A new real-world study of nearly 5,000 men with metastatic hormone-sensitive prostate cancer suggests that one specific treatment milestone may provide a clearer signal of survival than the percentage by which prostate-specific antigen, or PSA, falls. Patients whose PSA concentration dropped below 0.2 nanograms per milliliter within nine months of beginning therapy were substantially less likely to die during follow-up than those whose levels remained above that threshold, according to research published online in CANCER, a peer-reviewed journal of the American Cancer Society.
The analysis examined data from 4,890 patients treated through the Veterans Health Administration between 2018 and 2023. All had metastatic hormone-sensitive prostate cancer, meaning their disease had spread beyond the prostate but was still responsive to treatments that suppress testosterone and other androgen hormones. Most patients received testosterone deprivation therapy, also known as androgen-deprivation therapy, either alone or in combination with additional medicines designed to block androgen production or prevent testosterone from activating prostate cancer cells.
PSA is a protein produced primarily by prostate cells. Because prostate cancer cells often release PSA into the bloodstream, doctors routinely measure its concentration to monitor how the disease responds to treatment. A declining PSA level generally indicates that the cancer is becoming less active, while a rising level can signal resistance or progression. However, clinicians have used several different ways to interpret a response, including the percentage reduction from a patient’s starting PSA level and whether the concentration reaches a particular absolute value.
In the new study, the researchers focused on whether reaching a PSA level below 0.2 ng/mL was more closely associated with survival than achieving a decline of at least 90 percent. The 0.2 ng/mL threshold has emerged from several phase 3 clinical trials as a potentially meaningful measure of treatment response, but evidence from everyday clinical practice has been more limited. The investigators therefore used health records from a large national medical system to assess how these response measures performed in a community-based, real-world population.
During a median follow-up period of approximately two years, 896 patients died. Those who reached a PSA level below 0.2 ng/mL within nine months of starting treatment were 54 percent less likely to die than patients who did not reach that level. The association remained whether or not the patients also experienced a PSA reduction of at least 90 percent, indicating that the absolute PSA threshold carried prognostic information beyond the size of the decline alone.
The distinction is important because a dramatic percentage reduction does not always mean that the remaining cancer activity is minimal. For example, a patient whose PSA falls from 20 ng/mL to 2 ng/mL has experienced a 90 percent decline, but the final level remains well above 0.2 ng/mL. By contrast, a patient whose PSA drops from 1 ng/mL to 0.15 ng/mL has achieved a smaller percentage reduction but has reached the lower absolute threshold associated with more favorable outcomes in this analysis.
Patients who experienced at least a 90 percent decline but did not reach a PSA level below 0.2 ng/mL showed no significant survival improvement compared with patients who failed to achieve the 90 percent reduction. This finding suggests that the depth of suppression may be more clinically informative than the relative change from baseline. It also supports the idea that PSA response should be assessed using both the starting value and the level that remains after treatment, rather than relying on percentage decline alone.
The study further found that patients treated with testosterone deprivation therapy plus another androgen-blocking drug were more likely to reach a PSA level below 0.2 ng/mL than those receiving hormone suppression without treatment intensification. Modern combination approaches can inhibit the androgen pathway at multiple points: some medicines reduce testosterone production, while others block the androgen receptor that cancer cells use to receive growth signals. More complete disruption of this pathway may explain why combination therapy was associated with deeper PSA responses.
The findings could help physicians identify patients who may need closer monitoring or earlier treatment escalation. A patient whose PSA remains above 0.2 ng/mL during the first nine months of therapy may have a less favorable response and could be considered for additional treatment strategies, depending on overall health, cancer distribution, symptoms, genomic characteristics, and treatment goals. The researchers emphasize that the study shows an association rather than proving that changing therapy solely to force a lower PSA will extend life. Nevertheless, the results provide a practical target for evaluating response in routine care and reinforce the importance of achieving the deepest possible disease control in metastatic prostate cancer.
“ These data show that we need to target a PSA below 0.2 ng/ml as our metric of success to optimize outcomes for our patients with metastatic prostate cancer,” said corresponding author Stephen J. Freedland, MD, professor of urology at Cedars-Sinai and staff physician at the Durham VA Medical Center. Because the analysis was observational and based largely on Veterans Health Administration patients, future studies will need to determine whether the same threshold applies across broader populations and whether treatment decisions guided by this PSA target can improve survival in prospective clinical trials.
Subject of Research: Metastatic hormone-sensitive prostate cancer and PSA response to androgen-deprivation therapy
Article 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
News Publication Date: August 10, 2026
Web References: CANCER journal: https://acsjournals.onlinelibrary.wiley.com/journal/10970142; DOI: https://doi.org/10.1002/cncr.70494
References: Stephen J. Freedland, Wei Gao, Maëlys Touya, Hongbo Yang, Jingyi Chen, Grace Chen, and Jasmina I. Ivanova. “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.” CANCER. Published online August 10, 2026. DOI: 10.1002/cncr.70494
Keywords: Prostate cancer, metastatic cancer, PSA, prostate-specific antigen, androgen-deprivation therapy, hormone therapy, testosterone suppression, cancer treatment response, survival, oncology, urology, Veterans Health Administration
Tags: androgen deprivation therapymetastatic hormone-sensitive prostate cancerprostate cancer prognosisprostate cancer treatmentprostate-specific antigen monitoringPSA cutoff levelsPSA decline thresholdPSA level and survival correlationPSA response as survival indicatorreal-world cancer researchtestosterone deprivation therapytreatment milestones in prostate cancer
