The association of type and number of high-risk criteria with cancer specific mortality in prostate cancer patients treated with radiotherapy.

To assess the association between of type and number of D'Amico high-risk criteria (DHRCs) with rates of cancer-specific mortality (CSM) in prostate cancer (PCa) patients treated with external beam radiotherapy (RT).

In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 34,908 RT patients with at least one DHRCs, namely prostate-specific antigen (PSA) >20 ng/dL (hrPSA), biopsy Grade Group (hrGG) 4-5, clinical T stage (hrcT) ≥T2c. Multivariable Cox regression models (CRM), as well as competing risks regression (CRR) model, which further adjust for other cause mortality, tested the association between DHRCs and 5-year CSM.

Of 34,908 patients, 14,777 (42%) exclusively harbored hrGG, 5641 (16%) hrPSA, 4390 (13%) had hrcT. Only 8238 (23.7%) harbored any combination of two DHRCs and 1862 (5.3%) had all three DHRCs. Five-year CSM rates ranged from 2.4% to 5.0% when any individual DHRC was present (hrcT, hrPSA, hrGG, in that order), versus 5.2% to 10.5% when two DHRCs were present (hrPSA+hrcT, hrcT+hrGG, hrPSA+hrGG, in that order) versus 14.4% when all three DHRCs were identified. In multivariable CRM hazard ratios relative to hrcT ranged from 1.07 to 1.76 for one DHRC, 2.20 to 3.83 for combinations of two DHRCs, and 5.11 for all three DHRCs. Multivariable CRR yielded to virtually the same results.

Our study indicates a stimulus-response effect according to the type and number of DHRCs. This indicates potential for risk-stratification within HR PCa patients that could be applied in clinical decision making to increase or reduce treatment intensity.

The Prostate. 2023 Mar 15 [Epub ahead of print]

Francesco Chierigo, Rocco Simone Flammia, Gabriele Sorce, Benedikt Hoeh, Lukas Hohenhorst, Zhe Tian, Fred Saad, Marcus Graefen, Michele Gallucci, Alberto Briganti, Francesco Montorsi, Felix K H Chun, Shahrokh F Shariat, Giovanni Guano, Guglielmo Mantica, Marco Borghesi, Nazareno Suardi, Carlo Terrone, Pierre I Karakiewicz

IRCCS Ospedale Policlinico San Martino, Genova, Italy., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Maternal-Child and Urological Sciences, Policlinico Umberto I Hospital, Sapienza Rome University, Rome, Italy., Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.