Time to castration-resistant prostate cancer and prostate cancer death according to PSA response in men with non-metastatic prostate cancer treated with gonadotropin releasing hormone agonists

<b>Objectives:</b> To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). <b>Materials and Methods:</b> PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (<i>pre-GnRH PSA</i>) and 3–6 months after (<i>post-GnRH PSA</i>) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. <b>Results:</b> 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. <i>Post-GnRH PSA</i> predicted CRPC regardless of <i>pre-GnRH PSA</i>. CRPC risk increased with higher <i>post-GnRH PSA</i>, HR 4.7 (95% CI: 3.4–6.7) for PSA &gt; 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of <i>post-GnRH PSA</i> and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). <b>Conclusion:</b> A risk score based on <i>post-GnRH PSA</i> and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.