Urology Annals
About UA | Search | Ahead of print | Current Issue | Archives | Instructions | Online submissionLogin 
Urology Annals
  Editorial Board | Subscribe | Advertise | Contact
Users Online: 284   Home Print this page  Email this page Small font size Default font size Increase font size


 
Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 10  |  Issue : 2  |  Page : 150-153  

Incremental value of 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography in patients with abnormal prostate-specific antigen and benign transrectal ultrasound biopsy


1 Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Uro - Gynae Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
3 Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

Date of Submission10-Apr-2017
Date of Acceptance19-Jun-2017
Date of Web Publication09-Apr-2018

Correspondence Address:
Dr. Manoj Gupta
Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi
India
Login to access the Email id


DOI: 10.4103/UA.UA_55_17

PMID: 29719325

Rights and Permissions
   Abstract 


Introduction: Bladder outlet obstruction due to prostate enlargement is a common health problem in male and frequently investigated with prostate-specific antigen (PSA) and transrectal ultrasound (TRUS). TRUS-guided biopsy is critical to differentiate benign prostatic hyperplasia (BPH) or prostate cancer (PCa) even though it has been associated with false negative with reported 3%–16% incidence of PCa in BPH specimens. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), a targeted molecular imaging for PCa, has showed promising results in recurrence and staging. We analyzed its role in patients with abnormal PSA and benign TRUS biopsy.
Material and Methods: Of 558 68Ga-PSMA PET/CT performed from July 2014 to February 2017, we found six patients with abnormal PSA (range 8.2–24.2 ng/ml, median: 13.3 ng/ml) with benign 12 cores TRUS biopsy as indication. These cases were reanalyzed in detail. Spearman's rank test was used entire correlation using SPSS version 21.
Results: 68Ga-PSMA PET/CT showed mild diffuse tracer uptake in prostate in all patients with no focality and maximum standard uptake value normalized to body weight (SUVmax) range was 3.2-5.8 (median: 3.9). Two patients with PSA <10 ng/ml had normal 68Ga-PSMA PET/CT and underwent medical management. In other four patients with PSA >10 ng/ml, two showed metastatic disease in pelvic lymph node in both and in lung in one; hence, 68Ga-PSMA PET/CT changed these patients' management. Spearman's rank test showed no correlation with baseline PSA and SUVmaxof prostate (rs −0.0287, P = 0.9571) while strong positive correlation was seen with baseline PSA and 68Ga-PSMA PET/CT scan positivity for extraprostatic disease (rs = 0.828, P = 0.042).
Conclusions: 68Ga-PSMA whole-body PET/CT can provide useful incremental information in patient with high PSA and negative TRUS biopsy and has a potential to guide management in this subgroup of PCa patients.

Keywords: 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography, abnormal prostate-specific antigen, benign prostatic hyperplasia, lung metastasis, negative 12 cores transrectal ultrasound biopsy


How to cite this article:
Gupta M, Choudhury PS, Rawal S, Gupta G. Incremental value of 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography in patients with abnormal prostate-specific antigen and benign transrectal ultrasound biopsy. Urol Ann 2018;10:150-3

How to cite this URL:
Gupta M, Choudhury PS, Rawal S, Gupta G. Incremental value of 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography in patients with abnormal prostate-specific antigen and benign transrectal ultrasound biopsy. Urol Ann [serial online] 2018 [cited 2021 Oct 19];10:150-3. Available from: https://www.urologyannals.com/text.asp?2018/10/2/150/226083




   Introduction Top


Bladder outlet obstruction (BOO) due to prostate enlargement is a common health problem in male and frequently investigated with prostate-specific antigen (PSA) and transrectal ultrasound (TRUS). TRUS-guided biopsy has been critical to differentiate benign prostatic hyperplasia (BPH) or prostate cancer (PCa) even though it has been associated with false negatives with reported 3-16% incidence of PCa in BPH specimens.[1],[2],[3],[4],[5] 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) is a targeted molecular imaging technique for PCa. Recent literature has proved its impact in PCa recurrence in comparison to current standard and other molecules in research.[6],[7] PSMA PET/CT has guided patient's management by detecting subcentimeter lymph node in staging patient as well.[8],[9] However, its role in patients with abnormal PSA and benign TRUS biopsy has not been reported in the literature to the best of our knowledge.


