Serum bone turnover markers (PINP and ICTP) for the early detection of bone metastases in patients with prostate cancer: a longitudinal approach.
OBJECTIVE
An increase in bone turnover markers in patients with prostate cancer may predict bone metastases but it can also reflect the effects of androgen deprivation treatment. To assess the diagnostic efficacy of early detection of skeletal metastases we retrospectively performed serial measurements of a bone formation marker (PINP) and a bone resorption marker (ICTP) in serum of patients with prostate cancer.


METHODS
Residual serum samples from 64 patients with prostate cancer treated between 1999 and 2004 were selected from our prostate specific antigen serum archive, and divided into 3 groups of patients with no metastases (N0M0), with lymph node metastases only (N1M0) and with skeletal metastases (M1). In the M1 group the T(1) sample was collected near the first positive bone scintigraph.


RESULTS
The N1M0 and M1 groups showed increased PINP levels (ANOVA T(0) p = 0.035, T(1) p <0.001). The PINP levels in the M1 group increased further (paired t test p = 0.028), while no increase was found in the other groups. There was no significant difference between the number of patients receiving androgen deprivation therapy in the N1M0 and the M1 groups. Increased PINP levels in the M1 group were detectable 8 months before the first positive bone scintigraph. The increase in ICTP in the M1 group differed significantly from the other groups (the Student t test in 45 patients p = 0.029). The increases in PINP and ICTP differentiated between patients with or without skeletal metastases (AUC 0.71, p = 0.002 and AUC 0.64, p = 0.045, respectively).


CONCLUSIONS
Followup measurement of serum PINP and ICTP is useful in the early assessment of skeletal metastases in patients with prostate cancer regardless of the confounding role of androgen deprivation treatment. The bone formation marker is the most indicative.
Koopmans
N
N
Department of Urology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. n.koopmans@uro.umcg.nl
de Jong
I J
IJ
Breeuwsma
A J
AJ
van der Veer
E
E
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D002277:Carcinoma / Q000175:diagnosis* / Q000556:secondary*; D024042:Collagen Type I; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides; D011347:Procollagen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide