Comparative diagnostic performance of 68 Ga-PSMA-11 PET/CT and 68 Ga-PSMA-11 PET/MRI in detecting biochemical recurrent bone metastasis in prostate cancer: a systematic review and meta-analysis
Restricted accessResearch articleFirst published online March, 2025
Comparative diagnostic performance of 68 Ga-PSMA-11 PET/CT and 68 Ga-PSMA-11 PET/MRI in detecting biochemical recurrent bone metastasis in prostate cancer: a systematic review and meta-analysis
The comparative diagnostic performance of 68Gallium (Ga)-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI in detecting bone metastases in prostate cancer (PCa) remains unclear.
Purpose
To systematically evaluate the early detection rate of biochemical recurrent (BCR) bone metastasis in PCa utilizing 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI.
Material and Methods
We searched PubMed, Embase, and Web of Science for relevant articles up to April 2023 and extracted studies that examined the positivity rate of both 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI in the context of the BCR bone metastasis of PCa patients. Random-effects model was used to compare positivity rates for two imaging modalities. Heterogeneity among studies was assessed using the I2 statistic. To evaluate the methodological quality of studies, we employed Quality Assessment of Diagnostic Performance Studies method. The study protocol was registered in PROSPERO (CRD42023454118).
Results
A total of 1670 publications were originally identified; 58 studies, encompassing a cohort of 8037 patients, met the inclusion criteria. Regarding the evaluation of BCR bone metastasis, results suggest no statistically significant difference in the utilization of 68Ga-PSMA-11 PET/CT versus 68Ga-PSMA-11 PET/MRI in 58 non–head-to-head studies (0.21, 95% CI=0.19–0.24 and 0.17, 95% CI=0.11–0.23; P = 0.19) and four head-to-head studies (0.16, 95% CI=0.08–0.27 and 0.16, 95% CI=0.08–0.27; P = 1.00). Meta-regression showed the study design of influenced the heterogeneity in the PET/MRI group (P < 0.01); but analysis of PET/CT did not identify the potential reason for heterogeneity.
Conclusion
There was no statistically significant difference in identifying BCR bone metastasis in PCa patients between 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI.
SungHFerlayJSiegelRL, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin2021;71:209–249.
2.
SathianathenNJButaneyMKonetyBR. The utility of PET-based imaging for prostate cancer biochemical recurrence: a systematic review and meta-analysis. World J Urol2019;37:1239–1249.
3.
HullGWRabbaniFAbbasF, et al.Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol2002;167:528–534.
4.
RoehlKAHanMRamosCG, et al.Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol2004;172:910–914.
5.
KfouryYBaryawnoNSevereN, et al.Human prostate cancer bone metastases have an actionable immunosuppressive microenvironment. Cancer Cell2021;39:1464–1478 e1468.
6.
WooSSuhCHKimSY, et al.The diagnostic performance of MRI for detection of lymph node metastasis in bladder and prostate cancer: an updated systematic review and diagnostic meta-analysis. AJR Am J Roentgenol2018;210:W95–W109.
7.
ChowKMSoWZLeeHJ, et al.Head-to-head comparison of the diagnostic accuracy of prostate-specific membrane antigen positron emission tomography and conventional imaging modalities for initial staging of intermediate- to high-risk prostate cancer: a systematic review and meta-analysis. Eur Urol2023;84:36–48.
8.
UprimnyCBayerschmidtSKroissAS, et al.Early injection of furosemide increases detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for (68)Ga-PSMA-11 PET/CT. J Nucl Med2021;62:1550–1557.
9.
UijenMJMDerksYHWMerkxRIJ, et al.PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports. Eur J Nucl Med Mol Imaging2021;48:4350–4368.
10.
PykaTOkamotoSDahlbenderM, et al.Comparison of bone scintigraphy and (68)Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging2016;43:2114–2121.
11.
CerciJJFantiSLobatoEE, et al.Diagnostic performance and clinical impact of 68Ga-PSMA-11 PET/CT imaging in early relapsed prostate cancer after radical therapy: a prospective multicenter study (IAEA-PSMA study). J Nucl Med2022;63:240–247.
12.
SchaefferEMSrinivasSAdraN, et al.NCCN guidelines(R) insights: prostate cancer, version 1.2023. J Natl Compr Canc Netw2022;20:1288–1298.
13.
