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European Journal of Nuclear Medicine and Molecular Imaging

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01-01-2020 | Prostate Cancer | Original Article

⁶⁸Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer

Authors: Daniela A. Ferraro, Urs J. Muehlematter, Helena I. Garcia Schüler, Niels J. Rupp, Martin Huellner, Michael Messerli, Jan Hendrik Rüschoff, Edwin E. G. W. ter Voert, Thomas Hermanns, Irene A. Burger

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

Abstract

Introduction

Radical prostatectomy with extended pelvic lymph node dissection (ePLND) is a curative treatment option for patients with clinically significant localised prostate cancer. The decision to perform an ePLND can be challenging because the overall incidence of lymph node metastasis is relatively low and ePLND is not free of complications. Using current clinical nomograms to identify patients with nodal involvement, approximately 75–85% of ePLNDs performed are negative. The aim of this study was to assess the added value of ⁶⁸Ga-PSMA-11 PET in predicting lymph node metastasis in men with intermediate- or high-risk prostate cancer.

Methods

⁶⁸Ga-PSMA-11 PET scans of 60 patients undergoing radical prostatectomy with ePLND were reviewed for qualitative (visual) assessment of suspicious nodes and assessment of quantitative parameters of the primary tumour in the prostate (SUV_max, total activity (PSMA_total) and PSMA positive volume (PSMA_vol)). Ability of quantitative PET parameters to predict nodal metastasis was assessed with receiver operating characteristics (ROC) analysis. A multivariable logistic regression model combining PSA, Gleason score, visual nodal status on PET and primary tumour PSMA_total was built. Net benefit at each risk threshold was compared with five nomograms: MSKCC nomogram, Yale formula, Roach formula, Winter nomogram and Partin tables (2016).

Results

Overall, pathology of ePLND specimens revealed 31 pelvic metastatic lymph nodes in 12 patients. ⁶⁸Ga-PSMA-11 PET visual analysis correctly detected suspicious nodes in 7 patients, yielding a sensitivity of 58% and a specificity of 98%. The area under the ROC curve for primary tumour SUV_max was 0.70, for PSMA_total 0.76 and for PSMA_vol 0.75. The optimal cut-off for nodal involvement was PSMA_total > 49.1. The PET model including PSA, Gleason score and quantitative PET parameters had a persistently higher net benefit compared with all clinical nomograms.

Conclusion

Our model combining PSA, Gleason score and visual lymph node analysis on ⁶⁸Ga-PSMA-11 PET with PSMA_total of the primary tumour showed a tendency to improve patient selection for ePLND over the currently used clinical nomograms. Although this result has to be validated, ⁶⁸Ga-PSMA-11 PET showed the potential to reduce unnecessary surgical procedures in patients with intermediate- or high-risk prostate cancer.

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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;71:618–29. https://doi.org/10.1016/j.eururo.2016.08.003.CrossRefPubMed

Ploussard G, Briganti A, de la Taille A, Haese A, Heidenreich A, Menon M, et al. Pelvic lymph node dissection during robot-assisted radical prostatectomy: efficacy, limitations, and complications-a systematic review of the literature. Eur Urol. 2014;65:7–16. https://doi.org/10.1016/j.eururo.2013.03.057.CrossRefPubMed

Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN, Yuan CY, Briers E, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol. 2017;72:84–109. https://doi.org/10.1016/j.eururo.2016.12.003.CrossRefPubMed

Bernstein AN, Shoag JE, Golan R, Halpern JA, Schaeffer EM, Hsu WC, et al. Contemporary incidence and outcomes of prostate cancer lymph node metastases. J Urol. 2018;199:1510–7. https://doi.org/10.1016/j.juro.2017.12.048.CrossRefPubMed

Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol. 2012;61:1132–8. https://doi.org/10.1016/j.eururo.2011.11.008.CrossRefPubMed

Hovels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008;63:387–95. https://doi.org/10.1016/j.crad.2007.05.022.CrossRefPubMed

Evangelista L, Guttilla A, Zattoni F, Muzzio PC, Zattoni F. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol. 2013;63:1040–8. https://doi.org/10.1016/j.eururo.2012.09.039.CrossRefPubMed

von Eyben FE, Kairemo K. Meta-analysis of (11)C-choline and (18)F-choline PET/CT for management of patients with prostate cancer. Nucl Med Commun. 2014;35:221–30. https://doi.org/10.1097/MNM.0000000000000040.CrossRef

Nguyen DP, Huber PM, Metzger TA, Genitsch V, Schudel HH, Thalmann GN. A specific mapping study using fluorescence sentinel lymph node detection in patients with intermediate- and high-risk prostate cancer undergoing extended pelvic lymph node dissection. Eur Urol. 2016;70:734–7. https://doi.org/10.1016/j.eururo.2016.01.034.CrossRefPubMed

10.