   Material and Methods Top


In our 68 Ga-PSMA PET/CT database of 558 patients referred for staging, restaging, response evaluation, suspected recurrence, and surveillance indications from July 2014 to February 2017, we identified that six patients with abnormal PSA and negative 12 cores TRUS-guided biopsy were referred to look for disease site. These patients were reanalyzed and reported by two independent nuclear medicine physicians for abnormalities in the prostate gland primarily and any other abnormal sites of PSMA avidity which could suggest disease.68 Ga-PSMA was synthesized in-house by a standard synthesis protocol.[10] Two MBq/kg body weight of labeled PSMA was injected intravenously and a full body scan (vertex to mid-thigh) was acquired with a dedicated full ring hybrid PET/CT system (Biograph TruePoint40 with LSO crystal from Siemens Healthcare at Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India) with 4 min per bed position in three-dimensional mode. A low-dose CT scan (40 mAs and 120 kVp) was used for attenuation correction and localization. Single voxel maximum standard uptake value normalized to body weight (SUVmax) was recorded for prostate gland and for all other abnormal PSMA positive lesions. Baseline PSA was correlated with prostate SUVmax and PSMA PET/CT scan positivity using Spearman's rank test. SPSS version 21 was used for statistical analysis.


   Results Top


Patient's details and the findings are summarized in [Table 1]. All patients showed mild diffuse tracer uptake in the prostate with SUVmax ranging from 3.2 to 5.8 (median: 3.9). No focal abnormality was seen in the prostate. Patients 1, 2, 3, and 6 did not show any PSMA avid lesion in rest of the body. Patient 4 and 5 showed abnormal PSMA avid pelvic lymph nodes in both and lung nodule only in patient 5 [Figure 1] and [Figure 2]. Subsequent histopathology with immunohistochemistry (NKX 3.1 and PSAP) from pelvic lymph node and lung nodule in case 4 and 5, respectively, showed metastatic adenocarcinoma from prostate. On Spearman's rank correlation [Table 2], we found no correlation of baseline PSA with SUVmax of prostate (rs − 0.029, P = 0.957). However, a strong positive correlation was seen of baseline PSA with 68 Ga-PSMA PET/CT scan positivity for extra-prostate disease (rs = 0.828, P = 0.042). Patient 1 underwent TURP for symptomatic relief with benign histology while patient 2 and 6 were treated medically. Patient 3 underwent radical prostatectomy (RP) with histopathology showing 5% tumor volume and 3 + 4 gleason score. Due to bilateral pelvic lymph node metastasis (one on each side) on 68 Ga-PSMA PET/CT scan in patient 4, RP with pelvic lymph node dissection was done. Histopathology showed acinar adenocarcinoma (1% tumor volume, Gleason 4+4) with bilateral pelvic lymph node metastasis (one on each side). Patient 5 was treated with androgen deprivation therapy.
Table 1: Patients demography with prostate-specific antigen, 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography, prostate maximum standard uptake value normalized to body weight, treatment, histopathology, and follow-up findings

Click here to view
Figure 1: 68-gallium-prostate-specific membrane antigen positron a emission tomography/computed tomography maximum intensity projection (a) and axial-fused images (b and c) showing mildly avid prostate and intensely avid bilateral pelvic lymphadenopathy

Click here to view
Figure 2: 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography maximum intensity projection (a) and axial fused images (b and c) showing mildly avid prostate and left lung lower lobe nodule

Click here to view
Table 2: Spearman's rank correlation of baseline prostate-specific antigen, maximum standard uptake value normalized to body weight of prostate, and 68-gallium-prostate-specific membrane antigen positron emission tomography/computed tomography positivity for extra-prostatic disease

Click here to view



   Discussion Top


Enlarged prostate is a most common cause of BOO in male which may be due to BPH or PCa.[11] PSA screening is used to differentiate these two pathologies with a 25% risk of PCa in range 4–10 ng/ml and 42%–64% for PSA >10 ng/ml.[12] Twelve cores TRUS-guided biopsy is used for further characterization as standard but has a low sensitivity and considerable false negative rate and a repeat biopsy may be required in highly suspected cases. We propose 68 Ga-PSMA PET/CT as a one stop shop to evaluate such cases.

