nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

05.07.2023 | Original Article

The significance of metabolic response to neoadjuvant androgen deprivation therapy detected with [⁶⁸Ga]Ga-PSMA-11-PET/CT in high-risk prostate cancer patients treated with definitive radiotherapy

verfasst von: Cem Onal, Ozan Cem Guler, Nese Torun, Ezgi Oymak, Mehmet Reyhan

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2023

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We examined the prognostic significance of early changes in primary tumor SUV measured with Gallium-68-labeled prostate-specific membrane antigen positron emission tomography ([⁶⁸Ga]Ga-PSMA-11-PET/CT) and serum PSA values after neoadjuvant androgen deprivation treatment (nADT) in high-risk prostate cancer (PCa) patients treated with definitive radiotherapy (RT).

Methods

The clinical data and SUV parameters of 71 PCa patients were reviewed retrospectively. The serum PSA and primary tumor SUV values were calculated before and after the start of ADT. Using univariable and multivariable analyses, the prognostic factors predicting biochemical disease free survival (bDFS) and prostate cancer specific survival (PCSS) were investigated. In addition, logistic regression analysis was used to identify predictors of biochemical failure (BF).

Results

All but one patient responded with a 98.8% reduction in serum PSA (21.8 ng/mL vs. 0.3 ng/mL; p < 0.001), and 64 patients (91.1%) had a median 66.6% decrease in primary tumor SUV after ADT (13.2 vs. 4.8, p < 0.001). The primary tumor SUV response rate was significantly higher in patients with Gleason score (GS) of 7 than in patients with GS > 7 (59.5% vs. 40.5%; p = 0.04), and it was significantly lower in patients with inadequate treatment response than in those with complete (CR) or partial response (PR) (1.1% vs. 66.1%; p < 0.001). There was a strong and significant correlation (Spearman = 0.41, p < 0.001) and a high concordance (91.5%) between PSA response and SUV response after ADT. With a median follow-up time of 76.1 months, the 5-year bDFS and PCSS rates were 77.2% and 92.2%, respectively. Nineteen patients (26.7%) patients had recurrence at a median of 44.6 months after the completion of RT. In multivariate analysis, lymph node metastasis, GS greater than 7, and SD/PD after nADT were independent predictors of worse bDFS. However, no significant factor for PCSS was identified. In the multivariable logistic regression analysis, advanced age, GS of > 7 disease, lymph node metastasis, and SD or PD after nADT were independent predictors of BF.

Conclusion

These results imply that the metabolic response measured with [⁶⁸Ga]Ga-PSMA-11-PET/CT after nADT could be used to predict progression in high-risk PCa patients treated with definitive RT.

Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, et al. Ten-year follow-up of radiation therapy oncology group protocol 92–02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008;26:2497–504. https://doi.org/10.1200/jco.2007.14.9021.CrossRefPubMed

Shipley WU, Lu JD, Pilepich MV, Heydon K, Roach M, Wolkov HB, et al. Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86–10. Int J Radiat Oncol Biol Phys. 2002;54:1302–10. https://doi.org/10.1016/s0360-3016(02)03052-3.CrossRefPubMed

Zilli T, Dal Pra A, Kountouri M, Miralbell R. Prognostic value of biochemical response to neoadjuvant androgen deprivation before external beam radiotherapy for prostate cancer: a systematic review of the literature. Cancer Treat Rev. 2016;46:35–41. https://doi.org/10.1016/j.ctrv.2016.03.016.CrossRefPubMed

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/10.1016/S0022-5347(05)64559-4.CrossRefPubMed

Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395:1208–16. https://doi.org/10.1016/s0140-6736(20)30314-7.CrossRefPubMed

Shagera QA, Artigas C, Karfis I, Critchi G, Chanza NM, Sideris S, et al. (68)Ga-PSMA PET/CT for response assessment and outcome prediction in metastatic prostate cancer patients treated with taxane-based chemotherapy. J Nucl Med. 2022;63:1191–8. https://doi.org/10.2967/jnumed.121.263006.CrossRefPubMed

Zukotynski KA, Emmenegger U, Hotte S, Kapoor A, Fu W, Blackford AL, et al. Prospective, single-arm trial evaluating changes in uptake patterns on prostate-specific membrane antigen-targeted (18)F-DCFPyL PET/CT in patients with castration-resistant prostate cancer starting abiraterone or enzalutamide. J Nucl Med. 2021;62:1430–7. https://doi.org/10.2967/jnumed.120.259069.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

10.

Hoberück S, Löck S, Winzer R, Zöphel K, Froehner M, Fedders D, et al. [(68)Ga]Ga-PSMA-11 PET before and after initial long-term androgen deprivation in patients with newly diagnosed prostate cancer: a retrospective single-center study. EJNMMI Res. 2020;10:135. https://doi.org/10.1186/s13550-020-00723-0.CrossRefPubMedPubMedCentral

11.