KranzbuhlerBNagelHBeckerAS, et al.Clinical performance of 68Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy. Eur J Nucl Med Mol Imaging2018;45:20–30.
14.
LiberatiAAltmanDGTetzlaffJ, et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med2009;6:e1000100.
15.
RadzinaMTiraneMRoznereL, et al.Accuracy of 68Ga-PSMA-11 PET/CT and multiparametric MRI for the detection of local tumor and lymph node metastases in early biochemical recurrence of prostate cancer. Am J Nucl Med Mol Imaging2022;10:106–118.
16.
HoffmannMABuchholzHGWielerHJ, et al.The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Oncotarget2019;10:6124–6137.
17.
LenganaTLawalIORensburgCV, et al.A comparison of the diagnostic performance of 18F-PSMA-1007 and 68GA-PSMA-11 in the same patients presenting with early biochemical recurrence. Hell J Nucl Med2021;24:178–185.
18.
Afshar-OromiehAHaberkornUSchlemmerHP, et al.Comparison of PET/CT and PET/MRI hybrid systems using a 68Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience. Eur J Nucl Med Mol Imaging2014;41:887–897.
19.
Afshar-OromiehAVollnbergBAlbertsI, et al.Comparison of PSMA-ligand PET/CT and multiparametric MRI for the detection of recurrent prostate cancer in the pelvis. Eur J Nucl Med Mol Imaging2019;46:2289–2297.
20.
AkdemirENTuncelMAkyolF, et al.68Ga-labelled PSMA ligand HBED-CC PET/CT imaging in patients with recurrent prostate cancer. World J Urol2019;37:813–821.
21.
AlonsoOdos SantosGGarcía FontesM, et al.68Ga-PSMA and 11C-Choline comparison using a tri-modality PET/CT-MRI (3.0 T) system with a dedicated shuttle. Eur J Hybrid Imaging2018;2:9.
22.
AriciSKaryagarSSCihanS. The factors determining positive detection rate of 68Ga PSMA PET/CT in patients with early biochemical recurrence prostate cancer. J Oncol Sci2019;5:100–104.
23.
AydinAMHaberalBArtykovM, et al.Clinicopathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer following definitive therapy. Ann Nucl Med2019;33:326–332.
24.
BarbaudMFrindelMFerrerL, et al.68Ga-PSMA-11 PET-CT study in prostate cancer patients with biochemical recurrence and non-contributive 18F-choline PET-CT: impact on therapeutic decision-making and biomarker changes. Prostate2019;79:454–461.
25.
CalaisJCzerninJCaoM, 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 Med2018;59:230–237.
26.
CaroliPSandlerIMatteucciF, et al.68Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients. Eur J Nucl Med Mol Imaging2018;45:2035–2044.
27.
DadgarHSeyedi VafaeeMNorouzbeigiN, et al.Dual-phase 68Ga-PSMA-11 PET/CT may increase the rate of detected lesions in prostate cancer patients. Urologia2021;88:355–361.
28.
DemirkolMOAcarOUcarB, et al.Prostate-specific membrane antigen-based imaging in prostate cancer: impact on clinical decision making process. Prostate2015;75:748–757.
29.
DietleinMKobeCKuhnertG, et al.Comparison of [(18)F]DCFPyL and [(68)Ga]Ga-PSMA-HBED-CC for PSMA-PET imaging in patients with relapsed prostate cancer. Mol Imaging Biol2015;17:575–584.
30.
DongLZhuYXinM, et al.Prospective evaluation of 68Ga-PSMA-11 PET/CT in Chinese men with biochemical recurrence after radical prostatectomy for prostate cancer: relationships between location of recurrence, time after prostatectomy, and serum PSA level. Med Oncol2020;37:89.
31.
EiberMMaurerTSouvatzoglouM, et al.Evaluation of hybrid 68Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med2015;56:668–674.
32.
EinspielerIRauscherIDuwelC, et al.Detection efficacy of hybrid 68Ga-PSMA ligand PET/CT in prostate cancer patients with biochemical recurrence after primary radiation therapy defined by Phoenix criteria. J Nucl Med2017;58:1081–1087.
33.
FarolfiACeciFCastellucciP, et al.68Ga-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 Imaging2019;46:11–19.
34.
FennessyNLeeJShinJ, et al.Frusemide aids diagnostic interpretation of 68 Ga-PSMA positron emission tomography/CT in men with prostate cancer. J Med Imaging Radiat Oncol2017;61:739–744.
