Conventional imaging modalities have been poor in characterizing the true extent of disease in men with biochemical recurrence following primary treatment for prostate cancer. Functional imaging with positron emission tomography (PET) has shown promise of being a superior imaging modality. We conducted a systematic review and meta-analysis to define the diagnostic accuracy of PET/CT using 11C-choline, 18F-FACBC, or 68Ga-PSMA in detecting recurrent prostate cancer.
We searched multiple databases in line with the preferred reporting items for systematic review and meta-analysis (PRISMA) statement to define the diagnostic accuracy of 11C-choline, 18F-FACBC, or 68Ga-PSMA PET/CT. Only studies secondarily staging participants with biochemical recurrence and those with an appropriate reference standard (pathology, further imaging, and/or clinical response) were eligible for analysis.
Twenty-one studies with 3202 participants met the inclusion criteria. Of these, 11C-choline, 18F-FACBC, and 68Ga-PSMA were the tracer investigated in 16, 5, and 1 studies, respectively. The summary sensitivity for each tracer was 80.9% (95% CI 70.4–88.3%), 79.7% (95% CI 51.9–93.4%), and 76.4% (95% CI 68.3–82.9%), respectively. The corresponding summary specificity was 84.1% (95% CI 70.2–92.2%), 61.9% (95% CI 41.1–79.0%), and 99.8% (95% CI 97.5–100%), respectively. Detection rates ranged between 58.6 and 82.8%. All included studies were judged to be at high risk of bias primarily due to study limitations pertaining to the reference standard.
There is a lack of high-quality data to verify the accuracy of PET-based imaging using 11C-choline, 18F-FACBC, or 68Ga-PSMA. The early results are encouraging that these techniques are superior to conventional imaging modalities, which would allow salvage therapies to be optimized.
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Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ (2004) Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3478 consecutive patients: long-term results. J Urol 172(3):910–914
Uchio EM, Aslan M, Wells CK, Calderone J, Concato J (2010) Impact of biochemical recurrence in prostate cancer among us veterans. Arch Intern Med 170(15):1390–1395
Paller CJ, Antonarakis ES (2013) Management of biochemically recurrent prostate cancer after local therapy: evolving standards of care and new directions. Clin Adv Hematol Oncol H&O 11(1):14–23
Maurer T, Eiber M, Fanti S, Budäus L, Panebianco V (2016) Imaging for prostate cancer recurrence. Eur Urol Focus 2(2):139–150
Rouvière O (2012) Imaging techniques for local recurrence of prostate cancer: for whom, why and how? Diagn Interv Imaging 93(4):279–290
Rouviere O, Vitry T, Lyonnet D (2010) Imaging of prostate cancer local recurrences: why and how? Eur Radiol 20(5):1254–1266
Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS, Thrasher JB, Foley JP, Riffenburgh RH, Moul JW (2003) Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology 61(3):607–611
Johnstone PA, Tarman GJ, Riffenburgh R, Rohde DC, Puckett ML, Kane CJ (1997) Yield of imaging and scintigraphy assessing biochemical failure in prostate cancer patients. Urol Oncol 3(4):108–112
Gomez P, Manoharan M, Kim SS, Soloway MS (2004) Radionuclide bone scintigraphy in patients with biochemical recurrence after radical prostatectomy: when is it indicated? BJU Int 94(3):299–302
Li R, Ravizzini GC, Gorin MA, Maurer T, Eiber M, Cooperberg MR, Alemozzaffar M, Tollefson MK, Delacroix SE, Chapin BF (2018) The use of PET/CT in prostate cancer. Prostate Cancer Prostatic Dis 21(1):4–21
Evans JD, Jethwa KR, Ost P, Williams S, Kwon ED, Lowe VJ, Davis BJ (2018) Prostate cancer-specific PET radiotracers: a review on the clinical utility in recurrent disease. Pract Radiat Oncol 8(1):28–39
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151(4):W65–W94
Leeflang MM, Deeks JJ, Takwoingi Y, Macaskill P (2013) Cochrane diagnostic test accuracy reviews. Syst Rev 2(1):82
Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, Freedland SJ, Greene K, Klotz LH, Makarov DV et al (2018) Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part II: recommended approaches and details of specific care options. J Urol 199(4):990–997
Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H (2006) 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 65(4):965–974
Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155(8):529–536
Doebler P, Holling H (2015) Meta-analysis of diagnostic accuracy with mada. Reterieved at: https://cran.rproject.org/web/packages/mada/vignettes/mada.pdf. Accessed Feb 2018
Schwarzer G, Schwarzer MG (2018) Package ‘meta’. Meta-Anal R
Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH (2005) Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 58(10):982–990
Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560
de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ (2003) 11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol 44(1):32–38 (discussion 38–39)
Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, Matarrese M, Matei DV, De Cobelli F, Del Maschio A et al (2003) Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol 169(4):1337–1340
Yoshida S, Nakagomi K, Goto S, Futatsubashi M, Torizuka T (2005) 11C-choline positron emission tomography in prostate cancer: primary staging and recurrent site staging. Urol Int 74(3):214–220
Rinnab L, Mottaghy FM, Blumstein NM, Reske SN, Hautmann RE, Hohl K, Moller P, Wiegel T, Kuefer R, Gschwend JE (2007) Evaluation of [11C]-choline positron-emission/computed tomography in patients with increasing prostate-specific antigen levels after primary treatment for prostate cancer. BJU Int 100(4):786–793
Richter JA, Rodriguez M, Rioja J, Penuelas I, Marti-Climent J, Garrastachu P, Quincoces G, Zudaire J, Garcia-Velloso MJ (2010) Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment. Mol Imaging Biol 12(2):210–217
Breeuwsma AJ, Pruim J, van den Bergh AC, Leliveld AM, Nijman RJ, Dierckx RA, de Jong IJ (2010) Detection of local, regional, and distant recurrence in patients with psa relapse after external-beam radiotherapy using (11)C-choline positron emission tomography. Int J Radiat Oncol Biol Phys 77(1):160–164
Giovacchini G, Picchio M, Coradeschi E, Bettinardi V, Gianolli L, Scattoni V, Cozzarini C, Di Muzio N, Rigatti P, Fazio F et al (2010) Predictive factors of [(11)C]choline PET/CT in patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging 37(2):301–309
Mitchell CR, Lowe VJ, Rangel LJ, Hung JC, Kwon ED, Karnes RJ (2013) Operational characteristics of (11)c-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment. J Urol 189(4):1308–1313
Mamede M, Ceci F, Castellucci P, Schiavina R, Fuccio C, Nanni C, Brunocilla E, Fantini L, Costa S, Ferretti A et al (2013) The role of 11C-choline PET imaging in the early detection of recurrence in surgically treated prostate cancer patients with very low PSA level < 0.5 ng/mL. Clin Nucl Med 38(9):e342–e345
Rybalov M, Breeuwsma AJ, Leliveld AM, Pruim J, Dierckx RA, de Jong IJ (2013) Impact of total PSA, PSA doubling time and PSA velocity on detection rates of 11C-choline positron emission tomography in recurrent prostate cancer. World J Urol 31(2):319–323
Castellucci P, Ceci F, Graziani T, Schiavina R, Brunocilla E, Mazzarotto R, Pettinato C, Celli M, Lodi F, Fanti S (2014) Early biochemical relapse after radical prostatectomy: which prostate cancer patients may benefit from a restaging 11C-choline PET/CT scan before salvage radiation therapy? J Nucl Med 55(9):1424–1429
Ceci F, Herrmann K, Castellucci P, Graziani T, Bluemel C, Schiavina R, Vollmer C, Droll S, Brunocilla E, Mazzarotto R et al (2014) Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial. Eur J Nucl Med Mol Imaging 41(12):2222–2231
Nanni C, Schiavina R, Boschi S, Ambrosini V, Pettinato C, Brunocilla E, Martorana G, Fanti S (2013) Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results. Eur J Nucl Med Mol Imaging 40(Suppl 1):S11–S17
Nanni C, Zanoni L, Pultrone C, Schiavina R, Brunocilla E, Lodi F, Malizia C, Ferrari M, Rigatti P, Fonti C et al (2016) (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial. Eur J Nucl Med Mol Imaging 43(9):1601–1610
