Refining Risk Stratification in Patients Undergoing RT, ADT for High-Risk, Locally Advanced Prostate Cancer

A presentation on an individual patient data analysis of randomized controlled trials (RCTs) from the International Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) consortium was given during the European Society for Medical Oncology Congress 2023.

Radiotherapy (RT) plus long-term androgen deprivation therapy (ltADT) for 18 to 36 months is considered standard of care in the treatment of high-risk/locally advanced (HR/LA) prostate cancer. Ongoing research is evaluating intensification of systemic therapy beyond ADT to improve outcomes in this population.

Praful Ravi, MB, Bchir, MRCP, of the Dana-Farber Cancer Institute, and colleagues designed a study to evaluate 5-year metastasis-free survival (MFS) rates in subgroups of patients with HR/LA prostate cancer to identify patients more likely to benefit from treatment intensification, as well as to guide design and interpretation of adjuvant trials in HR/LA prostate cancer. Individual patient data from 3604 patients treated with RT plus ltADT in 10 RCTs collated by the ICECaP consortium between 1987 and 2016 were included. HR/LA prostate cancer was defined by any of 3 risk factors (Gleason ≥8, ≥cT3, or prostate-specific antigen [PSA] >20) or cN1 disease.

Five-year MFS was determined by the Kaplan-Meier method in various risk groups and by number of risk factors. Multivariable Cox regression was used to estimate hazard ratios (HRs) for the 3 risk factors and cN1 disease. MFS was defined as distant metastasis on conventional imaging or death from any cause.

Among the total patient population, the median PSA was 24 (interquartile range, 12-48), 2602 (72%) patients were cT3/4, 1942 (54%) had Gleason 8-10, and 422 (12%) had cN1 disease.

The HR for MFS was 1.5 (95% CI, 1.4-1.7) for Gleason ≥8, 1.2 (1.1-1.4) for PSA >20, 1.2 (1.1-1.4) for cT3/T4, and 1.8 (1.5-2.1) for cN1 disease.

Dr. Ravi and colleagues reported that the 5-year MFS rate (95% CI) was 83%, 78%, and 77% for patients with 1, 2, and 3 risk factors, respectively. For cN1 disease, the 5-year MFS rate was 68%.

“Patients with HR/LA prostate cancer treated with RT pus ltADT who had at least 2 risk factors or cN1 disease had 5-year MFS rates less than 80% and are the ones most likely to benefit from treatment intensification,” they concluded. “This will guide patient counselling and the design and interpretation of adjuvant trials in HR/LA prostate cancer.”