35.
FourquetALahmiLRusuT, et al.Restaging the biochemical recurrence of prostate cancer with [68Ga]Ga-PSMA-11 PET/CT: Diagnostic performance and impact on patient disease management. Cancers (Basel)2021;13:1594.
36.
GlemserPARotkopfLTZienerCH, et al.Hybrid imaging with [68Ga]PSMA-11 PET-CT and PET-MRI in biochemically recurrent prostate cancer. Cancer Imaging2022;22:53.
37.
GuhneFRadkeSWinkensT, et al.Differences in distribution and detection rate of the [(68)Ga]Ga-PSMA ligands PSMA-617, -I&T and -11-inter-individual comparison in patients with biochemical relapse of prostate cancer. Pharmaceuticals (Basel)2021;15:
38.
HamedMAGBashaMAAAhmedH, et al.68Ga-PSMA PET/CT in patients with rising prostatic-specific antigen after definitive treatment of prostate cancer: detection efficacy and diagnostic accuracy. Acad Radiol2019;26:450–460.
39.
HohbergMKobeCTagerP, et al.Combined early and late [68Ga]PSMA-HBED-CC PET scans improve lesion detectability in biochemical recurrence of prostate cancer with low PSA levels. Mol Imaging Biol2019;21:558–566.
40.
HrubyGEadeTKneeboneA, et al.Delineating biochemical failure with 68Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer. Radiother Oncol2017;122:99–102.
41.
HuitsTHLuitingHBvan der PoelHG, et al.Distribution of prostate cancer recurrences on gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron-emission/computed tomography after radical prostatectomy with pathological node-positive extended lymph node dissection. BJU Int2020;125:876–883.
42.
IravaniAHofmanMSMulcahyT, et al.68Ga PSMA-11 PET with CT urography protocol in the initial staging and biochemical relapse of prostate cancer. Cancer Imaging2017;17:31.
43.
JentjensSMaiCAhmadi BidakhvidiN, et al.Prospective comparison of simultaneous [68Ga]Ga-PSMA-11 PET/MR versus PET/CT in patients with biochemically recurrent prostate cancer. Eur Radiol2022;32:901–911.
44.
JoshiARobertsMJPereraM, et al.The clinical efficacy of PSMA PET/MRI in biochemically recurrent prostate cancer compared with standard of care imaging modalities and confirmatory histopathology: results of a single-centre, prospective clinical trial. Clin Exp Metastasis2020;37:551–560.
45.
KranzbühlerBMüllerJBeckerAS, et al.Detection rate and localization of prostate cancer recurrence using (68)Ga-PSMA-11 PET/MRI in patients with low PSA values ≤ 0.5 ng/mL. J Nucl Med2020;61:194–201.
46.
Lawhn-HeathCFlavellRRBehrSC, et al.Single-center prospective evaluation of 68Ga-PSMA-11 PET in biochemical recurrence of prostate cancer. AJR Am J Roentgenol2019;213:266–274.
47.
LetangACrombeARousseauC, et al.Bone uptake in prostate cancer patients: diagnostic performances of PSMA-RADS v1.0, clinical, biological, and 68 Ga-PSMA-11 PET features to predict metastasis after biochemical recurrence. Clin Nucl Med2022;47:e529–e539.
48.
LutjeSCohnenJGomezB, et al.Integrated 68Ga-HBED-CC-PSMA-PET/MRI in patients with suspected recurrent prostate cancer. Nuklearmedizin2017;56:73–81.
49.
MattiolliABSantosAVicenteA, et al.Impact of 68GA-PSMA PET / CT on treatment of patients with recurrent / metastatic high risk prostate cancer - a multicenter study. Int Braz J Urol2018;44:892–899.
50.
McCarthyMFrancisRTangC, et al.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 Phys2019;104:801–808.
51.
MeredithGWongDYaxleyJ, et al.The use of 68 Ga-PSMA PET CT in men with biochemical recurrence after definitive treatment of acinar prostate cancer. BJU Int2016;118:49–55.
52.
MikschJBottkeDKrohnT, et al.Interobserver variability, detection rate, and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy. Eur J Nucl Med Mol Imaging2020;47:2339–2347.
53.
MorawitzJKirchnerJHertelendyJ, et al.Is there a diagnostic benefit of late-phase abdomino-pelvic PET/CT after urination as part of whole-body 68 Ga-PSMA-11 PET/CT for restaging patients with biochemical recurrence of prostate cancer after radical prostatectomy?EJNMMI Res2022;12:12.
