Abstract
BackgroundAfter radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC.MethodsTwo hundred and seventy-one men with localised PC treated with RP were included. RP specimens stained for p53 by immunohistochemistry were scored as (a) percentage of p53-positive tumour nuclei; and (b) clustering, where ≥12 p53-positive cells within a ×200 power field was deemed ‘cluster positive’. Associations between p53 status and clinical outcomes (BCR, MR and PCSM) were evaluated.ResultsIncreasing percentage of p53-positive nuclei was significantly associated with shorter time to BCR, MR and PCSM (All p < 0.001). Half of the patients were p53 cluster positive. p53 cluster positivity was significantly associated with poorer outcomes at all clinical endpoints (BCR: HR 2.0, 95% CI 1.51–2.65, p < 0.001; MR: HR 4.1, 95% CI 2.02–8.14, p < 0.001; PCSM: HR 12.2, 95% CI 1.6–93; p = 0.016). These associations were independent of other established prognostic variables.Conclusionsp53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM.
Highlights
After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM)
Half of the patients were p53 cluster positive. p53 cluster positivity was significantly associated with poorer outcomes at all clinical endpoints (BCR: HR 2.0, 95% CI 1.51–2.65, p < 0.001; MR: HR 4.1, 95% CI 2.02–8.14, p < 0.001; PCSM: HR 12.2, 95% CI 1.6–93; p = 0.016)
At a median follow-up of 15.8 years, 203 patients (75%) had relapsed: 156 patients (57.5%) had a biochemical only relapse, 42 (15%) patients had experienced a metastatic relapse and 25 (9%) patients had died from PC
Summary
After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC. In patients receiving radiation and androgen deprivation therapy for locally advanced disease, p53 mutations are associated with poor prognosis, but the effect on response to specific treatments is contradictory across the two major studies.[8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
