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.

Diagnosis and management of isolated C1 fractures: A systematic review.

Objective: Atlas fractures are a common craniocervical injury, often resulting from trauma. However, diagnosis and management of atlas fractures continues to be the subject of controversy. We aimed to characterize the factors related to diagnosis of atlas fractures, delineate important considerations in selecting the optimal management for a patient with an atlas fracture, and compare outcomes of surgical and conservative management. Methods: We performed a systematic review using PubMed, Embase, and Scopus to identify articles that analyzed diagnosis and management of isolated atlas fractures published between 2013 and 2020. Titles and abstracts were screened. Studies meeting prespecified inclusion criteria were reviewed in full. Results: Of 305 resultant articles, 13 were included. C1:C2 ratio and lateral mass displacement (LMD) were used to predict transverse atlantal ligament (TAL) injury. Surgery promoted high fusion rates overall. Stable atlas fractures achieved high fusion rates with conservative management, while spinal fusion promoted greater fusion rates than halo vest immobilization management for unstable fractures. Visual Analog Scale scores, range of motion, and/or LMD improved after surgery. LMD increased for unilateral sagittal split fractures with TAL injury after conservative treatment. Conclusion: Stable atlas fractures can be sufficiently treated conservatively. Unstable atlas fractures can be managed both conservatively and surgically, while surgery is associated with favorable outcomes for unstable isolated atlas fractures. Future studies are necessary to further guide risk stratification and treatment approaches in management of the patients with isolated atlas fractures.

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.

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.

68Ga-PSMA PET/CT tumour intensity pre-operatively predicts adverse pathological outcomes and progression-free survival in localised prostate cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy. METHODS: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis. RESULTS: 68Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4-48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity. CONCLUSION: Intraprostatic 68Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.

68Ga-PSMA PET/CT better characterises localised prostate cancer after MRI and transperineal prostate biopsy: Is 68Ga-PSMA PET/CT guided biopsy the future?

BACKGROUND: 68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear. METHODS: Retrospective analysis of patients undergoing mpMRI, prostate biopsy and 68Ga-PSMA PET/CT over a 3-year period. Diagnostic performance of 68Ga-PSMA PET/CT and mpMRI were assessed using biopsy histopathology for the entire cohort and radical prostatectomy specimen in a subset of patients. Lesion concordance and additional detection of each modality were determined, including in a dedicated cohort of patients with mpMRI PIRADS 2 scans. RESULTS: A total of 144 patients were included in the study. Index lesion/foci detection was similar between 68Ga-PSMA PET/CT and mpMRI (sensitivity 83.1% vs 90.1%; p = 0.267), however lesions missed by mpMRI were larger (1.66 cm3 vs 0.72 cm3; p = 0.034). Lesion detection rates were similar across the biopsy histopathology and radical prostatectomy specimen subset, with a high concordance for index (80.1%) and a moderate concordance for total (67%) lesions between the 2 imaging modalities. The additional detection yield favoured 68Ga-PSMA PET/CT over mpMRI for index (13.5% vs 4.3%) and total (18.2% vs 5.4%) lesions; both modalities missed 2.1% and 12.3% of index and total lesions, respectively. 68Ga-PSMA PET/CT identified 9 of 11 patients with PIRADS 2 mpMRI but subsequently diagnosed with Gleason ≥ 3 + 4 disease. CONCLUSIONS: Despite high concordance rates, 68Ga-PSMA PET/CT incrementally improved tumour localisation compared with mpMRI. These results suggest that 68Ga-PSMA PET/CT may have an incremental value to that of mpMRI in the diagnostic process for prostate.

Improved specificity with 68Ga PSMA PET/CT to detect clinically significant lesions "invisible" on multiparametric MRI of the prostate: a single institution comparative analysis with radical prostatectomy histology.

PURPOSE: Positron emission tomography (PET) for prostate-specific membrane antigen (PSMA) represents a promising method for prostate cancer diagnosis and staging. Comparisons of PSMA-based tumour characterisation to multiparametric MRI (mpMRI) are limited, hence this study sought to compare the diagnostic accuracy of 68Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland histopathology. METHODS: A retrospective cohort study of consecutive patients who underwent pre-operative mpMRI and 68Ga-PSMA PET/CT followed by a RP was performed. Standard clinical parameters were collected. "Per patient" and "per lesion" analyses for image-based detection according to RP histopathology were described using sensitivity, specificity and other measures of diagnostic accuracy. RESULTS: Fifty-eight patients (median age 65.5 years, median PSA 7.35 ng/mL) underwent RP, resulting in a high-risk cohort (≥pT3 69%). Sensitivities for identification of index lesion, bilateral and multifocal disease were 90%, 21%, 19% for mpMRI and 93%, 42%, 34% for 68Ga-PSMA PET/CT. Histology analyses revealed 88 cancer foci of Gleason grades 3 + 3 (4%), 3 + 4 (64%), 4 + 3 (19%), 4 + 4 (3%) and ≥ 4 + 5 (10%), of which 68Ga-PSMA PET/CT correctly detected more foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729). CONCLUSIONS: 68Ga-PSMA PET/CT may better reflect RP histopathology compared to mpMRI when considering multifocal and bilateral disease. These findings may influence surgical planning, targeted biopsy and focal therapy strategies and require further research.

