alessi S, Renne G, Bottero D, Brescia A, Cioffi A, Cordima G, Ferro M, Matei DV, Mazzoleni F, Musi G, Mistretta FA, Serino A, Tringali VML, Coman I, De Cobelli O (2016) Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy. Medicine (Baltimore) 95:e4519. CrossRefGoogle Scholar
  45. 45.
    Petralia G, Musi G, Padhani AR, Summers P, Renne G, Alessi S, Raimondi S, Matei DV, Renne SL, Jereczek-Fossa BA, De Cobelli O, Bellomi M (2015) Robot-assisted radical prostatectomy: multiparametric MR imaging-directed intraoperative frozen-section analysis to reduce the rate of positive surgical margins. Radiology 274:434–444. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Etienne Xavier Keller
    • 1
  • Jacqueline Bachofner
    • 1
  • Anna Jelena Britschgi
    • 1
  • Karim Saba
    • 1
  • Ashkan Mortezavi
    • 1
  • Basil Kaufmann
    • 1
  • Christian D. Fankhauser
    • 1
  • Peter Wild
    • 2
    • 3
  • Tullio Sulser
    • 1
  • Thomas Hermanns
    • 1
  • Daniel Eberli
    • 1
  • Cédric Poyet
    • 1
    Email author
  1. 1.Department of UrologyUniversity Hospital Zurich, University of ZurichZurichSwitzerland
  2. 2.Institute of Surgical PathologyUniversity Hospital Zurich, University of ZurichZurichSwitzerland
  3. 3.Dr. Senckenberg Institute of PathologyUniversity Hospital FrankfurtFrankfurt am MainGermany

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