Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer.
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Date
2016-11-01Author
Rescigno, P
Lorente, D
Bianchini, D
Ferraldeschi, R
Kolinsky, MP
Sideris, S
Zafeiriou, Z
Sumanasuriya, S
Smith, AD
Mehra, N
Jayaram, A
Perez-Lopez, R
Mateo, J
Parker, C
Dearnaley, DP
Tunariu, N
Reid, A
Attard, G
de Bono, JS
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an intermediate endpoint for overall survival (OS). OBJECTIVE: To evaluate the association between early PSA decline and OS following abiraterone acetate (AA) treatment. DESIGN, SETTING, AND PARTICIPANTS: We identified mCRPC patients treated with AA before or after docetaxel at the Royal Marsden NHS Foundation Trust between 2006 and 2014. Early PSA decline was defined as a 30% decrease in PSA at 4 wk relative to baseline, and early PSA rise as a 25% increase. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman's rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 wk and 12 wk. RESULTS AND LIMITATIONS: There were 274 patients eligible for this analysis. A 30% PSA decline at 4 wk was associated with longer OS (25.8 vs 15.1 mo; hazard ratio [HR] 0.47, p<0.001), and a 25% PSA rise at 4 wk with shorter OS (15.1 vs 23.8 mo; HR 1.7, p=0.001) in both univariate and multivariable models. The percentage PSA decline at 4 wk was significantly correlated with the percentage PSA change at 12 wk (r=0.82; p<0.001). Patients achieving a 30% PSA decline at 4 wk were 11.7 times more likely to achieve a 50% PSA decrease at 12 wk (sensitivity 90.9%, specificity 79.4%). Limitations include the retrospective design of this analysis. CONCLUSIONS: Patients not achieving 30% PSA decline after 4 wk of AA have a lower likelihood of achieving PSA response at 12 wk and significantly inferior OS. Prospective multicentre validation studies are needed to confirm these findings. PATIENT SUMMARY: Prostate-specific antigen (PSA) is commonly used to evaluate response to treatment in metastatic castration-resistant prostate cancer. Expert recommendations discourage reliance on PSA changes earlier than 12 wk after treatment initiation. Our data suggest that early PSA changes are associated with survival in patients receiving abiraterone acetate.
Subject
Humans
Neoplasm Metastasis
Taxoids
Prostate-Specific Antigen
Antineoplastic Agents
Drug Monitoring
Neoplasm Staging
Registries
Survival Analysis
Aged
Middle Aged
Male
Statistics as Topic
Prostatic Neoplasms, Castration-Resistant
Abiraterone Acetate
United Kingdom
Docetaxel
Outcome Assessment, Health Care
Research team
Cancer Biomarkers
Prostate Cancer Targeted Therapy Group
Clinical Academic Radiotherapy (Dearnaley)
Treatment Resistance
Language
eng
Date accepted
2016-02-21
License start date
2016-11
Citation
European urology, 2016, 70 (5), pp. 724 - 731
Publisher
ELSEVIER SCIENCE BV