Increasing, Persistent PSA Levels Linked to Higher All-Cause Mortality

TOPLINE:

Higher persistent PSA levels post-surgery were linked to increased mortality risk, with 8-year prostate cancer–specific mortality reaching 13.86% for a prostate-specific antigen (PSA) ≥ 1 ng/mL.

METHODOLOGY:

• The conventional 1.5-month to 2.0-month time interval following radical prostatectomy (RP) for assessing persistent PSA remained questionable for accuracy.
• Analysis included 43,298 patients with clinical stage T1N0M0 to T3N0M0 prostate cancer treated with RP between 1992 and 2020 at two academic centers, with follow-up data collected until November 2023.
• Researchers evaluated whether a significant interaction existed between pre-RP PSA level (> 20 ng/mL vs ≤ 20 ng/mL) and persistent vs undetectable PSA after RP on mortality risk, adjusting for known prognostic factors.
• Investigators assessed the impact of increasing persistent PSA levels on prostate cancer–specific mortality and all-cause mortality risk, with a median follow-up of 6.23 years.
• Patients with PSA > 20 ng/mL or Gleason score 8-10 underwent CT or MRI and bone scan prior to surgery.

TAKEAWAY:

• Among patients with persistent PSA, those with pre-RP PSA > 20 ng/mL showed significantly reduced all-cause mortality risk (adjusted hazard ratio [aHR], 0.69; 95% CI, 0.51-0.91; P = .01) and prostate cancer–specific mortality risk (aHR, 0.41; 95% CI, 0.25-0.66; P < .001).
• Increasing persistent PSA levels were associated with higher all-cause mortality risk (aHR, 1.14; 95% CI, 1.04-1.24; P = .004) and prostate cancer–specific mortality risk (aHR, 1.27; 95% CI, 1.12-1.45; P < .001).
• Post-RP radiation therapy significantly reduced prostate cancer–specific mortality risk only in patients with persistent PSA (aHR, 0.54; 95% CI, 0.33-0.87; P = .01).
• Eight-year prostate cancer–specific mortality estimates were 13.86% (95% CI, 10.47-18.22) for persistent PSA ≥ 1 ng/mL vs 8.17% (95% CI, 6.08-10.93) for < 1 ng/mL.

IN PRACTICE:

“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,” wrote the authors of the study.

SOURCE:

The study was led by Derya Tilki, MD, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf in Hamburg, Germany. It was published online on March 13 in JAMA Oncology.

LIMITATIONS:

According to the authors, the validation cohort showed a significant association between reduced prostate cancer–specific mortality risk but not all-cause mortality risk in patients with persistent PSA and pre-RP PSA > 20 ng/mL vs ≤ 20 ng/mL. This limitation may be explained by the limited power to assess the all-cause mortality endpoint given the shorter median follow-up and smaller event rate in the validation cohort compared with the discovery cohort.

DISCLOSURES:

Tilki reported receiving personal fees from Amgen, Apogepha, AstraZeneca, Astellas, A3P Biomedical, Bayer, Exact Sciences, Johnson & Johnson, Ipsen, Novartis, Pfizer, Roche, Veracyte, and Takeda outside the submitted work. No other disclosures were reported.