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Platinum Priority – Collaborative Review – Prostate Cancer Editorial by Mark A. Preston and Michael L. Blute on pp. 314–315 of this issue| Volume 65, ISSUE 2, P303-313, February 01, 2014

Positive Surgical Margins After Radical Prostatectomy: A Systematic Review and Contemporary Update

      Abstract

      Context

      The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear.

      Objective

      To address pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management.

      Evidence acquisition

      A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP.

      Evidence synthesis

      A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5–32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer–specific mortality, and overall survival remains debatable.

      Conclusions

      Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative.

      Keywords

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      References

        • Yossepowitch O.
        • Bjartell A.
        • Eastham J.A.
        • et al.
        Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences.
        Eur Urol. 2009; 55: 87-99
        • Lowrance W.T.
        • Eastham J.A.
        • Savage C.
        • et al.
        Contemporary open and robotic radical prostatectomy practice patterns among urologists in the United States.
        J Urol. 2012; 187: 2087-2092
        • Tan P.H.
        • Cheng L.
        • Srigley J.R.
        • et al.
        International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 5: surgical margins.
        Mod Pathol. 2011; 24: 48-57
        • Bong G.W.
        • Ritenour C.W.
        • Osunkoya A.O.
        • Smith M.T.
        • Keane T.E.
        Evaluation of modern pathological criteria for positive margins in radical prostatectomy specimens and their use for predicting biochemical recurrence.
        BJU Int. 2009; 103: 327-331
        • Emerson R.E.
        • Koch M.O.
        • Daggy J.K.
        • Cheng L.
        Closest distance between tumor and resection margin in radical prostatectomy specimens: lack of prognostic significance.
        Am J Surg Pathol. 2005; 29: 225-229
        • Epstein J.I.
        • Sauvageot J.
        Do close but negative margins in radical prostatectomy specimens increase the risk of postoperative progression?.
        J Urol. 1997; 157: 241-243
        • Lu J.
        • Wirth G.J.
        • Wu S.
        • et al.
        A close surgical margin after radical prostatectomy is an independent predictor of recurrence.
        J Urol. 2012; 188: 91-97
        • Shikanov S.
        • Marchetti P.
        • Desai V.
        • et al.
        Short (≤1 mm) positive surgical margin and risk of biochemical recurrence after radical prostatectomy.
        BJU Int. 2013; 111: 559-563
        • Yossepowitch O.
        • Sircar K.
        • Scardino P.T.
        • et al.
        Bladder neck involvement in pathological stage pT4 radical prostatectomy specimens is not an independent prognostic factor.
        J Urol. 2002; 168: 2011-2015
        • Yossepowitch O.
        • Engelstein D.
        • Konichezky M.
        • Sella A.
        • Livne P.M.
        • Baniel J.
        Bladder neck involvement at radical prostatectomy: positive margins or advanced T4 disease?.
        Urology. 2000; 56: 448-452
        • Fontenot P.A.
        • Mansour A.M.
        Reporting positive surgical margins after radical prostatectomy: time for standardization.
        BJU Int. 2013; 111: E290-E299
        • Brimo F.
        • Partin A.W.
        • Epstein J.I.
        Tumor grade at margins of resection in radical prostatectomy specimens is an independent predictor of prognosis.
        Urology. 2010; 76: 1206-1209
        • Cao D.
        • Kibel A.S.
        • Gao F.
        • Tao Y.
        • Humphrey P.A.
        The Gleason score of tumor at the margin in radical prostatectomy is predictive of biochemical recurrence.
        Am J Surg Pathol. 2010; 34: 994-1001
        • Huang J.G.
        • Pedersen J.
        • Hong M.K.
        • et al.
        Presence or absence of a positive pathological margin outperforms any other margin-associated variable in predicting clinically relevant biochemical recurrence in Gleason 7 prostate cancer.
        BJU Int. 2013; 111: 921-927
        • Chuang A.Y.
        • Epstein J.I.
        Positive surgical margins in areas of capsular incision in otherwise organ-confined disease at radical prostatectomy: histologic features and pitfalls.
        Am J Surg Pathol. 2008; 32: 1201-1206
        • van Oort I.M.
        • Bruins H.M.
        • Kiemeney L.A.
        • Knipscheer B.C.
        • Witjes J.A.
        • Hulsbergen-van de Kaa C.A.
        The length of positive surgical margins correlates with biochemical recurrence after radical prostatectomy.
        Histopathology. 2010; 56: 464-471
        • Emerson R.E.
        • Koch M.O.
        • Jones T.D.
        • Daggy J.K.
        • Juliar B.E.
        • Cheng L.
        The influence of extent of surgical margin positivity on prostate specific antigen recurrence.
        J Clin Pathol. 2005; 58: 1028-1032
        • Barocas D.A.
        • Han M.
        • Epstein J.I.
        • et al.
        Does capsular incision at radical retropubic prostatectomy affect disease-free survival in otherwise organ-confined prostate cancer?.
        Urology. 2001; 58: 746-751
        • Djavan B.
        • Milani S.
        • Fong Y.K.
        Benign positive margins after radical prostatectomy means a poor prognosis—pro.
        Urology. 2005; 65: 218-220
        • Godoy G.
        • Tareen B.U.
