Multiparametric MRI (mpMRI) is used to detect and evaluate the clinical significance of prostatic lesions, to assess loco-regional extension (T stage) and metastasis to lymph node or bone marrow in pelvic region. The usage of Diffusion-Weight Imaging (DWI) with Dynamic Contrast Enhanced Imaging (DCE) in mpMRI has shown to improve the sensitivity of MRI to 90%, specificity over 70% with negative predictive value of 95% for more than 3+3 Gleason score tumors. Although mpMRI has a structured reporting system called Prostate Imaging Reporting and Data System (PIRADS), its wide clinical application is limited by inter observer variability and lack of reproducibility. Therefore, on account of the moderate specificity, the only way to make diagnosis in case of cancer remains biopsy of the prostate. Due to limitations of MRI, there is need of other imaging modalities which can be in this clinical scenario [1-5].

Prostate-Specific Membrane Antigen (PSMA) is a type II transmembrane glycoprotein that has shown considerably raised expression in PCa cells and has been successfully used as target for molecular imaging approaches. The density of PSMA expression in malignant prostate cancer has been found to be 1000 times higher compared to normal prostate tissue. For molecular imaging, PSMA can be targeted either with PSMA ligands or antibodies. PSMA targeting ligands get internalized after binding to receptor and undergo endosomal recycling, resulting in increased uptake and retention in PCa cells which can be imaged. ⁶⁸Ga-PSMA PET/CT (Positron Emission Tomography) is a relatively new diagnostic modality which targets PSMA binding on PCa cells and has shown potential in detection of nodal/distant metastasis and recurrence in PCa with high accuracy. A meta-analysis reported pooled specificity of ⁶⁸Ga-PSMA PET/CT for disease staging and restaging to be 84% and 97% respectively [6-11]. Many studies have evaluated the role of ⁶⁸Ga-PSMA PET/CT in biopsy proven PCa (done for staging) and evaluated tracer uptake in the primary tumor and compared it with mpMRI.

Aims and Objectives

To compare the Diagnostic performance of ⁶⁸Ga PSMA PET/CT and mpMRI in prostate cancer patients.

Study Design

Prospective pilot study.

Place of Study

This study has been conducted at the Department of Nuclear Medicine, PGIMER Chandigarh in collaboration with the Department Urology, Radiodiagnosis and Histopathology, PGIMER, Chandigarh.

Period of study

The study was done during the period between January, 2018 and June, 2019.

Inclusion Criteria

• Patients having suspicion of carcinoma prostate on clinical assessment and/or raised serum PSA levels (>4ng/mL)

• Patient not suffering from bleeding diathesis or renal failure

• Patient consent to participate in the stud

Exclusion Criteria

• Patient with prior diagnosed PCa or who underwent prostatic biopsy priorto 68Ga-PSMA PET/CT and mpMRI

• Patients with deranged renal function tests orcoagulogram

• Patient refused to participate in the study

Study Population

A total of 44patients suspected for PCa on the basis of clinical assessment and/or raised PSA were recruited for the study.

Patients suspected for prostate adenocarcinoma and/or serum PSA levels >4ng/ml and willing to participate in the study were recruited. Study was approved by Institutional Ethics Committee, PGIMER Chandigarh. Written informed consent was obtained. After clinical assessment, mpMRI and ⁶⁸Ga-PSMA PET/CT were done. Biopsy was done in cases with high clinical suspicion of PCa (Figure 1).

Statistical Analysis

Qualitative variables are described using number and percentages. Normally distributed continuous quantitative data is described using mean and standard deviation.

Skewed quantitative data is described using median and interquartile range. The normality of data will be checked by measures of Kolmogorov-Smirnov tests of normality. The sensitivity, specificity, NPV and PPV of ⁶⁸Ga-PSMA PET/CT and mpMRI was estimated using a 2x2 table. The statistical analysis was conducted using the IBM SPSS Statistics (version 23.0).

Figure 1: Study Methodology

In this prospective study, a total of 44 patients suspected to have PCa were recruited on the basis of clinical assessment and serum PSA levels. All patients were subjected to ⁶⁸Ga-PSMA PET/CT acquisition. Out of the total 44 patients, 33 underwent biopsy. The remaining 11 patients did not undergo biopsy after revised clinical assessment based on negative. Therefore, 33 patients underwent ⁶⁸Ga-PSMA PET/CT and biopsy. Out of total 44, 33 patients also underwent mpMRI. Out of the total 44 patients, 33 underwent biopsy. Only 22 out of these 33 patients underwent mpMRI.

