title: Patterns of Clinical Recurrence of Node-positive Prostate Cancer and Impact on Long-term Survival.
abstract: BACKGROUND
  The patterns of recurrence of patients with node-positive prostate cancer (PCa) at radical prostatectomy (RP) are still unknown.
  
  
  OBJECTIVE
  To describe recurrence patterns, to identify predictors of progression, and to test the impact of the site of clinical recurrence (CR) on cancer-specific mortality (CSM).
  
  
  METHODS
  We included 1003 patients with node-positive PCa treated with RP and extended pelvic lymph node dissection. Patients who experienced biochemical recurrence (BCR; n=370) and CR (n=183) were identified. CR was defined as positive imaging after BCR. Patients were stratified according to the first site of CR: local and/or nodal (recurrence in the prostatic bed and/or pelvic nodes), retroperitoneal, bony, or visceral.
  
  
  METHODS
  Multivariable competing-risks regression analyses identified predictors of systemic recurrence (ie, retroperitoneal, bony, and/or visceral) and tested the association between the site of recurrence and CSM after accounting for the risk of other-cause mortality.
  
  
  CONCLUSIONS
  When considering patients experiencing BCR, pathologic Gleason score, time to BCR, and the administration of a positron emission tomography/computed tomography scan represented predictors of systemic recurrence (all p ≤ 0.002). Among patients who experienced CR, recurrence was local and/or nodal in 56 (30.5%), retroperitoneal in 25 (13.7%), skeletal in 77 (42.1%), and visceral in 25 (13.7%). Among patients experiencing local recurrence, 27 (48.2%) had positive margins, 29 (51.8%) had adjuvant radiotherapy, and 22 (39.5%) had salvage radiotherapy. Patients experiencing local and/or nodal recurrence had higher 5-yr CSM-free survival rates compared with those with retroperitoneal, skeletal, and visceral recurrence (79.3%, 76.3%, 50.8%, and 35.3%, respectively; p<0.001). The site of recurrence represented an independent predictor of CSM (p ≤ 0.04).
  
  
  CONCLUSIONS
  In approximately one-third of patients who are pN+ and experience CR, the prostatic bed and pelvic lymph nodes represent the first sites of recurrence. These patients have a more favorable prognosis compared with those with skeletal and visceral metastases. These data have important implications for the selection of the optimal postoperative management of pN+ patients who experience CR. Although patients with local and/or pelvic nodal recurrence might benefit from nonsystemic salvage therapies, men with visceral and skeletal recurrence might represent ideal candidates for systemic approaches.
  
  
  RESULTS
  Not all patients with pN+ prostate cancer who experience clinical recurrence harbor distant metastatic disease. Local and/or nodal recurrence occurs in one-third of these cases. These patients share a more favorable prognosis than their counterparts with systemic recurrence. These results are important for tailoring the optimal postoperative management for each node-positive patient with recurrent disease after surgery.
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nini
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fossati
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Nazareno
authors.initials: N
authors.lastname: Suardi
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Cucchiara
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Dell'Oglio
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cazzaniga
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Luzzago
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: briganti.alberto@hsr.it.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000401:mortality* / Q000556:secondary; D002423:Cause of Death; D018572:Disease-Free Survival; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018714:Radiotherapy, Adjuvant; D012044:Regression Analysis; D012186:Retroperitoneal Neoplasms / Q000401:mortality* / Q000556:secondary; D012189:Retrospective Studies; D016879:Salvage Therapy
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Cancer-specific mortality; Clinical recurrence; Distant metastases; Lymph node dissection; Lymph node metastases; Prostate cancer