Chun FK, Karakiewicz PI, Briganti A, Gallina A, Kattan MW, Montorsi F, et al. Prostate cancer nomograms: an update. Eur Urol. 2006;50:914–26; discussion 26. https://doi.org/10.1016/j.eururo.2006.07.042.CrossRefPubMed

11.

Bianchi L, Gandaglia G, Fossati N, Suardi N, Moschini M, Cucchiara V, et al. Pelvic lymph node dissection in prostate cancer: indications, extent and tailored approaches. Urologia. 2017;84:9–19. https://doi.org/10.5301/uro.5000139.CrossRefPubMed

12.

Mohler JL, Armstrong AJ, Bahnson RR, D'Amico AV, Davis BJ, Eastham JA, et al. Prostate Cancer, version 1.2016. J Natl Compr Cancer Netw. 2016;14:19–30.CrossRef

13.

Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol. 2012;61:480–7. https://doi.org/10.1016/j.eururo.2011.10.044.CrossRefPubMed

14.

Banapour P, Schumacher A, Lin JC, Finley DS. Radical prostatectomy and pelvic lymph node dissection in Kaiser Permanente Southern California: 15-year experience. Perm J. 2019;23. https://doi.org/10.7812/TPP/17-233.

15.

Roscigno M, Nicolai M, La Croce G, Pellucchi F, Scarcello M, Sacca A, et al. Difference in frequency and distribution of nodal metastases between intermediate and high risk prostate cancer patients: results of a superextended pelvic lymph node dissection. Front Surg. 2018;5:52. https://doi.org/10.3389/fsurg.2018.00052.CrossRefPubMedPubMedCentral

16.

Hope TA, Goodman JZ, Allen IE, Calais J, Fendler WP, Carroll PR. Meta-analysis of (68)Ga-PSMA-11 PET accuracy for the detection of prostate Cancer validated by histopathology. J Nucl Med. 2018. https://doi.org/10.2967/jnumed.118.219501.CrossRefPubMed

17.

Thalgott M, Duwel C, Rauscher I, Heck MM, Haller B, Gafita A, et al. One-stop shop whole-body (68)Ga-PSMA-11 PET/MRI compared to clinical Nomograms for preoperative T- and N-Staging of High-Risk Prostate Cancer. J Nucl Med. 2018. https://doi.org/10.2967/jnumed.117.207696.CrossRefPubMed

18.

Uprimny C, Kroiss AS, Decristoforo C, Fritz J, von Guggenberg E, Kendler D, et al. (68)Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–9. https://doi.org/10.1007/s00259-017-3631-6.CrossRefPubMed

19.

von Klot CJ, Merseburger AS, Boker A, Schmuck S, Ross TL, Bengel FM, et al. (68)Ga-PSMA PET/CT imaging predicting Intraprostatic tumor extent, extracapsular extension and seminal vesicle invasion prior to radical prostatectomy in patients with prostate cancer. Nucl Med Mol Imaging. 2017;51:314–22. https://doi.org/10.1007/s13139-017-0476-7.CrossRef

20.

Ross JS, Sheehan CE, Fisher HA, Kaufman RP Jr, Kaur P, Gray K, et al. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003;9:6357–62.PubMed

21.

Bravaccini S, Puccetti M, Bocchini M, Ravaioli S, Celli M, Scarpi E, et al. PSMA expression: a potential ally for the pathologist in prostate cancer diagnosis. Sci Rep. 2018;8:4254. https://doi.org/10.1038/s41598-018-22594-1.CrossRefPubMedPubMedCentral

22.

Uslu-Besli L, Asa S, Bakir B, Sayman H, Sager S, Khosroshahi BR, et al. Correlation of SUVmax and ADC values detected by Ga-68 PSMA PET/MRI in primary prostate lesions and their significance in lymph node metastasis. Eur J Nucl Med Mol Imaging. 2018;45:S20-S.CrossRef

23.

