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Published in: BMC Cancer 1/2020

01-12-2020 | Prostate Cancer | Research article

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy

Authors: Ann-Kathrin Oehus, Stephanie G. C. Kroeze, Nina-Sophie Schmidt-Hegemann, Marco M. E. Vogel, Simon Kirste, Jessica Becker, Irene A. Burger, Thorsten Derlin, Peter Bartenstein, Matthias Eiber, Michael Mix, Christian la Fougère, Claus Belka, Stephanie E. Combs, Anca-Ligia Grosu, Arndt-Christian Müller, Matthias Guckenberger, Hans Christiansen, Christoph Henkenberens

Published in: BMC Cancer | Issue 1/2020

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Abstract

Background

A substantial number of patients will develop further biochemical progression after radical prostatectomy (RP) and salvage radiotherapy (sRT). Recently published data using prostate-specific membrane antigen ligand positron emission tomography (PSMA - PET) for re-staging suggest that those recurrences are often located outside the prostate fossa and most of the patients have a limited number of metastases, making them amenable to metastasis-directed treatment (MDT).

Methods

We analyzed 78 patients with biochemical progression after RP and sRT from a retrospective European multicenter database and assessed the biochemical recurrence-free survival (bRFS; PSA < nadir + 0.2 ng/ml or no PSA decline) as well as the androgen deprivation therapy- free survival (ADT-FS) using Kaplan-Meier curves. Log-rank test and multivariate analysis was performed to determine influencing factors.

Results

A total of 185 PSMA – PET positive metastases were detected and all lesions were treated with radiotherapy (RT). Concurrent ADT was prescribed in 16.7% (13/78) of patients. The median PSA level before RT was 1.90 ng/mL (range, 0.1–22.1) and decreased statistically significantly to a median PSA nadir level of 0.26 ng/mL (range, 0.0–12.25; p < 0.001). The median PSA level of 0.88 ng/mL (range, 0.0–25.8) at the last follow-up was also statistically significantly lower (p = 0.008) than the median PSA level of 1.9 ng/mL (range, 0.1–22.1) before RT. The median bRFS was 17.0 months (95% CI, 14.2–19.8). After 12 months, 55.3% of patients were free of biochemical progression. Multivariate analyses showed that concurrent ADT was the most important independent factor for bRFS (p = 0.01). The median ADT-FS was not reached and exploratory statistical analyses estimated a median ADT-FS of 34.0 months (95% CI, 16.3–51.7). Multivariate analyses revealed no significant parameters for ADT-FS.

