Miguel Bronchud, Co-Founder at Regenerative Medicine Solutions, shared on LinkedIn:
”What (if any) is the Optimal PSA to Determine Prostate Cancer Treatment Efficacy ?
The mathematical modeling of Prostate-Specific Antigen (PSA) decline following surgical or medical castration (Androgen Deprivation Therapy, or ADT) relies on ordinary differential equations (ODEs).
These models combine cellular kinetics (the shrinking population of cancer cells) with intracellular production dynamics (how tightly androgen levels control the expression of the PSA protein).
In clinical practice, the immediate response of total serum PSA following the initiation of castration is mathematically observed as a biphasic exponential decline.
- First Phase : A rapid, steep drop occurring during the first few weeks. This represents the immediate clearance of circulating PSA from the blood alongside the massive shut-down of androgen-regulated PSA transcription.
- Second Phase: A slower, prolonged decline lasting months. This represents the true clearance of androgen-dependent tumor cells via apoptosis (programmed cell death).
- PSA nadir : The lowest stable PSA level achieved before potential recurrence.
Multiple phase III clinical trials have shown that a prostate-specific antigen (PSA) level below 0.2 ng/mL is the best cut-off for determining a patient’s prognosis.
Real-world data are lacking, however, and physicians often use other metrics—such as percentage of PSA decline – to assess treatment response.
After treatment for metastatic prostate cancer, a decline in prostate-specific antigen (PSA) levels is an indicator that the treatment is effective.
Findings from a recent real-world study published by Freedland et al (2026) in the journal Cancer indicate that reaching a PSA level below 0.2 ng/mL is an indicator of improved patient survival.
See: How low do you need to go? Association between various prostate-specific antigen response measures and clinical outcomes in metastatic castration-sensitive prostate cancer.
To determine whether there is a PSA response target associated with a favorable outcome, investigators analyzed Veterans Health Administration data on 4,890 patients with metastatic hormone-sensitive prostate cancer who received testosterone deprivation therapy with or without other treatments during 2018 to 2023.
Over a median follow-up of approximately 2 years, 896 patients died. Patients whose PSA levels dropped below 0.2 ng/mL within 9 months of starting treatment were 54% less likely to die than patients whose levels did not decline this low.
No improvement was noted in patients who had at least a 90% PSA decline but did not achieve a PSA of less than 0.2 ng/mL.
The findings suggest that patients who do not experience a PSA drop below 0.2 ng/mL could be candidates for more aggressive treatments.
Also, patients who received testosterone deprivation therapy plus another drug to further block testosterone were more likely to achieve a PSA below 0.2 ng/mL.”
Title: How low do you need to go? Association between various prostate-specific antigen response measures and clinical outcomes in metastatic castration-sensitive prostate cancer in the Veterans Health Administration data
Authors: Stephen J. Freedland, Wei Gao, Maëlys Touya, Hongbo Yang, David Russell, Jingyi Chen, Grace Chen, Jasmina I. Ivanova
You can also read: GETUG-AFU 18: Dose Escalation in High-Risk Prostate Cancer