Hueting TA, Cornel EB, Somford DM, Jansen H, van Basten J-PA, Pleijhuis RG, et al. External validation of models predicting the probability of lymph node involvement in prostate cancer patients. Eur Urol Oncol. 2018.

24.

Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol. 2003;170:1798–803. https://doi.org/10.1097/01.ju.0000091805.98960.13.CrossRefPubMed

25.

Yu JB, Makarov DV, Gross C. A new formula for prostate cancer lymph node risk. Int J Radiat Oncol Biol Phys. 2011;80:69–75. https://doi.org/10.1016/j.ijrobp.2010.01.068.CrossRefPubMed

26.

Roach M 3rd, Marquez C, Yuo HS, Narayan P, Coleman L, Nseyo UO, et al. Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 1994;28:33–7.CrossRefPubMed

27.

Winter A, Kneib T, Rohde M, Henke RP, Wawroschek F. First nomogram predicting the probability of lymph node involvement in prostate cancer patients undergoing radioisotope guided sentinel lymph node dissection. Urol Int. 2015;95:422–8. https://doi.org/10.1159/000431182.CrossRefPubMed

28.

Tosoian JJ, Chappidi M, Feng Z, Humphreys EB, Han M, Pavlovich CP, et al. Prediction of pathological stage based on clinical stage, serum prostate-specific antigen, and biopsy Gleason score: Partin Tables in the contemporary era. BJU Int. 2017;119:676–83. https://doi.org/10.1111/bju.13573.CrossRefPubMed

29.

D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRefPubMed

30.

Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, et al. Ga-68-PSMA PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017;44:1014–24. https://doi.org/10.1007/s00259-017-3670-z.CrossRefPubMed

31.

Kranzbuhler B, Nagel H, Becker AS, Muller J, Huellner M, Stolzmann P, et al. Clinical performance of (68)Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy. Eur J Nucl Med Mol Imaging. 2018;45:20–30. https://doi.org/10.1007/s00259-017-3850-x.CrossRefPubMed

32.

Hofman MS, Hicks RJ, Maurer T, Eiber M. Prostate-specific membrane antigen PET: clinical utility in prostate cancer, normal patterns, pearls, and pitfalls. Radiographics. 2018;38:200–17. https://doi.org/10.1148/rg.2018170108.CrossRefPubMed

33.

Fendler WP, Calais J, Allen-Auerbach M, Bluemel C, Eberhardt N, Emmett L, et al. (68)Ga-PSMA-11 PET/CT interobserver agreement for prostate cancer assessments: an international multicenter prospective study. J Nucl Med. 2017;58:1617–23. https://doi.org/10.2967/jnumed.117.190827.CrossRefPubMed

34.

Feicke A, Baumgartner M, Talimi S, Schmid DM, Seifert HH, Muntener M, et al. Robotic-assisted laparoscopic extended pelvic lymph node dissection for prostate cancer: surgical technique and experience with the first 99 cases. Eur Urol. 2009;55:876–83. https://doi.org/10.1016/j.eururo.2008.12.006.CrossRefPubMed

35.

Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology. 2010;21:128–38. https://doi.org/10.1097/EDE.0b013e3181c30fb2.CrossRefPubMedPubMedCentral

36.

Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Mak. 2006;26:565–74. https://doi.org/10.1177/0272989X06295361.CrossRef

37.

Kerr KF, Brown MD, Zhu K, Janes H. Assessing the clinical impact of risk prediction models with decision curves: guidance for correct interpretation and appropriate use. J Clin Oncol. 2016;34:2534–40. https://doi.org/10.1200/JCO.2015.65.5654.CrossRefPubMedPubMedCentral

38.

Van Calster B, Wynants L, Verbeek JFM, Verbakel JY, Christodoulou E, Vickers AJ, et al. Reporting and interpreting decision curve analysis: a guide for investigators. Eur Urol. 2018;74:796–804. https://doi.org/10.1016/j.eururo.2018.08.038.CrossRefPubMedPubMedCentral

39.

Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol. 2016;40:244–52. https://doi.org/10.1097/PAS.0000000000000530.CrossRefPubMed

40.