Conclusions

RT as MDT based on PSMA - PET of all metastases of recurrent prostate cancer after RP and sRT represents a viable treatment option for well-informed and well-selected patients.
Literature
1.
go back to reference Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate Cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate Cancer. Eur Urol. 2017;71(4):630–42.PubMedCrossRef Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate Cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate Cancer. Eur Urol. 2017;71(4):630–42.PubMedCrossRef
2.
go back to reference Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016;17(6):747–56.PubMedCrossRef Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016;17(6):747–56.PubMedCrossRef
3.
go back to reference Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, et al. Radiation with or without Antiandrogen therapy in recurrent prostate Cancer. N Engl J Med. 2017;376(5):417–28.PubMedPubMedCentralCrossRef Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, et al. Radiation with or without Antiandrogen therapy in recurrent prostate Cancer. N Engl J Med. 2017;376(5):417–28.PubMedPubMedCentralCrossRef
4.
go back to reference van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, Thompson B, et al. (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int. 2016;117(5):732–9.PubMedCrossRef van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, Thompson B, et al. (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int. 2016;117(5):732–9.PubMedCrossRef
5.
go back to reference Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. 68Ga-PSMA-11 PET/CT mapping of prostate Cancer biochemical recurrence after radical prostatectomy in 270 patients with a PSA level of less than 1.0 ng/mL: impact on salvage radiotherapy planning. J Nucl Med. 2018;59(2):230–7.PubMedPubMedCentralCrossRef Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. 68Ga-PSMA-11 PET/CT mapping of prostate Cancer biochemical recurrence after radical prostatectomy in 270 patients with a PSA level of less than 1.0 ng/mL: impact on salvage radiotherapy planning. J Nucl Med. 2018;59(2):230–7.PubMedPubMedCentralCrossRef
6.
go back to reference Schmidt-Hegemann NS, Eze C, Li M, Rogowski P, Schaefer C, Stief C, et al. Impact of 68Ga-PSMA PET/CT on the Radiotherapeutic Approach to Prostate Cancer in Comparison to CT: A Retrospective Analysis. J Nucl Med. 2019;60(7):963–70.PubMedPubMedCentralCrossRef Schmidt-Hegemann NS, Eze C, Li M, Rogowski P, Schaefer C, Stief C, et al. Impact of 68Ga-PSMA PET/CT on the Radiotherapeutic Approach to Prostate Cancer in Comparison to CT: A Retrospective Analysis. J Nucl Med. 2019;60(7):963–70.PubMedPubMedCentralCrossRef
7.
go back to reference Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, et al. The impact of 68Ga-PSMA PET/CT on management intent in prostate Cancer: results of an Australian prospective multicenter study. J Nucl Med. 2018;59(1):82–8.PubMedCrossRef Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, et al. The impact of 68Ga-PSMA PET/CT on management intent in prostate Cancer: results of an Australian prospective multicenter study. J Nucl Med. 2018;59(1):82–8.PubMedCrossRef
8.
go back to reference Triggiani L, Alongi F, Buglione M, Detti B, Santoni R, Bruni A, et al. Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study. Br J Cancer. 2017;116(12):1520–5.PubMedPubMedCentralCrossRef Triggiani L, Alongi F, Buglione M, Detti B, Santoni R, Bruni A, et al. Efficacy of stereotactic body radiotherapy in oligorecurrent and in oligoprogressive prostate cancer: new evidence from a multicentric study. Br J Cancer. 2017;116(12):1520–5.PubMedPubMedCentralCrossRef
9.
go back to reference Soldatov A, von Klot CAJ, Walacides D, Derlin T, Bengel FM, Ross TL, et al. Patterns of progression after 68Ga-PSMA-ligand PET/CT-guided radiation therapy for recurrent prostate Cancer. Int J Radiat Oncol Biol Phys. 2019;103(1):95–104.PubMedCrossRef Soldatov A, von Klot CAJ, Walacides D, Derlin T, Bengel FM, Ross TL, et al. Patterns of progression after 68Ga-PSMA-ligand PET/CT-guided radiation therapy for recurrent prostate Cancer. Int J Radiat Oncol Biol Phys. 2019;103(1):95–104.PubMedCrossRef
10.
go back to reference Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for Oligometastatic prostate Cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446–53.CrossRefPubMed Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for Oligometastatic prostate Cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446–53.CrossRefPubMed
