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European Journal of Nuclear Medicine and Molecular Imaging

Open Access 22-09-2023 | Radiotherapy | Original Article

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

Authors: Sonja Adebahr, Alexander Althaus, Sophia Scharl, Iosif Strouthos, Andrea Farolfi, Francesca Serani, Helena Lanzafame, Christian Trapp, Stefan A. Koerber, Jan C. Peeken, Marco M. E. Vogel, Alexis Vrachimis, Simon K. B. Spohn, Anca-Ligia Grosu, Stephanie G. C. Kroeze, Matthias Guckenberger, Stefano Fanti, George Hruby, Louise Emmett, Claus Belka, Nina-Sophie Schmidt-Hegemann, Christoph Henkenberens, Daniel M. Aebersold, Thomas Wiegel, Ali Afshar-Oromieh, Constantinos Zamboglou, Mohamed Shelan

Published in: European Journal of Nuclear Medicine and Molecular Imaging

Abstract

Aim

The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding.

Methods

This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes.

Results

Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20–46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p < 0.001), pre-SRT PSA level of > 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS.

Conclusion

Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings.

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Bottke D, Bartkowiak D, Siegmann A, Thamm R, Böhmer D, Budach V, Wiegel T. Effect of early salvage radiotherapy at PSA < 0.5 ng/ml and impact of post-SRT PSA nadir in post-prostatectomy recurrent prostate cancer. Prostate Cancer Prostatic Dis. 2019;22(2):344–9. https://doi.org/10.1038/s41391-018-0112-3. CrossRefPubMed

Tendulkar RD, Agrawal S, Gao T, Efstathiou JA, Pisansky TM, Michalski JM, Koontz BF, Hamstra DA, Feng FY, Liauw SL, Abramowitz MC, Pollack A, Anscher MS, Moghanaki D, Den RB, Stephans KL, Zietman AL, Lee WR, Kattan MW, Stephenson AJ. Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol. 2016;34(30):3648–54. https://doi.org/10.1200/JCO.2016.67.9647. CrossRefPubMed

Tilki D, Chen MH, Wu J, Huland H, Graefen M, Wiegel T, Böhmer D, Mohamad O, Cowan JE, Feng FY, Carroll PR, Trock BJ, Partin AW, D'Amico AV. Adjuvant versus early salvage radiation therapy for men at high risk for recurrence following radical prostatectomy for prostate cancer and the risk of death. J Clin Oncol. 2021;39(20):2284–93. https://doi.org/10.1200/JCO.20.03714. CrossRefPubMed

Sargos P, Chabaud S, Latorzeff I, Magné N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulié M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020;21(10):1341–52. https://doi.org/10.1016/S1470-2045(20)30454-X. CrossRefPubMed

Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, Sargos P, Sydes MR, Brawley C, Brihoum M, Brown C, Chabaud S, Cook A, Forcat S, Fraser-Browne C, Latorzeff I, MKB P, Tierney JF, ARTISTIC Meta-analysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020;396(10260):1422–31. https://doi.org/10.1016/S0140-6736(20)31952-8. CrossRefPubMedPubMedCentral

Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, et al. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020;21. https://doi.org/10.1016/S1470-2045(20)30456-3.

Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. The Lancet. 2020;396. https://doi.org/10.1016/S0140-6736(20)31553-1.

Sabbagh A, Mohamad O, Lichter KE, Hope TA. Management of patients with recurrent and metachronous oligometastatic prostate cancer in the era of PSMA PET. Cancers (Basel). 2022;14. https://doi.org/10.3390/cancers14246194.

Treglia G, Pereira Mestre R, Ferrari M, Bosetti DG, Pascale M, Oikonomou E, et al. Radiolabelled choline versus PSMA PET/CT in prostate cancer restaging: a meta-analysis. Am J Nucl Med Mol Imaging. 2019;9.

10.

Zamboglou C, Strouthos I, Sahlmann J, Farolfi A, Serani F, Medici F, et al. Metastasis-free survival and patterns of distant metastatic disease after prostate-specific membrane antigen positron emission tomography (PSMA-PET)-guided salvage radiation therapy in recurrent or persistent prostate cancer after prostatectomy. Int J Radiat Oncol Biol Phys [Internet]. 2022 [cited 2023 May 9];113:1015–24. Available from: https://pubmed.ncbi.nlm.nih.gov/35659629/. CrossRefPubMed

11.

Bouchelouche K, Choyke PL, Capala J. Prostate specific membrane antigen- a target for imaging and therapy with radionuclides. Discov Med. 2010;9(44):55–61. PubMedPubMedCentral

12.

Afshar-Oromieh A, da Cunha ML, Wagner J, Haberkorn U, Debus N, Weber W, et al. Performance of [68Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy-a multi-centre evaluation of 2533 patients. Eur J Nucl Med Mol Imaging [Internet]. 2021 [cited 2023 May 22];48:2925–34. Available from: https://pubmed.ncbi.nlm.nih.gov/33543325/. CrossRefPubMed

13.

