The present study failed to demonstrate an independent
The present study failed to demonstrate an independent association of preoperative ChE with BCR. This is in contrast to Koie et al. who reported that pretreatment serum ChE was significantly associated with BCR in 535 patients with CaP who underwent RP (5-year BRFS rates were 77.7% and 55.0%, respectively, P < 0.001) . However they used a cut-off for serum ChE which was under the lowest normal range reported in their study and also included patients with different characteristics with most patients having localized disease. Their multivariable model included only initial PSA, clinical stage, and Gleason score at biopsy . It may be that ChE measures a phenomenon that may not be of such importance in locally advance CaP. To this, we assessed the prognostic value of ChE with regard to hard endpoints such as MFS, OS, and CSS .
We found that patients with decreased pretreatment serum ChE were more likely to develop metastases and to die. Serum ChE as a continuous variable was associated with all 3, MFS, OS, and CSS. In agreement with our findings, Battisti et al. demonstrated that decreased serum ChE is associated with presence of bone metastases at diagnosis in 66 CaP patients . Furthermore, we found that the addition of pretreatment serum ChE to a histamine receptor antagonist multivariable model that includes all established clinicopathologic characteristics  increased the accuracy for prediction of metastases by 3%, OS by 2.54%, and CSS by 0.6%.
The biological reason underlying the association of ChE with metastatic phenomenon, especially micrometastasis, remains unknown. This could represent a highly interesting area of research , . Regarding clinical implications of these findings, patients with decreased pre-SRP serum ChE might benefit from a more extended PLND, multimodal therapy or a closer follow-up.
Results of this study should be regarded with caution as it suffers from several limitations. First are its retrospective design and short follow-up . Second, ChE is a sensitive, but nonspecific, serum biomarker and decreased ChE levels could be influenced by inflammation, physical stress, poor performance status, secondary malnutrition, or previous LHRH treatment. While, this would rather weaken an association with outcomes, this undermines its overall performance as a biomarker . Third, some heterogeneity in laboratory pathology results could be a potential bias as our study included 5 centers. However, the same technique and kits were used for serum ChE determination and we stratified patients according to normal and low range and analyzed it also as a continuous variable to avoid cut-off related bias.
Conflict of interest
Introduction Up to 30% of patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa) will experience biochemical recurrence (BCR) within 10 years from surgery . Identifying the patients most likely to fail surgery is of importance for risk stratification and counseling regarding adjuvant therapy and survivorship. Prognostic models based on standard clinicopathologic characteristics have been created to help in this task , , . While these tools have a good performance, they are not perfect as they fail to measure the biologic and immunologic potential of the individual cancer, its microenvironment, and the host in general , . Therefore, our current ability to differentiate patients with dissimilar outcomes (discrimination) and the discrepancies between the predictions and the actual outcomes (calibration) need improvement . Several protein based and genomic biomarkers have been investigated over the last few years , , , , but due to limitations in study design and the lack of structured phased-approach to development and validation , , , none of these tools have been implemented in widespread clinical use. Moreover, the development of novel targeted therapies has put the focus on the tumor's own microenvironment and the immune system as potential predictive and prognostic biomarkers , .