11.
go back to reference Siva S, Bressel M, Murphy DG, Shaw M, Chander S, Violet J, et al. Stereotactic Abative body radiotherapy (SABR) for Oligometastatic prostate Cancer: a prospective clinical trial. Eur Urol. 2018;74(4):455–62.PubMedCrossRef Siva S, Bressel M, Murphy DG, Shaw M, Chander S, Violet J, et al. Stereotactic Abative body radiotherapy (SABR) for Oligometastatic prostate Cancer: a prospective clinical trial. Eur Urol. 2018;74(4):455–62.PubMedCrossRef
12.
go back to reference McCarthy M, Francis R, Tang C, Watts J, Campbell A. A multicenter prospective clinical trial of 68Gallium PSMA HBED-CC PET-CT restaging in biochemically relapsed prostate carcinoma: Oligometastatic rate and distribution compared with standard imaging. Int J Radiat Oncol Biol Phys. 2019;104(4):801–8.PubMedCrossRef McCarthy M, Francis R, Tang C, Watts J, Campbell A. A multicenter prospective clinical trial of 68Gallium PSMA HBED-CC PET-CT restaging in biochemically relapsed prostate carcinoma: Oligometastatic rate and distribution compared with standard imaging. Int J Radiat Oncol Biol Phys. 2019;104(4):801–8.PubMedCrossRef
13.
go back to reference Gillessen S, Attard G, Beer TM, Beltran H, Bossi A, Bristow R, et al. Management of Patients with advanced prostate Cancer: the report of the advanced prostate Cancer consensus conference APCCC 2017. Eur Urol. 2018;73(2):178–211.PubMedCrossRef Gillessen S, Attard G, Beer TM, Beltran H, Bossi A, Bristow R, et al. Management of Patients with advanced prostate Cancer: the report of the advanced prostate Cancer consensus conference APCCC 2017. Eur Urol. 2018;73(2):178–211.PubMedCrossRef
14.
go back to reference Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017;14(1):15–25.PubMedCrossRef Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017;14(1):15–25.PubMedCrossRef
15.
go back to reference Eder M, Schäfer M, Bauder-Wüst U, Hull WE, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23(4):688–97.PubMedCrossRef Eder M, Schäfer M, Bauder-Wüst U, Hull WE, Wängler C, Mier W, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem. 2012;23(4):688–97.PubMedCrossRef
16.
go back to reference Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. 68Ga-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44(6):1014–24.PubMedCrossRef Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. 68Ga-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44(6):1014–24.PubMedCrossRef
17.
go back to reference Baumann M, Hölscher T, Denham J. Fractionation in prostate cancer--is it time after all? Radiother Oncol. 2010;96(1):1–5.PubMedCrossRef Baumann M, Hölscher T, Denham J. Fractionation in prostate cancer--is it time after all? Radiother Oncol. 2010;96(1):1–5.PubMedCrossRef
18.
go back to reference Thompson IM, Valicenti RK, Albertsen P, Davis BJ, Goldenberg SL, Hahn C, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol. 2013;190(2):441–9.PubMedCrossRef Thompson IM, Valicenti RK, Albertsen P, Davis BJ, Goldenberg SL, Hahn C, et al. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline. J Urol. 2013;190(2):441–9.PubMedCrossRef
20.
go back to reference Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate Cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71(4):618–29.CrossRefPubMed Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate Cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71(4):618–29.CrossRefPubMed
21.
go back to reference Kroeze SGC, Henkenberens C, Schmidt-Hegemann NS, Vogel MME, Kirste S, Becker J, et al. Prostate-specific membrane antigen positron emission tomography-detected Oligorecurrent prostate Cancer treated with metastases-directed radiotherapy: role of addition and duration of androgen deprivation. Eur Urol Focus. [Epub ahead of print]. Kroeze SGC, Henkenberens C, Schmidt-Hegemann NS, Vogel MME, Kirste S, Becker J, et al. Prostate-specific membrane antigen positron emission tomography-detected Oligorecurrent prostate Cancer treated with metastases-directed radiotherapy: role of addition and duration of androgen deprivation. Eur Urol Focus. [Epub ahead of print].
22.
go back to reference Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44(8):1258–68.PubMedPubMedCentralCrossRef Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44(8):1258–68.PubMedPubMedCentralCrossRef
23.
