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.

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

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.

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

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).

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.

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.

European urology oncology. 2019 Jul 12 [Epub ahead of print]

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

The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK; University of Naples Federico II, Naples, Italy., Clinical Trials and Statistics Unit, The Institute of Cancer Research, London, UK., Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy., The Institute of Cancer Research, Sutton, UK; Jules Bordet Institut, Brussels, Belgium., The Royal Marsden NHS Foundation Trust, Sutton, UK., The Ottawa Hospital Cancer Centre, Ottawa, Canada., Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, University of Bern, Bern, Switzerland., Santa Chiara Hospital, Trento, Italy., Ospedale dell’Angelo Mestre, AULSS3 Serenissima, UOC Oncologia, Venice, Italy., Monash University and Eastern Health, Box Hill, Australia., Spanish National Cancer Research Center, Madrid, Spain., Hospital Virgen de la Victoria, Malaga, Spain., Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands., Jules Bordet Institut, Brussels, Belgium., Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia., Englander Institute for Precision Medicine, Weill Cornell Medicine, New York-Presbyterian, New York, NY, USA., The Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: .