The Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Primary Staging of Selected Renal Tumours: Initial Experience in a Multicentre Cohort.

BACKGROUND: Accurate primary staging of renal cancer with conventional imaging is challenging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) may serve to improve the accuracy of renal cancer staging. OBJECTIVE: To determine clinicopathological and management differences for primary renal cancer staged with PSMA PET/CT in comparison to conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of PSMA PET/CT scans performed for primary staging of renal cancer and incidental renal lesions at three sites in Brisbane, Australia between June 2015 and June 2020. Clinical characteristics, imaging, and histopathology were reviewed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinicopathological and management differences according to staging modality (PSMA PET/CT, conventional imaging) were assessed. Descriptive statistics were used to report demographics and clinical parameters. Nonparametric methods were used for statistical analysis. Fisher's exact test was used for comparison of small-cell size categorical variables. RESULTS AND LIMITATIONS: From a total of 120 PSMA PET/CT scans, 61 were included (52 staging, 9 incidental) for predominantly males (74%) with a mean age of 65.1 yr (standard deviation 12.0). Most primary lesions (40/51) were clear-cell renal cell carcinoma (ccRCC; 98% PSMA-avid), eight were non-ccRCC (75% PSMA-avid), and three were non-RCC (oncocytoma; 67% PSMA-avid). PSMA PET identified a greater number of presumed metastatic lesions than conventional imaging (195 vs 160). A management change was observed for 32% of patients (20% major, 12% minor). Limitations include the retrospective design and selection bias, lack of blinding to PSMA reporting, and the use of different PSMA radiotracers. CONCLUSIONS: PSMA PET/CT detected more metastases than conventional imaging and most renal cancers were PSMA-avid, resulting in a management change for one-third of the patients. PATIENT SUMMARY: We looked at a newer type of scan called PSMA PET/CT for first staging of kidney cancer. We found that this detects more metastasis and helps in decisions on changes in treatment for some patients. This type of imaging is a useful addition to conventional scans in tricky cases and may help in better selection of suitable treatments, but more studies are required.

Clinical impact of Prostate-Specific Membrane Antigen Positron Emission Tomography (PET) on intensification or deintensification of advanced renal cell carcinoma management.

PURPOSE: There is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment.

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

INTRODUCTION: Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning. METHODS: Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality. RESULTS: Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement. CONCLUSIONS: PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.

18 F-FET PET maximum standard uptake value and WHO tumour classification grade in glioma.

BACKGROUND: In the area of oncology, molecular imaging techniques are becoming increasingly utilised. In neuro-oncology imaging, 18 Fluoro-O-(2) fluoroethyl-L-tyrosine (18 F-FET) is one of the molecular tracers used in positron-emission tomography (PET). Here, we investigated the correlation between maximum standard uptake value (SUV) of 18 F-FET PET and histologically determined World Health Organization (WHO) grade in glioma. PATIENTS AND METHODS: This was a retrospective review of all 18 F-FET PET studies conducted between August 2014 and August 2019. Review was conducted to identify imaging studies performed on patients who had a glioma with histopathology results from surgical resection or biopsy available. RESULTS: A total of 31 18 F-FET PET studies of histologically confirmed glioma were included. WHO grades ranged from II-IV. A positive correlation between maximum SUV uptake on 18 F-FET PET and WHO grade was observed. CONCLUSIONS: There was a correlation identified between WHO glioma grade and maximum SUV on 18 F-FET PET. Further studies are recommended to explore this relationship.

The role of dual tracer PSMA and FDG PET/CT in renal cell carcinoma (RCC) compared to conventional imaging: A multi-institutional case series with intra-individual comparison.

PURPOSE: The objective of this study was to perform an intra-individual dual tracer comparison of Fluorodeoxyglucose (FDG) and Prostate Specific Membrane Antigen (PSMA) computed tomography (CT)/Positron Emission Tomography (PET) against standard of care (SOC) imaging for the characterisation, staging and restaging of renal cell carcinoma (RCC). METHODS: A multicentre retrospective cohort study was performed at 3 major tertiary referral institutions in Brisbane, Australia between 2015 and 2020. All patients who underwent both PSMA and FDG PET/CT following SOC imaging for investigation of RCC were identified. Clinical details, imaging characteristics and histopathology were collected prior to univariate statistical analysis. RESULTS: Eleven patients who underwent dual tracer PET/CT were included. Mean age was 65.5 years (SD 8.8). Most patients were male (64%) with clear cell morphology (91%). The indication for dual tracer PET was staging (36%) and restaging after radical/partial nephrectomy (64%). Primary tumour assessment showed mixed avidity patterns (concordant 40%, discordant favouring PSMA 20%, and FDG 40%). Metastatic disease assessment showed concordant avidity in 6 patients (55%), concordant negative in 3 (27%), and discordant uptake favouring PSMA. PET outperformed SOC imaging for assessment of metastatic disease in 5 patients (45%) and equivalent for the remainder. A change in management was noted in three cases (27%). CONCLUSION: Dual tracer FDG and PSMA PET/CT for assessment of primary and metastatic RCC were mostly concordant. PET imaging outperformed conventional imaging and led to a change in management for 1 in 4 patients. Further studies with larger samples sizes are required to validate these findings and identify characteristics to guide patient selection for selective or dual tracer use.

