title: The Role of Prostate-specific Antigen Persistence After Radical Prostatectomy for the Prediction of Clinical Progression and Cancer-specific Mortality in Node-positive Prostate Cancer Patients.
abstract: A complete biochemical response (BR) immediately after surgery could be considered an indicator of optimal cancer control after radical prostatectomy (RP).
  
  
  
  To evaluate the prognostic value of early postoperative prostate-specific antigen (PSA) levels after RP in patients with lymph node invasion (LNI).
  
  
  
  The study included 319 prostate cancer patients with LNI who were treated with RP and extended pelvic lymph node dissection (ePLND) at a single institution between 1998 and 2013. All men had complete clinical, pathologic, and follow-up data, including PSA value at 6 wk after surgery. Patients were divided into two groups according to PSA value at 6 wk after surgery: complete BR (PSA <0.1 ng/ml) and PSA persistence (PSA ≥0.1 ng/ml).
  
  
  
  Kaplan-Meier analyses were used to assess 8-yr clinical recurrence (CR) and cancer-specific mortality (CSM) rates according to PSA persistence after RP. Multivariable Cox regression analysis was used to test the association between PSA persistence and CR. Covariates consisted of pathologic Gleason score (≤7 vs ≥8), number of positive nodes, surgical margins status (negative vs positive), and adjuvant therapies (none vs androgen deprivation therapy (ADT) vs adjuvant radiotherapy plus ADT). When we performed multivariable analyses assessing the association between PSA persistence and CSM pathologic Gleason score represented the only covariate due to the low number of events (n=13).
  
  
  
  Overall, 83 patients (26%) had PSA persistence. Men with PSA persistence had higher 8-yr CR and CSM rates than those with complete BR (69% vs 12% and 16% vs 4.2%, respectively; all p≤0.002). This was confirmed in multivariable analyses, where PSA persistence at 6 wk after surgery was an independent predictor of both CR (hazard ratio [HR]: 8.3; 95% confidence interval [CI], 4.73-14.7; p≤0.001) and CSM (HR: 2.16; 95% CI, 1.63-2.86; p≤0.001). Pathologic stage lower than pT3a, biopsy and pathologic Gleason score ≥8, positive surgical margins, and three or more positive lymph nodes were significantly associated with PSA persistence (all p≤0.04). Our study is limited by its retrospective design.
  
  
  
  Early BR can be achieved in approximately 75% of men with LNI submitted to RP and ePLND. PSA assessment early after surgery has an important prognostic role in the prediction of CR and CSM in node-positive patients. A risk stratification of these patients based on PSA persistence could guide physicians to properly select patients who may benefit the most from timely multimodal treatments.
  
  
  
  The risk of clinical recurrence and cancer-specific mortality is heterogeneous in patients with prostate cancer with lymph node invasion. Node-positive patients with complete biochemical response early after surgery share more favorable oncologic outcomes than those with PSA persistence. These results are important to plan the optimal postoperative patient management.
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Department of Urology, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nini
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Doctorate Research Program, Magna Graecia University of Catanzaro, Catanzaro, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fossati
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Nazareno
authors.initials: N
authors.lastname: Suardi
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Moschini
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Dell'Oglio
authors.affiliation: Department of Urology, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Schiavina
authors.affiliation: Unit of Oncology, Division of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Unit of Oncology, Division of Urology, 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; D000726:Androgen Antagonists / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D009367:Neoplasm Staging; D011184:Postoperative Period; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen
keywords: Biochemical response; Cancer-specific mortality; Clinical recurrence; Lymph node invasion; PSA persistence; Prostate cancer; Radical prostatectomy