title: Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection.
abstract: OBJECTIVE
  To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP).
  
  
  METHODS
  In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD.
  
  
  RESULTS
  Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% (n= 671). Final Gleason score (GS) was 2-6 in 12.7% (n= 158), 7 in 52% (n= 649), and 8-10 in 35.4% (n= 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%;p< 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p< 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS.
  
  
  CONCLUSIONS
  Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven, Leuven, Belgium; Laboratory of Molecular Endocrinology, KULeuven, Leuven, Belgium.
authors.forename: Lisa
authors.initials: L
authors.lastname: Moris
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven, Leuven, Belgium; Laboratory of Molecular Endocrinology, KULeuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van den Broeck
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven, Leuven, Belgium; Nuclear Medicine and Molecular Imaging, KULeuven, Leuven, Belgium.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Tosco
authors.affiliation: Department of Urology, Maria Middelares , Ghent , Belgium.
authors.forename: Anthony
authors.initials: A
authors.lastname: Van Baelen
authors.affiliation: A.O.U. San Giovanni Battista-le Molinette, Department of Urology, University of Turin , Turin , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.affiliation: Department of Urology, Mayo Clinic , Rochester, MN , USA.
authors.forename: Robert Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven , Leuven , Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Everaerts
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven , Leuven , Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Albersen
authors.affiliation: Urologische Klinik Und Poliklinik, Klinikum Der Universität München Campus Großhadern, Ludwig Maximilians Universität , Munich , Germany.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.affiliation: Department of Urology, Jagiellonian University Medical College , Krakow , Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Chlosta
authors.affiliation: Laboratory of Molecular Endocrinology, KULeuven , Hamburg , Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
authors.affiliation: Department of Urology, University of Hamburg , Hamburg , Germany.
authors.forename: Felix K
authors.initials: FK
authors.lastname: Chun
authors.affiliation: Martini Klinik am UKE GmbH , Hamburg , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Urologische Klinik Und Poliklinik, Klinikum Der Universität München Campus Großhadern, Ludwig Maximilians Universität , Munich , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.affiliation: Department of Urology and Pediatric Urology, University Hospital Wurzburg , Wurzburg , Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kneitz
authors.affiliation: Department of Urology, University of Piemonte Orientale , Novara , Italy.
authors.forename: Giansilvio
authors.initials: G
authors.lastname: Marchioro
authors.affiliation: Department of Urology, Institut Mutualiste Montsouris and Paris Descartes University , Paris , France.
authors.forename: Rafael Sanchez
authors.initials: RS
authors.lastname: Salas
authors.affiliation: Department of Urology, Cliniques Universitaires SaintLuc , Brussels , Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Department of Urology, Netherlands Cancer Institute , Amsterdam , Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Van Der Poel
authors.affiliation: Department of Urology, Institut Paoli Calmettes Cancer Centre , Marseille , France.
authors.forename: Jochen Christoph
authors.initials: JC
authors.lastname: Walz
authors.affiliation: Department of Radiation Oncology, University Hospitals Leuven , Leuven , Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Meerleer
authors.affiliation: Department of Radiation Oncology, Gustave Roussy Cancer Institute , Villejuif , France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bossi
authors.affiliation: Department of Radiation Oncology, University Hospitals Leuven , Leuven , Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
authors.affiliation: San Raffaele Hospital, Department of Urology, University VitaSalute , Milan , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven , Leuven , Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.affiliation: University Hospital Bern, Inselspital, Department of Urology , Berne , Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Spahn
authors.affiliation: San Raffaele Hospital, Department of Urology, University VitaSalute , Milan , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Development and Regeneration, Urology, University Hospitals Leuven , Leuven , Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
keywords: high-risk prostate cancer; lymph node dissection; positive lymph node; prognosis; surgery