A recent cohort study evaluated the relationship between persistent prostate-specific antigen levels following radical prostatectomy for prostate cancer and mortality risk.
Published in JAMA Oncology, the study included 43,298 patients treated with radical prostatectomy (RP) between 1992 and 2020 at two academic centers: University Hospital Hamburg-Eppendorf, Germany, and Johns Hopkins Medical Institutions, USA. The findings indicated that a higher pre-RP prostate-specific antigen (PSA) level was significantly associated with reduced all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) risk among patients with persistent PSA levels. Specifically, patients with a pre-RP PSA level greater than 20 ng/mL had a significantly lower ACM risk (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.51-0.91; P = .01) and PCSM risk (aHR, 0.41; 95% CI, 0.25-0.66; P < .001) compared to those with a pre-RP PSA level of 20 ng/mL or less.
The study also found that increasing persistent PSA levels were associated with an increased risk of ACM (aHR, 1.14; 95% CI, 1.04-1.24; P = .004) and PCSM (aHR, 1.27; 95% CI, 1.12-1.45; P < .001), underscoring the importance of ongoing PSA monitoring after RP.
According to Derya Tilki from the Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Germany, the study’s findings suggest that PSA level assessment for at least 3 months after RP may minimize overtreatment. The study suggested that a higher proportion of patients with a pre-RP PSA greater than 20 ng/mL could have achieved an undetectable PSA level if given additional time for assessment before initiating post-RP therapy.
Persistent PSA was defined as a PSA level of 0.10 ng/mL or higher measured at a median time of 2.17 months post-RP. Among the 30,461 patients in the discovery cohort, the median age was 64 years, while the validation cohort of 12,837 patients had a median age of 59 years. The study reported that 4.7% of patients in the discovery cohort had persistent PSA levels, while 2.5% of patients in the validation cohort had persistent PSA levels. Additionally, 850 patients (6.6%) died during a median follow-up of 5.00 years, including deaths from both prostate cancer and other causes.
The researchers noted that patients with a pre-RP PSA greater than 20 ng/mL experienced a shorter median time to post-RP radiation therapy (RT) and androgen deprivation therapy (ADT) compared to those with lower pre-RP PSA levels. Specifically, 54.7% of patients with a pre-RP PSA greater than 20 ng/mL received post-RP RT plus ADT at a median of 2.68 months, while only 34.8% of patients with a pre-RP PSA of 20 ng/mL or less received treatment at a median of 3.30 months.
The study concluded that the timing of PSA assessments post-RP is critical in determining treatment pathways and outcomes for patients, underscoring the importance of extending the monitoring period for PSA levels beyond the conventional timeframe to avoid premature treatment decisions that may not align with the patient's actual prognosis.
The authors acknowledged that the validation cohort showed a significant reduction in PCSM risk but not ACM risk among patients with a persistent PSA and pre-RP PSA greater than 20 ng/mL. This may be due to the shorter median follow-up and smaller event rate compared to the discovery cohort.
Full disclosures are available in the study.