Should Lutetium-prostate specific membrane antigen radioligand therapy for metastatic prostate cancer be used earlier in men with lymph node only metastatic prostate cancer?

PURPOSE: Lutetium labelled prostate-specific membrane antigen radioligand therapy (Lu-PSMA RLT) has shown pleasing early results in management of high-volume metastatic castration resistant prostate cancer (mCRPC), but its role in the early treatment of men with only lymph node metastasis (LNM) is unknown. The aim was to assess the outcome of Lu-PSMA RLT earlier in the treatment of men with only LNM. MATERIALS AND METHODS: Single institution retrospective review of men with only LNM on staging Ga-PSMA PET PSMA who proceeded with Lu-PSMA RLT. RESULTS: There were 17 men with only LNM, including 13 with mCRPC and 3 who were both hormone and chemotherapy naïve. The median PSA was 3.7 (0.46-120 ng/mL). A PSA decline of ≥50% occurred in 10/17 (58.8%), decreasing to <0.2 ng/mL in 35.3% (6/17). The PSA continues to decline or remain stable in 10/17 (58.8%) with a median follow-up of 13 months, and 8/17 (47.1%) have not reached their pre-treatment levels. There were no significant side effects. There was a better PSA response in men without prior chemotherapy (p=0.05). The prostate cancer specific and overall survival is 82.4% (14/17). CONCLUSIONS: Our results identify improved PSA response to Lu-PSMA RLT in men with only LNM, especially in the chemotherapy naïve cohort, compared to previous series with more advanced mCRPC. These findings provide important proof of principle to aid with planning of future prospective randomized trials evaluating the role of Lu-PSMA RLT earlier in the management of node metastatic prostate cancer, including men naïve of ADT and chemotherapy.

A novel technique for a rare diagnosis: MRI-guided vaginal biopsy of Skene gland adenocarcinoma: Pictorial Essay.

FDG-PET and MRI imaging of the pelvis identified a suspicious lesion in a patient with a history of small cell neuroendocrine tumour of the vagina, and after a negative surgical biopsy, a multidisciplinary team meeting decided to proceed with MRGB (magnetic resonance-guided biopsy). The patient remains well and in remission two years after anterior exenteration, with final histology of the lesion determined to be Skene gland adenocarcinoma. MRGB is a novel and effective way to diagnose vaginal lesions.

Intracranial Metastasis from Prostate Cancer: Investigation, Incidence, and Imaging Findings in a Large Cohort of Australian Men.

OBJECTIVES: Prostate cancer metastasizing to the brain is remarkably uncommon, with the incidence never having been described in the modern setting. The objective of this study was to determine the incidence and imaging pattern of intracranial metastasis from prostate cancer in a large cohort of Australian men with prostate cancer. MATERIAL AND METHODS: Retrospective review was undertaken of imaging reports for all known prostate cancer patients, who underwent an imaging examination inclusive of the brain, between July 1, 2014, and July 1, 2020. Once an intracranial lesion was identified, all available imaging and clinical notes were reviewed. RESULTS: A total of 5644 imaging examinations which included the brain were identified in 4341 prostate cancer patients. The majority (92.1%) of examinations were 68-Gallium-labeled prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT). Eight patients were identified as having an intracranial metastasis from prostate cancer, yielding an incidence of 0.18%. All patients had a Gleason score of 9 (where known), and the majority of patients (5/8) had a non-acinar variant of prostate cancer. At the time of diagnosis of intracranial metastasis, all patients had extensive metastatic disease. Imaging characteristics of the intracranial lesions were highly variable. CONCLUSION: The incidence of intracranial metastasis in prostate cancer patients has never been well-established. In this study, we determined the incidence as being 0.18%. Given the majority of metastasis constituted unexpected findings on routine restaging 68Ga-PSMA PET/CT, the incidence determined in our study is arguably the most accurate and clinically relevant described to date.

