ASTRO 2021: Individual Patient Data Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium: Impact of ADT Use and Duration with Definitive Radiotherapy for Localized Prostate Cancer

(UroToday.com) In the Clinical Trials and Innovation session of the American Society for Radiation Oncology (ASTRO) Annual Congress, Dr. Kishan presented results of an analysis assessing the impact of androgen deprivation therapy (ADT) use and duration with definitive radiotherapy in the treatment of patients with localized prostate cancer based on an individual patient data meta-analysis of randomized controlled trials based on the MARCAP consortium dataset.

Dr. Kishan began by highlighting that meta-analyses of randomized controlled trials represent the highest levels of evidence to guide clinical practice. These studies are further strengthened when they are based on individual patient data (IPD). In early breast cancer and in head an neck cancers, collaborative groups have coordinated to undertaken such efforts. However, to date, no comparable effort has been successfully completed in prostate cancer to assess common questions in localized prostate cancer (eg. the use of androgen deprivation therapy, the duration of ADT, the role of dose escalation, and others) using IPD meta-analysis. The MARCAP (Meta-Analysis of Randomized trial in Cancer of the Prostate) Consortium represents the first such effort.

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In the first analysis from this group, the authors sought to assess three well-studied therapeutic questions among patients receiving radiotherapy for localized prostate cancer: (1) the use of ADT; (2) the role of neoadjuvant ADT prolongation; and (3) the role of adjuvant ADT prolongation. Following an initial literature search which identified 1514 results of which 1148 were unique, 12 randomized trials met eligibility criteria and were included.

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The authors utilized metastasis-free survival as the primary endpoint and secondarily considered biochemical recurrence, distant metastasis, and overall survival. They used competing risks analysis from other causes when examining biochemical recurrence and distant metastasis. The authors calculated the number needed to treat to avoid one distant metastasis at 10-years.

Among the 12 included trials, a total of 10,853 patients were included. The median follow-up duration was 11.4 years (IQR 9.0-15.0). This cohort comprised predominantly intermediate (43.3%) and high-risk disease (46.6%).

For each of the three questions, the authors found that treatment arms were well balanced in terms of risk group.

Assessing first the question of the benefit of adding ADT, the authors found significant improvements in both metastasis free survival (HR 0.83, 95% CI 0.77-0.89) and overall survival (HR 0.86, 95% CI 0.80-0.92). Operationalized in absolute rather than relative terms, the addition of ADT was associated with significant risk reductions in both biochemical recurrence rates at 4-years and distant metastasis rates at 8-years.

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This risk reduction varied based on disease risk: in terms of 10-year distant metastasis, the number needed to treat to prevent 1 event was 8.4 for those with high risk disease and 18.0 for those with intermediate risk disease. However, the authors found no evidence of significant interaction in the benefit of ADT by radiotherapy dose or NCCN risk group with benefits observed in each case.

Assessing their second outcome, the authors found no benefit in the prolongation of neoadjuvant ADT with respect to any oncologic outcome. Examining the primary and key secondary endpoints, metastasis free survival (HR 0.95, 95% CI 0.83-1.09) and overall survival (HR 0.95, 95% CI 0.82-1.10) did not significantly differ between standard and prolonged groups.

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In contrast to these data on neoadjuvant ADT, the authors did find a benefit with long-term adjuvant ADT prolongation, both in terms of metastasis-free survival (HR 0.84, 95% CI 0.78-0.91) and overall survival (HR 0.85, 95% CI 0.78-0.94).

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The authors then considered the absolute benefit of adjuvant ADT prolongation. In this analysis, when examining 10-year distant metastasis rates, a greater benefit was observed among patients with high risk disease (number needed to treat = 10.4) compared to intermediate-risk disease (NNT = 16.1). However, there again was no statistically significant interaction between NCCN risk group or radiotherapy dose and outcome.

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In closing, beyond the data presented above, Dr. Kishan highlighted that NCCN risk groups themselves do not sufficiently identify patients who do or do not benefit from short- vs long-term ADT, highlighting the need for biomarkers to personalized treatment intensification.

Presented by: Amar U. Kishan, MD, Associate Professor, is the Vice-Chair of Clinical and Translational Research and Chief of the Genitourinary Oncology Service for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center 


Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.

 

 

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