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.CrossRefPubMedPubMedCentral

12.

Onal C, Guler OC, Torun N, Reyhan M, Yapar AF. The effect of androgen deprivation therapy on (68)Ga-PSMA tracer uptake in non-metastatic prostate cancer patients. Eur J Nucl Med Mol Imaging. 2020;47:632–41. https://doi.org/10.1007/s00259-019-04581-4.CrossRefPubMed

13.

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.CrossRefPubMed

14.

Onal C, Sonmez S, Erbay G, Guler OC, Arslan G. Simultaneous integrated boost to intraprostatic lesions using different energy levels of intensity-modulated radiotherapy and volumetric-arc therapy. Br J Radiol. 2014;87:20130617. https://doi.org/10.1259/bjr.20130617.CrossRefPubMedPubMedCentral

15.

Harris VA, Staffurth J, Naismith O, Esmail A, Gulliford S, Khoo V, et al. Consensus guidelines and contouring atlas for pelvic node delineation in prostate and pelvic node intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys. 2015;92:874–83. https://doi.org/10.1016/j.ijrobp.2015.03.021.CrossRefPubMed

16.

Onal C, Ozyigit G, Guler OC, Hurmuz P, Torun N, Tuncel M, et al. Role of 68-Ga-PSMA-PET/CT in pelvic radiotherapy field definitions for lymph node coverage in prostate cancer patients. Radiother Oncol. 2020;151:222–7. https://doi.org/10.1016/j.radonc.2020.08.021.CrossRefPubMed

17.

Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006;65:965–74. https://doi.org/10.1016/j.ijrobp.2006.04.029.CrossRefPubMed

18.

Onal C, Torun N, Oymak E, Guler OC, Reyhan M, Yapar AF. Retrospective correlation of (68)ga-psma uptake with clinical parameters in prostate cancer patients undergoing definitive radiotherapy. Ann Nucl Med. 2020;34:388–96. https://doi.org/10.1007/s12149-020-01462-x.CrossRefPubMed

19.

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-S150. https://doi.org/10.2967/jnumed.108.057307.CrossRefPubMed

20.

Zelefsky MJ, Lyass O, Fuks Z, Wolfe T, Burman C, Ling CC, et al. Predictors of improved outcome for patients with localized prostate cancer treated with neoadjuvant androgen ablation therapy and three-dimensional conformal radiotherapy. J Clin Oncol. 1998;16:3380–5. https://doi.org/10.1200/JCO.1998.16.10.3380.CrossRefPubMed

21.

Mitchell DM, McAleese J, Park RM, Stewart DP, Stranex S, Eakin RL, et al. Failure to achieve a PSA level <or=1 ng/mL after neoadjuvant LHRHa therapy predicts for lower biochemical control rate and overall survival in localized prostate cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2007;69:1467–71. https://doi.org/10.1016/j.ijrobp.2007.05.008.CrossRefPubMed

22.

Foo M, Lavieri M, Pickles T. Impact of neoadjuvant prostate-specific antigen kinetics on biochemical failure and prostate cancer mortality: results from a prospective patient database. Int J Radiat Oncol Biol Phys. 2013;85:385–92. https://doi.org/10.1016/j.ijrobp.2012.04.009.CrossRefPubMed

23.

Zelefsky MJ, Gomez DR, Polkinghorn WR, Pei X, Kollmeier M. Biochemical response to androgen deprivation therapy before external beam radiation therapy predicts long-term prostate cancer survival outcomes. Int J Radiat Oncol Biol Phys. 2013;86:529–33. https://doi.org/10.1016/j.ijrobp.2013.02.004.CrossRefPubMed

24.

Zilli T, Jorcano S, Escude L, Linero D, Rouzaud M, Dubouloz A, et al. Hypofractionated external beam radiotherapy to boost the prostate with >/=85 Gy/equivalent dose for patients with localised disease at high risk of lymph node involvement: feasibility, tolerance and outcome. Clin Oncol (R Coll Radiol). 2014;26:316–22. https://doi.org/10.1016/j.clon.2014.02.014.CrossRefPubMed

25.

di Sant’Agnese PA. Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer. 1992;70:254–68. https://doi.org/10.1002/1097-0142(19920701)70:1+<254::aid-cncr2820701312>3.0.co;2-e

26.

Jiborn T, Bjartell A, Abrahamsson PA. Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology. 1998;51:585–9. https://doi.org/10.1016/s0090-4295(97)00684-5.CrossRefPubMed

27.

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.CrossRefPubMedPubMedCentral

28.

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.CrossRefPubMed

29.

Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. JAMA Oncol. 2020;6:650–9. https://doi.org/10.1001/jamaoncol.2020.0147.CrossRefPubMedPubMedCentral

30.

