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The effect of androgen deprivation therapy on 68Ga-PSMA tracer uptake in non-metastatic prostate cancer patients

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Abstract

Purpose

To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate-specific membrane antigen (PSMA) tracer uptake demonstrated in 68Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer (PC) patients.

Materials and methods

The clinical data of 108 PC patients who received neoadjuvant ADT were retrospectively analyzed. All patients had a baseline 68Ga-PSMA-PET/CT scan, and a second scan was delivered median of 2.9 months after the initiation of ADT. The maximum standardized uptake value (SUVmax) of primary tumor (SUVp) and metastatic lymph nodes (SUVln) as well as PSA response were assessed between pre- and post-ADT 68Ga-PSMA-PET/CT scans.

Results

There were significant decreases in posttreatment serum PSA, SUVp, and SUVln. A decrease in SUVp was seen in 91 patients (84%) with a median value of 66% (range, 5–100%), while 17 patients (16%) had no change in or an increase in PSMA tracer uptake with a median value of 24% (range, 0–198%). Patients with Gleason score (GS) of 7 had significantly higher metabolic response rates compared to other patients. The disease progression was significantly higher only in patients with GS > 7 disease compared to GS 7 disease. The PSA response to ADT was the lowest in patients with ISUP high-grade tumors. A total of 16 patients (15%) had progressive disease, and in 9 patients (8%), radiotherapy decisions were modified according to posttreatment 68Ga-PSMA-PET/CT scans.

Conclusions

The current study includes the largest number of patients analyzed to date and demonstrates that ADT causes a significant decrease in serum PSA values and SUVp and SUVln. The authors demonstrate that 68Ga-PSMA-PET/CT may be used as a quantitative imaging modality after neoadjuvant ADT in hormone-naïve non-metastatic PC patients.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. https://doi.org/10.3322/caac.21442.

    Article  PubMed  Google Scholar 

  2. Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010;11:1066–73. https://doi.org/10.1016/s1470-2045(10)70223-0.

    Article  CAS  PubMed  Google Scholar 

  3. Lawton CA, Winter K, Murray K, Machtay M, Mesic JB, Hanks GE, et al. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001;49:937–46.

    Article  CAS  PubMed  Google Scholar 

  4. Forman JD, Kumar R, Haas G, Montie J, Porter AT, Mesina CF. Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation. Cancer Investig. 1995;13:8–15.

    Article  CAS  Google Scholar 

  5. Onal C, Topkan E, Efe E, Yavuz M, Arslan G, Yavuz A. The effect of concurrent androgen deprivation and 3D conformal radiotherapy on prostate volume and clinical organ doses during treatment for prostate cancer. Br J Radiol. 2009;82:1019–26. https://doi.org/10.1259/bjr/65939531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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;71:630–42. https://doi.org/10.1016/j.eururo.2016.08.002.

    Article  PubMed  Google Scholar 

  7. Kwak C, Jeong SJ, Park MS, Lee E, Lee SE. Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer. J Urol. 2002;168:995–1000. https://doi.org/10.1097/01.ju.0000024925.67014.21.

    Article  PubMed  Google Scholar 

  8. Fitzpatrick JM, Banu E, Oudard S. Prostate-specific antigen kinetics in localized and advanced prostate cancer. BJU Int. 2009;103:578–87. https://doi.org/10.1111/j.1464-410X.2009.08345.x.

    Article  PubMed  Google Scholar 

  9. Kim AY, Kim CK, Park SY, Park BK. Diffusion-weighted imaging to evaluate for changes from androgen deprivation therapy in prostate cancer. AJR Am J Roentgenol. 2014;203:W645–50. https://doi.org/10.2214/ajr.13.12277.

    Article  PubMed  Google Scholar 

  10. Hotker AM, Mazaheri Y, Zheng J, Moskowitz CS, Berkowitz J, Lantos JE, et al. Prostate cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI. Eur Radiol. 2015;25:2665–72. https://doi.org/10.1007/s00330-015-3688-1.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52:637–40.

    Article  CAS  PubMed  Google Scholar 

  12. Giovacchini G, Picchio M, Coradeschi E, Scattoni V, Bettinardi V, Cozzarini C, et al. [(11)C]choline uptake with PET/CT for the initial diagnosis of prostate cancer: relation to PSA levels, tumour stage and anti-androgenic therapy. Eur J Nucl Med Mol Imaging. 2008;35:1065–73. https://doi.org/10.1007/s00259-008-0716-2.

    Article  CAS  PubMed  Google Scholar 

  13. 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;5:66. https://doi.org/10.1186/s13550-015-0145-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hope TA, Truillet C, Ehman EC, Afshar-Oromieh A, Aggarwal R, Ryan CJ, et al. 68Ga-PSMA-11 PET imaging of response to androgen receptor inhibition: first human experience. J Nucl Med. 2017;58:81–4. https://doi.org/10.2967/jnumed.116.181800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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;42:197–209. https://doi.org/10.1007/s00259-014-2949-6.

    Article  CAS  PubMed  Google Scholar 

  16. Afshar-Oromieh A, Holland-Letz T, Giesel FL, Kratochwil C, Mier W, Haufe S, et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44:1258–68. https://doi.org/10.1007/s00259-017-3711-7.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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;45:2045–54. https://doi.org/10.1007/s00259-018-4079-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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. https://doi.org/10.2967/jnumed.118.223099.