68 Ga-PSMA PET-CT is a promising molecular imaging modality currently investigated in high-risk PCa primary staging and for restaging/metastatic workup in biochemical recurrence (BCR).[6],[7],[8],[9],[13] PSMA is a type II transmembrane glycoprotein exhibits folate hydrolase/glutamate carboxypeptidase II enzymatic activity and associated with prostatic carcinogenesis.[14],[15] Its expression is directly proportional to gleason score, metastasis, and hormone resistance in PCa.[16] In the last several years, a number of small molecules with PSMA enzyme inhibitor property have been developed. Small molecule inhibitor developed by the Heidelberg group 68 Ga-HBED-CC-PSMA-11 (68 Ga-PSMA) has been shown to be a novel radiotracer with high cell uptake and prolonged retention after internalization for PCa.[17],[18]

A recent systematic review and meta-analysis of 68 Ga-PSMA PET-CT showed that overall percentage of positive 68 Ga-PSMA PET was 40% for primary staging and 76% for BCR. For the PSA categories 0–0.2, 0.2–1, 1–2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive for BCR.[19] Maurer et al.[9] in a retrospective review of 130 consecutive patients undergoing 68 Ga-PSMA PET before primary lymphadenectomy in high-risk PCa showed sensitivity of 65.9% and specificity of 98.9%. In our experience for lymph node staging in high-risk PCa,68 Ga-PSMA PET-CT and MRI showed sensitivity and specificity of 66.67%, 98.61% and 25.93%, 98.61%, respectively.[13] However, no literature is available citing its role in benign TRUS biopsy cases with abnormal PSA. It has been a common practice to put these patients on follow-up due to no evidence of disease in routine imaging. We have identified a subset of patients who would need active treatment in this group.

Due to technical limitation,68 Ga-PSMA PET/CT is expected to be negative in BPH cases harboring early stage (≤T1b) cancer.[20] Mild diffuse 68 Ga-PSMA uptake has been reported with SUVmax range from 2.4 to 5.5 and the highest median value of 8.3 after 60 min of tracer injection even in normal cases.[21],[22] In our case series, SUVmax ranged from 3.2 to 5.8 (median: 3.9) and two patient (case 3 and 4) who underwent radical surgery had early stage PCa not detected by 68 Ga-PSMA PET/CT. However,68 Ga-PSMA PET/CT had incremental value in picking up extra-prostatic and extra-pelvic disease. In case 5, lung was the only site of extra-pelvic metastasis which is atypical in PCa.[23]

Our study was associated with limitations as well. Main limitations were the small number of patients, retrospective study, and no control group. Due to very specific cohort selection and PSMA PET/CT is still in developmental stage, not many patients were investigated with this indication. However, these initial results in this subset were encouraging, and hence, we believe future studies will make PSMA PET/CT a strong contender in this indication as well.


