RPS 206 - Advanced prostate cancer imaging

Author Block: H. Duan, V. Ferri, P. Ghanouni, B. Daniel, G. Davidzon, C. Mari Aparici, G. Sonn, C. Kunder, A. Iagaru; Stanford, CA/US
Purpose or Learning Objective: High intensity focused ultrasound (HIFU) is a non-invasive local treatment procedure that uses thermal energy to ablate prostate cancer (PC) lesions. In this study, we evaluated 68Ga-RM2 and 68Ga-PMSA11 PET/MRI before and after treatment with HIFU to assess the accuracy of localisation and response to treatment.
Methods or Background: Fourteen men with newly diagnosed PC were prospectively enrolled. Pre HIFU, patients underwent prostate biopsy, multiparametric MRI (mpMRI), 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. Response to HIFU treatment was assessed with 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. For localisation, the prostate was divided into 12 segments (apex, mid, and base, medial and lateral respectively, left and right) using PET/MRI data and MIM software. Maximum standardised uptake values (SUVmax) of PC lesions and the background of each segment were collected.
Results or Findings: Pre HIFU biopsy revealed 23 lesions of which 18 were clinically significant with Gleason score (GS) ≥7 and mpMRI showed 15 lesions with 13 being ≥PIRADS 4. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI each identified 25 positive lesions including all index lesions. Post-HIFU imaging was available in 9 participants. 68Ga-PSMA11 and 68Ga-RM2 PET/MRI were negative for the respective treated area in all patients. SUVmax of target lesions decreased significantly after HIFU for both radiopharmaceuticals (68Ga-PSMA11: from 12.63±10.63 [3.2736.90] to 3.58±3.37 [1.6512.23], P=0.03; 68Ga-RM2: from 8.56±4.96 [1.9217.37] to 2.72±0.95 [1.494.12], P=0.00). Pretreatment prostate-specific antigen (PSA) and PSA density were 8.23±3.60ng/mL and 0.19±0.09ng/ml2, respectively, and decreased significantly after HIFU by 55% to 4.00±2.42ng/mL (0.107.97ng/mL, P=0.00) and 0.10±0.07ng/mL2 (0.000.24ng/mL2, P=0.00).
Conclusion: Our preliminary results show that both 68Ga-PSMA11 and 68Ga-RM2 PET/MRI identified the dominant lesion for HIFU ablation pretreatment and were able to accurately verify response to treatment in 100%.
Limitations: This study is limited by the small number of participants.
Ethics committee approval: The ethics committee approval was obtained.
Funding for this study: This study is partially funded by GE Healthcare.

Author Block: H. Duan, V. Ferri, P. Ghanouni, B. Daniel, G. Davidzon, C. Mari Aparici, G. Sonn, C. Kunder, A. Iagaru; Stanford, CA/US
Purpose or Learning Objective: Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20-65% of highly suspicious lesions on MRI prove to be false positives (FP) at biopsy. We evaluated the potential utility of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC and prior negative biopsy or equivocal MRI.
Methods or Background: Ten men with suspected PC were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI, including mpMRI. The prostate was divided into 12 segments (apex, mid, and base, lateral and medial, respectively, left and right) using PET/MRI data and MIM software. Maximum standardised uptake values (SUVmax) of suspected PC lesions and background for each segment were collected. Biopsies after PET/MRI included 1 core through each of the 12 segments and targeted sampling of any lesions seen on PET.
Results or Findings: PSA and PSA density were 10.77±6.27 ng/mL and 0.19±0.11 ng/mL2, respectively. mpMRI was negative in 5 patients, 4 showed PIRADS 4 and 1 PIRADS 5. 68Ga-PSMA11 identified 25 lesions of which 52% were verified PC and 68Ga-RM2 PET/MRI showed 26 lesions with PC verification in 50%. PET/MRI guided biopsy led to the additional finding of 3 clinically significant tumours and 2 GS 6 cancers. For 68Ga-PSMA11, mean SUVmax for true positives (TP) was slightly higher than FP, however not statistically significant whereas for 68Ga-RM2, SUVmax of TP PC lesions were significantly higher than FP (11.56 ± 9.11 [5.57 40.69] vs 7.93 ± 3.74 [3.7318.21], P=0.007).
Conclusion: Our preliminary results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC, and most importantly identified additional clinically significant cancers not seen on mpMRI.
Limitations: This study is limited by the small number of patients.
Ethics committee approval: The ethics committee approval was obtained.
Funding for this study: This study is partially funded by GE Healthcare.