Francolini G, Ganovelli M, Di Cataldo V, Detti B, Caini S, Loi M, et al. Early biochemical outcomes following PSMA guided approach for bIoCHEmical relapse after prostatectomy-PSICHE trial (NCT05022914): preliminary results. Clin Exp Metastasis. 2023;40:197–201. https://doi.org/10.1007/s10585-023-10204-y.CrossRefPubMedPubMedCentral

31.

Ettala O, Malaspina S, Tuokkola T, Luoto P, Loyttyniemi E, Bostrom PJ, et al. Prospective study on the effect of short-term androgen deprivation therapy on PSMA uptake evaluated with (68)Ga-PSMA-11 PET/MRI in men with treatment-naive prostate cancer. Eur J Nucl Med Mol Imaging. 2020;47:665–73. https://doi.org/10.1007/s00259-019-04635-7.CrossRefPubMed

32.

Malaspina S, Ettala O, Tolvanen T, Rajander J, Eskola O, Bostrom PJ, et al. Flare on [(18)F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naive metastatic prostate cancer patients. Eur J Nucl Med Mol Imaging. 2023;50:613–21. https://doi.org/10.1007/s00259-022-05970-y.CrossRefPubMed

33.

Aggarwal R, Wei X, Kim W, Small EJ, Ryan CJ, Carroll P, et al. Heterogeneous flare in prostate-specific membrane antigen positron emission tomography tracer uptake with initiation of androgen pathway blockade in metastatic prostate cancer. Eur Urol Oncol. 2018;1:78–82. https://doi.org/10.1016/j.euo.2018.03.010.CrossRefPubMed

34.

Emmett L, 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. 2019;60:950–4. https://doi.org/10.2967/jnumed.118.223099.CrossRefPubMed

35.

Han S, Woo S, Kim YI, Lee JL, Wibmer AG, Schoder H, et al. Concordance between response assessment using prostate-specific membrane antigen PET and serum prostate-specific antigen levels after systemic treatment in patients with metastatic castration resistant prostate cancer: a systematic review and meta-analysis. Diagnostics (Basel). 2021;11. https://doi.org/10.3390/diagnostics11040663

36.

Fanti S, Goffin K, Hadaschik BA, Herrmann K, Maurer T, MacLennan S, et al. Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer. Eur J Nucl Med Mol Imaging. 2021;48:469–76. https://doi.org/10.1007/s00259-020-04934-4.CrossRefPubMed

37.

Fendler WP, Eiber M, Beheshti M, Bomanji J, Calais J, Ceci F, et al. PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023;50:1466–86. https://doi.org/10.1007/s00259-022-06089-w

38.

Seifert R, Emmett L, Rowe SP, Herrmann K, Hadaschik B, Calais J, et al. Second version of the prostate cancer molecular imaging standardized evaluation framework including response evaluation for clinical trials (PROMISE V2). Eur Urol. 2023. https://doi.org/10.1016/j.eururo.2023.02.002.CrossRefPubMed

39.

Gafita A, Rauscher I, Fendler WP, Murthy V, Hui W, Armstrong WR, et al. Measuring response in metastatic castration-resistant prostate cancer using PSMA PET/CT: comparison of RECIST 1.1, aPCWG3, aPERCIST, PPP, and RECIP 1.0 criteria. Eur J Nucl Med Mol Imaging. 2022;49:4271–81. https://doi.org/10.1007/s00259-022-05882-x

Titel: The significance of metabolic response to neoadjuvant androgen deprivation therapy detected with [68Ga]Ga-PSMA-11-PET/CT in high-risk prostate cancer patients treated with definitive radiotherapy
verfasst von: Cem Onal
Ozan Cem Guler
Nese Torun
Ezgi Oymak
Mehmet Reyhan
Publikationsdatum: 05.07.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2023
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-023-06321-1

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

The significance of metabolic response to neoadjuvant androgen deprivation therapy detected with [⁶⁸Ga]Ga-PSMA-11-PET/CT in high-risk prostate cancer patients treated with definitive radiotherapy

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2023

[68Ga]Ga-FAPI-04 and [18F]FDG PET/ CT in a patient with MDA5 dermatomyositis

Multiple myeloma mimicking metastatic skull base paraganglioma in [68 Ga]Ga-DOTATOC-PET/CT and 2-[18F]FDG-PET/CT imaging

Radiofrequency ablation for autonomously functioning nodules as treatment for hyperthyroidism: subgroup analysis of toxic adenoma and multinodular goitre and predictors for treatment success

Standing on the shoulders of giants: 50 years of EJNM and EJNMMI

Urinary excretion kinetics of [177Lu]Lu-PSMA-617

PSMA-based alpha therapy in prostate cancer