Pasquale Rescigno1, David Dolling2, Vincenza Conteduca3, Mattia Rediti4, Diletta Bianchini5, Cristian Lolli3, Michael Ong6, Haoran Li6, Aurelius G Omlin7, Sabine Schmid7, Orazio Caffo8, Andrea Zivi9, Carmel J Pezaro10, Courtney Morley10, David Olmos11, Nuria Romero-Laorden11, Elena Castro11, Maria I Saez12, Niven Mehra13, Stella Smeenk13, Spyridon Sideris14, Thyerry Gil14, Patricia Banks15, Shaneen K Sandhu15, Cora N Sternberg16, Ugo De Giorgi3, Johann S De Bono17. 1. The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK; University of Naples Federico II, Naples, Italy. 2. Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK. 3. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy. 4. The Institute of Cancer Research, Sutton, UK; Jules Bordet Institut, Brussels, Belgium. 5. The Royal Marsden NHS Foundation Trust, Sutton, UK. 6. The Ottawa Hospital Cancer Centre, Ottawa, Canada. 7. Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, University of Bern, Bern, Switzerland. 8. Santa Chiara Hospital, Trento, Italy. 9. Ospedale dell'Angelo Mestre, AULSS3 Serenissima, UOC Oncologia, Venice, Italy. 10. Monash University and Eastern Health, Box Hill, Australia. 11. Spanish National Cancer Research Center, Madrid, Spain. 12. Hospital Virgen de la Victoria, Malaga, Spain. 13. Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. 14. Jules Bordet Institut, Brussels, Belgium. 15. Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. 16. Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY, USA. 17. The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: johann.de-bono@icr.ac.uk.
Abstract
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.
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.
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