Positive surgical margins after radical prostatectomy: a systematic review and contemporary update.
BACKGROUND
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.


METHODS
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.


RESULTS
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.
Department of Urology, Rabin Medical Center, Petach-Tikva, Israel, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: oferyoss@netvision.net.il.
Ofer
O
Yossepowitch
Department of Urology, Università Vita Salute San Raffaele, Milan, Italy.
Alberto
A
Briganti
Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
James A
JA
Eastham
Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA.
Jonathan
J
Epstein
Martini Clinic, Prostate Cancer Center, University of Hamburg, Hamburg, Germany.
Markus
M
Graefen
Section of Pathological Anatomy, Polytechnic University of the Marche Region, Ancona, Italy.
Rodolfo
R
Montironi
Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Karim
K
Touijer
D018450:Disease Progression; D005629:Frozen Sections; D006801:Humans; D010535:Laparoscopy; D008297:Male; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D011237:Predictive Value of Tests; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome
Frozen-section analysis; Metastasis; Nerve sparing; Positive surgical margins; Prostate cancer; Radiation therapy; Robot-assisted laparoscopic radical prostatectomy; Survival