Combes AD, Palma CA, Calopedos R, Wen L, Woo H, Fulham M, et al. PSMA PET-CT in the Diagnosis and Staging of Prostate Cancer. Diagnostics. 2022;12. https://doi.org/10.3390/diagnostics12112594.

14.

Bianchi L, Ceci F, Costa F, Balestrazzi E, Droghetti M, Piazza P, et al. The impact of PSMA-PET on oncologic control in prostate cancer patients who experienced PSA persistence or recurrence. Cancers (Basel). 2023;15. https://doi.org/10.3390/cancers15010247.

15.

Morawitz J, Kirchner J, Lakes J, Bruckmann NM, Mamlins E, Hiester A, et al. PSMA PET/CT vs. CT alone in newly diagnosed biochemical recurrence of prostate cancer after radical prostatectomy: Comparison of detection rates and therapeutic implications. Eur J Radiol. 2021;136. https://doi.org/10.1016/j.ejrad.2021.109556.

16.

Scharl S, Zamboglou C, Strouthos I, Farolfi A, Serani F, Lanzafame H, et al. Salvage radiotherapy is effective in patients with PSMA-PET-negative biochemical recurrence- results of a retrospective study. Radiother Oncol [Internet]. 2023;184:109678. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0167814023002165. Accessed 22 May 2023.

17.

Schmidt-Hegemann NS, Stief C, Kim TH, Eze C, Kirste S, Strouthos I, et al. Outcome after PSMA PET/CT based salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy: a bi-institutional retrospective analysis. J Nucl Med [Internet]. 2019 [cited 2023 May 10];60:227–33. Available from: https://pubmed.ncbi.nlm.nih.gov/30002108/. CrossRefPubMed

18.

Emmett L, Tang R, Nandurkar R, Hruby G, Roach P, Watts JA, et al. 3-year freedom from progression after 68Ga-PSMA PET/CT-Triaged management in men with biochemical recurrence after radical prostatectomy: Results of a prospective multicenter trial. J Nucl Med. 2020;61. https://doi.org/10.2967/jnumed.119.235028.

19.

Shelan M, Odermatt S, Bojaxhiu B, Nguyen DP, Thalmann GN, Aebersold DM, et al. Disease control with delayed salvage radiotherapy for macroscopic local recurrence following radical prostatectomy. Front Oncol. 2019;9. https://doi.org/10.3389/fonc.2019.00012.

20.

Meijer D, Eppinga WSC, Mohede RM, Vanneste BGL, Meijnen P, Meijer OWM, et al. Prostate-specific membrane antigen positron emission tomography/computed tomography is associated with improved oncological outcome in men treated with salvage radiation therapy for biochemically recurrent prostate cancer. Eur Urol Oncol. 2022;5. https://doi.org/10.1016/j.euo.2022.01.001.

21.

Stish BJ, Pisansky TM, Harmsen WS, Davis BJ, Tzou KS, Choo R, et al. Improved metastasis-free and survival outcomes with early salvage radiotherapy in men with detectable prostate-specific antigen after prostatectomy for prostate cancer. J Clin Oncol [Internet]. 2016 [cited 2023 May 22];34:3864–71. Available from: https://pubmed.ncbi.nlm.nih.gov/27480153/. CrossRefPubMed

22.

Tilki D, Chen M-H, Wu J, Huland H, Graefen M, Mohamad O, et al. Prostate-specific antigen level at the time of salvage therapy after radical prostatectomy for prostate cancer and the risk of death. J Clin Oncol [Internet]. 2023 [cited 2023 May 22]:41. Available from: https://pubmed.ncbi.nlm.nih.gov/36857638/.

23.

Brand DH, Parker JI, Dearnaley DP, Eeles R, Huddart R, Khoo V, et al. Patterns of recurrence after prostate bed radiotherapy. Radiother Oncol. 2019;141

24.

Pollack A, Karrison TG, Balogh AG, Gomella LG, Low DA, Bruner DW, et al. The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. The Lancet. 2022;399. https://doi.org/10.1016/S0140-6736(21)01790-6.

25.

PEACE V: Salvage treatment of oligorecurrent nodal prostate cancer metastases (STORM) | ClinicalTrials.gov [Internet]. [cited 2023 Sep 8]. Available from: https://clinicaltrials.gov/study/NCT0356924126.

26.

Zilli T, Dirix P, Heikkilä R, Liefhooghe N, Siva S, Gomez-Iturriaga A, et al. The multicenter, randomized, phase 2 PEACE V-STORM trial: defining the best salvage treatment for oligorecurrent nodal prostate cancer metastases. Eur Urol Focus. 2021.