Author Block: N. Sushentsev, M. McLean, A. Warren, F. A. Gallagher, T. Barrett; Cambridge/UK
Purpose or Learning Objective: To evaluate the ability of hyperpolarised [1-13C]pyruvate magnetic resonance imaging (HP 13C-MRI) to visualize biopsy-proven areas of prostate cancer (PCa) and correlate tumour [1-13C]lactate production with standard pathologic and imaging biomarkers of tumour aggressiveness.
Methods or Background: Patients with MR-visible biopsy-proven PCa scheduled for radical prostatectomy underwent 3T HP 13C-MRI, with tumour-derived signal-to-noise ratios (SNR) of pyruvate, lactate, and total carbon calculated in addition to [1-13C]pyruvate-to-[1-13C]lactate conversion rate (kPL). Multiparametric MRI (mpMRI) of the prostate was subsequently performed on the same magnet, with apparent diffusion coefficient (ADC) values calculated automatically and extracted from the same tumour regions. Whole-mount surgical sections were stained with haematoxylin and eosin, with tumour grade and per cent Gleason pattern 4 (%GP4) evaluated by an experienced genitourinary pathologist.
Results or Findings: The study included 10 patients with 15 lesions, of which 2, 11, and 2 harboured grade 1, 2, and 3 disease, respectively. 2/15 lesions were not reported prospectively on mpMRI and were detected retrospectively on HP 13C-MRI using whole-mount pathology as reference. Spearman’s correlation analysis revealed the presence of strong correlations between lactate SNR and %GP4 (rs=0.65, P=0.03), lactate SNR and ADC (rs=-0.69, P=0.02), %GP4 and ADC (rs=-0.62, P=0.03), as well as total carbon SNR and kPL (rs=0.62, P=0.04).
Conclusion: HP 13C-MRI was superior to mpMRI for evaluating the true burden of disease in patients with multifocal PCa, with lesion-derived [1-13C]lactate production acting as a metabolic surrogate of tumour aggressiveness. Non-invasive assessment of %GP4 using HP 13C-MRI may be used clinically to improve the selection of suitable candidates for active surveillance, for which %GP4 is critical.
Limitations: Not applicable.
Ethics committee approval: NREC East of England, 16/EE/0205.
Funding for this study: This study was funded by the Prostate Cancer UK, Cancer Research UK.

Author Block: N. Sushentsev, M. McLean, A. Warren, T. Barrett, F. A. Gallagher; Cambridge/UK
Purpose or Learning Objective: To identify biological mechanisms underpinning differential hyperpolarised [1-13C]lactate labelling in prostate cancer (PCa) and the benign prostate (BP) in patients undergoing radical prostatectomy following hyperpolarised [1-13C]pyruvate magnetic resonance imaging (HP-13C-MRI).
Methods or Background: All patients underwent 3T HP-13C-MRI, with a signal-to-noise ratio (SNR) of lactate derived from areas of PCa and contralateral BP as derived from whole-mount histopathology (WMH). Multiparametric MRI of the prostate was subsequently performed in the same sitting, with apparent diffusion coefficient (ADC) and Ktrans values extracted from identical regions-of-interest. Matching WMH sections were used for immunohistochemical analysis of monocarboxylate transporters (MCT) 1 and 4. RNAscope was used to quantify mRNA expression of lactate dehydrogenase (LDH) subunits A and B, alongside pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1).
Results or Findings: The study included 8 patients with 10 low-to-intermediate risk lesions. Lactate SNR, Ktrans, and WMP-derived cell density were significantly higher in PCa compared to BP (10.76 vs 1.66, 0.39 min-1 vs 0.11 min-1, and 3227.0 cells/mm2 vs 1944.0 cells/mm2; P<0.0001, 0.002, and 0.005, respectively), and ADC values were significantly lower in PCa compared to BP (922.4 10-6 mm2/s vs 1351.0 10-6 mm2/s; P=0.002). MCT1 and MCT4 did not differ between the two tissue types (P=0.796 and 0.684, respectively). Total LDH density and LDHA/PDHA1 mRNA expression ratio were, however, significantly higher in BP compared to PCa (8483.0 103 copies/mm2 vs 5389.0 103 copies/mm2 and 1.15 vs 0.68; P=0.004 and 0.03, respectively).
Conclusion: Lactate SNR was significantly higher in areas of low-to-intermediate risk PCa despite significant overexpression of glycolytic enzymes in BP. This may be explained by the increased perfusion/permeability and cellularity of tumour areas, leading to the increased hyperpolarised [1-13C]pyruvate delivery and [1-13C]lactate labelling.
Limitations: Not applicable.
Ethics committee approval: NREC East of England, 16/EE/0205.
Funding for this study: This study was funded by the Prostate Cancer UK, CRUK.

