Better Oncological Outcomes After Prostate-specific Membrane Antigen Positron Emission Tomography-guided Salvage Radiotherapy Following Prostatectomy

Constantinos Zamboglou; Paulina Staus; Martin Wolkewitz; Jan C Peeken; Konstantinos Ferentinos; Iosif Strouthos; Andrea Farolfi; Stefan A Koerber; Alexis Vrachimis; Simon K B Spohn; Daniel M Aebersold; Anca-Ligia Grosu; Stephanie G C Kroeze; Stefano Fanti; George Hruby; Thomas Wiegel; Louise Emmett; Stefanie Hayoz; Francesco Ceci; Matthias Guckenberger; Claus Belka; Nina-Sophie Schmidt-Hegemann; Pirus Ghadjar; Mohamed Shelan

doi:10.1016/j.euf.2024.11.006

Better Oncological Outcomes After Prostate-specific Membrane Antigen Positron Emission Tomography-guided Salvage Radiotherapy Following Prostatectomy

Eur Urol Focus. 2024 Nov 27:S2405-4569(24)00247-5. doi: 10.1016/j.euf.2024.11.006. Online ahead of print.

Authors

Constantinos Zamboglou¹, Paulina Staus², Martin Wolkewitz², Jan C Peeken³, Konstantinos Ferentinos⁴, Iosif Strouthos⁴, Andrea Farolfi⁵, Stefan A Koerber⁶, Alexis Vrachimis⁷, Simon K B Spohn⁸, Daniel M Aebersold⁹, Anca-Ligia Grosu¹⁰, Stephanie G C Kroeze¹¹, Stefano Fanti⁵, George Hruby¹², Thomas Wiegel¹³, Louise Emmett¹⁴, Stefanie Hayoz¹⁵, Francesco Ceci¹⁶, Matthias Guckenberger¹⁷, Claus Belka¹⁸, Nina-Sophie Schmidt-Hegemann¹⁸, Pirus Ghadjar¹⁹, Mohamed Shelan²⁰

Affiliations

¹ Department of Radiation Oncology, University of Freiburg Medical Center, Freiburg, Germany; German Cancer Consortium, Freiburg Partner Site, Freiburg, Germany; Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Radiation Oncology, German Oncology Center, European University Cyprus, Limassol, Cyprus.
² Institute of Medical Biometry and Statistics, Methods in Clinical Epidemiology Division, University of Freiburg Medical Center, Freiburg, Germany.
³ Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; Institute of Radiation Medicine, Department of Radiation Sciences, Helmholtz Zentrum, Munich, Germany; Deutsches Konsortium für Translationale Krebsforschung, Munich Partner Site, Munich, Germany.
⁴ Department of Radiation Oncology, German Oncology Center, European University Cyprus, Limassol, Cyprus.
⁵ Division of Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶ Department of Radiation Oncology, Barmherzige Brüder Hospital Regensburg, Regensburg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
⁷ CARIC Cancer Research and Innovation Center, Limassol, Cyprus; Department of Nuclear Medicine, German Oncology Center, European University Cyprus, Limassol, Cyprus.
⁸ Department of Radiation Oncology, University of Freiburg Medical Center, Freiburg, Germany; German Cancer Consortium, Freiburg Partner Site, Freiburg, Germany; Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁹ Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁰ Department of Radiation Oncology, University of Freiburg Medical Center, Freiburg, Germany; German Cancer Consortium, Freiburg Partner Site, Freiburg, Germany.
¹¹ Department of Radiation Oncology KSA-KSB, Cantonal Hospital Aarau, Aarau, Switzerland.
¹² Department of Radiation Oncology, Royal North Shore Hospital, University of Sydney, Sydney, Australia.
¹³ Department of Radiation Oncology, University of Ulm, Ulm, Germany.
¹⁴ Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital Sydney, Sydney, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, Australia.
¹⁵ Swiss Group for Clinical Cancer Research Competence Center, Bern, Switzerland.
¹⁶ Division of Nuclear Medicine, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
¹⁷ Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
¹⁸ Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
¹⁹ Department of Radiation Oncology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
²⁰ Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: mohamed.shelan@insel.ch.

PMID: 39609244
DOI: 10.1016/j.euf.2024.11.006

Abstract

Background and objective: Up to 50% of patients with prostate cancer experience prostate-specific antigen (PSA) relapse following primary radical prostatectomy (RP). Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is increasingly being used for staging after RP owing to its high detection rate. Our aim was to compare outcomes for patients who received salvage radiotherapy (sRT) with versus without PSMA PET guidance.

Methods: In this observational case-control study, the control group consisted of 344 patients from the SAKK09/10 trial (sRT without PSMA PET guidance from 2011 to 2014). The treatment group consisted of 1548 patients from a retrospective multicenter cohort (PSMA PET-guided sRT from July 2013 to 2020). Data were collected up to November 2023. Patients with pN1 status at RP, initial cM1 status, cM1 status on PET, or PSA >0.5 ng/ml were excluded. Patients with detectable PSA after RP who were treated with sRT were eligible. We assessed 3-yr biochemical recurrence-free survival (BRFS) and metastasis-free survival (MFS).

Key findings and limitations: The study population of 717 patients comprised a control group (n = 255) with median follow-up of 75 mo and a PSMA PET group (n = 462) with median follow-up of 31 mo. In the PSMA PET cohort, 103 patients (22.3%) had PSMA-positive pelvic lymph nodes (PLNs), 85 (18.4%) received androgen deprivation therapy (ADT), and 104 (22.5%) underwent PLN irradiation. The BRFS rate at 3 yr was 71% (95% confidence interval [CI] 64-78%) for the control group and 77% (95% CI 72-82%) for the PSMA PET group. The PSMA PET group had favorable BRFS at 18-24 mo after sRT (hazard ratio 0.32, 95% CI 0.0.14-0.75; p = 0.01) and a lower rate of lymph node relapse after sRT (standardized mean difference 0.603). The MFS rate at 3 yr was 89.2% (95% CI 84.6-94.1%) for the control group and 91.2% (95% CI 88.1-94.4%) for the PSMA PET group.

Conclusions and clinical implications: Our results suggest a moderate improvement in short-term BRFS if PSMA PET is used to guide sRT. One possible reason is individualized PLN coverage facilitated by PET. MFS was not improved by PSMA PET guidance for sRT.

Patients' summary: For patients who experience recurrence of prostate cancer after surgical removal of their prostate, salvage radiotherapy (sRT) is a further treatment option. We found that a type of scan called PSMA PET (prostate-specific membrane antigen positron emission tomography) to identify recurrence and guide sRT can improve recurrence-free survival because of better targeting of pelvic lymph nodes that may contain cancer cells.

Keywords: Positron emission tomography; Prostate-specific membrane antigen; Prostatectomy; Salvage radiotherapy.