Berglund E, Maaskola J, Schultz N, Friedrich S, Marklund M, Bergenstrahle J, et al. Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity. Nat Commun. 2018;9:2419. https://doi.org/10.1038/s41467-018-04724-5.CrossRefPubMedPubMedCentral

41.

Tu SM, Lin SH, Logothetis CJ. Stem-cell origin of metastasis and heterogeneity in solid tumours. Lancet Oncol. 2002;3:508–13.CrossRefPubMed

42.

Hupe MC, Philippi C, Roth D, Kumpers C, Ribbat-Idel J, Becker F, et al. Expression of Prostate-Specific Membrane Antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol. 2018;8:623. https://doi.org/10.3389/fonc.2018.00623.CrossRefPubMedPubMedCentral

43.

Blanchard P, Faivre L, Lesaunier F, Salem N, Mesgouez-Nebout N, Deniau-Alexandre E, et al. Outcome according to elective pelvic radiation therapy in patients with high-risk localized prostate cancer: a secondary analysis of the GETUG 12 phase 3 randomized trial. Int J Radiat Oncol Biol Phys. 2016;94:85–92. https://doi.org/10.1016/j.ijrobp.2015.09.020.CrossRefPubMed

44.

Seaward SA, Weinberg V, Lewis P, Leigh B, Phillips TL, Roach M 3rd. Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 1998;42:1055–62.CrossRefPubMed

45.

Aizer AA, Yu JB, McKeon AM, Decker RH, Colberg JW, Peschel RE. Whole pelvic radiotherapy versus prostate only radiotherapy in the management of locally advanced or aggressive prostate adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009;75:1344–9. https://doi.org/10.1016/j.ijrobp.2008.12.082.CrossRefPubMed

46.

Roach M, Moughan J, Lawton CAF, Dicker AP, Zeitzer KL, Gore EM, et al. Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial. Lancet Oncol. 2018;19:1504–15. https://doi.org/10.1016/S1470-2045(18)30528-X.CrossRefPubMedPubMedCentral

47.

Daoud MA, Aboelnaga EM, Alashry MS, Fathy S, Aletreby MA. Clinical outcome and toxicity evaluation of simultaneous integrated boost pelvic IMRT/VMAT at different dose levels combined with androgen deprivation therapy in prostate cancer patients. Onco Targets Ther. 2017;10:4981–8. https://doi.org/10.2147/OTT.S141224.CrossRefPubMedPubMedCentral

48.

Ishii K, Ogino R, Hosokawa Y, Fujioka C, Okada W, Nakahara R, et al. Comparison of dosimetric parameters and acute toxicity after whole-pelvic vs prostate-only volumetric-modulated arc therapy with daily image guidance for prostate cancer. Br J Radiol. 2016;89:20150930. https://doi.org/10.1259/bjr.20150930.CrossRefPubMedPubMedCentral

49.

White KL, Varrassi E, Routledge JA, Barraclough LH, Livsey JE, McLaughlin J, et al. Does the use of volumetric modulated arc therapy reduce gastrointestinal symptoms after pelvic radiotherapy? Clin Oncol (R Coll Radiol). 2018;30:e22–e8. https://doi.org/10.1016/j.clon.2017.10.016.CrossRef

50.

Choo MS, Kim M, Ku JH, Kwak C, Kim HH, Jeong CW. Extended versus standard pelvic lymph node dissection in radical prostatectomy on oncological and functional outcomes: a systematic review and meta-analysis. Ann Surg Oncol. 2017;24:2047–54. https://doi.org/10.1245/s10434-017-5822-6.CrossRefPubMed

Title: 68Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer
Authors: Daniela A. Ferraro
Urs J. Muehlematter
Helena I. Garcia Schüler
Niels J. Rupp
Martin Huellner
Michael Messerli
Jan Hendrik Rüschoff
Edwin E. G. W. ter Voert
Thomas Hermanns
Irene A. Burger
Publication date: 01-01-2020
Publisher: Springer Berlin Heidelberg
Keywords: Prostate Cancer
Computed Tomography
Metastasis
Computed Tomography
Prostate Cancer
Positron Emission Tomography
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/s00259-019-04511-4

At a glance: The STEP trials

Springer Medicine

⁶⁸Ga-PSMA-11 PET has the potential to improve patient selection for extended pelvic lymph node dissection in intermediate to high-risk prostate cancer

Abstract

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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