Diagnostic performance of 68Ga-PSMA PET/CT in the detection of prostate cancer prior to initial biopsy: comparison with cancer-predicting nomograms
To assess the diagnostic performance of 68Ga-PSMA PET/CT for detecting suspected prostate cancer (PCa) and to compare it with that of two cancer-predicting nomograms.
We performed a retrospective analysis of 146 consecutive patients with suspected PCa based on symptoms or elevated total prostate-specific antigen (tPSA) levels who underwent 68Ga-PSMA PET/CT and histopathologic examinations from April 2017 to April 2018 in a large tertiary care hospital in China. The 68Ga-PSMA PET/CT results (PCa or benignancy) were evaluated by two experienced nuclear medicine specialists. The risk of positive PCa was evaluated using ERSPC and PCPT nomograms. The diagnostic performances of 68Ga-PSMA PET/CT and that of the two nomograms were compared via receiver operating characteristic (ROC) curve analysis, decision curve analysis, and logistic regression.
A total of 58 patients with tPSA of 0.4–50 ng/ml were included in the final analysis; PCa diagnosis was confirmed in 37 patients and excluded in 21 patients. ROC analysis showed that the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 68Ga-PSMA PET/CT were 91.67, 81.82, 89.19, and 85.71%, respectively, in per-patient analyses. 68Ga-PSMA PET/CT exhibited a higher AUC (0.867) than those of ERSPC-RC3 (0.855) and PCPT-RC (0.770). The net benefit of 68Ga-PSMA PET/CT was greatest for patients within threshold probabilities of 15–90%. Among the 58 patients, 11 (19%) biopsies suggested by ERSPC-RC3 were unnecessary and could have been avoided if judged by the 68Ga-PSMA PET/CT results. Multivariate analysis revealed that the maximum standardised uptake value (SUVmax) and prostate volume were significant predictive factors for positive PCa results.
In suspected PCa patients with tPSA of 0.4–50 ng/ml, 68Ga-PSMA PET/CT outperformed the nomograms in predicting cancer and reducing unnecessary biopsies. In addition, the risk of PCa was positively correlated with a higher SUVmax and lower prostate volume, which could help clinicians in making preliminary estimates of individual cancer risk, monitoring 68Ga-PSMA PET/CT false-positive results and making biopsy decisions in daily medical practice.
Keywords68Ga-PSMA PET/CT Prostate cancer Biopsy Nomogram Multivariate analysis Decision curve analysis
This study was funded by the National Natural Science Foundation of China (grant nos. 81372771, 81772734, 81871379, 816771713), the Shaanxi Science and Technology Co-ordination and Innovation Project (grant no. 2016KTCQ03–09), the National Key R&D Program of China (grant no. 2016YFC0103804), the Natural Science Foundation of Shaanxi Province (grant no. 2018SF-228, 2018PT-08), and the International Cooperation Program of Xijing Hospital (grant no. XJZT15G01).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All of the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this study type, formal consent is not required.
- 2.Gerstenbluth RE, Seftel AD, Hampel N, Oefelein MG, Resnick MI. The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng./ml.) in predicting prostate cancer: is biopsy always required? J Urol. 2002;168(5):1990–3. https://doi.org/10.1097/01.ju.0000033330.06269.6d.CrossRefPubMedGoogle Scholar
- 5.Rauscher I, Duwel C, Haller B, Rischpler C, Heck MM, Gschwend JE, 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. https://doi.org/10.1016/j.eururo.2018.01.006.CrossRefPubMedGoogle Scholar
- 7.Ankerst DP, Hoefler J, Bock S, Goodman PJ, Vickers A, Hernandez J, et al. Prostate Cancer prevention trial risk calculator 2.0 for the prediction of low- vs high-grade prostate cancer. Urology. 2014;83(6):1362–7. https://doi.org/10.1016/j.urology.2014.02.035.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. (68)Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol. 2016;70(4):553–7. https://doi.org/10.1016/j.eururo.2015.12.051.CrossRefPubMedGoogle Scholar