Ventilation perfusion single photon emission computed tomography: Referral practices and diagnosis of acute pulmonary embolism in the quaternary clinical setting.

INTRODUCTION: Ventilation perfusion single photon emission computed tomography (V/Q SPECT) and CTPA are the two leading imaging studies used to investigate acute pulmonary embolism. V/Q SPECT is often the first line investigation for pregnant patients and young females. Historically, V/Q Planar studies have high rates of indeterminate findings resulting in a preference for CTPA studies. The purpose of this research is to examine current V/Q SPECT referral practices in the quaternary clinical setting and to confirm V/Q SPECT studies have low rates of equivocal findings. METHODS: Retrospective study of a 6-month period of all completed V/Q SPECT studies (± LDCT) indicated for investigation of acute PE. V/Q SPECT studies were reported using the European Association of Nuclear Medicine guidelines. Patient demographic data and V/Q SPECT findings were recorded. CTPA and Doppler Ultrasound report findings were included if performed 48 hours prior to, or following V/Q SPECT study. Standard descriptive statistical analysis was undertaken. RESULTS: Ninety-nine percent of V/Q SPECT studies had reports positive or negative for acute PE, with 1% inconclusive. Twenty-two percent of patients had either CTPA or Doppler Ultrasound studies within a 48- hour period prior to, or following V/Q SPECT, with the majority having a negative Doppler ultrasound prior to negative V/Q SPECT. Sixty-eight percent of patients referred for V/Q SPECT were females under the age of 55, 40% of whom were pregnant. CONCLUSIONS: Ventilation perfusion single photon emission computed tomography has low rates of equivocal findings with referral practices indicating pregnant patients and young women are considered to most benefit from V/Q SPECT as a first line investigation for acute PE.

Bilateral cryptorchidism mimicking external iliac lymphadenopathy in a patient with leg melanoma: role of FDG-PET and ultrasound in management.

Cryptorchidism is the most common congenital anomaly present at birth in males. Spontaneous testicular descent occurs in the majority of patients, typically before 6 months of age. Radiology plays an important role, predominantly in the assessment of the nonpalpable testis, with ultrasound being the most commonly employed modality. Magnetic resonance imaging is however the most accurate modality for the assessment of the nonpalpable testis, particularly with the use of fat suppressed T2 and diffusion weighted sequences. While traditionally treated in infancy, the untreated or occult form can radiologically be mistaken for lymphadenopathy. Fluorodeoxyglucose (FDG) positron emission tomography can play an important role in differentiating cryptorchidism from lymphadenopathy, most commonly in patients with known malignancy, although FDG uptake can be variable. We present a case of bilateral cryptorchidism in an adult male which masqueraded as lymphadenopathy in a patient with lower limb melanoma.

Predicting tumour response.

Response prediction is an important emerging concept in oncologic imaging, with tailored, individualized treatment regimens increasingly becoming the standard of care. This review aims to define tumour response and illustrate the ways in which imaging techniques can demonstrate tumour biological characteristics that provide information on the likely benefit to be received by treatment. Two imaging approaches are described: identification of therapeutic targets and depiction of the treatment-resistant phenotype. The former approach is exemplified by the use of radionuclide imaging to confirm target expression before radionuclide therapy but with angiogenesis imaging and imaging correlates for genetic response predictors also demonstrating potential utility. Techniques to assess the treatment-resistant phenotype include demonstration of hypoperfusion with dynamic contrast-enhanced computed tomography and magnetic resonance imaging (MRI), depiction of necrosis with diffusion-weighted MRI, imaging of hypoxia and tumour adaption to hypoxia, and 99mTc-MIBI imaging of P-glycoprotein mediated drug resistance. To date, introduction of these techniques into clinical practice has often been constrained by inadequate cross-validation of predictive criteria and lack of verification against appropriate response end points such as survival. With further refinement, imaging predictors of response could play an important role in oncology, contributing to individualization of therapy based on the specific tumour phenotype. This ability to predict tumour response will have implications for improving efficacy of treatment, cost-effectiveness and omission of futile therapy.