Investig Clin Urol.  2016 Dec;57(Suppl 2):S147-S154. 10.4111/icu.2016.57.S2.S147.

Updates of prostate cancer staging: Prostate-specific membrane antigen

• Sathianathen NJ
• Lamb A
• Nair R
• Geurts N
• Mitchell C
• Lawrentschuk NL
• Moon DA
• Murphy DG

• KMID: 2361680
• DOI: http://doi.org/10.4111/icu.2016.57.S2.S147

Abstract

The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting.

Keyword

Local neoplasm recurrence; Positron-emission tomography; Prostatic neoplasms; X-ray computed tomography

MeSH Terms

Magnetic Resonance Imaging
Membranes*
Neoplasm Recurrence, Local
Positron-Emission Tomography
Prostate*
Prostatic Neoplasms*
Recurrence
Sensitivity and Specificity
Tomography, X-Ray Computed

Figure

• 

  Fig. 1 68Ga positron-emission tomography computed tomography scan of recurrent lesion 10 years after 74-Gy radical radiotherapy. (A) Axial reconstruction showing strong avid area in left peripheral zone. Further avidity evident but less intense on right side. (B) Sagittal reconstruction showing avid lesion in left peripheral zone prostate (arrow). Nonspecific avidity evident in kidney and bladder due to renal clearance of radio-ligand. (C) Haematoxylin and eosin (H&E, ×100 magnification) photomicrograph from transperineal biopsy targeting avid area confirmed recurrent prostate cancer, Gleason grade group 2 (Gleason 3+4). (D) Radical prostatectomy specimen megablock with area outlined showing cancer focus.

Reference

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65:5–29.

2. Griffeth LK. Use of PET/CT scanning in cancer patients: technical and practical considerations. Proc (Bayl Univ Med Cent). 2005; 18:321–330.

3. Jadvar H, Desai B, Ji L, Conti PS, Dorff TB, Groshen SG, et al. Prospective evaluation of 18F-NaF and 18F-FDG PET/CT in detection of occult metastatic disease in biochemical recurrence of prostate cancer. Clin Nucl Med. 2012; 37:637–643.

4. Murphy GP, Greene TG, Tino WT, Boynton AL, Holmes EH. Isolation and characterization of monoclonal antibodies specific for the extracellular domain of prostate specific membrane antigen. J Urol. 1998; 160(6 Pt 2):2396–2401.

5. Kiess AP, Banerjee SR, Mease RC, Rowe SP, Rao A, Foss CA, et al. Prostate-specific membrane antigen as a target for cancer imaging and therapy. Q J Nucl Med Mol Imaging. 2015; 59:241–268.

6. Santoni M, Scarpelli M, Mazzucchelli R, Lopez-Beltran A, Cheng L, Cascinu S, et al. Targeting prostate-specific membrane antigen for personalized therapies in prostate cancer: morphologic and molecular backgrounds and future promises. J Biol Regul Homeost Agents. 2014; 28:555–563.

7. Chang SS, Reuter VE, Heston WD, Gaudin PB. Comparison of anti-prostate-specific membrane antigen antibodies and other immunomarkers in metastatic prostate carcinoma. Urology. 2001; 57:1179–1183.

8. Ross JS, Sheehan CE, Fisher HA, Kaufman RP Jr, Kaur P, Gray K, et al. Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res. 2003; 9:6357–6362.

9. Douglas TH, Connelly RR, McLeod DG, Erickson SJ, Barren R 3rd, Murphy GP. Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men. J Surg Oncol. 1995; 59:246–250.

10. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014; 65:467–479.

11. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014; 65:124–137.

12. Hovels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008; 63:387–395.

13. Eiber M, Beer AJ, Holzapfel K, Tauber R, Ganter C, Weirich G, et al. Preliminary results for characterization of pelvic lymph nodes in patients with prostate cancer by diffusion-weighted MR-imaging. Invest Radiol. 2010; 45:15–23.

14. van Leeuwen PJ, Roobol MJ, Kranse R, Zappa M, Carlsson S, Bul M, et al. Towards an optimal interval for prostate cancer screening. Eur Urol. 2012; 61:171–176.

15. 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; 195:1436–1443.

16. Beheshti M, Imamovic L, Broinger G, Vali R, Waldenberger P, Stoiber F, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology. 2010; 254:925–933.

17. 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; 54:392–401.

