Prognostic Impact of TP53 and RB1 Alterations in Metastatic Castration-Resistant Prostate Cancer Treated with Docetaxel

Abstract

Background: Docetaxel remains a standard treatment for metastatic castration-resistant prostate cancer (mCRPC), yet reliable prognostic markers are lacking. TP53 and RB1, key tumor suppressor genes regulating cell-cycle control and genomic stability, have been linked to aggressive disease and lineage plasticity in advanced prostate cancer. We evaluated the prognostic impact of TP53 and/or RB1 alterations in mCRPC patients treated with docetaxel. Methods: We retrospectively analyzed 125 mCRPC patients treated with docetaxel. Genetic alterations were assessed using the TruSight Oncology 500 v2 panel. Progression-free survival (PFS) and overall survival (OS) were analyzed according to TP53 and RB1 alteration status. Results: TP53 alterations were present in 45 patients (36.0%) and RB1 alterations in 16 (12.8%). Patients with alterations in either TP53 or RB1 had significantly shorter OS (median OS = 18.10 vs. 32.23 months; HR = 1.83, 95% CI = 1.19-2.84; p =.006). Co-altered patients showed the poorest OS (median OS = 11.40 months; HR = 5.09, 95% CI = 1.97-13.19; p <.001). PFS was also shorter in patients with TP53 or RB1 alterations. Conclusion: TP53 and RB1 alterations, particularly TP53/RB1 co-alteration, are associated with poor prognosis in mCRPC treated with docetaxel.