Assessment of Neuroendocrine Features Using 99mTc-Octreotide Scintigraphy in Patients with Metastatic Castration-Resistant Prostate Cancer: Does it Predict Response to 177Lu-PSMA Radioligand Therapy?
Urology Journal,
Vol. 23 No. 03 (2026),
29 August 2026
,
Page 100-106
https://doi.org/10.22037/uj.v23i03.8610
Abstract
Purpose: Neuroendocrine differentiation is a recognized phenotypic change in advanced prostate cancer. Neuroendocrine-like cells may lack androgen receptor or prostate-specific membrane antigen expression, potentially contributing to treatment resistance. This study evaluated octreotide scan positivity as a surrogate marker of neuroendocrine differentiation and its association with response to 177Lu-prostate-specific membrane antigen radioligand therapy in patients with metastatic castration-resistant prostate cancer.
Materials and Methods: Thirty-six patients with metastatic castration-resistant prostate cancer who were candidates for 177Lu-prostate-specific membrane antigen radioligand therapy were enrolled. Whole-body octreotide scintigraphy was performed after intravenous administration of 750 MBq of 99mTc-octreotide. Abnormal uptake was classified as mild, moderate, or severe relative to liver uptake. All patients subsequently received standard 177Lu-prostate-specific membrane antigen radioligand therapy and were followed for treatment response after at least two treatment cycles.
Results: Of the 36 enrolled patients, 8 who died within 2 months after the first treatment cycle were excluded from response assessment; therefore, 28 patients were included in the final response analysis. Among these 28 patients, 19 (67.9%) responded to treatment and 9 (32.1%) did not. Eight patients (28.6%) had negative octreotide scans, whereas 20 (71.4%) had positive scans, all showing mild uptake. Positive scans were observed in 13 of 19 responders (68.4%) and 7 of 9 non-responders (77.8%). No significant association was observed between octreotide scan positivity and treatment response (P = 1.00).
Conclusion: Octreotide scan positivity was relatively common in patients with metastatic castration-resistant prostate cancer but was not significantly associated with response to 177Lu-prostate-specific membrane antigen radioligand therapy. Larger studies are needed to confirm these findings.
- prostate cancer
- neuroendocrine differentiation
- mCRPC
- 177Lu-PSMA
How to Cite
References
1. Gandaglia G, Leni R, Bray F, Fleshner N, et al. Epidemiology and prevention of prostate cancer. Eur Urol Oncol. 2021;4:877-892.
2. Bergengren O, Pekala KR, Matsoukas K, et al. 2022 update on prostate cancer epidemiology and risk factors—a systematic review. Eur Urol. 2023;84:191-206.
3. Aghdam RA, Amoui M, Ghodsirad M, et al. Efficacy and safety of 177Lutetium-prostate-specific membrane antigen therapy in metastatic castration-resistant prostate cancer patients: first experience in West Asia—a prospective study. World J Nucl Med. 2019;18:258-265.
4. Patell K, Kurian M, Garcia JA, et al. Lutetium-177 PSMA for the treatment of metastatic castrate-resistant prostate cancer: a systematic review. Expert Rev Anticancer Ther. 2023;23:731-744.
5. Hofman MS, Emmett L, Sandhu S, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397:797-804.
6. Stuparu AD, Capri JR, Meyer CAL, et al. Mechanisms of resistance to prostate-specific membrane antigen-targeted radioligand therapy in a mouse model of prostate cancer. J Nucl Med. 2021;62:989-995.
7. Merkens L, Sailer V, Lessel D, et al. Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation. J Exp Clin Cancer Res. 2022;41:46.
8. Yamada Y, Beltran H. Clinical and biological features of neuroendocrine prostate cancer. Curr Oncol Rep. 2021;23:1-10.
9. Wang Y, Wang Y, Ci X, et al. Molecular events in neuroendocrine prostate cancer development. Nat Rev Urol. 2021;18:581-596.
10. Refardt J, Hofland J, Wild D, Christ E. Molecular imaging of neuroendocrine neoplasms. J Clin Endocrinol Metab. 2022;107:e2662-e2670.
11. Ahmadzadehfar H, Aryana K, Pirayesh E, et al. The Iranian Society of Nuclear Medicine practical guideline on radioligand therapy in metastatic castration-resistant prostate cancer using 177Lu-PSMA. Iran J Nucl Med. 2018;26:2.
12. Surcel CI, van Oort IM, Sooriakumaran P, et al. Prognostic effect of neuroendocrine differentiation in prostate cancer: a critical review. Urol Oncol. 2015;33:265.e1-265.e7.
13. Hu CD, Choo R, Huang J. Neuroendocrine differentiation in prostate cancer: a mechanism of radioresistance and treatment failure. Front Oncol. 2015;5:90.
14. Santoni M, Conti A, Burattini L, et al. Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives. Biochim Biophys Acta. 2014;1846:630-637.
15. Tan M, Karaoğlan Ü, Çelik B, Ataoğlu Ö, Biri H, Bozkirli I. Prostate cancer and neuroendocrine differentiation. Int Urol Nephrol. 1999;31:75-82.
16. Parimi V, Goyal R, Poropatich K, Yang XJ. Neuroendocrine differentiation of prostate cancer: a review. Am J Clin Exp Urol. 2014;2:273-285.
17. Derlin T, Werner RA, Lafos M, et al. Neuroendocrine differentiation and response to PSMA-targeted radioligand therapy in advanced metastatic castration-resistant prostate cancer: a single-center retrospective study. J Nucl Med. 2020;61:1602-1606.
18. Kessel K, Seifert R, Weckesser M, et al. Molecular analysis of circulating tumor cells of metastatic castration-resistant prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy. Theranostics. 2020;10:7645-7655.
19. Bakht MK, Derecichei I, Li Y, et al. Neuroendocrine differentiation of prostate cancer leads to PSMA suppression. Endocr Relat Cancer. 2018;26:131-146.
20. Assadi M, Pirayesh E, Rekabpour SJ, et al. 177Lu-PSMA and 177Lu-DOTATATE therapy in a patient with metastatic castration-resistant prostate cancer and neuroendocrine differentiation. Clin Nucl Med. 2019;44:978-980.
21. Webb M. An exceptional response to 177LuPSMA undermined by neuroendocrine transformation. Urol Case Rep. 2021;34:101467.
22. Priftakis D, Kritikos N, Stavrinides S, Kleanthous S, Baziotis N. Neuroendocrine differentiation in castration-resistant prostate cancer: a case report. Mol Clin Oncol. 2015;3:1392-1394.
23. Karimzadeh A, Heck M, Tauber R, et al. 177Lu-PSMA-I&T for treatment of metastatic castration-resistant prostate cancer: prognostic value of scintigraphic and clinical biomarkers. J Nucl Med. 2023;64:402-409.
24. Heck MM, Tauber R, Schwaiger S, et al. Treatment outcome, toxicity, and predictive factors for radioligand therapy with 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. Eur Urol. 2019;75:920-926.
25. Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. 177Lu-PSMA radioligand therapy for prostate cancer. J Nucl Med. 2017;58:1196-1200.
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