Lu177-PSMA therapy for men with advanced prostate cancer: 18 months survival analysis in a single Australian tertiary institution.

INTRODUCTION: Radioligand therapies, or 'theranostics', have an emerging role in patients with metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177 (Lu), targeting prostate-specific membrane antigen (PSMA), has demonstrated promising outcomes including reduced disease progression and improved overall survival. We aim to determine overall survival demonstrated by our LuPSMA patient cohort to date. METHODS: Kaplan-Meier survival analysis and log-rank test were performed on all LuPSMA therapy patients with at least 12 months of follow-up data available (n = 68). Comparison across patients was made based on several variables including the baseline characteristics of prostate-specific antigen (PSA) level, maximum standard uptake value (SUVmax ) and metastasis site and by biochemical response. RESULTS: The 18-month overall survival estimate for the patient cohort was 63.8%. Patients with baseline serum PSA <20 µg/L had a greater 18-month survival estimate (79.9%) compared to PSA ≥20 µg/L (53.8%; P < 0.05). Patients with an SUVmax  >15 had an 18-month survival estimate of 56.0%, compared to 38.0% in patients with SUVmax  ≤15 (P < 0.05). No significant difference in overall survival was observed by metastasis site. Both a decrease in PSA after two LuPSMA therapy cycles and the maximum response over the treatment course being a decline in PSA were indicative of greater overall survival (P < 0.01 and P < 0.001 respectively). CONCLUSION: Our study reported an 18-month overall survival of 64% in patients with mCRPC who have undergone LuPSMA therapy. Our study identified that baseline serum PSA, SUVmax and biochemical response to treatment are prognostic markers for increased overall survival.

Combined Intravenous Urogram and 68Ga-PSMA PET/ CT for Improved Staging and Restaging of Prostate Cancer.

Staging/restaging of prostate cancer utilizing Gallium-68 (68Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in combination with an intravenous urogram allows improved discrimination between radiotracer activity in the renal tract and small pelvic nodes or local recurrences. Within this pictorial essay, we describe the imaging protocol utilized at our institution and present cases which demonstrate the utility of this combined imaging approach.

Solitary rib lesions showing prostate-specific membrane antigen (PSMA) uptake in pre-treatment staging 68 Ga-PSMA-11 positron emission tomography scans for men with prostate cancer: benign or malignant?

OBJECTIVES: To determine the proportion of solitary rib lesions on pre-treatment 68 Gallium-labelled prostate-specific membrane antigen (PSMA)/computed tomography (CT) scans in men with prostate cancer that are malignant and examine any predictive factors. PATIENTS AND METHODS: This retrospective single tertiary referral institution cohort study of men reviewed the results of 68 Ga-PSMA-11 positron emission tomography (PET)/CT scans performed for primary staging prior to treatment of prostate cancer from July 2014 to September 2019. Men with PSMA uptake outside the prostate in only the rib lesion were included. A solitary rib lesion was considered to be malignant if it increased in size on follow-up imaging. A lesion was considered benign if the prostate-specific antigen (PSA) level remained <0.1 µg/L following a radical prostatectomy (RP), <2 µg/L above nadir following radiotherapy (RT) as per the Phoenix criteria, histology was benign on rib biopsy, or follow-up imaging showed no growth of the rib lesion. If a lesion did not meet these criteria it was considered indeterminate. RESULTS: A total of 62 men had PSMA uptake in a solitary rib lesion; 54 went on to have RPs and eight underwent RT. In all, 61 of the men (98.4%) met the criteria for a benign rib lesion. Only one man had a false-negative malignant lesion. This man had a rib lesion with a low maximum standardised uptake value (SUVmax ) of 2.21 reported as benign, but the postoperative PSA level was 0.67 µg/L and the rib lesion progressed on follow-up imaging, with development of widespread metastases. Of the benign rib lesions, there were four false positives reported as possible metastases. Three had percutaneous rib biopsies, two of which came back with benign histology and one was indeterminate. The indeterminate biopsy patient had a RP and his postoperative PSA level was <0.1 µg/L. A total of 43 (69.4%) men with benign rib lesions had a SUVmax greater than the SUVmax of the malignant lesion. CONCLUSION: To our knowledge, this is the first cohort study of men with PSMA-avid solitary rib lesions on pre-treatment 68 Ga-PSMA PET/CT staging scans for prostate cancer. Our results indicate that the vast majority of these lesions have low-intensity uptake and are benign. Intervention to confirm this is not usually required.