- 12.Schiavina R, Scattoni V, Castellucci P, Picchio M, Corti B, Briganti A, et al. 11C-choline positron emission tomography/computerized tomography for preoperative lymph-node staging in intermediate-risk and high-risk prostate cancer: comparison with clinical staging nomograms. Eur Urol. 2008;54(2):392–401. https://doi.org/10.1016/j.eururo.2008.04.030.CrossRefPubMedGoogle Scholar
- 14.Gayet M, Mannaerts CK, Nieboer D, Beerlage HP, Wijkstra H, Mulders PFA, et al. Prediction of prostate cancer: external validation of the ERSPC risk calculator in a contemporary Dutch clinical cohort. Eur Urol Focus. 2018;4(2):228–34. https://doi.org/10.1016/j.euf.2016.07.007.CrossRefPubMedGoogle Scholar
- 15.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. https://doi.org/10.1186/s13550-015-0145-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.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. https://doi.org/10.1007/s00259-018-4079-z.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Weiss BE, Wein AJ, Malkowicz SB, Guzzo TJ. Comparison of prostate volume measured by transrectal ultrasound and magnetic resonance imaging: is transrectal ultrasound suitable to determine which patients should undergo active surveillance? Urol Oncol. 2013;31(8):1436–40. https://doi.org/10.1016/j.urolonc.2012.03.002.CrossRefPubMedGoogle Scholar
- 22.Kang F, Wang Z, Li G, Wang S, Liu D, Zhang M, et al. Inter-heterogeneity and intra-heterogeneity of alphavbeta3 in non-small cell lung cancer and small cell lung cancer patients as revealed by (68)Ga-RGD2 PET imaging. Eur J Nucl Med Mol Imaging. 2017;44(9):1520–8. https://doi.org/10.1007/s00259-017-3696-2.CrossRefPubMedGoogle Scholar
- 25.Lete I, de la Viuda E, Perez-Campos E, Martinez MA, Sanchez-de la Rosa R, Novalbos J, et al. Effect on quality of life of switching to combined oral contraception based on natural estrogen: an observational, multicentre, prospective phase IV study (ZOCAL study). Eur J Contracept Reprod Health Care. 2016;21(4):276–84. https://doi.org/10.3109/13625187.2016.1174206.CrossRefPubMedGoogle Scholar
- 29.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(6):941–9. https://doi.org/10.1007/s00259-017-3631-6.CrossRefPubMedGoogle Scholar
- 34.Parida GK, Tripathy S, Datta Gupta S, Singhal A, Kumar R, Bal C, et al. Adenocarcinoma prostate with neuroendocrine differentiation: potential utility of 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT over 68Ga-PSMA PET/CT. Clin Nucl Med. 2018;43(4):248–9. https://doi.org/10.1097/RLU.0000000000002013.CrossRefPubMedGoogle Scholar
- 37.Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, et al. Diagnostic efficacy of (68)gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol. 2016;195(5):1436–43. https://doi.org/10.1016/j.juro.2015.12.025.CrossRefPubMedGoogle Scholar
- 39.Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. The novel theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med. 2015;56(11):1697–705. https://doi.org/10.2967/jnumed.115.161299.CrossRefPubMedGoogle Scholar
- 40.Benesova M, Schafer M, Bauder-Wust U, Afshar-Oromieh A, Kratochwil C, Mier W, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med. 2015;56(6):914–20. https://doi.org/10.2967/jnumed.114.147413.CrossRefPubMedGoogle Scholar
- 41.Liu C, Liu T, Zhang N, Liu Y, Li N, Du P, et al. (68)Ga-PSMA-617 PET/CT: a promising new technique for predicting risk stratification and metastatic risk of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2018;45(11):1852–61. https://doi.org/10.1007/s00259-018-4037-9.CrossRefPubMedGoogle Scholar
- 42.Finne P, Auvinen A, Aro J, Juusela H, Maattanen L, Rannikko S, et al. Estimation of prostate cancer risk on the basis of total and free prostate-specific antigen, prostate volume and digital rectal examination. Eur Urol. 2002;41(6):619–26; discussion 26-7. https://doi.org/10.1016/S0302-2838(02)00179-3.CrossRefPubMedGoogle Scholar
- 44.Westenfelder KM, Lentes B, Rackerseder J, Navab N, Gschwend JE, Eiber M, et al. Gallium-68 HBED-CC-PSMA positron emission tomography/magnetic resonance imaging for prostate fusion biopsy. Clin Genitourin Cancer. 2018;16(4):245–7. https://doi.org/10.1016/j.clgc.2018.05.009.CrossRefPubMedGoogle Scholar
- 45.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;59(12):1850–6. https://doi.org/10.2967/jnumed.117.207696.CrossRefPubMedGoogle Scholar