Post-Radical Prostatectomy PSA Levels Reduced Overtreatment Risk After 3 Months

A cohort study found that pre-radical prostatectomy levels greater than 20 ng/mL were associated with increased all-cause mortality risk and prostate cancer-specific mortality risk.

When prostate-specific antigen (PSA) were assessed at least 3 months after radical prostatectomy, the risk of overtreatment may be reduced compared with when PSA was assessed sooner, according to a cohort study published in JAMA Oncology.¹

Pre-radical prostatectomy PSA levels greater than 20 ng/mL were significantly associated with reduced all-cause mortality risk (adjusted HR [aHR], 0.69; 95% CI, 0.51-0.91; P = .01; P for interaction < .001) and prostate cancer-specific mortality risk (aHR, 0.41; 95% CI, 0.25-0.66; P <.001; P for interaction = .02) when compared with PSA levels of 20 ng/mL or less. Results were consistent after adjustment for prostate volume.

Patients with a pre-radical prostatectomy PSA level greater than 20 ng/mL had a more frequent usage of post-radical prostatectomy radiation therapy plus androgen deprivation therapy (ADT) or ADT alone (54.7%) compared with patients who had a PSA level of 20 ng/mL or less (34.8%); the median times to these therapies were 2.68 months (IQR, 1.51-4.40) and 3.30 months (IQR, 2.00-5.39), respectively. The study authors noted that these treatment times (median, 2.96 months; IQR, 1.84-3.29) were shorter than the amount of time it took for an undetectable PSA level to be observed in patients (median, 3.37 months; IQR, 2.35-4.09).

In patients with an observed increasing persistent PSA level, 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) were higher.

“Checking the PSA level too soon can lead clinicians to mislabel a patient as having recurred and prompt referral to radiation and medical oncologists to initiate salvage radiation and hormonal therapy,” senior study author Anthony D’Amico, MD, PhD, chief of Genitourinary Radiation Oncology at Brigham and Women’s Hospital and a founding member of the Mass General Brigham healthcare system, stated in a press release.² “It can take longer than 3 months for many patients who have PSA levels [greater than] 20 [ng/mL] prior to surgery to completely clear the PSA from their bloodstream.”

This cohort study assessed a total of 30,461 patients in the discovery cohort who received radical prostatectomy for clinical stage T1N0M0 to T3N0M0 prostate adenocarcinoma at the University Hospital Hamburg-Eppendorf in Hamburg, Germany from 1992 to 2020; the validation cohort from Johns Hopkins Medical Institutions enrolled a total of 12,837 patients who were treated with radical prostatectomy from 1990 to 2017.

Staging was completed with CT or magnetic resonance imaging of the abdominal pelvic region and bone scan prior to radical prostatectomy and performed on patients with a pre-radical prostatectomy PSA level greater than 20 ng/mL or a biopsy Gleason score of 8 to 10. The prostatectomy specimens were assessed by a pathologist with expertise in genitourinary pathology and assigned a prostatectomy T category, Gleason score, margin, and pelvic lymph node status.

In the discovery cohort, the median age was 64 years (IQR, 59-68) and 4.7% had persistent PSA (0.10 ng/mL or greater) at a median of 2.17 months (IQR, 1.45-3.02) from the time of radical prostatectomy to first PSA assessment. In the validation cohort, the median age was 59 years (IQR, 54-64) and 2.5% had persistent PSA.

The main outcomes of this cohort study were the adjusted HRs of all-cause mortality and prostate cancer-specific mortality.

Also, 14.0% of patients had a pre-radical prostatectomy PSA level greater than 20 ng/mL vs 3.6% that had a PSA level of 20 ng/mL or less (P <.001); the median persistent PSA level was 0.65 ng/mL (IQR, 0.22-2.04) and 0.30 ng/mL (IQR, 0.12-1.00), respectively (P <.001). It was observed that PSA levels greater than 20 ng/mL were identified at a median of 2.00 months (IQR, 1.41-2.99) after radical prostatectomy whereas PSA levels of 20 ng/mL or less were identified at a median of 2.23 months (IQR, 1.45-3.06) after radical prostatectomy.

“The clinical significance of these findings is that they highlight the need to monitor PSA after [radical prostatectomy] for longer than the commonly practiced 1.5-month to 2.0-month interval before concluding a persistent PSA exists and initiating post-[radical prostatectomy] therapy to minimize the risk of overtreatment,” the study authors wrote in the paper.¹

References

1. Tilki D, Chen MH, Wu J, et al. Persistent prostate-specific antigen following radical prostatectomy for prostate cancer and mortality risk. JAMA Oncol. Published online March 13, 2025. doi:10.1001/jamaoncol.2025.0110
2. Checking PSA levels too soon after prostate cancer surgery can lead to overtreatment. News release. Mass General Brigham. March 13, 2025. Accessed March 17, 2025. https://tinyurl.com/3c72a33h