54.
NatarajanAAgrawalAMurthyV, et al.Initial experience of Ga-68 prostate-specific membrane antigen positron emission tomography/computed tomography imaging in evaluation of biochemical recurrence in prostate cancer patients. World J Nucl Med2019;18:244–250.
55.
PernthalerBKulnikRGstettnerC, et al.A prospective head-to-head comparison of 18F-fluciclovine with 68Ga-PSMA-11 in biochemical recurrence of prostate cancer in PET/CT. Clin Nucl Med2019;44:e566–e573.
56.
Prado JuniorLMMarinoFMBarraR, et al.One-year experience with 68Ga-PSMA PET/CT: applications and results in biochemical recurrence of prostate cancer. Radiol Bras2018;51:151–155.
57.
RauscherIDuwelCHallerB, 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 Urol2018;73:656–661.
58.
RauscherIKronkeMKonigM, et al.Matched-Pair comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med2020;61:51–57.
59.
RaveenthiranSYaxleyJGianduzzoT, et al.The use of 68Ga-PET/CT PSMA to determine patterns of disease for biochemically recurrent prostate cancer following primary radiotherapy. Prostate Cancer Prostatic Dis2019;22:385–390.
60.
RousseauCLe ThiecMFerrerL, et al.Preliminary results of a 68 Ga-PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: diagnostic performance and impact on therapeutic decision-making. Prostate2019;79:1514–1522.
61.
SachpekidisCEderMKopkaK, et al.(68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer. Eur J Nucl Med Mol Imaging2016;43:1288–1299.
62.
SchwenckJRemppHReischlG, et al.Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging2017;44:92–101.
63.
SeniarayNVermaRKhannaS, et al.Localization and restaging of carcinoma prostate by 68Gallium prostate-specific membrane antigen positron emission tomography computed tomography in patients with biochemical recurrence. Indian J Urol2020;36:191–199.
64.
SterzingFKratochwilCFiedlerH, et al.(68)Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients. Eur J Nucl Med Mol Imaging2016;43:34–41.
65.
TanJSHGohCXYKohYS, et al.68Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy. Cancer Biol Med2019;16:157–166.
66.
TsengJRYuKJLiuFY, et al.Comparison between 68Ga-PSMA-11 PET/CT and multiparametric magnetic resonance imaging in patients with biochemically recurrent prostate cancer following robot-assisted radical prostatectomy. J Formos Med Assoc2021;120:688–696.
67.
VerburgFAPfisterDHeidenreichA, et al.Extent of disease in recurrent prostate cancer determined by [(68)Ga]PSMA-HBED-CC PET/CT in relation to PSA levels, PSA doubling time and Gleason score. Eur J Nucl Med Mol Imaging2016;43:397–403.
68.
YuminagaYRotheCKamJ, et al.68Ga-PSMA PET/CT versus CT and bone scan for investigation of PSA failure post radical prostatectomy. Asian J Urol2021;8:170–175.
69.
ZachoHDNielsenJBDettmannK, et al.68Ga-PSMA PET/CT in patients with biochemical recurrence of prostate cancer: a prospective, 2-center study. Clin Nucl Med2018;43:579–585.
70.
WhitingPFRutjesAWWestwoodME, et al.QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med2011;155:529–536.
71.
BagadeSFowlerKJSchwarzJK, et al.PET/MRI evaluation of gynecologic malignancies and prostate cancer. Semin Nucl Med2015;45:293–303.
72.
KranzbuhlerBMullerJBeckerAS, et al.Detection rate and localization of prostate cancer recurrence using 68Ga-PSMA-11 PET/MRI in patients with low PSA values </= 0.5 ng/mL. J Nucl Med2020;61:194–201.
73.
HuoHShenSHeD, et al.Head-to-head comparison of 68Ga-PSMA-11 PET/CT and 68Ga-PSMA-11 PET/MRI in the detection of biochemical recurrence of prostate cancer: summary of head-to-head comparison studies. Prostate Cancer Prostatic Dis2023;26:16–24.
74.
WangRShenGYangR, et al.68Ga-PSMA PET/MRI for the diagnosis of primary and biochemically recurrent prostate cancer: a meta-analysis. Eur J Radiol2020;130:109131.
