A recent study led by Dr. Derya Tilki from the Martini-Klinik Prostate Cancer Center at the University Hospital Hamburg-Eppendorf in Germany has highlighted the significant risks associated with increasing persistent prostate-specific antigen (PSA) levels. The research, which focused on prostate cancer–specific mortality and all-cause mortality risk, involved a comprehensive analysis of 43,298 patients treated between 1992 and 2020. The data was meticulously collected up to November 2023, offering a median follow-up period of 6.23 years.
The study's findings suggest that the conventional 1.5 to 2-month interval for assessing persistent PSA levels post-radical prostatectomy (RP) may not be sufficiently accurate. Instead, increasing persistent PSA levels have been associated with a higher risk of mortality, prompting researchers to evaluate the interaction between pre-RP PSA levels and post-operative PSA status on patients' outcomes.
Study Methodology and Findings
The study included patients with clinical stage T1N0M0 to T3N0M0 prostate cancer, treated at two academic centers, who underwent RP. Researchers adjusted their analysis for known prognostic factors to ensure the validity of their findings. Notably, patients with a PSA level greater than 20 ng/mL or a Gleason score between 8 and 10 underwent additional imaging procedures such as CT or MRI and bone scans before surgery.
Persistent PSA levels were linked to an increased all-cause mortality risk with an adjusted hazard ratio (aHR) of 1.14 and a 95% confidence interval (CI) of 1.04-1.24 (P = .004). Similarly, prostate cancer–specific mortality risk increased significantly, with an aHR of 1.27 and a 95% CI of 1.12-1.45 (P < .001).
Impact of Post-Operative Treatments
Post-RP radiation therapy was found to significantly reduce prostate cancer–specific mortality risk in patients with persistent PSA, showing an aHR of 0.54 and a 95% CI of 0.33-0.87 (P = .01). The study also revealed that patients with pre-RP PSA levels above 20 ng/mL experienced reduced all-cause and prostate cancer–specific mortality risks.
Validation cohorts confirmed a significant reduction in prostate cancer–specific mortality risk for patients with persistent PSA levels and pre-RP PSA over 20 ng/mL, compared to those with lower levels. However, this association did not extend to all-cause mortality risk.
Clinical Implications
These findings underscore the importance of revisiting current protocols for PSA assessment following RP. The authors of the study emphasized the need for a minimum three-month interval before assessing PSA levels post-surgery to minimize overtreatment.
"PSA level assessed for at least 3 months after RP may minimize overtreatment, and in this study, a higher persistent PSA level was associated with a worse prognosis," stated the authors.
The research was published online on March 13 in JAMA Oncology, contributing valuable insights into the management of prostate cancer post-surgery.
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