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The following is a summary of “Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials,” published in the May 2024 issue of Urology by Ravi et al.

Radiotherapy (RT) combined with long-term androgen deprivation therapy (ltADT; 18–36 months) represents the standard treatment approach for high-risk localized or locoregional prostate cancer (HRLPC). This study aimed to assess outcomes among patients receiving RT + ltADT, identifying prognostic factors associated with poorer prognosis under standard therapy.

Individual patient data were compiled from randomized controlled trials involving patients with HRLPC defined by any of the following risk factors (RFs) in the context of cN0 disease: Gleason score ≥8, clinical stage T3–4, prostate-specific antigen (PSA) >20 ng/ml, or cN1 disease. The analysis focused on metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression models were used to estimate hazard ratios (HRs) for each RF and cN1 disease.

The study included 3,604 patients from ten trials, with a median PSA of 24 ng/ml. RFs such as Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), clinical stage T3–4 (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with inferior outcomes. Adjusted 5-year MFS rates were 83% and 78%, and 10-year MFS rates were 63% and 53% for patients with one and two to three RFs, respectively. Corresponding 10-year adjusted OS rates were 67% and 60%. In patients with cN1 disease, adjusted 5-year and 10-year MFS rates were 67% and 36%, respectively, with a 10-year OS rate of 47%.

Patients with HRLPC exhibiting two to three RFs (in cN0 disease) or cN1 disease demonstrated the poorest outcomes under RT and ltADT. These findings provide critical insights for patient counseling in routine clinical practice and offer guidance for future adjuvant trials aimed at improving outcomes in HRLPC.

Source: sciencedirect.com/science/article/abs/pii/S0302283824023807