Gomez-de la Fuente FJ, Martinez-Rodriguez I, de Arcocha-Torres M, Quirce R, Jimenez-Bonilla J, Martinez-Amador N, Banzo I (2017) Contribution of (11)C-choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml. Rev Esp Med Nucl Imagen Mol 37:156–162
Parker WP, Davis BJ, Park SS, Olivier KR, Choo R, Nathan MA, Lowe VJ, Welch TJ, Evans JD, Harmsen WS et al (2017) Identification of site-specific recurrence following primary radiation therapy for prostate cancer using C-11 choline positron emission tomography/computed tomography: a nomogram for predicting extrapelvic disease. Eur Urol 71(3):340–348
Schuster DM, Votaw JR, Nieh PT, Yu W, Nye JA, Master V, Bowman FD, Issa MM, Goodman MM (2007) Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med 48(1):56–63
Schuster DM, Savir-Baruch B, Nieh PT, Master VA, Halkar RK, Rossi PJ, Lewis MM, Nye JA, Yu W, Bowman FD et al (2011) Detection of recurrent prostate carcinoma with anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT and 111In-capromab pendetide SPECT/CT. Radiology 259(3):852–861
Kairemo K, Rasulova N, Partanen K, Joensuu T (2014) Preliminary clinical experience of trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) PET/CT imaging in prostate cancer patients. Biomed Res Int 2014:305182
Bach-Gansmo T, Nanni C, Nieh PT, Zanoni L, Bogsrud TV, Sletten H, Korsan KA, Kieboom J, Tade FI, Odewole O et al (2017) Multisite experience of the safety, detection rate and diagnostic performance of fluciclovine ((18)F) positron emission tomography/computerized tomography imaging in the staging of biochemically recurrent prostate cancer. J Urol 197(3 Pt 1):676–683
Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, Eisenhut M, Boxler S, Hadaschik BA, Kratochwil C et al (2015) 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 42(2):197–209
Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, Bolton D, Lawrentschuk N (2016) Sensitivity, specificity, and predictors of positive (68)Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol 70(6):926–937
Cremers RG, van Lin EN, Gerrits WL, van Tol-Geerdink JJ, Kiemeney LA, Vergunst H, Smans AJ, Kaanders JH, Witjes JA (2010) Efficacy and tolerance of salvage radiotherapy after radical prostatectomy, with emphasis on high-risk patients suited for adjuvant radiotherapy. Radiother Oncol 97(3):467–473
Hegarty SE, Hyslop T, Dicker AP, Showalter TN (2015) Radiation therapy after radical prostatectomy for prostate cancer: evaluation of complications and influence of radiation timing on outcomes in a large, population-based cohort. PLoS One 10(2):e0118430
Rigatti P, Suardi N, Briganti A, Da Pozzo LF, Tutolo M, Villa L, Gallina A, Capitanio U, Abdollah F, Scattoni V et al (2011) Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol 60(5):935–943
Stish BJ, Pisansky TM, Harmsen WS, Davis BJ, Tzou KS, Choo R, Buskirk SJ (2016) Improved metastasis-free and survival outcomes with early salvage radiotherapy in men with detectable prostate-specific antigen after prostatectomy for prostate cancer. J Clin Oncol 34(32):3864–3871
Suardi N, Gandaglia G, Gallina A, Di Trapani E, Scattoni V, Vizziello D, Cucchiara V, Bertini R, Colombo R, Picchio M et al (2015) Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single-institution series with a minimum follow-up of 5 years. Eur Urol 67(2):299–309
Briganti A, Karnes RJ, Joniau S, Boorjian SA, Cozzarini C, Gandaglia G, Hinkelbein W, Haustermans K, Tombal B, Shariat S et al (2014) Prediction of outcome following early salvage radiotherapy among patients with biochemical recurrence after radical prostatectomy. Eur Urol 66(3):479–486
Pfister D, Porres D, Heidenreich A, Heidegger I, Knuechel R, Steib F, Behrendt FF, Verburg FA (2016) Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with 68Ga-PSMA-HBED-CC than with 18F-fluoroethylcholine PET/CT. Eur J Nucl Med Mol Imaging 43(8):1410–1417
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Sathianathen, N.J., Butaney, M. & Konety, B.R. The utility of PET-based imaging for prostate cancer biochemical recurrence: a systematic review and meta-analysis. World J Urol 37, 1239–1249 (2019) doi:10.1007/s00345-018-2403-7
- Cancer staging
- Positron emission tomography
- Prostate cancer
- Systematic review