Prostate penile metastasis: Incidence and imaging pattern on 68 Ga-PSMA PET/CT.

BACKGROUND: Prostate cancer commonly metastasises to bone and regional lymphatics and more rarely to locations such as the brain, skin and penis. Gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has widely become the routine imaging modality for prostate cancer staging and re-staging in Australia. The aim of this study was to retrospectively review all 68 Ga-PSMA PET/CT examinations performed to date at our institution to determine the frequency of penile metastases. METHODS: A total of 4860 68 Ga-PSMA PET/CT examinations were performed between 16/07/2014 and 31/10/2019. Radiology reports for each examination were filtered to identify those with the words 'penis' or 'penile'. Once identified, relevant reports and images were individually reviewed to confirm the presence of a PSMA-avid penile lesion. RESULTS: The incidence of penile metastasis of prostate cancer observed in this study was 0.1% with six examinations identified as having PSMA-avid penile lesions in five prostate cancer patients (age range: 71-88 years). The patients had a 1-8 year history of prostate cancer with varying severity of disease. Appearance of PSMA-avidity varied between single focal lesion, multiple focal lesions and diffuse lesion. CONCLUSIONS: An incidence of 0.1% in our study confirms the rarity of penile metastases of prostate cancer. Although rare, identification of prostate cancer penile metastases is important for appropriate treatment management and symptom-relief.

What does coal mine dust lung disease look like? A radiological review following re-identification in Queensland.

INTRODUCTION: Coal mine dust lung disease (CMDLD), including the pneumoconioses, dust-related diffuse fibrosis (DDF) and chronic obstructive pulmonary disease (COPD), are occupational lung diseases attributed to respirable coal mine dust. Following the re-identification of CMDLD in Queensland in 2015, we undertook a case series to understand their radiological presentation. METHODS: Chest radiographs and high-resolution computed tomography (HRCT) were retrospectively reviewed for 79 male individuals diagnosed by a respiratory physician with a CMDLD since 2015. Radiological findings were characterised as per the International Labour Office Classification System (ILO system) and the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD). RESULTS: Subjects with pneumoconiosis (n = 56) demonstrated widespread opacities with bilateral upper zone predominance. The majority of the lung was impacted, with 72% and 79% of zones demonstrating opacities on chest radiograph and HRCT, respectively. Most pneumoconiosis subjects (71%) demonstrated ILO category 1 disease, while 29% had advanced disease (ILO grades ≥ 2/1). A high proportion (81%) of pneumoconiosis subjects demonstrated at least one radiological feature associated with exposure to respirable crystalline silica (RCS). DDF subjects (n = 5) had radiologically severe disease (mean ILO 2/1) with lower zone-predominant irregular opacities. Widespread emphysema, with no zone dominance, was the key radiological feature in those with COPD (n = 18). CONCLUSION: Radiological findings of particular interest included the high burden of opacities observed and the presence of RCS-associated features in the majority of subjects. Radiologists are at the front line in occupational lung disease screening/diagnosis and must be aware of the imaging spectrum.

Five-year trends of bone scan and prostate-specific membrane antigen positron emission tomography utilization in prostate cancer: A retrospective review in a private centre.

INTRODUCTION: In the last 5 years, there has been a significant focus on the use of positron emission tomography (PET) for primary and secondary staging of prostate cancer. In this study, we aim to describe the trends of use between Gallium-68 prostate-specific membrane antigen ligand (Ga-68 PSMA) PET/computed tomography (PSMA PET/CT) and nuclear medicine bone scan (NMBS) for prostate cancer staging in the first institution in Australia to offer both modalities. METHODS: We evaluated trends in prostate cancer staging/restaging imaging modalities at our facility between the time period January 2013-April 2018. Imaging logs were filtered to identify NMBS and PSMA PET/CT scans done within the time period for prostate cancer. Sub-analysis was undertaken (i) to investigate the number of patients who were imaged using both modalities, (ii) to compare the age of the patients in the NMBS group and the PSMA PET/CT group and (iii) to compare the use of PSMA PET/CT for pre-treatment staging compared to the detection of recurrence or metastatic disease (secondary staging). RESULTS: A total of 3144 examinations were performed in the time period reviewed, with 546 NMBS and 2598 PSMA PET/CT scans performed. In the 6 months after PSMA PET/CT was introduced, there was a 45.7% decrease in the number of NMBS performed and 95.3% decrease across the duration of the study. In the PSMA PET/CT cohort, 1569 examinations were performed for pre-treatment staging and 1029 performed for secondary staging. There was a significant difference in the proportion of PSMA PET/CT conducted for pre-treatment staging compared with secondary staging when comparing the first and final 500 examinations (P < 0.05). CONCLUSION: After the introduction of PSMA PET/CT there was a marked decline in the use of NMBS for prostate cancer staging. This finding is of note as it occurred before there was clinical data or guidelines supporting the use of PSMA PET/CT for prostate cancer imaging.

