The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown.
To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy.
The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016.
We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM.
We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%.
PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials.
We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.
European urology oncology. 2021 Jun 24 [Epub ahead of print]
Carlo A Bravi, Matteo Droghetti, Nicola Fossati, Giorgio Gandaglia, Nazareno Suardi, Elio Mazzone, Vito Cucchiara, Simone Scuderi, Francesco Barletta, Riccardo Schiavina, Daniar Osmonov, Klaus-Peter Juenemann, Luca Boeri, R Jeffrey Karnes, Alexander Kretschmer, Alexander Buchner, Christian Stief, Andreas Hiester, Alessandro Nini, Peter Albers, Gaëtan Devos, Steven Joniau, Hendrik Van Poppel, Bernhard Grubmüller, Shahrokh F Shariat, Axel Heidenreich, David Pfister, Derya Tilki, Markus Graefen, Inderbir S Gill, Alexandre Mottrie, Pierre I Karakiewicz, Francesco Montorsi, Alberto Briganti
Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: ., Division of Urology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, Policlinico San Martino Hospital, University of Genova, Genova, Italy., Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany., Department of Urology, Mayo Clinic, Rochester, MN, USA; Department of Urology, IRCCS Foundation Ca Granda, Maggiore Policlinico Hospital, University of Milan, Milan, Italy., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Ludwig-Maximilians University, Munich, Germany., Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Department of Urology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Homburg, Germany., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Department of Urology, University of Cologne, Cologne, Germany., Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., USC Institute of Urology, University of Southern California, Los Angeles, CA, USA., Department of Urology, OLV Ziekenhuis Aalst, Aalst, Belgium; Orsi Academy, Melle, Belgium., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.