(UroToday.com) The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a joint session of the EAU and the Advanced Prostate Cancer Consensus (APCCC). Dr. Derya Tilki discussed whether all PSA persistence is created equal, and what definition/diagnostic work-up should be accordingly used.
Dr. Tilki noted that 5 to 30% of prostate cancer patients will experience detectable or persistent PSA levels following radical prostatectomy. This may result from undetected micrometastatic disease, malignant residual disease in the surgical bed, or residual benign tissue at surgical margins. Persistent PSA in the post-operative setting is defined as detectable PSA >0.1 ng/ml within four to eight weeks of surgery.
What is the diagnostic yield of molecular imaging in the persistent PSA setting? A 2019 study demonstrated that among 45 patients with persistent PSA following radical prostatectomy and who had undergone a 68Ga-PSMA-11 PET/CT, the disease detection rate was 65%. Similar to findings from the biochemically recurrent setting, the PSMA PET yield improved as the PSA at time of imaging increased.1 Currently, the EAU has a weak recommendation for performing a PSMA PET/CT in patients with a persistent PSA >0.2 ng/ml, if the results will influence subsequent treatment decisions.
Dr. Tilki’s group has previously published on their own experience of patients undergoing radical prostatectomy and who experienced persistent PSA. Of 11,604 evaluable patients who underwent a radical prostatectomy between 1992 and 2016, 8.8% had post-operative findings of a persistent PSA. Long-term follow-up demonstrated that the 15-year rates of metastasis-free and cancer-specific survivals were significantly worse for patients with persistent PSA, compared to those with undetectable PSA findings.2
Predictors of increased odds of a persistent PSA included higher pre-operative PSA levels, more advanced pathologic tumor stage, pathologic Grade Group 3–5 disease, positive surgical margins, and pN1 status. Notably, even after adjusting for all these variables, a persistent PSA post-operatively remained predictive of adverse survival outcomes.2
In a 2021 systematic review of 25 studies (n=5,217), Ploussard and colleagues demonstrated that PSA persistence was significantly correlated with disease aggressiveness and associated with worse oncologic outcomes, compared to men with undetectable PSA levels. The 5-year recurrence-free survival rates varied between 21.5% and 67%. The 10-year cancer-specific survival ranged between 75 and 88%.3
One possible reason for a PSA persistence post-operatively is incomplete resection of the prostate, whereby benign glands may be left at the surgical margins leading to this laboratory finding. This is more likely to occur in patients with larger glands and those with higher Gleason Scores. This phenomenon is also most likely to focally involve the apex.4
Can we use additional tools to further risk stratify patients with PSA persistence? In 2018, Spratt and colleagues evaluated whether a 22-gene genomic classifier (Decipher®) could be used to independently predict the risk of development of metastases in men with PSA persistence post-operatively. They included a multi-institutional cohort of 477 men from three academic centers who had undergone a radical prostatectomy between 1990 and 2015. Patients were categorized as having detectable PSA (n=150) or undetectable PSA (n=327), based on a post-operative PSA nadir cut-off of 0.1 ng/ml.
On multivariable analysis, Spratt and colleagues demonstrated that a genomic high-risk score (HR: 5.95) was significantly predictive of the rate of subsequent metastasis. Among patients with a persistent PSA, the 5-year metastasis rate was 0.9% for patients with Decipher® low/intermediate risk scores and 18% for patients with Decipher® high-risk scores.5
Dr. Tilki concluded her presentation by noting:
- PSA persistence is most commonly defined as PSA >0.1 ng/ml
- PSA persistence is strongly and independently associated with adverse pathology features and with poorer survival outcomes across studies when data are compared with those of patients achieving an undetectable PSA.
- Risk stratification according to pathologic features, PSA levels/kinetics, and genomic classifier may aid in personalization of treatment
- The usefulness of molecular imaging in this setting remains under-evaluated.
Presented by: Professor Derya Tilki, MD, Associate Professor of Urology, Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Written by: Rashid Sayyid, MD, MSc - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024
References:- Ceci F, Castellucci P, Graziani T, et al. 68Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy. Eur J Nucl MedMol Imaging. 2019;46(1): 31 –39.
- Preisser F, Chun FKH, Pompe RS, et al. Persistent Prostate-Specific Antigen After Radical Prostatectomy and Its Impact on Oncologic Outcomes. Eur Urol. 2019;76(1): 106-114.
- Ploussard G, Fossati N, Wiegel T, et al. Management of Persistently Elevated Prostate-specific Antigen After Radical Prostatectomy: A Systematic Review of the Literature. Eur Urol Oncol. 2021;4(2): 150-169.
- Shah R, Bassily N, Wei J, et al. Benign prostatic glands at surgical margins of radical prostatectomy specimens: frequency and associated risk factors. Urology. 2000;56(5): 721-5.
- Spratt DE, Dai DLY, Den RB, et al. Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy. Eur Urol. 2018;74(1): 107-114.