Risk Stratification in High-Risk Prostate Cancer: Long-Term vs Short Term ADT

A recent study has analyzed the efficacy of clinical risk stratification in determining the benefit of long-term versus short-term androgen deprivation therapy (ADT) for patients with high-risk localized prostate cancer (HRLPC).

As patients with HRLPC and one high-risk factor treated with a combination of radiotherapy (RT) and long-term ADT have had better outcomes than patients with two to three high-risk factors or cN1 disease (very high-risk), researchers evaluated if risk stratification can determine the potential benefit of long-term ADT over short-term ADT.

Data on eligible patients and trials were collected from The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials. Outcomes of interest included metastasis-free survival (MFS), overall survival (OS), time to metastasis (TTM) and prostate cancer-specific mortality (PCSM).

Stratified Cox and Gray’s regression models were used to obtain the overall treatment effect for outcomes and risk groups, and the Wald interaction test was used to estimate whether treatment benefit differed by risk group or trial. Cochran’s Q and I2 were used to assess the heterogeneity of studies.

Of three trials analyzed, 2,780 patients were included in the study. Patients that had very high-risk disease experienced greater benefit from long-term ADT use compared to patients with high-risk disease (MFS HR 0.77 [0.68–0.88] vs 0.89 [0.76–1.03]; TTM 0.61 [0.51–0.74] vs 0.77 [0.59–0.99]; PCSM 0.71 [0.56–0.90] vs 0.82 [0.59–1.14]; OS 0.87 [0.76–1.00] vs 0.93 [0.79–1.08]).

However, no statistically significant difference in treatment effect by risk group was seen (P>.1). The heterogeneity of treatment effect across trials was low in the very high-risk group and moderate in the high-risk group.

The use of risk stratification warrants further investigation in clinical trials to determine which patients with HRLPC may benefit from long-term versus short-term ADT.