The value of mpMRI combined with 99mTc-PSMA SPECT/CT in the detection of significant residual prostate cancer after neoadjuvant androgen deprivation therapy

doi:10.19401/j.cnki.1007-3639.2022.02.005

Abstract

Abstract:

Background and purpose: Androgen deprivation therapy (ADT) is a key primary treatment for prostate cancer. However, there is still a lack of direct and accurate assessment method for the changes in the lesions after ADT treatment. The aim of this study was to explore the value of multiparametric magnetic resonance imaging (mpMRI) combined with technetium-99m labelled small molecule against prostate specific membrane antigen (PSMA) (HYNIC-Glu-Urea-A, ^99mTc-PSMA) single photon emission computed tomography (SPECT)/computed tomography (CT) in the detection of significant residual prostate cancer after neoadjuvant ADT with the reference standard of postoperative pathology. Methods: A retrospective analysis of 154 prostate cancer patients treated in Fudan University Shanghai Cancer Center from March 2017 to July 2021 who underwent radical prostatectomy (RP) after neoadjuvant ADT was performed. All patients underwent preoperative mpMRI and ^99mTc-PSMA SPECT/CT. Patients were divided into two groups according to the postoperative pathology: the significant residual group and complete response or minimum residual disease (CR/MRD) group. The clinical characteristics, the scores of Prostate Magnetic Resonance Imaging for Local Recurrence Reporting (PI-RR) system and the positive rate of ^99mTc-PSMA SPECT/CT of the two groups were compared. The differences among the diagnostic efficacy of mpMRI and ^99mTc-PSMA SPECT/CT alone and in combination were analyzed by the receiver operating characteristic (ROC) curve and the area under curve (AUC). Results: In total, the significant residual group consisted of 128 patients, and the CR/MRD group consisted of 26 patients. The average and median age of the patients were 66.88±7.79 (ranged from 47 to 85) years and 68 years, respectively. There was no statistical difference in age, PSA before neoadjuvant ADT and Gleason scores between the two groups, while PSA after neoadjuvant ADT of the significant residual group was significantly higher than that of the CR/MRD group. The AUC of mpMRI was 0.713, the sensitivity and specificity were 78.13% and 30.77%, respectively, with a cut-off of PI-RR score 3, while sensitivity and specificity were 68.75% and 69.23%, respectively, with a cut-off of PI-RR score 4. The AUC of ^99mTc-PSMA SPECT/CT was 0.729, the sensitivity and specificity were 76.56% and 69.23%, respectively. The AUC of mpMRI combined with ^99mTc-PSMA SPECT/CT was 0.809, which was significantly higher compared with the two alone (P<0.05). Conclusion: The combination of mpMRI and ^99mTc-PSMA SPECT/CT can significantly improve the diagnostic efficiency for significant residual prostate cancer after neoadjuvant ADT.

Key words: Prostate cancer, Neoadjuvant androgen deprivation therapy, Magnetic resonance imaging, Prostate specific membrane antigen, Single photon emission computed tomography

CLC Number:

R737.25

ZHOU Bingni, LIU Xiaohang, GU Bingxin, ZHOU Liangping, GU Yajia. The value of mpMRI combined with ^99mTc-PSMA SPECT/CT in the detection of significant residual prostate cancer after neoadjuvant androgen deprivation therapy[J]. China Oncology, 2022, 32(2): 134-141.

