Surgery (RMH) - Research Publications
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ItemSynchronous vs independent reading of prostate-specific membrane antigen positron emission tomography (PSMA-PET) and magnetic resonance imaging (MRI) to improve diagnosis of prostate cancer(Wiley, 2023-05-01)Objectives: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (prostate-specific membrane antigen [PSMA-PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA-PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. Methods: This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual-trained radiologist/nuclear medicine physicians re-reported the mpMRI and PSMA-PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA-PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. ‘Concordance’ between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the individual reporters for each modality. Results: International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA-PET increased sensitivity compared to mpMRI or PSMA-PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA-PET read synchronously and mpMRI or PSMA-PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions; 12%). When mpMRI/PSMA-PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA-PET alone was compared to synchronous PSMA-PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Conclusion: Synchronous mpMRI/PSMA-PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA-PET alone. However, synthesizing the results of independently read PSMA-PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA-PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.
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ItemImpact of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in the Management of Oligometastatic Renal Cell Carcinoma(ELSEVIER, 2022-10)BACKGROUND: Prostate-specific membrane antigen (PSMA) is overexpressed in the neovasculature of renal cell carcinoma (RCC). However, there remains limited evidence regarding the use of PSMA positron emission tomography/computed tomography (PET/CT) in RCC. OBJECTIVE: To assess the impact of PSMA PET/CT in the management of metastatic RCC. DESIGN SETTING AND PARTICIPANTS: This was a retrospective review of patients who underwent PSMA PET/CT from 2014 to 2020 for restaging or suspected metastatic RCC in a tertiary academic setting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Management plans before and after PSMA PET/CT were recorded. Impact was classified as high (change of treatment intent, modality, or site), medium (change in treatment method), or low. Secondary outcomes included the patient-level detection rate, PSMA PET/CT parameters, sensitivity, and comparison to CT and, if available, fluorodeoxyglucose (FDG) PET/CT. RESULTS AND LIMITATIONS: Sixty-one patients met the inclusion criteria, of whom 54 (89%) had clear cell RCC. PSMA-positive disease was detected in 51 patients (84%). For 30 patients (49%) there was a change in management due to PSMA PET/CT (high impact, 29 patients, 48%). In 15 patients (25%), more metastases were detected on PSMA PET/CT than on CT. The sensitivity of combined PSMA PET/CT and diagnostic CT was 91% (95% confidence interval 77-98%). In a subcohort of 40 patients, the detection rate was 88% for PSMA and 75% for FDG PET/CT (p = 0.17). The maximum standardised uptake value (SUVmax) was higher for PSMA than for FDG PET/CT (15.2 vs 8.0; p = 0.02). Limitations include selection bias due to the retrospective design, and a lack of corresponding histopathology for all patients. CONCLUSIONS: PSMA PET/CT is a promising imaging modality in metastatic RCC and led to a change in management in 49% of patients. PSMA PET/CT detected additional metastases compared to CT in 25% of patients and registered a significantly higher SUVmax than FDG PET/CT. Prospective studies are required to further define its role. PATIENT SUMMARY: We report on a group of patients undergoing a new type of imaging for suspected advanced kidney cancer, called PSMA PET/CT. This imaging changed the management plan in 49% of the patients. PSMA PET/CT detected metastases in 84% of our patients and detected more metastases than computed tomography imaging in 25%.
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ItemTumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes(BMJ PUBLISHING GROUP, 2022-06)BACKGROUND: Aberrations in homologous recombination repair (HRR) genes are emerging as important biomarkers for personalized treatment in prostate cancer (PCa). HRR deficiency (HRD) could affect the tumor immune microenvironment (TIME), potentially contributing to differential responses to poly ADP-ribose polymerase (PARP) inhibitors and immune checkpoint inhibitors. Spatial distribution of immune cells in a range of cancers identifies novel disease subtypes and is related to prognosis. In this study we aimed to determine the differences in the TIME of PCa with and without germline (g) HRR mutations. METHODS: We performed gene expression analysis, multiplex immunohistochemistry of T and B cells and quantitative spatial analysis of PCa samples from 36 patients with gHRD and 26 patients with sporadic PCa. Samples were archival tumor tissue from radical prostatectomies with the exception of one biopsy. Results were validated in several independent cohorts. RESULTS: Although the composition of the T cell and B cells was similar in the tumor areas of gHRD-mutated and sporadic tumors, the spatial profiles differed between these cohorts. We describe two T-cell spatial profiles across primary PCa, a clustered immune spatial (CIS) profile characterized by dense clusters of CD4+ T cells closely interacting with PD-L1+ cells, and a free immune spatial (FIS) profile of CD8+ cells in close proximity to tumor cells. gHRD tumors had a more T-cell inflamed microenvironment than sporadic tumors. The CIS profile was mainly observed in sporadic tumors, whereas a FIS profile was enriched in gHRD tumors. A FIS profile was associated with lower Gleason scores, smaller tumors and longer time to biochemical recurrence and metastasis. CONCLUSIONS: gHRD-mutated tumors have a distinct immune microenvironment compared with sporadic tumors. Spatial profiling of T-cells provides additional information beyond T-cell density and is associated with time to biochemical recurrence, time to metastasis, tumor size and Gleason scores.