        • Lepor H.
        Does benign prostatic tissue contribute to measurable PSA levels after radical prostatectomy?.
        Urology. 2009; 74: 167-170
        • Savdie R.
        • Horvath L.G.
        • Benito R.P.
        • et al.
        High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy.
        BJU Int. 2012; 109: 1794-1800
        • Tewari A.
        • Sooriakumaran P.
        • Bloch D.A.
        • Seshadri-Kreaden U.
        • Hebert A.E.
        • Wiklund P.
        Positive surgical margin and perioperative complication rates of primary surgical treatments for prostate cancer: a systematic review and meta-analysis comparing retropubic, laparoscopic, and robotic prostatectomy.
        Eur Urol. 2012; 62: 1-15
        • Touijer K.
        • Eastham J.A.
        • Secin F.P.
        • et al.
        Comprehensive prospective comparative analysis of outcomes between open and laparoscopic radical prostatectomy conducted in 2003 to 2005.
        J Urol. 2008; 179 (discussion 1817): 1811-1817
        • 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
        • Wiltz A.L.
        • Shikanov S.
        • Eggener S.E.
        • et al.
        Robotic radical prostatectomy in overweight and obese patients: oncological and validated-functional outcomes.
        Urology. 2009; 73: 316-322
        • Link B.A.
        • Nelson R.
        • Josephson D.Y.
        • et al.
        The impact of prostate gland weight in robot assisted laparoscopic radical prostatectomy.
        J Urol. 2008; 180: 928-932
        • Huang A.C.
        • Kowalczyk K.J.
        • Hevelone N.D.
        • et al.
        The impact of prostate size, median lobe, and prior benign prostatic hyperplasia intervention on robot-assisted laparoscopic prostatectomy: technique and outcomes.
        Eur Urol. 2011; 59: 595-603
        • Ginzburg S.
        • Hu F.
        • Staff I.
        • et al.
        Does prior abdominal surgery influence outcomes or complications of robotic-assisted laparoscopic radical prostatectomy?.
        Urology. 2010; 76: 1125-1129
        • Patel V.R.
        • Coelho R.F.
        • Rocco B.
        • et al.
        Positive surgical margins after robotic assisted radical prostatectomy: a multi-institutional study.
        J Urol. 2011; 186: 511-516
        • Boorjian S.A.
        • Karnes R.J.
        • Crispen P.L.
        • et al.
        The impact of positive surgical margins on mortality following radical prostatectomy during the prostate specific antigen era.
        J Urol. 2010; 183: 1003-1009
        • Chalfin H.J.
        • Dinizo M.
        • Trock B.J.
        • et al.
        Impact of surgical margin status on prostate-cancer-specific mortality.
        BJU Int. 2012; 110: 1684-1689
        • Mauermann J.
        • Fradet V.
        • Lacombe L.
        • et al.
        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. 2013; 64: 19-25
        • Pfitzenmaier J.
        • Pahernik S.
        • Tremmel T.
        • Haferkamp A.
        • Buse S.
        • Hohenfellner M.
        Positive surgical margins after radical prostatectomy: do they have an impact on biochemical or clinical progression?.
        BJU Int. 2008; 102: 1413-1418
        • Wright J.L.
        • Dalkin B.L.
        • True L.D.
        • et al.
        Positive surgical margins at radical prostatectomy predict prostate cancer specific mortality.
        J Urol. 2010; 183: 2213-2218
        • Corcoran N.M.
        • Hovens C.M.
        • Metcalfe C.
        • et al.
        Positive surgical margins are a risk factor for significant biochemical recurrence only in intermediate-risk disease.
        BJU Int. 2012; 110: 821-827
        • 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
        • Wilt T.J.
        • Brawer M.K.
        • Jones K.M.
        • et al.
        Radical prostatectomy versus observation for localized prostate cancer.
        New Engl J Med. 2012; 367: 203-213
        • Vickers A.
        • Bennette C.
        • Steineck G.
        • et al.
        Individualized estimation of the benefit of radical prostatectomy from the Scandinavian Prostate Cancer Group randomized trial.
        Eur Urol. 2012; 62: 204-209
        • Hong Y.M.
        • Hu J.C.
        • Paciorek A.T.
        • Knight S.J.
        • Carroll P.R.
        Impact of radical prostatectomy positive surgical margins on fear of cancer recurrence: results from CaPSURE.
        Urol Oncol. 2010; 28: 268-273
        • Vickers A.
        • Bianco F.
        • Cronin A.
        • et al.
        The learning curve for surgical margins after open radical prostatectomy: implications for margin status as an oncological end point.
        J Urol. 2010; 183: 1360-1365
        • Secin F.P.
        • Savage C.
        • Abbou C.
        • et al.
        The learning curve for laparoscopic radical prostatectomy: an international multicenter study.
        J Urol. 2010; 184: 2291-2296
        • Sooriakumaran P.
        • John M.
        • Wiklund P.
        • Lee D.
        • Nilsson A.
        • Tewari A.K.
        Learning curve for robotic assisted laparoscopic prostatectomy: a multi-institutional study of 3794 patients.
        Ital J Urol Nephrol. 2011; 63: 191-198
        • Albadine R.
        • Hyndman M.E.
        • Chaux A.
        • et al.
        Characteristics of positive surgical margins in robotic-assisted radical prostatectomy, open retropubic radical prostatectomy, and laparoscopic radical prostatectomy: a comparative histopathologic study from a single academic center.
        Hum Pathol. 2012; 43: 254-260
        • Williams S.B.
        • D’Amico A.V.
        • Weinberg A.C.
