Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2020

01-01-2020 | Prostate Cancer | Original Article

Prediction nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for prostate cancer

Authors: Francesco Ceci, Lorenzo Bianchi, Marco Borghesi, Giulia Polverari, Andrea Farolfi, Alberto Briganti, Riccardo Schiavina, Eugenio Brunocilla, Paolo Castellucci, Stefano Fanti

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2020

Login to get access

Abstract

Objective

The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure.

Materials and methods

Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced-stage PCa before second-line systemic therapies: group 4).
First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram’s derived cutoff. Decision curve analysis (DCA) was implemented to quantify nomogram’s clinical benefit.

Results

68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cutoff value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%.

Conclusions

This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cutoff in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kattan MW, Wheeler TM, Scardino PT. Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol. 1999;17(5):1499–507.CrossRef Kattan MW, Wheeler TM, Scardino PT. Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol. 1999;17(5):1499–507.CrossRef
2.
go back to reference Ost P, Bossi A, Decaestecker K, et al. Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2015;67(5):852–63.CrossRef Ost P, Bossi A, Decaestecker K, et al. Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature. Eur Urol. 2015;67(5):852–63.CrossRef
3.
go back to reference Schiavina R, Bianchi L, Borghesi M, Sabbatini R, Brunocilla E. Toward the future of the functional imaging of advanced prostate cancer. Eur Urol Focus. 2017;3(2–3):240–2.CrossRef Schiavina R, Bianchi L, Borghesi M, Sabbatini R, Brunocilla E. Toward the future of the functional imaging of advanced prostate cancer. Eur Urol Focus. 2017;3(2–3):240–2.CrossRef
4.
go back to reference Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56(8):1185–90.CrossRef Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56(8):1185–90.CrossRef
5.
go back to reference Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):11–20.CrossRef Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):11–20.CrossRef
6.
go back to reference Schwenck J, Rempp H, Reischl G, Kruck S, Stenzl A, Nikolaou K, et al. Comparison of (68)Ga-labelled PSMA-11 and (11)C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging. 2017;44(1):92–101.CrossRef Schwenck J, Rempp H, Reischl G, Kruck S, Stenzl A, Nikolaou K, et al. Comparison of (68)Ga-labelled PSMA-11 and (11)C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging. 2017;44(1):92–101.CrossRef
7.
go back to reference Calais J, Fendler WP, Herrmann K, Eiber M, Ceci F. Comparison of (68)Ga-PSMA-11 and (18)F-fluciclovine PET/CT in a case series of 10 patients with prostate cancer recurrence. J Nucl Med. 2018;59(5):789–94.CrossRef Calais J, Fendler WP, Herrmann K, Eiber M, Ceci F. Comparison of (68)Ga-PSMA-11 and (18)F-fluciclovine PET/CT in a case series of 10 patients with prostate cancer recurrence. J Nucl Med. 2018;59(5):789–94.CrossRef
8.
go back to reference Calais J, Ceci F, Eiber M, Hope TA, Hofman M, Rischpler C, et al. 18F-Fluciclovine and 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence after prostatectomy at PSA levels of ≤ 2.0ng/ml: a prospective, single-center, single-arm, comparative imaging trial. Lancet Oncol. 2019. https://doi.org/10.1016/S1470-2045(19)30415-2.CrossRef Calais J, Ceci F, Eiber M, Hope TA, Hofman M, Rischpler C, et al. 18F-Fluciclovine and 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence after prostatectomy at PSA levels of ≤ 2.0ng/ml: a prospective, single-center, single-arm, comparative imaging trial. Lancet Oncol. 2019. https://​doi.​org/​10.​1016/​S1470-2045(19)30415-2.CrossRef
9.
go back to reference Mottet N, van den Bergh RCN, Briers E, Cornford P, De Santis M, Fanti S, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. EAU Guidelines. Edn. presented at the EAU Annual Congress Barcelona 2019. ISBN 978-94-92671-04-2. Mottet N, van den Bergh RCN, Briers E, Cornford P, De Santis M, Fanti S, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. EAU Guidelines. Edn. presented at the EAU Annual Congress Barcelona 2019. ISBN 978-94-92671-04-2.
10.
go back to reference Perera M, Papa N, Roberts M, et al. Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a systematic review and meta-analysis. Eur Urol 2019. Perera M, Papa N, Roberts M, et al. Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a systematic review and meta-analysis. Eur Urol 2019.
