Higher post-treatment adiposity and intrapatient changes in lipid metabolite pathways were associated with inferior outcomes after pre-operative hormone therapy, supporting a stage-dependent link between cardiometabolic health and prostate cancer.
Key Findings
Results
Lower visceral and subcutaneous adiposity at radical prostatectomy were associated with pathologic response to pre-operative hormone therapy.
Pathologic response was defined as ≤ T2N0 at radical prostatectomy (RP)
Lower visceral adiposity index (VATi) at RP was associated with pathologic response (p = 0.002)
Lower subcutaneous adiposity index (SATi) at RP was associated with pathologic response (p = 0.004)
Body composition was quantified from L3 CT imaging at baseline and at RP (end-of-treatment n = 56)
The cohort included 104 men with localized high-risk prostate cancer treated with 3-6 months of preoperative ADT +/- ARPI across three trials
Results
Increasing adiposity at radical prostatectomy was associated with PSA progression-free survival outcomes.
Per 10-unit increase in VATi: HR 1.09, p = 0.04
Per 10-unit increase in SATi: HR 1.14, p = 0.03
PSA progression was defined as time from RP to PSA ≥ 0.2 ng/mL or initiation of radiotherapy
Higher post-treatment adiposity was associated with inferior outcomes after pre-operative hormone therapy
Results
Pathologic responders demonstrated distinct intrapatient changes in lipid metabolites compared to non-responders during treatment.
Analysis performed on paired baseline and end-of-treatment plasma samples (n = 59) profiled by UPLC-MS
Pathologic responders showed significant decreases (p < 0.05) in diacylglycerols and polyunsaturated fatty acyl chain-containing triacylglycerols (PUFA-TAGs)
Pathologic responders also showed elevations (p < 0.05) in ceramide species
Non-responders exhibited increases (p < 0.05) in PUFA-TAGs and glycerophospholipids
Non-responders showed reductions in lysophosphatidylcholine species, long-chain acylcarnitine, and cholesterol
Methods
The study cohort had high-risk disease characteristics, with the majority having high Gleason grade and a substantial proportion having advanced clinical stage.
Median age was 63 years
76.9% had Gleason grade group 4-5
43.7% had clinical T3-4 disease
104 men total were included in the post hoc analysis
Patients were treated across three clinical trials with 3-6 months of preoperative ADT +/- androgen receptor pathway inhibition (ARPI)
Results
Pathologic responders and non-responders showed opposing directional changes in PUFA-TAGs during treatment.
Pathologic responders demonstrated decreases in PUFA-TAGs (p < 0.05)
Non-responders exhibited increases in PUFA-TAGs (p < 0.05)
This opposing pattern suggests PUFA-TAG dynamics may reflect differential biological response to androgen deprivation therapy
Plasma lipid metabolites were profiled at baseline (n = 60) and in paired baseline/end-of-treatment samples (n = 59)
Background
Altered lipid metabolism, adiposity, and androgens have been previously linked to both cardiac disease and prostate cancer, forming the rationale for studying cardiometabolic factors in this setting.
Adiposity has been linked to increased risk of recurrence for prostate cancer
Adiposity may enhance response to androgen receptor pathway inhibition (ARPI)
The study evaluated whether adiposity and circulating lipid metabolites are associated with response to pre-operative ADT +/- ARPI in localized high-risk prostate cancer
The study authors describe this as supporting 'a stage-dependent link between cardiometabolic health and prostate cancer'
What This Means
This research examined whether body fat and blood lipid (fat molecule) levels affect how well pre-surgical hormone therapy works in men with aggressive, localized prostate cancer. The study looked at 104 men who received 3 to 6 months of hormone-blocking treatment before having their prostates surgically removed. Researchers measured body fat using CT scans and analyzed dozens of lipid molecules in blood samples taken before and after treatment.
The study found that men who still had higher amounts of body fat — both visceral fat (around internal organs) and subcutaneous fat (under the skin) — at the time of surgery had worse treatment responses and were more likely to experience rising PSA levels (a sign of cancer recurrence) afterward. Additionally, men whose tumors responded well to hormone therapy showed specific changes in their blood lipid profiles during treatment — particularly decreases in certain fats called diacylglycerols and PUFA-containing triglycerides, along with increases in ceramides. Men whose tumors did not respond well showed the opposite pattern in some of these same lipid categories.
This research suggests that cardiometabolic health — specifically body composition and lipid metabolism — may play a meaningful role in how prostate cancer responds to hormone-based treatment. The findings point to a potential connection between fat tissue, lipid biology, and cancer treatment outcomes that could eventually help identify which patients are most likely to benefit from pre-surgical hormone therapy, and whether targeting metabolic factors alongside standard hormone treatment could improve results.
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M. Boshkos, Maria Júlia Moura Nascimento Santos, R. Tidwell, Neha Venkatesh, Sagar S. Mukhida, P. Pilié, et al.. (2026). Cardiometabolic health's influence on the efficacy of pre-operative hormone therapy for men with localized high-risk prostate cancer.. Prostate Cancer and Prostatic Diseases. https://doi.org/10.1038/s41391-026-01163-y