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.
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.
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.
TP53 and RB1 alterations, particularly TP53/RB1 co-alteration, are associated with poor prognosis in mCRPC treated with docetaxel.
Cancer investigation. 2026 May 15 [Epub ahead of print]
Ja Yoon Heo, Chung Lee, Heesun Shin, Sungmin Cho, Seung Hoon Beom, Young-Deuk Choi, Woong Kyu Han, Won Sik Ham, Won Sik Jang, Hyunho Han, Jongsoo Lee, Ji Eun Heo, Daniel Khalaf, Urban Emmenegger, Sangwoo Kim, Chang Gon Kim, Minsun Jung, Sang Joon Shin
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea., Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Republic of Korea., Department of Urology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea., Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada., Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.