Neuroendocrine differentiation in castration resistant prostate cancer. Nuclear medicine radiopharmaceuticals and imaging techniques: A narrative review

Affiliations


Abstract

Background: Androgen Deprivation Therapy (ADT) is the primary treatment for patients suffering from relapsing or advanced prostate cancer (PC). Hormone therapy generally guarantees adequate clinical control of the disease for some years, even in those patients affected by widespread skeletal and soft tissue metastases. Despite ADT, however, most patients treated with hormones eventually progress to castration-resistant prostate cancer (CRPC), for which there are no effective treatments. This clinical reality is an open challenge to the oncologist because of those neoplasms which elaborate neuroendocrine differentiation (NED).

Methods: An online search of current and past literature on NED in CRPC was performed. Relevant articles dealing with the biological and pathological basis of NED, with nuclear medicine imaging in CRPC and somatostatin treatment in NED were analyzed.

Evidence from the literature: NED may arise in prostate cancer patients in the late stages of ADT. The onset of NED offers prognostic insight because it reflects a dramatic increase in the aggressive nature of the neoplasm. Several genetic, molecular, cytological and immunohistochemical markers are associated with this transformation. Among these, overexpression of somatostatin receptors, seen through Nuclear Medicine testing, is one of the most studied.

Conclusions: Preliminary studies show that the overexpression of somatostatin receptors related to NED in CRPC may easily be studied in vivo with PET/CT. This finding offers a potentially useful objective for targeted therapy in CRPC. If the overexpression of SSTRs is shown to afflict a significant segment of patients with CRPC, this will open further study of possible therapeutic options based on this marker.

Keywords: Androgen deprivation therapy; Castration-resistant prostate cancer; Neuroendocrine differentiation; Positron Emission Tomography; Somatostatin analogs; Somatostatin receptors.


Similar articles

PET/CT With 68Ga-DOTA-TATE for Diagnosis of Neuroendocrine: Differentiation in Patients With Castrate-Resistant Prostate Cancer.

Gofrit ON, Frank S, Meirovitz A, Nechushtan H, Orevi M.Clin Nucl Med. 2017 Jan;42(1):1-6. doi: 10.1097/RLU.0000000000001424.PMID: 27775942

Somatostatin receptors over-expression in castration resistant prostate cancer detected by PET/CT: preliminary report of in six patients.

Savelli G, Muni A, Falchi R, Zaniboni A, Barbieri R, Valmadre G, Minari C, Casi C, Rossini P.Ann Transl Med. 2015 Jun;3(10):145. doi: 10.3978/j.issn.2305-5839.2015.06.10.PMID: 26207238 Free PMC article.

Elevated circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) levels are associated with neuroendocrine differentiation in castration resistant prostate cancer.

Gong Y, Chippada-Venkata UD, Galsky MD, Huang J, Oh WK.Prostate. 2015 May;75(6):616-27. doi: 10.1002/pros.22945. Epub 2015 Jan 5.PMID: 25560638

Neuroendocrine differentiation in prostate cancer: current and emerging therapy strategies.

Conteduca V, Aieta M, Amadori D, De Giorgi U.Crit Rev Oncol Hematol. 2014 Oct;92(1):11-24. doi: 10.1016/j.critrevonc.2014.05.008. Epub 2014 May 27.PMID: 24952997 Review.

Radiopharmaceuticals for the Diagnosis and Therapy of Neuroendocrine Differentiated Prostate Cancer.

Giovacchini G, Giovannini E, Riondato M, Ciarmiello A.Curr Radiopharm. 2017;10(1):6-15. doi: 10.2174/1874471009666161229123126.PMID: 28034291 Review.


Cited by

The Combined Effect of Downregulated RB1 and Overexpressed lncRNA SSTRS-AS1 on Prediction Time to Castration-Resistant Prostate Cancer: Indonesian Cohort Studies.

Soerohardjo I, Zulfiqqar A, Widodo I, Setyo Heriyanto D, Lukman Anwar S.Turk J Urol. 2022 Mar;48(2):112-117. doi: 10.5152/tud.2022.21282.PMID: 35420053 Free PMC article.

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol.

Pouliot F, Beauregard JM, Saad F, Trudel D, Richard PO, Turcotte É, Rousseau É, Probst S, Kassouf W, Anidjar M, Camirand Lemyre F, Bouvet GF, Neveu B, Tétu A, Guérin B.BJU Int. 2022 Sep;130(3):314-322. doi: 10.1111/bju.15621. Epub 2021 Nov 11.PMID: 34674367 Free PMC article.

Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment.

Makino T, Izumi K, Mizokami A.Biomedicines. 2021 Apr 12;9(4):414. doi: 10.3390/biomedicines9040414.PMID: 33921329 Free PMC article. Review.

New Frontiers in Molecular Imaging Using Peptide-Based Radiopharmaceuticals for Prostate Cancer.

Li X, Cai H, Wu X, Li L, Wu H, Tian R.Front Chem. 2020 Dec 1;8:583309. doi: 10.3389/fchem.2020.583309. eCollection 2020.PMID: 33335885 Free PMC article. Review.


KMEL References