go back to reference Lecouvet FE, Oprea-Lager DE, Liu Y, Ost P, Bidaut L, Collette L, et al. Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC imaging group. Lancet Oncol. 2018;19(10):e534–45.PubMedCrossRef Lecouvet FE, Oprea-Lager DE, Liu Y, Ost P, Bidaut L, Collette L, et al. Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC imaging group. Lancet Oncol. 2018;19(10):e534–45.PubMedCrossRef
24.
go back to reference Morgans AK, Stockler MR. Patient-reported outcomes in metastatic castration-sensitive prostate Cancer in the adjuvant setting. Eur Urol Focus. 2019;5(2):144–6.PubMedPubMedCentralCrossRef Morgans AK, Stockler MR. Patient-reported outcomes in metastatic castration-sensitive prostate Cancer in the adjuvant setting. Eur Urol Focus. 2019;5(2):144–6.PubMedPubMedCentralCrossRef
25.
go back to reference Kneebone A, Hruby G, Ainsworth H, Byrne K, Brown C, Guo L, et al. Stereotactic body radiotherapy for Oligometastatic prostate Cancer detected via prostate-specific membrane antigen positron emission tomography. Eur Urol Oncol. 2018;1(6):531–7.PubMedCrossRef Kneebone A, Hruby G, Ainsworth H, Byrne K, Brown C, Guo L, et al. Stereotactic body radiotherapy for Oligometastatic prostate Cancer detected via prostate-specific membrane antigen positron emission tomography. Eur Urol Oncol. 2018;1(6):531–7.PubMedCrossRef
26.
go back to reference Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353–66.PubMedPubMedCentralCrossRef Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353–66.PubMedPubMedCentralCrossRef
28.
go back to reference Nuhn P, De Bono JS, Fizazi K, Freedland SJ, Grilli M, Kantoff PW, et al. Update on systemic prostate Cancer therapies: Management of Metastatic Castration-resistant Prostate Cancer in the era of precision oncology. Eur Urol. 2019;75(1):88–99.PubMedCrossRef Nuhn P, De Bono JS, Fizazi K, Freedland SJ, Grilli M, Kantoff PW, et al. Update on systemic prostate Cancer therapies: Management of Metastatic Castration-resistant Prostate Cancer in the era of precision oncology. Eur Urol. 2019;75(1):88–99.PubMedCrossRef
29.
go back to reference Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate Cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080–7.PubMedPubMedCentralCrossRef Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate Cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018;36(11):1080–7.PubMedPubMedCentralCrossRef
30.
go back to reference Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019;381(2):121–31.PubMedCrossRef Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med. 2019;381(2):121–31.PubMedCrossRef
31.
go back to reference Pompe RS, Tilki D, Preisser F, Leyh-Bannurah SR, Bandini M, Marchioni M, et al. Survival benefit of local versus no local treatment for metastatic prostate cancer-impact of baseline PSA and metastatic substages. Prostate. 2018;78(10):753–7.PubMedCrossRef Pompe RS, Tilki D, Preisser F, Leyh-Bannurah SR, Bandini M, Marchioni M, et al. Survival benefit of local versus no local treatment for metastatic prostate cancer-impact of baseline PSA and metastatic substages. Prostate. 2018;78(10):753–7.PubMedCrossRef
32.
go back to reference Berghen C, Joniau S, Ost P, Everaets W, Decaestecker K, Haustermanns K, Devos G, et al. Progression-directed Therapy for Oligoprogression in Castration-refractory Prostata Cancer. Eur Eurol Oncol. 2019; [Epub ahead of print]. Berghen C, Joniau S, Ost P, Everaets W, Decaestecker K, Haustermanns K, Devos G, et al. Progression-directed Therapy for Oligoprogression in Castration-refractory Prostata Cancer. Eur Eurol Oncol. 2019; [Epub ahead of print].
33.
go back to reference D'Angelillo RM, Francolini G, Ingrosso G, Ravo V, Triggiani L, et al. Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: a position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO). Crit Rev Oncol Hematol. 2019;138:24–8.PubMedCrossRef D'Angelillo RM, Francolini G, Ingrosso G, Ravo V, Triggiani L, et al. Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: a position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO). Crit Rev Oncol Hematol. 2019;138:24–8.PubMedCrossRef
Metadata
Title
Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy
Authors
Ann-Kathrin Oehus
Stephanie G. C. Kroeze
Nina-Sophie Schmidt-Hegemann
Marco M. E. Vogel
Simon Kirste
Jessica Becker
Irene A. Burger
Thorsten Derlin
Peter Bartenstein
Matthias Eiber
Michael Mix
Christian la Fougère
Claus Belka
Stephanie E. Combs
Anca-Ligia Grosu
Arndt-Christian Müller
Matthias Guckenberger
Hans Christiansen
Christoph Henkenberens
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-06883-5

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