Elise De Bleser1, Barbara Alicja Jereczek-Fossa2, David Pasquier3, Thomas Zilli4, Nicholas Van As5, Shankar Siva6, Andrei Fodor7, Piet Dirix8, Alfonso Gomez-Iturriaga9, Fabio Trippa10, Beatrice Detti11, Gianluca Ingrosso12, Luca Triggiani13, Alessio Bruni14, Filippo Alongi15, Dries Reynders16, Gert De Meerleer17, Alessia Surgo18, Kaoutar Loukili19, Raymond Miralbell4, Pedro Silva5, Sarat Chander6, Nadia Gisella Di Muzio7, Ernesto Maranzano10, Giulio Francolini11, Andrea Lancia20, Alison Tree5, Chiara Lucrezia Deantoni7, Elisabetta Ponti12, Giulia Marvaso18, Els Goetghebeur16, Piet Ost17. 1. Department of Urology, Ghent University Hospital, Ghent, Belgium. Electronic address: elise.debleser@ugent.be. 2. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Department of Radiation Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy. 3. Academic Department of Radiation Oncology, Centre Oscar Lambret, Lille, France; CRIStAL UMR CNRS 9189, Lille University, Lille, France. 4. Radiation Oncology, Geneva University Hospital, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland. 5. The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK. 6. Radiation Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia. 7. Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy. 8. Department of Radiation Oncology, Iridium Cancer Network, Antwerp, Belgium; Department of Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO), University of Antwerp, Antwerp, Belgium. 9. Department of Radiation Oncology, Cruces University Hospital, Biocruces Health Research Institute, Baracaldo, Spain. 10. Radiation Oncology, Azienda Ospedaliera Santa Maria di Terni, Terni, Italy. 11. Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. 12. Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, Tor Vergata General Hospital, Rome, Italy. 13. Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy. 14. Radiotherapy Unit, Oncology and Hematology Department, University Hospital of Modena, Modena, Italy. 15. Radiation Oncology, Ospedale Sacro Cuore-Don Calabria, Verona, Italy. 16. Department of Applied Mathematics, Computer Science and Statistics, University of Ghent, Ghent, Belgium. 17. Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium. 18. Department of Radiation Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy. 19. Academic Department of Radiation Oncology, Centre Oscar Lambret, Lille, France. 20. Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Abstract
BACKGROUND: Stereotactic body radiotherapy (SBRT) and elective nodal radiotherapy (ENRT) are being investigated as metastasis-directed treatments in oligorecurrent prostate cancer (PC); however, comparative data are still lacking. OBJECTIVE: To compare outcome and toxicity between both treatments. Primary endpoint was metastasis-free survival, adjusted for selected variables (aMFS). DESIGN, SETTING, AND PARTICIPANTS: This was a multi-institutional, retrospective analysis of 506 (SBRT: 309, ENRT: 197) patients with hormone-sensitive nodal oligorecurrent PC (five or fewer lymph nodes (LNs; N1/M1a), treated between 2004 and 2017. Median follow-up was 36 mo (interquartile range 23-56). INTERVENTION: SBRT was defined as a minimum of 5 Gy per fraction to each lesion with a maximum of 10 fractions. ENRT was defined as a minimum dose of 45 Gy in up to 25 fractions to the elective nodes, with or without a simultaneous boost to the suspicious node(s). The choice of radiotherapy (RT) was at the discretion of the treating physician, with treatments being unbalanced over the centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In total, 506 patients from 15 different treatment centers were included. Primary treatment was radical prostatectomy, RT, or their combination. Nodal recurrences were detected by positron emission tomography/computer tomography (97%) or conventional imaging (3%). Descriptive statistics was used to summarize patient characteristics. RESULTS AND LIMITATIONS: ENRT was associated with fewer nodal recurrences compared with SBRT (p < 0.001). In a multivariable analysis, patients with one LN at recurrence had longer aMFS after ENRT (hazard ratio: 0.50, 95% confidence interval 0.30-0.85, p = 0.009). Late toxicity was higher after ENRT compared with that after SBRT (16% vs. 5%, p < 0.01). Limitations include higher use of hormone therapy in the ENRT cohort and nonstandardized follow-up. CONCLUSIONS: ENRT reduces the number of nodal recurrences as compared with SBRT, however at higher toxicity. Our findings hypothesize that ENRT should be preferred to SBRT in the treatment of nodal oligorecurrences. This hypothesis needs to be evaluated in a randomized trial. PATIENT SUMMARY: This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal radiotherapy might be the preferred treatment.
BACKGROUND: Stereotactic body radiotherapy (SBRT) and elective nodal radiotherapy (ENRT) are being investigated as metastasis-directed treatments in oligorecurrent prostate cancer (PC); however, comparative data are still lacking. OBJECTIVE: To compare outcome and toxicity between both treatments. Primary endpoint was metastasis-free survival, adjusted for selected variables (aMFS). DESIGN, SETTING, AND PARTICIPANTS: This was a multi-institutional, retrospective analysis of 506 (SBRT: 309, ENRT: 197) patients with hormone-sensitive nodal oligorecurrent PC (five or fewer lymph nodes (LNs; N1/M1a), treated between 2004 and 2017. Median follow-up was 36 mo (interquartile range 23-56). INTERVENTION: SBRT was defined as a minimum of 5 Gy per fraction to each lesion with a maximum of 10 fractions. ENRT was defined as a minimum dose of 45 Gy in up to 25 fractions to the elective nodes, with or without a simultaneous boost to the suspicious node(s). The choice of radiotherapy (RT) was at the discretion of the treating physician, with treatments being unbalanced over the centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: In total, 506 patients from 15 different treatment centers were included. Primary treatment was radical prostatectomy, RT, or their combination. Nodal recurrences were detected by positron emission tomography/computer tomography (97%) or conventional imaging (3%). Descriptive statistics was used to summarize patient characteristics. RESULTS AND LIMITATIONS: ENRT was associated with fewer nodal recurrences compared with SBRT (p < 0.001). In a multivariable analysis, patients with one LN at recurrence had longer aMFS after ENRT (hazard ratio: 0.50, 95% confidence interval 0.30-0.85, p = 0.009). Late toxicity was higher after ENRT compared with that after SBRT (16% vs. 5%, p < 0.01). Limitations include higher use of hormone therapy in the ENRT cohort and nonstandardized follow-up. CONCLUSIONS: ENRT reduces the number of nodal recurrences as compared with SBRT, however at higher toxicity. Our findings hypothesize that ENRT should be preferred to SBRT in the treatment of nodal oligorecurrences. This hypothesis needs to be evaluated in a randomized trial. PATIENT SUMMARY: This study investigated the difference between stereotactic and elective nodal radiotherapy in treating limited nodal metastatic prostate cancer. Nodal relapse was less frequent following elective nodal radiotherapy than following stereotactic body radiotherapy, and thus elective nodal radiotherapy might be the preferred treatment.
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