After visual interpretation,68Ga-PSMA PET/CT data was compared to histopathology (gold standard). Results of 68Ga-PSMA and biopsy findings were shown in Table 1. 

Table 1: Results of 68Ga-PSMA PET/CT

*TP: True Positive, TN: True Negative, FP: False Positive and FN: False Negative

The sensitivity, specificity, PPV, NPV and accuracy of 68Ga-PSMA PET/CT to detect PCa was 81.25%, 88.24%, 86.67%, 83.33% and 84.85% respectively.

About 11/22 (50%) patients who underwent mpMRI were diagnosed with malignancy. When PIRADS III-V were considered as positive lesions on mpMRI and compared with gold standard, the analysis revealed sensitivity, specificity, PPV, NPV and accuracy of mpMRI to be 100%, 81.82%, 84.62%, 100% and 90.91% respectively to detect the adenocarcinoma PCa. Table 2 and 3 showed the mpMRI results.

Table 2: Showing mpMRI (Multi-parametric Magnetic Resonance Imaging) Results Compared with Biopsy

*TP: True Positive, TN: True Negative, FP: False Positive and FN: False Negative

Data of twenty-two patients who underwent both MRI and ⁶⁸Ga PSMA PET/CT were separately evaluated and 19/22 (86.4%) had concordant findings between mpMRI and ⁶⁸Ga PSMA PET/CT. Out of these, 9 had no finding to suggest PCa on both modalities whereas 10 had lesion suggestive of malignancy on both imaging modalities. In 3/22 (13.6%) patients were having discordant finding with mpMRI positive in all of them and no lesion on 68Ga PSMA PET/CT. Out of these 3, one was positive for malignancy (adenocarcinoma, GS 3+3) and 2 had no evidence of malignancy on biopsy. Agreement was evaluated between mpMRI and PSMA PET/CT findings. On assessment, substantial agreement was found between these two modalities (kappa value 0.732).

Table 3: Diagnostic Performance Comparison between 68Ga PSMA PET/CT and mpMRI

To best of our knowledge, this study is first prospective study to assess the diagnostic role of ⁶⁸Ga-PSMA PET-CT in patients with suspected prostate adenocarcinoma and compare it with mpMRI.

In our study, biopsy and 68Ga-PSMA PET/CT was done in 33 patients. The sensitivity, specificity, NPV, PPV and accuracy of ⁶⁸Ga-PSMA PET/CT was found to be 81.25%, 88.24%, 83.33%, 86.67% and 84.85% respectively. In the only retrospective study done till date by Zhang et al. [12], the reported sensitivity, specificity, NPV, PPV of ⁶⁸Ga-PSMA PET/CT was 91.67%, 81.82%, 89.19% and 85.71%. Specificity in our study was found to be higher and sensitivity is lower as compared to study by Zhang et al. [12]. This is due to presence of fewer false positive and more false negative cases in our study. The reason for lesser sensitivity in our study could be that the two of false negative cases had low grade PCa with lower tumor burden.

mpMRI showed very high accuracy in our study when PIRADS score ≥3 were considered positive for PCa with sensitivity and specificity of 100 and 81.82% respectively. However, on taking PIRADS III as negative for malignancy the sensitivity falls to 81.82% and the specificity increases to 90.9%. A meta-analysis by Woo et al. [13], showed pooled sensitivity and specificity of mpMRI to be 0.89 and 0.73, respectively. We found substantial agreement between ⁶⁸Ga-PSMA PET/CT and mpMRI (kappa value 0.732). 

mpMRI is an established investigation with good diagnostic efficacy in detecting potentially significant PCa cases. mpMRI reporting has a standardized protocol which is universally followed (PIRADS V2.0). However, there can be false positive interpretations due to complex reporting, inter-observer variability, reproducibility and contraindication in case of metallic implants/renal failure are few of the limitations [3] Our study results show relatively high accuracy of ⁶⁸Ga PSMA PET/CT (84.8%) in suspected PCa cases and shows high concordance with mpMRI.

There is significant agreement/concordance between ⁶⁸Ga PSMA PET/CT and mpMRI in suspected PCa cases. ⁶⁸Ga PSMA PET/CT should be used as a complimentary modality to mpMRI in patients with suspected PCa especially in cases with equivocal findings on mpMRI and high clinical suspicion.

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