    Article  PubMed  Google Scholar 

  19. D'Amico AV, Whittington R, Schultz D, Malkowicz SB, Tomaszewski JE, Wein A. Outcome based staging for clinically localized adenocarcinoma of the prostate. J Urol. 1997;158:1422–6.

    Article  CAS  PubMed  Google Scholar 

  20. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(Suppl 1):122S–50S. https://doi.org/10.2967/jnumed.108.057307.

    Article  CAS  PubMed  Google Scholar 

  21. Fuccio C, Schiavina R, Castellucci P, Rubello D, Martorana G, Celli M, et al. Androgen deprivation therapy influences the uptake of 11C-choline in patients with recurrent prostate cancer: the preliminary results of a sequential PET/CT study. Eur J Nucl Med Mol Imaging. 2011;38:1985–9. https://doi.org/10.1007/s00259-011-1867-0.

    Article  CAS  PubMed  Google Scholar 

  22. Chondrogiannis S, Marzola MC, Ferretti A, Grassetto G, Maffione AM, Rampin L, et al. Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy? Eur J Nucl Med Mol Imaging. 2014;41:1293–300. https://doi.org/10.1007/s00259-014-2720-z.

    Article  CAS  PubMed  Google Scholar 

  23. Bansal A, Singhi SC, Jayashree M. Penicillin and gentamicin therapy vs amoxicillin/clavulanate in severe hypoxemic pneumonia. Indian J Pediatr. 2006;73:305–9.

    Article  PubMed  Google Scholar 

  24. Minner S, Wittmer C, Graefen M, Salomon G, Steuber T, Haese A, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 2011;71:281–8. https://doi.org/10.1002/pros.21241.

    Article  PubMed  Google Scholar 

  25. Obek C, Doganca T, Demirci E, Ocak M, Kural AR, Yildirim A, et al. The accuracy of (68)Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer. Eur J Nucl Med Mol Imaging. 2017;44:1806–12. https://doi.org/10.1007/s00259-017-3752-y.

    Article  PubMed  Google Scholar 

  26. Evans MJ, Smith-Jones PM, Wongvipat J, Navarro V, Kim S, Bander NH, et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci U S A. 2011;108:9578–82. https://doi.org/10.1073/pnas.1106383108.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gupta M, Choudhury PS, Rawal S, Goel HC, Rao SA. Evaluation of RECIST, PERCIST, EORTC, and MDA criteria for assessing treatment response with Ga68-PSMA PET-CT in metastatic prostate cancer patient with biochemical progression: a comparative study. Nucl Med Mol Imaging. 2018;52:420–9. https://doi.org/10.1007/s13139-018-0548-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schmidkonz C, Cordes M, Schmidt D, Bauerle T, Goetz TI, Beck M, et al. (68)Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45:1862–72. https://doi.org/10.1007/s00259-018-4042-z.

    Article  PubMed  Google Scholar 

  29. Schmuck S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester HJ, et al. Initial experience with volumetric (68)Ga-PSMA I&T PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med. 2017;58:1962–8. https://doi.org/10.2967/jnumed.117.193581.

    Article  CAS  PubMed  Google Scholar 

  30. Koerber SA, Utzinger MT, Kratochwil C, Kesch C, Haefner MF, Katayama S, et al. (68)Ga-PSMA-11 PET/CT in newly diagnosed carcinoma of the prostate: correlation of intraprostatic PSMA uptake with several clinical parameters. J Nucl Med. 2017;58:1943, 8. https://doi.org/10.2967/jnumed.117.190314.

    Article  CAS  PubMed  Google Scholar 

  31. Bakht MK, Derecichei I, Li Y, Ferraiuolo RM, Dunning M, Oh SW, et al. Neuroendocrine differentiation of prostate cancer leads to PSMA suppression. Endocr Relat Cancer. 2018;26:131–46. https://doi.org/10.1530/ERC-18-0226.

    Article  PubMed  Google Scholar 

  32. Park SC, Rim JS, Choi HY, Kim CS, Hong SJ, Kim WJ, et al. Failing to achieve a nadir prostate-specific antigen after combined androgen blockade: predictive factors. Int J Urol. 2009;16:670–5. https://doi.org/10.1111/j.1442-2042.2009.02329.x.

    Article  CAS  PubMed  Google Scholar 

  33. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77. https://doi.org/10.1016/S0140-6736(15)01037-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60. https://doi.org/10.1056/NEJMoa1704174.

    Article  CAS  PubMed  Google Scholar 

  35. 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;36:1080–7. https://doi.org/10.1200/JCO.2017.75.3657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hara T, Bansal A, DeGrado TR. Effect of hypoxia on the uptake of [methyl-3H]choline, [1-14C] acetate and [18F]FDG in cultured prostate cancer cells. Nucl Med Biol. 2006;33:977–84. https://doi.org/10.1016/j.nucmedbio.2006.08.002.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Cem Onal.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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This article is part of the Topical Collection on Oncology – Genitourinary

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Onal, C., Guler, O.C., Torun, N. et al. The effect of androgen deprivation therapy on 68Ga-PSMA tracer uptake in non-metastatic prostate cancer patients. Eur J Nucl Med Mol Imaging 47, 632–641 (2020). https://doi.org/10.1007/s00259-019-04581-4

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