The management of prostate cancer (PCa) is an ever-evolving field with researchers now focusing on the exploration of early surrogate measures to predict long-term outcomes and assist in treatment decisions. In a novel individual patient data (IPD) analysis of randomized trials from the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) collaborative, the prognostic impact of prostate-specific antigen (PSA) nadir >=0.1 ng/mL within 6 months after the completion of radiotherapy (RT) for localized PCa was investigated. The compelling findings presented at the 2023 ASCO Annual Meeting shed light on a potential new marker for treatment response and patient selection (Abstract 5002).
The standard of care for intermediate- and high-risk localized PCa involves combining RT with androgen deprivation therapy (ADT). However, the identification of early predictors for long-term outcomes, such as PCa-specific survival (PCSS), metastasis-free survival (MFS), and overall survival (OS), is crucial for optimizing treatment strategies and identifying patients who may benefit from therapy escalation or de-escalation.
Study Details
To conduct this IPD analysis, Ravi and colleagues collected data from the RT+/-ADT trials stored in the ICECAP repository. Patients with evaluable PSA follow-up were included in the analysis and categorized based on their trial-allocated treatment: RT alone, RT + short-term ADT (STADT; 3-6 months), or RT + long-term ADT (LTADT; 18-36 months). PSA nadir (PSAn) was defined as the lowest PSA level recorded within 6 months after the completion of RT. Landmark analyses were performed at the 12-month mark to account for guarantee-time bias.
The analysis included a total of 10,415 patients from 16 randomized controlled trials. Among the patients, 25 percent were allocated to RT alone, 58 percent to RT + STADT, and 17 percent to RT + LTADT. The median follow-up duration was 10.1 years. Notably, 98 percent of patients allocated to RT, 84 percent of those receiving RT + STADT, and 77 percent of patients on RT + LTADT achieved a PSAn >=0.1 ng/mL within 6 months after completing RT.
After adjusting for various factors such as age, ECOG performance status, clinical T stage, Gleason score, and PSA at randomization, the analysis revealed significant associations between PSAn >=0.1 ng/mL and poorer PCSS, MFS, and OS in patients allocated to both RT + STADT and RT + LTADT. In patients allocated to RT alone, a weaker association was observed.
Oncology Times reached out to lead author, Praful Ravi, MB, BChir, MRCP, a Medical Oncologist at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, for his insights into a potential novel marker for treatment response assessment and patient selection.
Oncology Times: Were there any significant differences in outcomes between patients who achieved a PSA nadir <0.1 ng/mL and those who achieved a nadir >=0.1 ng/mL?
Ravi: "Yes, those with PSA nadir <0.1 had significantly better MFS at 5 years as well as 10-year OS, and a lower rate of prostate cancer death at 10 years. This held true both in patients treated with RT alone, as well as RT and either short- or long-term ADT."
Oncology Times: What are the clinical implications of the study findings for the management of localized prostate cancer patients after completion of radiotherapy?
Ravi: "This aids in counseling patients treated with RT +/- ADT for localized prostate cancer in routine practice. It also has implications for the design of clinical trials evaluating intensification or deintensification approaches, as well as potential novel agents along with ADT and RT for localized disease."
Oncology Times: Are there any limitations to the study that should be considered when interpreting the results?
Ravi: "Most men were treated before 2000 and spanned a wide range of treatment eras with different radiotherapy techniques. There was also a small number of patients achieving a PSA <0.1 with RT alone, giving rise to wider confidence intervals for this group with respect to the hazard ratios for MFS, OS, and prostate cancer-specific mortality. We also could not evaluate trial-level surrogacy for a PSA < or >=0.1 ng/mL."
Dibash Kumar Das is a contributing writer.