        • Gu X.
        • Lipsitz S.R.
        • Hu J.C.
        Population-based determinants of radical prostatectomy surgical margin positivity.
        BJU Int. 2011; 107: 1734-1740
        • Wolanski P.
        • Chabert C.
        • Jones L.
        • Mullavey T.
        • Walsh S.
        • Gianduzzo T.
        Preliminary results of robot-assisted laparoscopic radical prostatectomy (RALP) after fellowship training and experience in laparoscopic radical prostatectomy (LRP).
        BJU Int. 2012; 110: 64-70
        • Tewari A.K.
        • Patel N.D.
        • Leung R.A.
        • et al.
        Visual cues as a surrogate for tactile feedback during robotic-assisted laparoscopic prostatectomy: posterolateral margin rates in 1340 consecutive patients.
        BJU Int. 2010; 106: 528-536
        • Patel V.R.
        • Schatloff O.
        • Chauhan S.
        • et al.
        The role of the prostatic vasculature as a landmark for nerve sparing during robot-assisted radical prostatectomy.
        Eur Urol. 2012; 61: 571-576
        • Tewari A.K.
        • Srivastava A.
        • Mudaliar K.
        • et al.
        Anatomical retro-apical technique of synchronous (posterior and anterior) urethral transection: a novel approach for ameliorating apical margin positivity during robotic radical prostatectomy.
        BJU Int. 2010; 106: 1364-1373
        • Sasaki H.
        • Miki J.
        • Kimura T.
        • et al.
        Lateral view dissection of the prostato-urethral junction to reduce positive apical margin in laparoscopic radical prostatectomy.
        Int J Urol. 2009; 16: 664-669
        • Guru K.A.
        • Perlmutter A.E.
        • Sheldon M.J.
        • et al.
        Apical margins after robot-assisted radical prostatectomy: does technique matter?.
        J Endourol. 2009; 23: 123-127
        • Sasaki H.
        • Miki J.
        • Kimura T.
        • et al.
        Upfront transection and subsequent ligation of the dorsal vein complex during laparoscopic radical prostatectomy.
        Int J Urol. 2010; 17: 960-961
        • Preston M.A.
        • Carrière M.
        • Raju G.
        • et al.
        The prognostic significance of capsular incision into tumor during radical prostatectomy.
        Eur Urol. 2011; 59: 613-618
        • Secin F.P.
        • Serio A.
        • Bianco Jr., F.J.
        • et al.
        Preoperative and intraoperative risk factors for side-specific positive surgical margins in laparoscopic radical prostatectomy for prostate cancer.
        Eur Urol. 2007; 51: 764-771
        • Eichelberg C.
        • Erbersdobler A.
        • Haese A.
        • et al.
        Frozen section for the management of intraoperatively detected palpable tumor lesions during nerve-sparing scheduled radical prostatectomy.
        Eur Urol. 2006; 49 (discussion 1016–8): 1011-1018
        • Tsuboi T.
        • Ohori M.
        • Kuroiwa K.
        • et al.
        Is intraoperative frozen section analysis an efficient way to reduce positive surgical margins?.
        Urology. 2005; 66: 1287-1291
        • Lepor H.
        • Kaci L.
        Role of intraoperative biopsies during radical retropubic prostatectomy.
        Urology. 2004; 63: 499-502
        • Kakiuchi Y.
        • Choy B.
        • Gordetsky J.
        • et al.
        Role of frozen section analysis of surgical margins during robot-assisted laparoscopic radical prostatectomy: a 2608-case experience.
        Hum Pathol. 2013; 44: 1556-1562
        • Ye H.
        • Kong X.
        • He T.W.
        • et al.
        Intraoperative frozen section analysis of urethral margin biopsies during radical prostatectomy.
        Urology. 2011; 78: 399-404
        • Schlomm T.
        • Tennstedt P.
        • Huxhold C.
        • et al.
        Neurovascular structure-adjacent frozen-section examination (NeuroSAFE) increases nerve-sparing frequency and reduces positive surgical margins in open and robot-assisted laparoscopic radical prostatectomy: experience after 11 069 consecutive patients.
        Eur Urol. 2012; 62: 333-340
        • von Bodman C.
        • Brock M.
        • Roghmann F.
        • et al.
        Intraoperative frozen section of the prostate decreases positive margin rate while ensuring nerve sparing procedure during radical prostatectomy.
        J Urol. 2013; 190: 515-520
        • 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
        • Bolla M.
        • van Poppel H.
        • Collette L.
        • et al.
        Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911).
        Lancet. 2005; 366: 572-578
        • Thompson Jr., I.M.
        • Tangen C.M.
        • Paradelo J.
        • et al.
        Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.
        JAMA. 2006; 296: 2329-2335
        • 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
        • Van der Kwast T.H.
        • Bolla M.
        • Van Poppel H.
        • et al.
        Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911.
        J Clin Oncol. 2007; 25: 4178-4186
        • Spahn M.
        • Joniau S.
        Positive surgical margin at radical prostatectomy: futile or surgeon-dependent predictor of prostate cancer death?.
        Eur Urol. 2013; 64: 26-28
        • Eggener S.E.
        • Scardino P.T.
        • Walsh P.C.
        • et al.
        Predicting 15-year prostate cancer specific mortality after radical prostatectomy.
        J Urol. 2011; 185: 869-875
      1. Suardi N, Gallina A, Lista G, et al. Impact of adjuvant radiation therapy on urinary continence recovery after radical prostatectomy. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.01.027.