11.
go back to reference Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56(5):668–74.CrossRef Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med. 2015;56(5):668–74.CrossRef
12.
go back to reference Ceci F, Castellucci P, Graziani T, Farolfi A, Fonti C, Lodi F, et al. (68)Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy. Eur J Nucl Med Mol Imaging. 2019;46(1):31–9.CrossRef Ceci F, Castellucci P, Graziani T, Farolfi A, Fonti C, Lodi F, et al. (68)Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy. Eur J Nucl Med Mol Imaging. 2019;46(1):31–9.CrossRef
13.
go back to reference Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(2):197–209.CrossRef Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42(2):197–209.CrossRef
14.
go back to reference Caroli P, Sandler I, Matteucci F, De Giorgi U, Uccelli L, Celli M, et al. (68)Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients. Eur J Nucl Med Mol Imaging. 2018;45(12):2035–44.CrossRef Caroli P, Sandler I, Matteucci F, De Giorgi U, Uccelli L, Celli M, et al. (68)Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients. Eur J Nucl Med Mol Imaging. 2018;45(12):2035–44.CrossRef
15.
go back to reference Abramowitz MC, Li T, Buyyounouski MK, Ross E, Uzzo RG, Pollack A, et al. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer. Cancer. 2008;112(1):55–60.CrossRef Abramowitz MC, Li T, Buyyounouski MK, Ross E, Uzzo RG, Pollack A, et al. The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer. Cancer. 2008;112(1):55–60.CrossRef
16.
go back to reference Bianchi L, Nini A, Bianchi M, et al. The role of prostate-specific antigen persistence after radical prostatectomy for the prediction of clinical progression and cancer-specific mortality in node-positive prostate cancer patients. Eur Urol. 2016;69(6):1142–8.CrossRef Bianchi L, Nini A, Bianchi M, et al. The role of prostate-specific antigen persistence after radical prostatectomy for the prediction of clinical progression and cancer-specific mortality in node-positive prostate cancer patients. Eur Urol. 2016;69(6):1142–8.CrossRef
17.
go back to reference Wiegel T, Bartkowiak D, Bottke D, et al. Prostate-specific antigen persistence after radical prostatectomy as a predictive factor of clinical relapse-free survival and overall survival: 10-year data of the ARO 96-02 trial. Int J Radiat Oncol Biol Phys. 2015;91(2):288–94.CrossRef Wiegel T, Bartkowiak D, Bottke D, et al. Prostate-specific antigen persistence after radical prostatectomy as a predictive factor of clinical relapse-free survival and overall survival: 10-year data of the ARO 96-02 trial. Int J Radiat Oncol Biol Phys. 2015;91(2):288–94.CrossRef
18.
go back to reference Van den Broeck T, van den Bergh RCN, Arfi N, et al. Prognostic value of biochemical recurrence following treatment with curative intent for prostate cancer: a systematic review. Eur Urol 2018. Van den Broeck T, van den Bergh RCN, Arfi N, et al. Prognostic value of biochemical recurrence following treatment with curative intent for prostate cancer: a systematic review. Eur Urol 2018.
19.
go back to reference Gillessen S, Omlin A, Attard G, et al. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 2016. Gillessen S, Omlin A, Attard G, et al. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO 2016.
20.
go back to reference Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals (Basel). 2014;7(7):779–96.CrossRef Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals (Basel). 2014;7(7):779–96.CrossRef
21.
go back to reference Farolfi A, Ceci F, Castellucci P, Graziani T, Siepe G, Lambertini A, et al. (68)Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy. Eur J Nucl Med Mol Imaging. 2019;46(1):11–9.CrossRef Farolfi A, Ceci F, Castellucci P, Graziani T, Siepe G, Lambertini A, et al. (68)Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy. Eur J Nucl Med Mol Imaging. 2019;46(1):11–9.CrossRef
22.
go back to reference Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. (68)Ga-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.CrossRef Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. (68)Ga-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.CrossRef
23.
go back to reference Fanti S, Minozzi S, Morigi JJ, Giesel F, Ceci F, Uprimny C, et al. Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions. Eur J Nucl Med Mol Imaging. 2017;44(10):1622–35.CrossRef Fanti S, Minozzi S, Morigi JJ, Giesel F, Ceci F, Uprimny C, et al. Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions. Eur J Nucl Med Mol Imaging. 2017;44(10):1622–35.CrossRef