Author Block: N. Taha, M. Shalaby, J. AbdAllah, Y. O. H. Omar; Cairo/EG
Purpose or Learning Objective: To evaluate the role of 68Ga PSMA PET/CT in the staging of patients with pathologically proved prostatic adenocarcinoma.
Methods or Background: Prostate cancer is the 2nd most common male malignancy and is the 4th leading cause of death from malignancies. The key issue for optimal patient management is accurate pretreatment staging. 50 patients with pathologically proven prostate cancer, without any treatment or intervention, were included in this study. The PET/CT findings were correlated with the pathology reports, Gleason score and PSA levels. The patients were evaluated for local staging (T stage), including prostatic lesions extra-prostatic extension and seminal vesicles invasion, the regional nodal staging (N stage), and distant metastatic spread (M stage), including distant nodal, osseous and visceral metastases.
Results or Findings: A significant statistical relationship was found between PSA level, Gleason score and the findings in PET/CT including the pathological grade of the prostatic lesions with their extensions, the regional nodal deposits and the distant metastatic deposits. 68Ga PSMA shows 94% sensitivity in detecting prostatic lesions and its sensitivity increased with the increase of the PSA level of the patient, also it shows a significant P-value in detecting extra-prostatic spread either regional or distant.
Conclusion: 68Ga PSMA PET/CT is a powerful staging tool showing high sensitivity and specificity in the staging of patients with recently diagnosed prostate cancer.
Limitations: Nothing significant.
Ethics committee approval: This study was ethically approved from the ethical committee at the Faculty of Medicine, Ain Shams University.
Funding for this study: No funding was received for this study.

Author Block: X. A. G. Ballesteros, A. E. Mercado Sánchez, H. Solis Lara; Monterrey/MX
Purpose or Learning Objective: Prostate cancer is the third leading cause of death in men who die from malignant neoplasia, so new tools are being sought to objectively predict the probability of malignant infiltration of the lymph nodes for the adequate staging of the disease. Radiomics is the process of converting medical images into data allowing the extraction of quantitative characteristics. The aim of the study was the analysis of radiomic features of lymph nodes, using 68Ga-PSMA PET/CT, as a standard reference.
Methods or Background: The design was a retrospective, cross-sectional, analytical study, which was developed with a total of 41 patients with prostate cancer diagnosis randomly selected from a database of 253 patients. 3DSlicer software was used to obtain radiomic features. Sixteen nodes were segmented per patient (pelvis, retroperitoneum, mediastinal, axillary, and cervical). The nodes segmented were those with the highest SUVmax value in the positive studies and those with the highest short axis in the negative studies.
Results or Findings: Thirty-three variables of shape and textural analysis of radiomic tomographic features were found that allow differentiating between positive and negative lymph nodes for malignancy.
Conclusion: Radiomic analysis of lymph nodes in prostate cancer could detect the nodal metastatic disease even in lymph nodes of normal morphology and size.
Limitations: The limitations of our study were the small sample size and that it had a retrospective design, but it was performed by a blinded observer. Also, the PET/CT images were evaluated and segmented by a single observer, so the reproducibility of the results between different observers was not evaluated.
Ethics committee approval: This study was approved by the ethics in investigation committee with the number RA20-00009.
Funding for this study: This study was funded by the radiology department of "Dr. José Eleuterio González" University Hospital.

Author Block: M. Maksudov, U. Khaydarov; Tashkent/UZ
Purpose or Learning Objective: To present the results of gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 PET/CT and magnetic resonance (MR) imaging in patients with prostate cancer.
Methods or Background: Forty-five men who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. Multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast materialenhanced imaging) and PET/CT data were correlated with results of final pathologic examination and pelvic nodal dissection to yield diagnostic accuracy. PET/CT with 68Ga-PSMA-11 was performed according to the whole-body protocol. Interpretation of images was carried out visually and quantitatively with the calculation of SUVmax. A mean dose of 3.8 mCi ± 0.6 (140.6 MBq ± 22.2) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 60-90 minutes after injection by using a Philips Ingenuity TF PET/CT scanner. Metabolic parameters were compared by using a paired t-test and were correlated with clinical and histopathologic variables.
Results or Findings: High focal (24 cases) or diffuse (21 cases) 68Ga-PSMA-11 uptake was found in the prostate gland in all patients with primary prostate cancer. Whereas multiparametric MR imaging depicted PI-RADS (Prostate Imaging Reporting and Data System) 4 or 5 lesions in 36 patients and PI-RADS 3 lesions in five patients. Pathologic examination confirmed prostate cancer in all patients. In 18 patients, nodal metastases were additionally diagnosed.
Conclusion: 68Ga-PSMA-11 PET/CT has a high potential in the work-up of prostate cancer patients, including primary diagnosis and staging, while MR imaging provides detailed anatomic guidance. The combined use of both imaging methods provides valuable diagnostic information and may inform the need for pelvic node dissection.
Limitations: Limitations are not required.
Ethics committee approval: Approved by Ministry of Health of Uzbekistan
Funding for this study: No funding was received for this study.