title: [-2]proPSA versus ultrasensitive PSA fluctuations over time in the first year from radical prostatectomy, in an high-risk prostate cancer population: A first report.
abstract: BACKGROUND
  [-2]proPSA and its derivatives have an higher diagnostic accuracy than PSA in predicting prostate cancer (PCa). In alternative to PSA, ultrasensitive PSA (uPSA) and [-2]proPSA could be potentially useful in recurrent disease detection. This research focused on [-2]proPSA and uPSA fluctuations over time and their possible clinical and pathological determinants, in the first year after RP.
  
  
  METHODS
  A cohort of 106 consecutive patients, undergoing RP for high-risk prostate cancer (pT3/pT4 and/or positive margins), was enrolled. No patient received either preoperative/postoperative androgen deprivation therapy or immediate adjuvant RT, this latter for patient choice. [-2]proPSA and uPSA were measured at 1, 3, 6, 9, 12 months after RP; their trends over time were estimated by the mixed-effects linear model. The uPSA relapse was defined either as 3 rising uPSA values after nadir or 2 consecutive uPSA >0.2 ng/ml after RP.
  
  
  RESULTS
  The biochemical recurrence (BCR) rate at 1 year after RP was either 38.6 % (in case of 3 rising uPSA values) or 34.9 % (in case of PSA >0.2 ng/ml after nadir), respectively. The main risk factors for uPSA fluctuations over time were PSA at diagnosis >8 ng/ml (p = 0.014), pT (p = 0.038) and pN staging (p = 0.001). In turn, PSA at diagnosis >8 ng/ml (p = 0.012) and pN (p < 0.001) were the main determinants for [-2]proPSA trend over time. In a 39 patients subgroup, uPSA decreased from month 1 to 3, while [-2]proPSA increased in 90 % of them; subsequently, both uPSA and [-2]proPSA increased in almost all cases. The [-2]proPSA trend over time was independent from BCR status either in the whole cohort as well in the 39 men subgroup.
  
  
  CONCLUSIONS
  Both uPSA and [-2]proPSA had independent significant fluctuations over time. PSA at diagnosis >8 ng/ml and pathological staging significantly modified both these trends over time. Since BCR was not confirmed as determinant of [-2]proPSA fluctuations, its use as marker of early biochemical relapse may not be actually recommended, in an high-risk prostate cancer patients population.
authors.affiliation: Division of Urology, San Luigi Gonzaga Hospital and University of Torino, Orbassano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: De Luca
authors.affiliation: Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Corso AM Dogliotti 14, 10126, Torino, Italy. passera.roberto@gmail.com.
authors.forename: R
authors.identifier: http://orcid.org/0000-0003-3372-2248
authors.initials: R
authors.lastname: Passera
authors.affiliation: Division of Laboratory Medicine, Candiolo Cancer Institute, Candiolo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sottile
authors.affiliation: Division of Urology, San Luigi Gonzaga Hospital and University of Torino, Orbassano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fiori
authors.affiliation: Division of Urology, San Luigi Gonzaga Hospital and University of Torino, Orbassano, Italy.
authors.forename: R M
authors.initials: RM
authors.lastname: Scarpa
authors.affiliation: Division of Urology, San Luigi Gonzaga Hospital and University of Torino, Orbassano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Porpiglia
mesh_terms: D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D016014:Linear Models; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D011498:Protein Precursors / Q000097:blood*; D012189:Retrospective Studies; D065287:Robotic Surgical Procedures; D054063:Superior Sagittal Sinus
chemical_list: C583834:(-2)pro-prostate-specific antigen, human; D014408:Biomarkers, Tumor; D011498:Protein Precursors; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: (−2)pro-prostate-specific antigen; Biochemical recurrence; Prostate cancer; Prostate-specific antigen