Persistent prostate-specific antigen (PSA) after radical prostatectomy (RP) for prostate cancer (PC) is associated with a worse prognosis than undetectable levels of PSA. PSA is typically assessed 1.5-2 months after RP. However, this interval may be too short for complete PSA clearance, especially in patients with high pre-RP PSA levels, which could lead to unnecessary post-RP therapy.
The recent study published in JAMA Oncology used data from two academic center databases to investigate whether persistent PSA at approximately 2 months post-RP in patients with pre-RP PSA >20 ng/mL is associated with lower risk of both all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM). This study also assessed if raising persistent PSA correlates with higher mortality risks after adjusting for prognostic factors and therapies.
In this cohort study, patients with T1N0M0 to T3N0M0 PC who underwent RP from 1992 to 2020 at two academic centers were included. Follow-up information was gathered through November 2023. Patients usually received PSA tests every 2 to 3 months for the first year of follow-up, then every 6 months for the next 4 years, and then once a year after that. Coprimary endpoints, such as ACM and PCSM were evaluated using multivariable Fine and Gray and Cox-regression analysis techniques. After adjusting to various factors, PCSM and ACM were analyzed using the Kaplan-Meier technique.
A total of 30,461 patients (median age = 64 [59-68] years) were included in the discovery cohort and 12,837 (median age = 59 [54-64] years) were included in the validation cohort. A pre-RP PSA level of >20 ng/mL compared to ≤ 20 ng/mL was significantly correlated with lower PCSM risk (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.25-0.66; P <0.001; P for interaction = 0.02) and ACM risk (aHR, 0.69; 95% CI, 0.51-0.91; P = 0.01; P for interaction <0.001) and PCM risk in patients with persistent PSA as compared to those with undetectable PSA. These findings persisted after controlling prostate volume which was validated for PCSM in the validation cohort. It might indicate a larger percentage of patients with pre-RP PSA of >20 ng/mL as opposed to ≤ 20 ng/mL who might have achieved an undetectable PSA level if more time had been given for PSA evaluation prior to starting post-RP therapy for suspected persistent PSA.
Particularly, 54.7% of patients with a >20 ng/mL pre-RP PSA (244/446) at a median of 2.68 months (1.51-4.40) had a shorter median time to post-RP radiation therapy (RT) plus androgen deprivation therapy or ADT use. This was more common compared to 34.8% of those with <20 ng/mL pre-RP PSA (338/972) at a median of 3.30 months (2.00-5.39). The median of these therapy duration was found to be 2.96 months (1.84-3.29) whereas the patient’s duration to an undetectable PSA was found to be 3.37 months (2.35-4.09). Additionally, rising persistent PSA levels were correlated with raised PCSM risk with aHR of 1.27 (95% CI, 1.12-1.45; P <0.001) and ACM risk with aHR of 1.14 (95% CI, 1.04-1.24; P = 0.004).
This study’s limitation includes reduced power access ACM risk due to shorter follow-up and fewer events in the validation cohort.
In conclusion, higher persistent PSA level is associated with a worse prognosis in this trial and PSA levels measured for at least 3 months following RP may reduce overtreatment.
Reference:
Tilki D, Chen M, Wu J, et al. Persistent Prostate-Specific Antigen Following Radical Prostatectomy for Prostate Cancer and Mortality Risk. JAMA Oncol. 2025. Persistent Prostate-Specific Antigen Following Radical Prostatectomy for Prostate Cancer and Mortality Risk | Oncology | JAMA Oncology | JAMA Network
