The role of PCA 3 as a prognostic factor in patients with castration-resistant prostate cancer (CRPC) treated with docetaxel

Andreas Bourdoumis, Michael Chrisofos, Theodora Stasinou, Athanasios Papatsoris, Panagiotis Christopoulos, Athanasios Kostakopoulos, Charalambos Deliveliotis

Abstract


Purpose: To investigate potential fluctuations in PCA 3 scores in castration-resistant prostate cancer (CRPC) patients treated with docetaxel and investigate the assay as a potential prognostic factor.

Materials and Methods: This was a prospective observational cohort study. Inclusion criteria included patients on hormonal treatment that were recently diagnosed with CRPC. Exclusion criteria included patients previously having radical treatment (surgery or radiotherapy) and patients who have completed the first cycle of chemotherapy. All  urine samples were collected and analyzed using the Progensa® assay (Gen-Probe, San Diego, CA). Samples were collected before starting chemotherapy and at 12 months. A prospective database was created including routine blood tests, prostate staging and PSA levels throughout the study period. The effects of chemotherapy were also recorded.

Results: Between January 2010 and February 2013, 12 patients were included in the study out of an initial cohort of 23 patients with CRPC. Mean follow up was 14.8 months. Mean age at CRPC diagnosis was 73.8 years (+/-3.6 SD). Mean Gleason score was 8, with PSA 84.23 ng/ml (+/- 158 SD). Mean duration of androgen deprivation treatment was 45.16 months (+/- 34.9 SD). Mean time to castrate resistant state  was 46.58 months (+/- 35.3 SD). All twelve (n=12, 100%) patients had non-assessable PCA 3 scores at baseline and at 12 months follow up. As a direct consequence, statistical analysis did not take place as the anticipated change in PCA 3 scores was not identified and correlation between measurable differences was not possible. All patients tolerated chemotherapy and completed the scheduled cycles with no serious adverse effects.

Conclusion: To our knowledge, this is the first prospective study that demonstrates lack of expression of PCA3 in castration-resistant prostate cancer, with the result apparently not influenced by chemotherapy. There appears to be a strong association between hormonal treatment and lack of PCA 3 expression. It is still unknown whether disease progression per se affects PCA 3 scores. The gradual reduction and eventual complete non expression of PCA 3 with ongoing treatment and disease progression provide an insight towards molecular pathways that may be connected to  castration resistant state.

 

Ο πρωταρχικός σκοπός της μελέτης ήταν η ανεύρεση διακυμάνσεων του αθροίσματος του PCA 3 σε ασθενείς με προχωρημένη νόσο που μόλις μετέπεσαν σε ορμονοαντοχή και υπεβλήθησαν σε αγωγή με δοσιταξέλη (docetaxel) και η πιθανή προγνωστική σημασία. Όλοι οι ασθενείς υπεβλήθησαν σε δακτυλική εξέταση και προστατική μάλλαξη ώστε να γίνει συλλοξή δείγματος ούρων κατάλληλο για επεξεργασία και ανάλυση επιπέδων PCA 3 με τη χρήση του αντιδραστηρίου Progensa assay  σύμφωνα με τις προδιαγραφές της κατασκευάστριας εταιρείας (Gen-Probe, San Diego, CA, USA) κατά την ένταξη στη μελέτη και μετά από πάροδο 12 μηνών υπό χημειοθεραπεία. Συντάχτηκε έτσι μια προοπτική βάση δεδομένων που συμπεριλάμβανε το είδος και τη διάρκεια θεραπείας ορμονοαποκλεισμού καθώς και τις παρενέργειες των θεραπευτικών σχημάτων καθ’όλη τη διάρκεια της μελέτης.

Το συνολό των ασθενών (n=12, 100%) παρουσίασε μη ανιχνεύσημο άθροισμα PCA 3, τόσο στην αρχή όσο και στο τέλος της μελέτης. Το χημειοθεραπευτικό θεραπευτικό σχήμα έγινε καλά ανεκτό από τη πλειοψηφία των ασθενών κατά το πρώτο τρίμηνο, χωρίς την εμφάνιση ανεπιθύμητων παρενεργειών και με βελτίωση του οστικού άλγους σε ασθενείς με μεταστάσεις.

Η μελέτη μας αποτελεί τη πρώτη και μοναδική αναφορά στην ανεύρεση και το ρόλο του PCA 3 σε ασθενείς με ορμονοάντοχο καρκίνο του προστάτη, και μετά από χημειοθεραπεία. Φαίνεται να υπάρχει μια καλή συσχέτιση μεταξύ της μη ανίχνευσης αθροίσματος PCA 3 και ορμονοθεραπείας, πιθανώς μέσω μιας μοριακής οδού που επιφέρει αναστολή έκφρασης του αντίστοιχου γονιδίου. Έμμεσα, ένα τέτοιο εύρημα θα μπορούσε να χρησιμοποιηθεί για τον νωρίτερο εντοπισμό ασθενών που εμπίπτουν σε ορμονοαντοχή.


Keywords


Castration-Resistant Prostate Cancer (CRPC); PCA 3; Androgen Deprivation Treatment (ADT); Prognostic factor; Docetaxel; ευνουχοάντοχος καρκίνος pροστάτη (CRPC); PCA 3; Θεραπεία ορμονοαποκλεισμού (ADT); προγνωστκός παράγοντας; δοσιταξέλη

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DOI: http://dx.doi.org/10.19264/hj.v28i3.132