Adding docetaxel to ADT and RT cuts mortality in high-risk prostate cancer with normal testosterone

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Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer Published June 2, 2026 Medically reviewed June 2, 2026 Study authors: Zeng Johnathan, Chen Ming-Hui, Wu Jing, Xie Wanling, Ravi Praful, Nguyen Paul, Sandler Howard, D'Ami… PubMed ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider baseline testosterone as a potential predictor of docetaxel benefit in high-risk prostate cancer, but await confirmatory trials.

This analysis of two RCT cohorts examined whether baseline testosterone level predicts benefit from adding docetaxel to radiation therapy (RT) and androgen deprivation therapy (ADT) in nonmetastatic high-risk prostate cancer. The discovery cohort included 255 patients with minimal or no comorbidity; the validation cohort included 563 patients with ECOG PS 0/1. Median follow-up was 10.4 years (discovery) and 10.6 years (validation).

The primary outcome was all-cause mortality (ACM). Among patients with normal baseline testosterone, adding docetaxel to RT+ADT significantly reduced ACM risk, whereas no benefit was seen in those with low testosterone. The interaction p-values were .048 (discovery) and .042 (validation). Effect sizes and absolute numbers were not reported.

Safety data were not reported. The analysis is observational (subgroup analysis from randomized trials), so results are hypothesis-generating. Effect sizes were not provided, limiting clinical interpretation. The interaction p-values are borderline significant.

Clinicians should interpret these findings cautiously. Baseline testosterone may be a predictive biomarker for docetaxel benefit, but prospective trials are needed before changing practice.

Study Details

Study typeRct

Sample sizen = 255

EvidenceLevel 2

Follow-up780.0 mo

PublishedJun 2026

PMID42175549

View Original Abstract ↓

BACKGROUND: Prostate cancer (PC) arising in patients with low testosterone is often more aggressive and less responsive to androgen deprivation therapy (ADT). This study evaluated whether baseline testosterone group (low vs. normal) modifies the mortality benefit of adding docetaxel to radiation therapy (RT) and ADT in nonmetastatic high-risk PC. METHODS: From two randomized trials of docetaxel plus RT and ADT versus RT and ADT for T1c-4N0M0 PC, 255 patients with minimal or no comorbidity comprised the discovery cohort (median age, 65 years; follow-up, 10.4 years) and 563 patients with Eastern Cooperative Oncology Group performance status 0/1 formed the validation cohort (median age, 66 years; follow-up, 10.6 years). Multivariable Cox regression with an interaction between treatment arm and testosterone group (normal or low level) was used to evaluate all-cause mortality (ACM) risk by adjusting for age, T category, Gleason score, prostate-specific antigen (PSA) level, percent positive biopsy cores, and performance status. RESULTS: Randomization to RT, ADT, and docetaxel was associated with a significant reduction in ACM risk among patients with normal but not low testosterone, with a significant treatment-by-testosterone group interaction in both the discovery (p = .048) and validation cohorts (p = .042). Among patients with normal testosterone, those most likely to benefit from docetaxel had a PSA level of >20 ng/mL, T3/4 disease, or a Gleason score of 9/10 in both cohorts. CONCLUSIONS: Low testosterone at diagnosis does not appear to predict a reduced mortality risk when adding docetaxel to RT and ADT in otherwise healthy patients with nonmetastatic high-risk PC, whereas normal testosterone does, which provides evidence to support testosterone group as a predictive biomarker.