# The telomere biomarker as a tool to inform decision-making for aggressive salvage therapy in men with rising PSA post prostatectomy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $505,583

## Abstract

Men with biochemical recurrence after prostatectomy receiving salvage radiation (RT) may benefit from added
anti-androgen therapy (AAT) by decreasing their likelihood of progressing to distant metastasis and death.
However, in RTOG 9601, not all men benefitted. No predictive biomarker currently exists to identify who is
more likely or less likely to benefit from aggressive salvage therapy (RT+AAT). To address this unmet need for
precision treatment decision-making, we will evaluate the telomere biomarker as a predictive biomarker for
treatment response in this setting. Our conceptually innovative hypothesis is that the telomere biomarker – the
combination of cancer cell-to-cell variability in telomere length coupled with stromal cell telomere length –
captures information about tumor behavior beyond currently used indicators and thus, identifies men who are
more likely or less likely to benefit from aggressive salvage therapy. We discovered that the telomere
biomarker is an independent prognostic marker for lethal disease in surgically-treated men, identifying 3
prognostic categories: good, intermediate, and poor. The telomere biomarker has not been tested as predictive
of treatment response in any setting. We will address the aims in 2 complementary settings, trial and clinical
practice, totaling 839 men and 165 metastatic events. In the trial setting, we will use RTOG 9601, in which men
were randomized to RT+/-AAT. In the clinical practice setting, we use cohorts who received RT+/-AAT at
Johns Hopkins or Boston Medical Center and have tissue microarrays; in the analysis, we will weight by a
propensity score to minimize bias due to patient and tumor factors. We will evaluate these aims stratified by
the telomere biomarker: 1. In the standardized setting, test if rate of progression to metastasis and death from
prostate cancer differs between RT+AAT and RT only. 2. In the clinical practice setting, test if rate of
progression to metastasis and death from prostate cancer differs between RT+AAT and RT only. We will stain
for telomeres and cell-type specific immunofluorescence markers and perform image capture and quantitative
image analysis, and derive each man’s telomere biomarker. We will stratify by biomarker category and use
Cox models to estimate associations between RT+AAT and progression, and determine if the biomarker adds
to predictive capability for response to RT+AAT beyond currently used post-biochemical recurrence prognostic
indicators. In men with the biomarker category associated with intermediate prognosis, we hypothesize that the
progression rate is lower in men who received RT+AAT compared to men who received RT only. In men with
biomarker categories associated with good or poor prognosis, we hypothesize that the progression rate in men
who received RT+AAT is similar to the rate in men who received RT only. In RTOG 9601, RT+AAT was more
efficacious than RT only in some subgroups. For optimized decision-making, we will determine if...

## Key facts

- **NIH application ID:** 10911785
- **Project number:** 5R01CA279594-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Christopher M Heaphy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $505,583
- **Award type:** 5
- **Project period:** 2023-08-22 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911785

## Citation

> US National Institutes of Health, RePORTER application 10911785, The telomere biomarker as a tool to inform decision-making for aggressive salvage therapy in men with rising PSA post prostatectomy (5R01CA279594-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10911785. Licensed CC0.

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