27.

Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. New Engl J Med. 2017;376. https://doi.org/10.1056/nejmoa1607529.

28.

Carrie C, Magné N, Burban-Provost P, Sargos P, Latorzeff I, Lagrange JL, et al. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial. Lancet Oncol. 2019;20. https://doi.org/10.1016/S1470-2045(19)30486-3.

29.

Parker CC, Clarke N, Cook A, Catton C, Cross WR, Kynaston H, et al. LBA9 Duration of androgen deprivation therapy (ADT) with post-operative radiotherapy (RT) for prostate cancer: First results of the RADICALS-HD trial (ISRCTN40814031). Ann Oncol. 2022;33. https://doi.org/10.1016/j.annonc.2022.08.064.

30.

Multicenter Randomized Trial of 68Ga-PSMA-11 PET/CT Based SRT after radical prostatectomy - ClinicalTrials.gov [Internet]. [cited 2023 May 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT03582774.

31.

PSMA-PET Guided radiotherapy - ClinicalTrials.gov [Internet]. [cited 2023 May 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT03525288 .

32.

Testing the addition of the drug relugolix to the usual radiation therapy for advanced-stage prostate cancer - full text view - ClinicalTrials.gov [Internet]. [cited 2023 May 10]. Available from: https://clinicaltrialsgov.translate.goog/ct2/show/NCT05053152?_x_tr_sl=en&_x_tr_tl=ar&_x_tr_hl=ar&_x_tr_pto=sc.

33.

Treating prostate cancer that has come back after surgery with apalutamide and targeted radiation using PET/CT imaging - ClinicalTrials.gov [Internet]. [cited 2023 May 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT04423211.

34.

PSMA guided approach for biochemical relapse after prostatectomy-PSICHE - ClinicalTrials.gov [Internet]. [cited 2023 Sep 8]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05022914.

35.

Stereotactic salvage radiotherapy for macroscopic prostate bed recurrence after prostatectomy-a prospective observational study - ClinicalTrials.gov [Internet]. [cited 2023 Sep 8]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05455736?term=NCT05455736&draw=2&rank=1.

36.

Zhao SG, Chang SL, Spratt DE, Erho N, Yu M, Ashab HAD, et al. Development and validation of a 24-gene predictor of response to postoperative radiotherapy in prostate cancer: a matched, retrospective analysis. Lancet Oncol [Internet]. 2016 [cited 2023 May 22];17:1612–20. Available from: http://www.thelancet.com/article/S1470204516304910/fulltext. CrossRefPubMed

37.

Den RB, Yousefi K, Trabulsi EJ, Abdollah F, Choeurng V, Feng FY, et al. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol. 2015;33:944–51. CrossRefPubMedPubMedCentral

38.

Ross AE, Den RB, Yousefi K, Trock BJ, Tosoian J, Davicioni E, et al. Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk. Prostate Cancer Prostatic Dis. 2016;19(3):277–82. Available from: https://www.nature.com/articles/pcan201615. CrossRefPubMedPubMedCentral

39.

Dal Pra A, Ghadjar P, Hayoz S, Liu VYT, Spratt DE, Thompson DJS, et al. Validation of the decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy – an ancillary study of the SAKK 09/10 randomized clinical trial. Ann Oncol. 2022;33.

40.

Zamboglou C, Peeken JC, Janbain A, Katsahian S, Strouthos I, Ferentinos K, et al. Development and validation of a multi-institutional nomogram of outcomes for PSMA-PET–based salvage radiotherapy for recurrent prostate cancer. JAMA Netw Open [Internet]. 2023;6:e2314748–8. Available from: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2805173. CrossRefPubMed

Title: The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy
Authors: Sonja Adebahr
Alexander Althaus
Sophia Scharl
Iosif Strouthos
Andrea Farolfi
Francesca Serani
Helena Lanzafame
Christian Trapp
Stefan A. Koerber
Jan C. Peeken
Marco M. E. Vogel
Alexis Vrachimis
Simon K. B. Spohn
Anca-Ligia Grosu
Stephanie G. C. Kroeze
Matthias Guckenberger
Stefano Fanti
George Hruby
Louise Emmett
Claus Belka
Nina-Sophie Schmidt-Hegemann
Christoph Henkenberens
Daniel M. Aebersold
Thomas Wiegel
Ali Afshar-Oromieh
Constantinos Zamboglou
Mohamed Shelan
Publication date: 22-09-2023
Publisher: Springer Berlin Heidelberg
Keywords: Radiotherapy
Prostatectomy
Prostatectomy
Prostate Cancer
Prostate Cancer
Published in: European Journal of Nuclear Medicine and Molecular Imaging
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06438-3

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The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy

Abstract

Aim

Methods

Results

Conclusion

Keynote Webinar | Spotlight on Diet and Diabetes

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

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