October 21, 2023
Risk Stratification in Patients With High-Risk/Locally Advanced Prostate Cancer
By Catlin Nalley
A recent study found that patients with high-risk/locally advanced prostate cancer who had two risk factors or cN1 disease and underwent treatment with radiotherapy plus long-term ADT had a 5-year metastasis-free survival (MFS) rate of less than 80 percent and, therefore, were the individuals most likely to benefit from treatment intensification.
These findings will not only help guide patient counseling, but also the design and interpretation of adjuvant trials in this patient population, according to study author Praful Ravi, MB, BChir, MRCP, a genitourinary oncologist in the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, who presented this research during the European Society for Medical Oncology (ESMO) Congress 2023, held October 20-24 in Madrid, Spain (Abstract 1770O).
“High-risk and/or locally advanced prostate cancer has been defined as any of the following: clinical T3/T4 disease, Gleason 8 or above, PSA greater than 20, and clinical evidence of node positivity,” he noted. “Radiotherapy and long-term ADT with testosterone suppression between 18 and 36 months is a standard of care in the treatment of [these patients].”
Recently, the addition of 2 years of abiraterone to radiotherapy and long-term ADT led to a significant improvement in metastasis-free and overall survival in selected high-risk patients in prior studies, according to Ravi.
“The addition of abiraterone has become a standard of care where it is available and in these specifically selected, high-risk patients,” he said, while noting that refinement of risk stratification in high-risk/locally advanced prostate cancer may help define which patients are likely to benefit from treatment intensification.
Research Specifics
Ravi and colleagues leveraged the ICECaP individual patient data repository to evaluate outcomes in different risk groups of patients with high-risk/locally advanced prostate cancer, including PSA, Gleason score, clinical T and N stage (based on conventional imaging), and the number of risk factors.
The researchers aimed to answer the question, “Is there a group of patients with high-risk and/or locally advanced disease who may be more likely to benefit from treatment intensification with a novel hormonal agent in addition to radiotherapy plus long-term ADT?”
In this study, individual patient data from individuals with high-risk/locally advanced prostate cancer—defined as any of the following risk factors: Gleason ≥8, ≥cT3, PSA > 20 ng/mL, or cN1—who were treated with radiotherapy plus long-term ADT in RCTs within ICECaP were pooled.
The endpoints of this analysis were MFS, time to metastasis (TTM), prostate cancer-specific mortality (PCSM), and overall survival. “Five-year MFS was calculated by Kaplan-Meier method in various risk groups and by the number of risk factors,” Ravi and colleagues stated.
“Multivariable Cox regression estimated hazard ratios (HR) for the three risk factors and cN1 disease, stratified by trials and years of enrolment,” they noted. “MFS was defined as distant metastasis on conventional imaging or death from any cause.”
This analysis included 3,604 patients with high-risk/locally advanced prostate cancer who were treated with the standard of care—radiotherapy plus long-term ADT—on 10 randomized trials between 1987 and 2016. The median follow-up was 9 years, according to Ravi. Of these eligible patients, the median age was 68 years and the median PSA was 24. Seventy-two percent (2,602 patients) were cT3/4, 54 percent (1,942 patients) had Gleason 8-10, and 12 percent (422 patients) had cN1 disease. Additionally, Ravi noted this is a fairly contemporary cohort with 52 percent of patients randomized after 2005.
The HR for metastasis-free survival 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, according to the study authors, who also reported that the 5-year MFS rate (95% CI) was 83 percent, 78 percent, and 77 percent for patients with one, two, and three risk factors, respectively. For patients with cN1 disease, the 5-year MFS rate was 68 percent.
“Gleason score, clinical T/N stage, and PSA have independent prognostic value (MFS, TTM, PCSM, OS) in patients with high-risk and/or locally advanced disease treated with radiotherapy and long-term ADT,” Ravi noted. “The long-term outcome measures are clearly differentiated by the overall number of risk factors present at baseline.”
Patients with two or three risk factors and/or cN1 disease had 5-year MFS rates of less than 80 percent and, therefore, are the most likely to benefit from treatment intensification beyond radiotherapy plus long-term ADT alone, he reiterated.
“These findings will help guide patient counseling and provide a framework to guide the interpretation of many of the ongoing adjuvant studies evaluating other novel agents in high-risk disease with radiation and long-term ADT,” Ravi concluded.
Catlin Nalley is a contributing writer.