   Conclusion Top


68 Ga-PSMA whole-body PET/CT can provide useful incremental information in patient with high PSA and negative TRUS biopsy and has a potential to guide management in this subgroup of PCa patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Patel ND, Parsons JK. Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet obstruction. Indian J Urol 2014;30:170-6.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Eichler K, Hempel S, Wilby J, Myers L, Bachmann LM, Kleijnen J. Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: A systematic review. J Urol 2006;175:1605-12.  Back to cited text no. 2
[PUBMED]    
3.
Lepor H, Owens RS, Rogenes V, Kuhn E. Detection of prostate cancer in males with prostatism. Prostate 1994;25:132-40.  Back to cited text no. 3
[PUBMED]    
4.
Merrill RM, Wiggins CL. Incidental detection of population-based prostate cancer incidence rates through transurethral resection of the prostate. Urol Oncol 2002;7:213-9.  Back to cited text no. 4
[PUBMED]    
5.
Lee DH, Chung DY, Lee KS, Kim IK, Rha KH, Choi YD, et al. Clinical experiences of incidental prostate cancer after transurethral resection of prostate (TURP) according to initial treatment: A study of a Korean high volume center. Yonsei Med J 2014;55:78-83.  Back to cited text no. 5
[PUBMED]    
6.
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;41:515-21.  Back to cited text no. 6
[PUBMED]    
7.
Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol 2016;13:226-35.  Back to cited text no. 7
[PUBMED]    
8.
Van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, et al. Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int 2017;119:209-215.  Back to cited text no. 8
    
9.
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;195:1436-43.  Back to cited text no. 9
[PUBMED]    
10.
Amor-Coarasa A, Schoendorf M, Meckel M, Vallabhajosula S, Babich JW. Comprehensive Quality Control of the ITG 68Ge/68Ga Generator and Synthesis of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC for Clinical Imaging. J Nucl Med 2016;57:1402-5.  Back to cited text no. 10
[PUBMED]    
11.
Dmochowski RR. Bladder outlet obstruction: Etiology and evaluation. Rev Urol 2005;7 Suppl 6:S3-13.  Back to cited text no. 11
[PUBMED]    
12.
Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, et al. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: Results of a multicenter clinical trial of 6,630 men. J Urol 1994;151:1283-90.  Back to cited text no. 12
[PUBMED]    
13.
Gupta M, Choudhury PS, Hazarika D, Rawal S. A comparative study of 68gallium-prostate specific membrane antigen positron emission tomography-computed tomography and magnetic resonance imaging for lymph node staging in high risk prostate cancer patients: An initial experience. World J Nucl Med 2017;16:186-91.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: Focus on prostate-specific membrane antigen. Curr Top Med Chem 2013;13:951-62.  Back to cited text no. 14
[PUBMED]    
15.
Yao V, Parwani A, Maier C, Heston WD, Bacich DJ. Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis. Cancer Res 2008;68:9070-7.  Back to cited text no. 15
[PUBMED]    
16.
Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997;3:81-5.  Back to cited text no. 16
[PUBMED]    
17.
Eder M, Schäfer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Kopka K. Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. Prostate 2014;74:659-68.  Back to cited text no. 17
    
18.
Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, et al. PET imaging with a [68Ga] gallium-labelled PSMA ligand for the diagnosis of prostate cancer: Biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013;40:486-95.  Back to cited text no. 18
[PUBMED]    
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;70:926-37.  Back to cited text no. 19
[PUBMED]    
20.
Otto B, Barbieri C, Lee R, Te AE, Kaplan SA, Robinson B, et al. Incidental prostate cancer in transurethral resection of the prostate specimens in the modern era. Adv Urol 2014;2014:627290.  Back to cited text no. 20
[PUBMED]    
21.
Demirci E, Sahin OE, Ocak M, Akovali B, Nematyazar J, Kabasakal L. Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging. Nucl Med Commun 2016;37:1169-79.  Back to cited text no. 21
[PUBMED]    
22.
Sachpekidis C, Kopka K, Eder M, Hadaschik BA, Freitag MT, Pan L, et al. 68Ga-PSMA-11 Dynamic PET/CT Imaging in Primary Prostate Cancer. Clin Nucl Med 2016;41:e473-9.  Back to cited text no. 22
[PUBMED]    
23.
Vinjamoori AH, Jagannathan JP, Shinagare AB, Taplin ME, Oh WK, Van den Abbeele AD, et al. Atypical metastases from prostate cancer: 10-year experience at a single institution. AJR Am J Roentgenol 2012;199:367-72.  Back to cited text no. 23
[PUBMED]    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Material and Methods
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed2666    
    Printed49    
    Emailed0    
    PDF Downloaded288    
    Comments [Add]    

Recommend this journal