By Lila Rouland | Published on November 12, 2025 | 3 min read
Metastatic
hormone-sensitive prostate cancer (mHSPC) is undergoing a therapeutic
revolution with the introduction of intensified combination regimens
incorporating darolutamide.
The ARASENS study, which demonstrated
a survival benefit with the addition of darolutamide to androgen deprivation
therapy (ADT) and docetaxel, has redefined the standard of care. However, a
biological endpoint deserves particular attention: achieving undetectable
prostate-specific antigen (PSA) levels — a well-known marker that has
rarely been used as a major predictive criterion.
This secondary
analysis of the ARASENS trial evaluated the depth and durability of
PSA responses according to tumor volume and their correlation with clinical
outcomes, including overall survival (OS).
Is an
undetectable PSA response a new prognostic marker?
The
analysis included 1305 patients from the ARASENS trial (ADT + docetaxel
± darolutamide), stratified by tumor volume (high or low) as defined by the CHAARTED
criteria. The main objective of this secondary analysis was to assess the
proportion of patients achieving a deep PSA response (≤0.2 ng/mL) at 12
months and its prognostic impact.
The results
are clear: 86% of patients treated with darolutamide achieved a PSA
response, compared with 77% in the placebo arm. The proportion of
patients reaching PSA ≤0.2 ng/mL at 12 months was significantly higher
in the darolutamide arm (59.1% vs 40.3%; p < 0.0001), and this
benefit was observed regardless of tumor volume.
In
high-volume disease,
53.5% of darolutamide-treated patients achieved PSA ≤0.2 ng/mL at 12
months, compared with 35.1% in the placebo arm. In
low-volume disease,
the difference was even more striking:
71.5% vs
53.4%.
Achieving undetectable
PSA at 12 months was strongly associated with improved overall survival
and prolonged radiographic progression-free survival (rPFS). Patients
who achieved PSA ≤0.2 ng/mL at 12 months had a 63% reduced risk of death (HR
= 0.37) across all treatment groups. These findings confirm the prognostic
value of the biological response and underscore the relevance of PSA
monitoring as an early indicator of therapeutic efficacy.
In terms of
safety, this analysis identified no new safety signals with the addition
of darolutamide. Adverse events were comparable between groups and consistent
with the original ARASENS results.
Will PSA
response guide future treatment strategies?
The
secondary analysis of ARASENS demonstrates that adding darolutamide to ADT +
docetaxel results in a significant and durable reduction in PSA levels, independent
of tumor volume. Moreover, achieving a PSA ≤0.2 ng/mL at 12 months
is strongly correlated with prolonged survival, establishing this marker
as a promising response criterion for guiding future therapeutic
decisions.
These
findings suggest that undetectable PSA could become an intermediate
treatment goal to stratify patients, tailor therapy intensity, or even
explore de-escalation strategies. This approach would enable a more
individualized management of mHSPC, integrating precise biological data beyond
traditional clinical parameters (volume, risk, etc.).
Prospective
studies are needed to validate PSA as a decision-making biomarker,
particularly in the context of new triplet regimens or targeted
therapies. This strategy paves the way for precision oncology, where
biological response dynamics guide treatment intensity — ultimately improving
both outcomes and patients’ quality of life.
Read next: Does the circulating tumor cell count predict survival in metastatic hormone-sensitive prostate cancer?
About the author – Lila RoulandDoctor of Oncology, specialized in Biotechnology and Management