        • Trock B.J.
        • Han M.
        • Freedland S.J.
        • et al.
        Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy.
        JAMA. 2008; 299: 2760-2769
        • Stephenson A.J.
        • Scardino P.T.
        • Kattan M.W.
        • et al.
        Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy.
        J Clin Oncol. 2007; 25: 2035-2041
        • Briganti A.
        • Wiegel T.
        • Joniau S.
        • et al.
        Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis.
        Eur Urol. 2012; 62: 472-487
        • Trabulsi E.J.
        • Valicenti R.K.
        • Hanlon A.L.
        • et al.
        A multi-institutional matched-control analysis of adjuvant and salvage postoperative radiation therapy for pT3–4N0 prostate cancer.
        Urology. 2008; 72 (discussion 1302–4): 1298-1302
        • Budiharto T.
        • Perneel C.
        • Haustermans K.
        • et al.
        A multi-institutional analysis comparing adjuvant and salvage radiation therapy for high-risk prostate cancer patients with undetectable PSA after prostatectomy.
        Radiother Oncol. 2010; 97: 474-479
        • Ost P.
        • De Troyer B.
        • Fonteyne V.
        • Oosterlinck W.
        • De Meerleer G.
        A matched control analysis of adjuvant and salvage high-dose postoperative intensity-modulated radiotherapy for prostate cancer.
        Int J Radiat Oncol Biol Phys. 2011; 80: 1316-1322