Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer.
To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT.
This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022.
Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible.
The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT.
In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort.
This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.
JAMA network open. 2023 May 01*** epublish ***
Constantinos Zamboglou, Jan C Peeken, Ali Janbain, Sandrine Katsahian, Iosif Strouthos, Konstantinos Ferentinos, Andrea Farolfi, Stefan A Koerber, Juergen Debus, Marco E Vogel, Stephanie E Combs, Alexis Vrachimis, Alessio Giuseppe Morganti, Simon K B Spohn, Mohamed Shelan, Daniel M Aebersold, Anca-Ligia Grosu, Francesco Ceci, Christoph Henkenberens, Stephanie G C Kroeze, Matthias Guckenberger, Stefano Fanti, Claus Belka, Peter Bartenstein, George Hruby, Sophia Scharl, Thomas Wiegel, Louise Emmett, Armelle Arnoux, Nina-Sophie Schmidt-Hegemann
Department of Radiation Oncology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany., Cité University, AP-HP, European Hospital Georges-Pompidou, Clinical research unit, Clinical Investigation Center 1418 Clinical Epidemiology, INSERM, INRIA, HeKA, Paris, France., Department of Radiation Oncology, German Oncology Center, University Hospital of the European University, Limassol, Cyprus., Division of Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany., Department of Nuclear Medicine, German Oncology Center, University Hospital of the European University, Limassol, Cyprus., Division of Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Department of Radiation Oncology, Inselspital Bern, University of Bern, Bern, Switzerland., Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, Milan, Italy., Department of Radiotherapy and Special Oncology, Medical School Hannover, Hannover, Germany., Department of Radiation Oncology, University Hospital Zürich, University of Zurich, Zurich, Switzerland., Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany., Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany., Department of Radiation Oncology, Royal North Shore Hospital-University of Sydney, Sydney, Australia., Department of Radiation Oncology, University of Ulm, Ulm, Germany., Department of Theranostics and Nuclear medicine, St Vincent's Hospital Sydney, Sydney, Australia., Department of Radiation Oncology KSA-KSB, Cantonal Hospital Aarau, Aarau, Switzerland.