24.
go back to reference Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Medical decision making: an international journal of the Society for Medical Decision Making. 2006;26(6):565–74.CrossRef Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Medical decision making: an international journal of the Society for Medical Decision Making. 2006;26(6):565–74.CrossRef
26.
go back to reference 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 2018. 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 2018.
27.
go back to reference Maurer T, Robu S, Schottelius M, et al. (99m)Technetium-based prostate-specific membrane antigen-radioguided surgery in recurrent prostate cancer. Eur Urol. 2019;75(4):659–66.CrossRef Maurer T, Robu S, Schottelius M, et al. (99m)Technetium-based prostate-specific membrane antigen-radioguided surgery in recurrent prostate cancer. Eur Urol. 2019;75(4):659–66.CrossRef
28.
go back to reference Pereira Mestre R, Treglia G, Ferrari M, Pascale M, Mazzara C, Azinwi NC, et al. Correlation between PSA kinetics and PSMA-PET in prostate cancer restaging: a meta-analysis. Eur J Clin Investig. 2019;49(3):e13063.CrossRef Pereira Mestre R, Treglia G, Ferrari M, Pascale M, Mazzara C, Azinwi NC, et al. Correlation between PSA kinetics and PSMA-PET in prostate cancer restaging: a meta-analysis. Eur J Clin Investig. 2019;49(3):e13063.CrossRef
29.
go back to reference Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. (68)Ga-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.CrossRef Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. (68)Ga-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.CrossRef
30.
go back to reference Rauscher I, Duwel C, Haller B, et al. Efficacy, predictive factors, and prediction nomograms for (68)Ga-labeled prostate-specific membrane antigen-ligand positron-emission tomography/computed tomography in early biochemical recurrent prostate cancer after radical prostatectomy. Eur Urol. 2018;73(5):656–61.CrossRef Rauscher I, Duwel C, Haller B, et al. Efficacy, predictive factors, and prediction nomograms for (68)Ga-labeled prostate-specific membrane antigen-ligand positron-emission tomography/computed tomography in early biochemical recurrent prostate cancer after radical prostatectomy. Eur Urol. 2018;73(5):656–61.CrossRef
31.
go back to reference Afshar-Oromieh A, Debus N, Uhrig M, Hope TA, Evans MJ, Holland-Letz T, et al. Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45(12):2045–54.CrossRef Afshar-Oromieh A, Debus N, Uhrig M, Hope TA, Evans MJ, Holland-Letz T, et al. Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45(12):2045–54.CrossRef
32.
go back to reference Emmett LM, Yin C, Crumbaker M, Hruby G, Kneebone A, Epstein R, et al. Rapid modulation of PSMA expression by androgen deprivation: serial (68)Ga-PSMA-11 PET in men with hormone sensitive and castrate resistant prostate cancer commencing androgen blockade. J Nucl Med 2018. Emmett LM, Yin C, Crumbaker M, Hruby G, Kneebone A, Epstein R, et al. Rapid modulation of PSMA expression by androgen deprivation: serial (68)Ga-PSMA-11 PET in men with hormone sensitive and castrate resistant prostate cancer commencing androgen blockade. J Nucl Med 2018.
33.
go back to reference Ceci F, Schiavina R, Castellucci P, Brunocilla E, Fuccio C, Colletti PM, et al. 11C-choline PET/CT scan in patients with prostate cancer treated with intermittent ADT: a sequential PET/CT study. Clin Nucl Med. 2013;38(7):e279–82.CrossRef Ceci F, Schiavina R, Castellucci P, Brunocilla E, Fuccio C, Colletti PM, et al. 11C-choline PET/CT scan in patients with prostate cancer treated with intermittent ADT: a sequential PET/CT study. Clin Nucl Med. 2013;38(7):e279–82.CrossRef
34.
go back to reference Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5(1):66.CrossRef Meller B, Bremmer F, Sahlmann CO, Hijazi S, Bouter C, Trojan L, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5(1):66.CrossRef
Metadata
Title
Prediction nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for prostate cancer
Authors
Francesco Ceci
Lorenzo Bianchi
Marco Borghesi
Giulia Polverari
Andrea Farolfi
Alberto Briganti
Riccardo Schiavina
Eugenio Brunocilla
Paolo Castellucci
Stefano Fanti
Publication date
01-01-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04505-2

Other articles of this Issue 1/2020

European Journal of Nuclear Medicine and Molecular Imaging 1/2020 Go to the issue