Defining and Staging Very High-Risk Localized Prostate Cancer

Welcome back to another Urology Times Investigator Perspectives series. In this episode, Tamim Niazi, MDCM, discusses very high-risk localized prostate cancer.

Niazi begins with the phase 3 DASL-HiCaP (NCT04136353) definition. In the primary radiation therapy cohort, patients with grade group 5 (Gleason 9-10) disease or pelvic nodal disease qualify as very high risk, whereas grade group 4 disease qualifies when paired with at least 1 additional risk factor, such as advanced T stage or prostate-specific antigen (PSA) level above 20 ng/mL. In the salvage setting, patients need a PSA that persists or rises above 0.1 ng/mL within 12 months of prostatectomy plus grade group 5 disease or pathologic or clinical pelvic nodal disease; grade group 4 also requires pT3a or higher. He notes the definition aligns more closely with STAMPEDE (NCT00268476).

Niazi explains that radical prostatectomy or locoregional radiation therapy plus long-term ADT remains the backbone, with abiraterone and prednisolone added for patients who meet STAMPEDE criteria. It is effective, he says, but many patients still progress to biochemical failure and metastasis. The goal, he says, is identifying who will benefit from intensification to reduce metastasis and castration resistance and improve survival.

Niazi then addresses prostate-specific membrane antigen (PSMA) PET. Metastasis-free survival by conventional imaging is a validated surrogate for overall survival in the localized setting; PSMA PET–detected disease is not. He asks whether a few extrapelvic nodes on PET should mean abandoning curative intent. He explains that DASL-HiCaP used conventional imaging for this reason, and that patients with PET-detected pelvic nodes usually carry other aggressive features, such as Gleason 9-10 disease or higher PSA, that meet the trial's definition.

In the next episode, Niazi walks through the trial's design, its metastasis-free survival benefit, and what the safety data mean for patient counseling.

REFERENCES

1. Niazi T, Thomas H, Zhang A, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: Interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Presented at: European Society for Medical Oncology Congress 2026; October 23-27, 2026, Madrid, Spain. Abstract LBA4 https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2026_abstracts/LBA4.html.pdf

2. Darolutamide plus ADT and radiation therapy reduces risk of metastasis or death by 58% in prostate cancer patients at high risk of recurrence. News release. Orion Pharma. October 24, 2026. Accessed October 25, 2026. https://www.orionpharma.com/newsroom/all-news/releases/press-releases/2026/darolutamide-plus-adt-and-radiation-therapy-reduces-risk-of-metastasis-or-death-by-58-in-prostate-cancer-patients-at-high-risk-of-recurrence/