Prognostic Significance of High-Risk versus Very High-Risk Classification in Non-Surgically Managed Prostate Cancer: A Retrospective Cohort Study

Gözde Ağdaş, Mehmet Salim Demir Department of Medical Oncology, Van Training and Research Hospital, Van, Turkey Correspondence : Gözde Ağda&#x015FDepartment of Medical Oncology, Van Training and Research Hospital, Van, Turkey, Tel +90 554 415 09 15, Email [email protected]: Risk stratification is one of the most critical parameters guiding treatment decisions in nonmetastatic prostate cancer. Although it is well established that high risk (HR) and very high risk (VHR) groups diverge prognostically, the real-world impact of this distinction in non-surgically managed patient populations has been less extensively evaluated.Methods: In this retrospective study, 81 patients with nonmetastatic prostate cancer were analyzed (HR: n=24; VHR: n=57). All patients received androgen deprivation therapy (ADT), and 65.4% additionally underwent radiotherapy (RT). Clinical and pathological characteristics, early PSA responses, overall survival (OS), and disease-free survival (DFS) were compared between HR and VHR groups.Results: At diagnosis, VHR patients presented with higher PSA values, worse Gleason scores, and more advanced stages. Although PSA responses at three and six months were similar between groups, long-term outcomes were significantly inferior in the VHR cohort. Median OS for the entire cohort was 72.1 months in VHR patients versus 97.1 months in HR patients (p=0.039). Among those receiving RT, the difference was preserved (HR: 104.5 months vs VHR: 75.1 months; p=0.032). Median DFS was 23.3 months in the VHR group and 44.5 months in the HR group (p=0.026). During follow-up, recurrence/metastasis occurred in 54.4% of VHR patients compared with 16.7% of HR patients (p=0.002).Conclusion: Our findings show that the VHR classification maintains strong prognostic value even in non-surgically managed patients, underscoring its role as a biologically distinct and aggressive disease entity. Standard RT+ADT seems insufficient in this subgroup. The study supports exploring intensified treatment strategies, such as prolonged ADT, brachytherapy boost, pelvic nodal RT, and, where appropriate, novel androgen receptor signaling inhibitors or chemotherapy.Keywords: prostate cancer, high risk, very high risk, radiotherapy, androgen deprivation therapy, survival