Lu177-PSMA therapy for men with advanced prostate cancer: Initial 18 months experience at a single Australian tertiary institution.

INTRODUCTION: Lutetium-177-PSMA (LuPSMA) is a targeted systemic radioligand treatment for metastatic castration-resistant prostate cancer (mCRPC). LuPSMA is considered as an experimental treatment not yet used in routine practice. Here, we report our experience following the introduction of LuPSMA therapy at our institution. METHODS: Referred mCRPC patients were assessed for treatment suitability including Gallium-68-PSMA PET/CT and blood tests. Suitable patients underwent up to four cycles of LuPSMA treatment. Response to treatment was assessed by changes in serum prostate-specific antigen (PSA) levels. Toxicity was assessed by recording of adverse events. RESULTS: In an 18 month period, 50 patients underwent 132 cycles of LuPSMA therapy. Patients underwent a median of three cycles each (range: 1-4) and the mean administered amount of activity per cycle was 5.9 GBq (range: 3.5-8.2 GBq). PSA decline could be calculated for 49 patients, with a best PSA decline of ≥ 50% observed in 22 patients (44.9%). Adverse events were reported across 45 of 132 LuPSMA cycles. Most adverse events were grade I (42/45) and the remaining three events were grade II. CONCLUSION: Initial experience at our site supports the use of LuPSMA as an emerging safe and effective treatment for mCRPC. Since introducing LuPSMA therapy at our institution, 44.9% of patients have experienced a decline in PSA level ≥ 50% with low or minimal toxicity. This is an important finding as these patients had previously exhausted all available treatment options. Overall, we have found patients and their primary care doctors have eagerly accepted LuPSMA as another line of defence against mCRPC.

Unexpected significant findings non-related to prostate cancer identified using combined prostate-specific membrane antigen positron emission tomography/CT and diagnostic CT scan in primary staging for prostate cancer.

INTRODUCTION: There is increasing scientific evidence that whole-body Gallium-68 prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) improves the sensitivity of prostate cancer detection above standard staging radiology. Diagnostic IV-contrasted CT scanning offers high-quality recognition and delineation of organs and structures with a high sensitivity and specificity for diagnoses of many non-prostate pathologies. At our institution, imaging for prostate cancer staging and restaging involves a 68 Ga-PSMA PET/CT scan combined with a diagnostic IV-contrasted CT scan of the head, neck, chest, abdomen and pelvis. In this study, we aimed to determine the incidence of significant findings unrelated to prostate cancer identified when this combined imaging approach is utilized for prostate cancer imaging. METHODS: In this single-centre retrospective review, 68 Ga-PSMA PET/CT and diagnostic IV-contrasted CT scans undertaken for prostate cancer staging over a 12-month period (n = 1200) were reviewed for significant findings not related to prostate cancer. In cases with a significant other finding, follow-up imaging and/or pathology results were reviewed, where available. The overall incidence of significant other non-prostate cancer findings was determined, as was the incidence of unsuspected neoplasms. RESULTS: Significant findings, unrelated to prostate cancer, were identified in a total of 5.7% of scans (n = 68) with 3.2% (n = 38) of findings being unsuspected neoplasms. CONCLUSION: Diagnostic quality IV-contrasted CT combined with 68 Ga-PSMA PET/CT for staging of prostate cancer identified significant other non-prostate cancer findings, including renal, lung, gastrointestinal and haematological malignancies. Many of these conditions impact on patient management and required further investigation or treatment prior to management of the prostate cancer.

Radiological appearance of coal mine dust lung diseases in Australian workers.

Coal Mine Dust Lung Disease (CMDLD) encompasses a spectrum of lung diseases caused by prolonged exposure to coal mine dust. This review presents high-resolution computed tomography (HRCT) images from men diagnosed with a CMDLD since the resurgence of these diseases in Queensland in 2015.