Figures/Tables 7

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References 30

[1]	SIEGEL R L,, MILLER K D,, FUCHS H E, et al. Cancer statistics, 2021[J]. CA Cancer J Clin, 2021,71(1):7-33.
[2]	HEDGIRE S,, KILCOYNE A,, TONYUSHKIN A, et al. Effect of androgen deprivation and radiation therapy on MRI fiber tractography in prostate cancer: can we assess treatment response on imaging?[J]. Br J Radiol, 2019,92(1093):20170170.
[3]	COAKLEY F V,, TEH H S,, QAYYUM A, et al. Endorectal MR imaging and MR spectroscopic imaging for locally recurrent prostate cancer after external beam radiation therapy: preliminary experience[J]. Radiology, 2004,233(2):441-448.
[4]	HOFMAN M S,, LAWRENTSCHUK N,, FRANCIS R J, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study[J]. Lancet, 2020,395(10231):1208-1216.
[5]	FENDLER W P,, FERDINANDUS J,, CZERNIN J, et al. Impact of ⁶⁸Ga-PSMA-11 PET on the management of recurrent prostate cancer in a prospective single-arm clinical trial [J]. J Nucl Med, 2020,61(12):1793-1799.
[6]	AFSHAR-OROMIEH A,, HABERKORN U,, SCHLEMMER H P, et al. Comparison of PET/CT and PET/MRI hybrid systems using a ⁶⁸Ga-labelled PSMA ligand for the diagnosis of recurrent prostate cancer: initial experience [J]. Eur J Nucl Med Mol Imaging, 2014,41(5):887-897.
[7]	EIBER M,, MAURER T,, SOUVATZOGLOU M, et al. Evaluation of hybrid ⁶⁸Ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy [J]. J Nucl Med, 2015,56(5):668-674.
[8]	MORIGI J J,, STRICKER P D,, VAN LEEUWEN P J, 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]. J Nucl Med, 2015,56(8):1185-1190.
[9]	LAWAL I O,, ANKRAH A O,, MOKGORO N P, et al. Diagnostic sensitivity of Tc- ^99m hynic PSMA SPECT/CT in prostate carcinoma: a comparative analysis with Ga-68 PSMA PET/CT [J]. Prostate, 2017,77(11):1205-1212.
[10]	ONAL C,, GULER O C,, TORUN N, et al. The effect of androgen deprivation therapy on ⁶⁸Ga-PSMA tracer uptake in non-metastatic prostate cancer patients [J]. Eur J Nucl Med Mol Imaging, 2020,47(3):632-641.
[11]	PANEBIANCO V,, VILLEIRS G,, WEINREB J C, et al. Prostate magnetic resonance imaging for local recurrence reporting (PI-RR): international consensus-based guidelines on multiparametric magnetic resonance imaging for prostate cancer recurrence after radiation therapy and radical prostatectomy[J]. Eur Urol Oncol, 2021,4(6):868-876.
[12]	胡四龙,, 许晓平,, 朱耀, 等. ^99mTc标记PSMA小分子抑制剂靶向前列腺癌分子影像初步临床研究 [J]. 中国癌症杂志, 2016,26(7):608-615.
	HU S L,, XU X P,, ZHU Y, et al. Preliminary clinical study of ^99mTc-labelled small molecules against PSMA for prostate cancer imaging [J]. China Oncol, 2016,26(7):608-615.
[13]	许晓平,, 张建平,, 何思敏, 等. 前列腺特异性膜抗原小分子抑制剂显像研究[J]. 肿瘤影像学, 2015,24(3):173-178.
	XU X P,, ZHANG J P,, HE S M, et al. The imaging study of a small-molecular inhibitor targeting prostate specific membrane antigen[J]. Oncoradiology, 2015,24(3):173-178.
[14]	MCKAY R R,, MONTGOMERY B,, XIE W L, et al. Post prostatectomy outcomes of patients with high-risk prostate cancer treated with neoadjuvant androgen blockade[J]. Prostate Cancer Prostatic Dis, 2018,21(3):364-372.
[15]	PETRAKI C D,, SFIKAS C P. Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma[J]. Histol Histopathol, 2007,22(1):107-118.
[16]	STABILE A,, GIGANTI F,, ROSENKRANTZ A B, et al. Multiparametric MRI for prostate cancer diagnosis: current status and future directions[J]. Nat Rev Urol, 2020,17(1):41-61.
[17]	KATELARIS N C,, BOLTON D M,, WEERAKOON M, et al. Current role of multiparametric magnetic resonance imaging in the management of prostate cancer[J]. Korean J Urol, 2015,56(5):337-345.
[18]	PADHANI A R,, MACVICAR A D,, GAPINSKI C J, et al. Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with MR imaging[J]. Radiology, 2001,218(2):365-374.
[19]	MURPHY W M,, SOLOWAY M S,, BARROWS G H. Pathologic changes associated with androgen deprivation therapy for prostate cancer[J]. Cancer, 1991,68(4):821-828.
[20]	JOSEPH I B,, NELSON J B,, DENMEADE S R, et al. Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue[J]. Clin Cancer Res, 1997,3(12 Pt 1):2507-2511.
[21]	BARRETT T,, GILL A B,, KATAOKA M Y, et al. DCE and DW MRI in monitoring response to androgen deprivation therapy in patients with prostate cancer: a feasibility study[J]. Magn Reson Med, 2012,67(3):778-785.
[22]	RØE K,, SEIERSTAD T,, KRISTIAN A, et al. Longitudinal magnetic resonance imaging-based assessment of vascular changes and radiation response in androgen-sensitive prostate carcinoma xenografts under androgen-exposed and androgen-deprived conditions[J]. Neoplasia, 2010,12(10):818-825.
[23]	RØE K,, KAKAR M,, SEIERSTAD T, et al. Early prediction of response to radiotherapy and androgen-deprivation therapy in prostate cancer by repeated functional MRI: a preclinical study[J]. Radiat Oncol, 2011,6:65.
[24]	CHRISTIE D R,, SHARPLEY C F,, MITINA N, et al. Is prospective MRI mapping of the changes in the volume of the prostate gland in prostate cancer patients undergoing 6 months of neo-adjuvant androgen deprivation therapy a step towards a trial to determine those who may benefit from treatment intensification or extended duration?[J]. J Med Imaging Radiat Oncol, 2020,64(2):287-292.
[25]	胡四龙,, 许晓平,, 朱耀, 等. ^99mTc-PSMA SPECT/CT探测前列腺癌病灶的临床应用价值 [J]. 肿瘤影像学, 2016,25(3):272-278.
	HU S L,, XU X P,, ZHU Y, et al. Clinical value of ^99mTc-PSMA SPECT/CT in detection of prostate cancer [J]. Oncoradiology, 2016,25(3):272-278.
[26]	REINFELDER J,, KUWERT T,, BECK M, et al. First experience with SPECT/CT using a ^99mTc-labeled inhibitor for prostate-specific membrane antigen in patients with biochemical recurrence of prostate cancer [J]. Clin Nucl Med, 2017,42(1):26-33.
[27]	GARCÍA-PÉREZ F O,, DAVANZO J,, LÓPEZ-BUENROSTRO S, et al. Head to head comparison performance of ^99mTc-EDDA/HYNIC-iPSMA SPECT/CT and ⁶⁸Ga-PSMA-11 PET/CT a prospective study in biochemical recurrence prostate cancer patients [J]. Am J Nucl Med Mol Imaging, 2018,8(5):332-340.
[28]	KWAK C,, JEONG S J,, PARK M S, et al. Prognostic significance of the nadir prostate-specific antigen level after hormone therapy for prostate cancer[J]. J Urol, 2002,168(3):995-1000.
[29]	EVANS M J,, SMITH-JONES P M,, WONGVIPAT J, et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen[J]. Proc Natl Acad Sci USA, 2011,108(23):9578-9582.
[30]	VAZ S,, HADASCHIK B,, GABRIEL M, et al. Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients[J]. Eur J Nucl Med Mol Imaging, 2020,47(1):9-15.

