Surgery (RMH) - Research Publications

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    Active surveillance versus enzalutamide for low-risk prostate cancer - was it really a trial we needed?
    Williams, ISC ; Perera, S ; Murphy, DG ; Corcoran, NM ; Bolton, DM ; Lawrentschuk, N (WILEY, 2022-11)
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    Low-grade prostate cancer should still be labelled cancer Comment
    Iczkowski, KA ; Molina, M ; Egevad, L ; Bostwick, DG ; van Leenders, GJLH ; La Rosa, FG ; van der Kwast, T ; Berney, DM ; Evans, AJ ; Wheeler, TM ; Leite, KRM ; Samaratunga, H ; Srigley, J ; Varma, M ; Tsuzuki, T ; Lucia, MS ; Crawford, ED ; Harris, RG ; Stricker, P ; Lawrentschuk, N ; Woo, HH ; Fleshner, NE ; Shore, ND ; Yaxley, J ; Bratt, O ; Wiklund, P ; Roberts, M ; Cheng, L ; Delahunt, B (WILEY, 2022-12)
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    Prostate-specific membrane antigen positron emission tomography/computed tomography funding grants free access to superior staging for Australian men with prostate cancer Comment
    O'Brien, JS ; McVey, A ; Kelly, BD ; Jenjitranant, P ; Buteau, J ; Hofman, MS ; Kasivisvanithan, V ; Eapen, R ; Moon, D ; Murphy, DG ; Lawrentschuk, N (WILEY, 2022-11)
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    Two decades of FDG-PET/CT in seminoma: exploring its role in diagnosis, surveillance and follow-up
    Conduit, C ; Koh, TT ; Hofman, MS ; Toner, GC ; Goad, J ; Lawrentschuk, N ; Tai, K-H ; Lewin, JH ; Tran, B (BMC, 2022-10-08)
    BACKGROUND: Survivors of testicular cancer may experience long-term morbidity following treatment. There is an unmet need to investigate techniques that can differentiate individuals who need additional therapy from those who do not. 2-18fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with computerised tomography (CT) may be helpful in select settings and may be used outside of current evidence-based recommendations in real-world practice. METHODS: A institutional FDG-PET/CT database of scans performed between 2000 and 2020 for adults with testicular seminoma was interrogated. Endpoints of interest included the positive (PPV) and negative (NPV) predictive value of FDG-PET/CT for identifying active seminoma (defined by progressive radiology, response to treatment or biopsy); or no active seminoma within 24-months for patients with stage 1 and advanced seminoma. An exploratory analysis examining predictive role of SUVmax was also performed. RESULTS: 249 patients met eligibility criteria for the analysis, including 184 patients with stage 1 and 77 patients with advanced testicular seminoma. Of 193 FDG-PET/CT performed in stage 1 seminoma with available follow-up data, 79 were performed during active surveillance. 18 (23%) of these were positive, all of which had confirmed recurrent seminoma (PPV 100%). Of 45 negative FDG-PET/CT during active surveillance, 4 recurrences developed corresponding to a NPV 91%. When clinical suspicion precipitated FDG-PET/CT (n = 36): PPV 100%, NPV 86%. Of 145 FDG-PET/CT in advanced seminoma with available follow-up data, 25 (17%) were performed at baseline (within 2 months of diagnosis), 70 (48%) post-treatment for evaluation of treatment response and 50 (34%) during follow-up following prior curative treatment. 10 (14%) post-treatment FDG-PET/CT were positive corresponding to a PPV 60%. Of 46 negative FDG-PET/CT, 5 recurrences occurred (NPV 89%). During follow-up after prior curative treatment, 24 (50%) FDG-PET/CT were positive corresponding to a PPV 83%; of 20 negative FDG-PET/CT, 1 recurrence occurred, NPV 95%. When clinical suspicion indicated FDG-PET/CT (n = 36): PPV 100%, NPV 94%. CONCLUSION: FDG-PET/CT offers high PPV for identifying seminoma and accurately predicts non-recurrence across a clinically relevant 24-months. Notably, FDG-PET/CT may prevent unnecessary treatment in 45% of patients undergoing investigation for clinical suspicion of recurrence during follow-up of advanced seminoma. The use of FDG-PET/CT in selected patients now, may help prevent unnecessary treatment of people with testicular seminoma.
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    Modern paradigms for prostate cancer detection and management
    Williams, ISC ; McVey, A ; Perera, S ; O'Brien, JS ; Kostos, L ; Chen, K ; Siva, S ; Azad, AA ; Murphy, DG ; Kasivisvanathan, V ; Lawrentschuk, N ; Frydenberg, M (WILEY, 2022-10-17)
    Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states.
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    Active surveillance versus nonradical treatment for low-risk men with prostate cancer: a review
    Perera, S ; McDonald, J ; Williams, I ; O'Brien, J ; Murphy, D ; Lawrentschuk, N (ELSEVIER INC, 2022-09)
    Low-risk prostate cancer has traditionally seen a preference towards avoiding treatment-related harms with active surveillance (AS) and multimodal monitoring protocols utilized to assess for disease progression. Large trials have shown variations in mortality and cancer survival benefit between AS and radical treatment, which has prompted further trials into the management of low-risk disease. Nonradical treatments for men on AS have been an emerging field and yet to enter mainstream guidelines or practice. These include pharmacological treatments, focal therapy, nutraceuticals, immunotherapy, and exercise. We present a review of all current major randomized clinical trials for nonradical treatment of men on AS and summarize their findings.
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    Impact of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in the Management of Oligometastatic Renal Cell Carcinoma
    Udovicich, C ; Callahan, J ; Bressel, M ; Ong, WL ; Perera, M ; Tran, B ; Azad, A ; Haran, S ; Moon, D ; Chander, S ; Shaw, M ; Eapen, R ; Goad, J ; Lawrentschuk, N ; Murphy, DG ; Hofman, M ; Siva, S (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%.