18. Budäus L, Leyh-Bannurah SR, Salomon G, Michl U, Heinzer H, Huland H, et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol. 2016; 69:393–396.

19. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive 68Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016; 06. 27. [Epub]. DOI: 10.1016/j.eururo.2016.06.021.

20. Daldrup-Link HE, Franzius C, Link TM, Laukamp D, Sciuk J, Jürgens H, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR Am J Roentgenol. 2001; 177:229–236.

21. Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016; 43:2114–2121.

22. Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016; 13:226–235.

23. King CR. The timing of salvage radiotherapy after radical prostatectomy: a systematic review. Int J Radiat Oncol Biol Phys. 2012; 84:104–111.

24. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999; 281:1591–1597.

25. Choueiri TK, Dreicer R, Paciorek A, Carroll PR, Konety B. A model that predicts the probability of positive imaging in prostate cancer cases with biochemical failure after initial definitive local therapy. J Urol. 2008; 179:906–910.

26. Cher ML, Bianco FJ Jr, Lam JS, Davis LP, Grignon DJ, Sakr WA, et al. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol. 1998; 160:1387–1391.

27. Okotie OT, Aronson WJ, Wieder JA, Liao Y, Dorey F, DeKERNION JB, et al. Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. J Urol. 2004; 171(6 Pt 1):2260–2264.

28. Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS, Thrasher JB, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology. 2003; 61:607–611.

29. Eiber M, Maurer T, Souvatzoglou M, Beer AJ, Ruffani A, Haller B, et al. Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. J Nucl Med. 2015; 56:668–674.

30. Shakespeare TP. Effect of prostate-specific membrane antigen positron emission tomography on the decision-making of radiation oncologists. Radiat Oncol. 2015; 10:233.

31. Rauscher I, Maurer T, Beer AJ, Graner FP, Haller B, Weirich G, et al. Value of 68Ga-PSMA HBED-CC PET for the assessment of lymph node metastases in prostate cancer patients with biochemical recurrence: comparison with histopathology after salvage lymphadenectomy. J Nucl Med. 2016; 57:1713–1719.

32. van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, Thompson B, et al. (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU Int. 2016; 117:732–739.

33. Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015; 56:1185–1190.

34. Bluemel C, Krebs M, Polat B, Linke F, Eiber M, Samnick S, et al. 68Ga-PSMA-PET/CT in patients with biochemical prostate cancer recurrence and negative 18F-Choline-PET/CT. Clin Nucl Med. 2016; 41:515–521.

35. Yu CY, Desai B, Ji L, Groshen S, Jadvar H. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature. Am J Nucl Med Mol Imaging. 2014; 4:580–601.

36. Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, et al. (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015; 42:1284–1294.

37. 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; 65:965–974.

38. 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.

39. Verburg FA, Pfister D, Heidenreich A, Vogg A, Drude NI, Vöö S, 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 Imaging. 2016; 43:397–403.

40. Sahlmann CO, Meller B, Bouter C, Ritter CO, Ströbel P, Lotz J, et al. Biphasic ⁶⁸Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging. 2016; 43:898–905.

41. Weineisen M, Simecek J, Schottelius M, Schwaiger M, Wester HJ. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Res. 2014; 4:63.

42. Kratochwil C, Giesel FL, Stefanova M, Benešová M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-Labeled PSMA-617. J Nucl Med. 2016; 57:1170–1176.

43. Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: Safety and Efficacy. J Nucl Med. 2016; 57:1006–1013.

44. Rahbar K, Schmidt M, Heinzel A, Eppard E, Bode A, Yordanova A, et al. Response and tolerability of a single dose of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: a multicenter retrospective analysis. J Nucl Med. 2016; 57:1334–1338.

45. Rahbar K, Bode A, Weckesser M, Avramovic N, Claesener M, Stegger L, et al. Radioligand therapy with 177Lu-PSMA-617 as a novel therapeutic option in patients with metastatic castration resistant prostate cancer. Clin Nucl Med. 2016; 41:522–528.

46. Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. 68Ga-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; 01. 19. [Epub]. DOI: 10.1016/j.eururo.2015.12.051.

47. Pfister D, Porres D, Heidenreich A, Heidegger I, Knuechel R, Steib F, et al. Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with (68)Ga-PSMA-HBED-CC than with (18)F-Fluoroethylcholine PET/CT. Eur J Nucl Med Mol Imaging. 2016; 43:1410–1417.