Sequence	Score	Pattern changes
T2WI	1	No abnormal signal intensity compared to the background
	2	Linear, wedge-shaped, or diffuse moderate hypointensity or residual benign prostatic hyperplasia nodules
	3	Focal or mass-like mild hypointensity not at the primary tumor site; includes others that do not qualify as 2, 4, or 5
	4	Focal or mass-like moderate hypointensity not at the same site as the primary tumor, or location of primary tumor not known
	5	Focal or mass-like marked hypointensity at the same site as the primary tumor
DWI	1	No abnormality on high b-value DWI and apparent diffusion coeffecient (ADC) map
	2	Diffuse moderate hyperintensity on high b-value DWI and/or diffuse moderate hypointensity on the ADC map
	3	Focal marked hyperintensity on high b-value DWI or focal marked hypointensity on the ADC map, but not on both
	4	Focal marked hyperintensity on high b-value DWI and marked hypointensity on the ADC map not at the same site as the primary tumor, or site of the primary tumor not known
	5	Focal marked hyperintensity on high b-value DWI and marked hypointensity on the ADC map at the same site as the primary tumor
DCE	1	No enhancement
	2	Diffuse or heterogeneous enhancement
	3	Focal or mass-like late enhancement
	4	Focal or mass-like early enhancement not at the same site as the primary tumor, or tumor site not known
	5	Focal or mass-like early enhancement at the same site as the primary tumor

	Average age	Initial PSA	PSA after neoadjuvant ADT	Gleason score
SR group	66.84±7.76	82.56 (21.39, 218.42)	0.236 (0.06, 2.50)	9 (8, 9)
CR/MRD group	67.08±8.26	138.00 (8.23, 200.00)	0.086 (0.01, 0.35)	8 (7, 9)
P value	0.854	0.514	0.021	0.073