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ItemStrategies for success: a multi-institutional study on robot-assisted partial nephrectomy for complex renal lesions(WILEY, 2018-05)OBJECTIVE: To describe our technique, illustrated with images and videos, of robot-assisted partial nephrectomy (RAPN) for challenging renal tumours. PATIENTS AND METHODS: A study of 249 patients who underwent RAPN in multiple institutions was performed. Patients were identified using prospective RAPN databases. Complex renal lesion were defined as those with a RENAL nephrometry score ≥10. Data were analysed and differences among groups examined. RESULTS: A total of 31 (12.4%) RAPNs were performed for complex renal tumours. The median (interquartile range [IQR]) patient age was 57 (50.5-70.5) years and 21 patients (67.7%) were men. The median (IQR) American Society of Anesthesiologists score was 2 (2-3). The median (IQR) operating time was 200 (50-265) min, warm ischaemia time was 23 (18.5-29) min, and estimated blood loss was 200 (50-265) mL. There were no intra-operative complications. Two patients (6.4%) had postoperative complications. One patient (3.2%) had a positive surgical margin. The median (IQR) length of stay was 3.5 (3-5) days and the median (IQR) follow-up was 12.5 (7-24) months. There were no recurrences. RAPN resulted in statistically significant changes in renal function 3 months after RAPN compared with preoperative renal function (P < 0.001). CONCLUSION: Our results showed that RAPN was a safe approach for selected patients with complex renal tumours and may facilitate tumour resection and renorrhaphy for challenging cases, offering a minimally invasive surgical option for patients who may otherwise require open surgery.
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ItemChanging face of robot-assisted radical prostatectomy in Melbourne over 12 years(WILEY, 2018-03)BACKGROUND: This study aims to characterize the trends in disease presentation for robot-assisted radical prostatectomy (RARP) over a 12-year period in Melbourne, Australia. METHODS: All patients undergoing an RARP between 2004 and October 2016 while under the care of six high-volume surgeons were included in this study. Data were collected prospectively regarding patient demographics and clinical details of their cancer. RESULTS: Over the 12-year time span of the study, 3075 men underwent an RARP with a median age of 63.01 years. Temporal analysis demonstrated that the median age of patients undergoing prostatectomy advanced with time with the median age in 2016 being 65.51 years compared with 61.0 years in 2004 (P < 0.001). There was also a significant trend to increased D'Amico risk groups over time with the percentage procedures for high-risk patients increasing from 12.6% to 28.10% from 2004 to 2016 (P < 0.001). Upgrade rates between biopsy and pathological Gleason grade scoring significantly trended down over the period of the study (P < 0.001). There was also a shift to increased pathological stage over the 12 years with 22.1% of men having T3 disease in 2004 compared with 49.8% in 2016. CONCLUSION: Our analysis demonstrates increasing treatment of older men with higher risk tumours, consistent with international trends. While this largely reflects a shift in case selection, further work is needed to assess whether the stage shift may relate partially to a decline in screening and increased presentation of higher risk disease.
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ItemAdverse impact of malnutrition markers on major abdominopelvic cancer surgery(WILEY, 2019-05)BACKGROUND: Malnutrition has been associated with adverse postoperative outcomes in a range of procedures but none have evaluated the interaction between clinical indicators of malnutrition. We aimed to comparatively evaluate how combinations of nutritional parameters impact postoperative outcomes amongst patients undergoing major cancer operations. METHODS: Major abdominopelvic cancer surgery cases (colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, nephrectomy, pancreatectomy, pneumonectomy and prostatectomy) were identified in the American College of Surgeons National Surgical Quality Improvement Program database from 2007-2016. Malnutrition was defined by the presence of the following parameters: body mass index <18.5 kg/m2 ; preoperative serum albumin <3.0 g/dL or more than 10% weight loss in the last 6 months. Malnourished cases were matched with cases with satisfactory nutritional status using propensity scores. The primary outcome was the incidence of Clavien III-IV complications. RESULTS: Of the 30 207 cases included, 8.5% had at least one marker of malnutrition. The incidence of Clavien III-IV complications across all cases was 5.8%. In the matched cohort, malnourished cases had a higher rate of complications than those with adequate nutritional status (11.3% versus 9.6%, P = 0.018). A correlation was observed between the number of malnutrition markers possessed and the incidence of Clavien III-V complications. Cases with all three makers had the highest likelihood of experiencing a complication (odds ratio 5.47, 95% confidence interval 1.85-16.17). CONCLUSION: Poor nutritional status confers an increased risk of major postoperative complications and being discharged to a facility in non-upper gastrointestinal cancer patients. There was a correlation between the number of malnutrition parameters and the risk of complications.
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ItemCytoreductive surgery for men with metastatic prostate cancer(ELSEVIER INC, 2016-09)BACKGROUND: Cytoreductive surgery for metastatic prostate cancer is an emerging area of interest with a potential upside that includes local control, delayed initiation of hormone therapy, and possibly improved cancer specific survival. In order for radical prostatectomy to be an effective treatment option for men in this group, the benefits must outweigh the surgical morbidity. The aim of this study was to present a case series and assess the literature feasibility of cytoreductive surgery for men with metastatic prostate cancer. METHODS: A retrospective review of clinical notes was performed to identify men with metastatic prostate cancer who underwent cytoreductive surgery between 2012 and 2014 for a group of urologists at a single institution in Melbourne. Each patient was evaluated with regard to preoperative prostate-specific antigen, grade, stage, adjuvant therapy, and surgical outcomes. RESULTS: Six cases were identified. This included 1 pelvic exenteration and 5 robot-assisted radical prostatectomies. The men who underwent RARP had uncomplicated recoveries, regained continence within 3 months and remained pad-free at follow up. All patients proceeded to additional treatment of sites of metastatic disease with a variable PSA response, however, 3 of 6 men required recommencement of ADT for biochemical progression at follow up. CONCLUSIONS: This data supports recent findings demonstrating that radical prostatectomy for metastatic prostate cancer is feasible. Further studies are needed to explore the role of cytoreductive surgery with regards to the potential oncological benefit.
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ItemUpdates of prostate cancer staging: Prostate-specific membrane antigen(KOREAN UROLOGICAL ASSOC, 2016-12)The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting.