Longitudinal modeling of ultrasensitive and traditional prostate-specific antigen and prediction of biochemical recurrence after radical prostatectomy.
Ultrasensitive prostate-specific antigen (u-PSA) remains controversial for follow-up after radical prostatectomy (RP). The aim of this study was to model PSA doubling times (PSADT) for predicting biochemical recurrence (BCR) and to capture possible discrepancies between u-PSA and traditional PSA (t-PSA) by utilizing advanced statistical modeling. 555 RP patients without neoadjuvant/adjuvant androgen deprivation from the Turku University Hospital were included in the study. BCR was defined as two consecutive PSA values >0.2 ng/mL and the PSA measurements were log2-transformed. One third of the data was reserved for independent validation. Models were first fitted to the post-surgery PSA measurements using cross-validation. Major trends were then captured using linear mixed-effect models and a predictive generalized linear model effectively identified early trends connected to BCR. The model generalized for BCR prediction to the validation set with ROC-AUC of 83.6% and 95.1% for the 1 and 3 year follow-up censoring, respectively. A web-based tool was developed to facilitate its use. Longitudinal trends of u-PSA did not display major discrepancies from those of t-PSA. The results support that u-PSA provides useful information for predicting BCR after RP. This can be beneficial to avoid unnecessary adjuvant treatments or to start them earlier for selected patients.
Computational Biomedicine Group, Turku Centre for Biotechnology, University of Turku, Turku, Finland.|Department of Mathematics and Statistics, University of Turku, Turku, Finland.
Teemu D
TD
Laajala
Department of Surgery, Central Hospital of Central Ostrobothnia, Kokkola, Finland.|Department of Urology, Turku University Hospital, Turku, Finland.
Heikki
H
Seikkula
Computational Biomedicine Group, Turku Centre for Biotechnology, University of Turku, Turku, Finland.|Department of Mathematics and Statistics, University of Turku, Turku, Finland.
Fatemeh
F
Seyednasrollah
Department of Pathology (HUSLAB), Helsinki University Hospital, Helsinki, Finland.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Tuomas
T
Mirtti
Department of Urology, Turku University Hospital, Turku, Finland.
Peter J
PJ
Boström
Computational Biomedicine Group, Turku Centre for Biotechnology, University of Turku, Turku, Finland.
Laura L
LL
Elo
D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D011467:Prostate / Q000473:pathology / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000009:adverse effects / Q000379:methods*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D012307:Risk Factors; D012669:Seminal Vesicles / Q000473:pathology / Q000601:surgery
D017430:Prostate-Specific Antigen