Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis

Publication

Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis

Journal Paper/Review - Jul 12, 2019

Rescigno Pasquale, Romero-Laorden Nuria, Castro Elena, Saez Maria I, Mehra Niven, Smeenk Stella, Sideris Spyridon, Gil Thyerry, Banks Patricia, Sandhu Shaneen K, Sternberg Cora N, De Giorgi Ugo, Olmos David, Morley Courtney, Pezaro Carmel J, Dolling David, Conteduca Vincenza, Rediti Mattia, Bianchini Diletta, Lolli Cristian, Ong Michael, Li Haoran, Omlin Aurelius, Schmid Sabine, Caffo Orazio, Zivi Andrea, de Bono Johann S

Citation

Rescigno P, Romero-Laorden N, Castro E, Saez M, Mehra N, Smeenk S, Sideris S, Gil T, Banks P, Sandhu S, Sternberg C, De Giorgi U, Olmos D, Morley C, Pezaro C, Dolling D, Conteduca V, Rediti M, Bianchini D, Lolli C, Ong M, Li H, Omlin A, Schmid S, Caffo O, Zivi A, de Bono J. Early Post-treatment Prostate-specific Antigen at 4 Weeks and Abiraterone and Enzalutamide Treatment for Advanced Prostate Cancer: An International Collaborative Analysis. Eur Urol Oncol 2019

Type

Journal Paper/Review (English)

Journal

Eur Urol Oncol 2019

Publication Date

Jul 12, 2019

Issn Electronic

2588-9311

Brief description/objective

BACKGROUND
Declines in prostate-specific antigen (PSA) levels at 12wk are used to evaluate treatment response in metastatic castration-resistant prostate cancer (mCRPC). PSA fall by ≥30% at 4wk (PSA4w30) has been reported to be associated with better outcome in a single-centre cohort study.

OBJECTIVE
To evaluate clinical relevance of early PSA decline in mCRPC patients treated with next-generation hormonal treatments (NGHTs) such as abiraterone and enzalutamide.

DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective multicentre analysis. Eligible patients received NGHT for mCRPC between 6 January 2006 and 31 December 2017 in 13 cancer centres worldwide, and had PSA levels assessed at baseline and at 4 and/or 12wk after treatment. PSA response was defined as a ≥30% decline (progression as a ≥25% increase) from baseline.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Association with overall survival (OS) was analysed using landmark multivariable Cox regression adjusting for previous chemotherapy, including cancer centre as a shared frailty term.

RESULTS AND LIMITATIONS
We identified 1358 mCRPC patients treated with first-line NGHT (1133 had PSA available at 4wk, and 948 at both 4 and 12wk). Overall, 583 (52%) had a PSA4w30; it was associated with longer OS (median: 23; 95% confidence interval [CI]: 21-25) compared with no change (median: 17; 95% CI: 15-18) and progression (median: 13; 95% CI: 10-15). A PSA12w30 was associated with lower mortality (median OS 22 vs 14; hazard ratio=0.57; 95% CI=0.48-0.67; p<0.001). PSA4w30 strongly correlated with PSA12w30 (ρ=0.91; 95% CI=0.90-0.92; p<0.001). In total, 432/494 (87%) with a PSA4w30 achieved a PSA12w30. Overall, 11/152 (7%) patients progressing at 4wk had a PSA12w30 (1% of the overall population).

CONCLUSIONS
PSA changes in the first 4wk of NGHT therapies are strongly associated with clinical outcome from mCRPC and can help guide early treatment switch decisions.

PATIENT SUMMARY
Prostate-specific antigen changes at 4wk after abiraterone/enzalutamide treatment are important to determine patients' outcome and should be taken into consideration in clinical practice.