- Design
- Post hoc landmark analyses of two phase 3 trial experimental arms
- Population
- 564 (LATITUDE) and 578 (ARASENS) men with metastatic hormone-sensitive prostate cancer
- Primary outcome
- Overall survival after the landmark
- Effect
- LATITUDE HR 1.49 (95% CI 1.07–2.08); ARASENS HR 1.18 (0.85–1.62)
Researchers analysed the experimental arms of two phase 3 trials in metastatic hormone-sensitive prostate cancer: LATITUDE (abiraterone with prednisone and ADT) and ARASENS (darolutamide with ADT and docetaxel). Breakthrough was any testosterone above 35 ng/dL during an early treatment window.
In LATITUDE (564 men), breakthrough was associated with worse overall survival (adjusted HR 1.49, 95% CI 1.07–2.08), with a similar but imprecise trend for progression. In ARASENS (578 men), there was no significant association with survival (HR 1.18, 0.85–1.62) or time to castration resistance.
The authors are explicit that this is exploratory and does not establish a testosterone target. It does suggest that a rising testosterone on ADT is worth noticing rather than ignoring, and checking that injections are being given on time is the obvious first step.
- Measure testosterone periodically in men on ADT for metastatic prostate cancer.
- Check injection timing and adherence when testosterone rises above castrate level.
- Consider whether a change of ADT formulation is needed for repeated breakthrough.
- Do not escalate systemic therapy on testosterone alone; this is not an established trigger.
Why it matters
It raises the question of whether castration quality still matters once potent hormonal agents are added.
Don't overread it
Post hoc associations in single trial arms cannot show that keeping testosterone lower improves survival.
The statistics, in plain English
A hazard ratio of 1.49 means men with breakthrough died at about one and a half times the rate during follow-up in LATITUDE. The ARASENS interval (0.85–1.62) includes no effect, so the two trials do not agree.
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