VERY high-risk prostate cancer predicted shorter survival than high-risk disease in nonmetastatic patients managed without surgery.
High-Risk vs Very High-Risk Prostate Cancer Outcomes
Risk stratification is central to treatment planning in nonmetastatic prostate cancer, yet the real-world impact of separating high risk from very high risk has been less clear in patients who do not undergo surgery. In a retrospective cohort of 81 patients treated without prostatectomy, investigators compared baseline features, early PSA responses, and long-term outcomes between high risk (n=24) and very high risk (n=57) groups.
At diagnosis, the very high-risk group presented with higher PSA levels, worse Gleason scores, and more advanced clinical stage than the high-risk group. Despite these baseline differences, early biochemical response did not distinguish the cohorts. PSA responses at three and six months were reported as similar, suggesting that short-term PSA change may not fully reflect the aggressiveness captured by very high-risk classification.
Similar Early PSA, Divergent Long-Term Survival
Long-term outcomes separated clearly by risk group. Median overall survival was 72.1 months in the very high-risk cohort versus 97.1 months in the high-risk cohort. Disease-free survival also favored high risk patients, with median disease-free survival of 44.5 months compared with 23.3 months for very high-risk disease.
During follow-up, recurrence or metastasis occurred in 54.4% of very high-risk patients, compared with 16.7% of high-risk patients. This gap supports the clinical value of distinguishing very high-risk disease, even when initial management is non-surgical and early PSA responses appear comparable.
Treatment Implications in Non-Surgically Managed Prostate Cancer
All patients received androgen deprivation therapy, and 65.4% also underwent radiotherapy. Among those receiving radiotherapy, the survival difference persisted, with median overall survival of 104.5 months for high-risk disease versus 75.1 months for very high-risk disease.
The authors conclude that very high-risk classification retains strong prognostic significance in non-surgically managed prostate cancer and may represent a biologically distinct and aggressive entity. They suggest standard radiotherapy plus androgen deprivation therapy may be insufficient for this subgroup and support evaluating intensified approaches, including prolonged androgen deprivation therapy, a brachytherapy boost, pelvic nodal radiotherapy, and, where appropriate, novel androgen receptor signaling inhibitors or chemotherapy.
Reference: Ağdaş G et al. Prognostic Significance of High-Risk versus Very High-Risk Classification in Non-Surgically Managed Prostate Cancer: A Retrospective Cohort Study. Cancer Manag Res. 2025;17:3299-3308.
