Surgery (RMH) - Research Publications

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    Tumor immune microenvironment of primary prostate cancer with and without germline mutations in homologous recombination repair genes
    Trigos, AS ; Pasam, A ; Banks, P ; Wallace, R ; Guo, C ; Keam, S ; Thorne, H ; Mitchell, C ; Lade, S ; Clouston, D ; Hakansson, A ; Liu, Y ; Blyth, B ; Murphy, D ; Lawrentschuk, N ; Bolton, D ; Moon, D ; Darcy, P ; Haupt, Y ; Williams, SG ; Castro, E ; Olmos, D ; Goode, D ; Neeson, P ; Sandhu, S (BMJ PUBLISHING GROUP, 2022-06-01)
    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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    PSMA PET-CT Imaging Predicts Treatment Progression in Men with Biochemically Recurrent Prostate Cancer-A Prospective Study of Men with 3 Year Follow Up
    Ong, S ; Pascoe, C ; Kelly, BD ; Ballok, Z ; Webb, D ; Bolton, D ; Murphy, D ; Sengupta, S ; Bowden, P ; Lawrentschuk, N (MDPI, 2022-06-01)
    Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24-40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men.
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    Robotic partial nephrectomy for hilar renal masses
    Chen, K ; O'Brien, J ; Jenjitranant, P ; Alghazo, O ; Kelly, B ; Murphy, D ; Moon, D (Elsevier BV, 2022-03)
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    Is Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Imaging Cost-effective in Prostate Cancer: An Analysis Informed by the proPSMA Trial
    Cardet, REDF ; Hofman, MS ; Segard, T ; Yim, J ; Williams, S ; Francis, RJ ; Frydenberg, M ; Lawrentschuk, N ; Murphy, DG ; Lourenco, RDA (ELSEVIER, 2021-02-11)
    BACKGROUND: Before integrating prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) into routine care, it is important to assess if the benefits justify the differences in resource use. OBJECTIVE: To determine the cost-effectiveness of PSMA-PET/CT when compared with conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: A cost-effectiveness analysis was developed using data from the proPSMA study. proPSMA included patients with high-risk prostate cancer assigned to conventional imaging or 68Ga-PSMA-11 PET/CT with planned health economics data collected. The cost-effectiveness analysis was conducted from an Australian societal perspective. INTERVENTION: 68Ga-PSMA-11 PET/CT compared with conventional imaging (CT and bone scan). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome from proPSMA was diagnostic accuracy (nodal and distant metastases). This informed a decision tree analysis of the cost per accurate diagnosis. RESULTS AND LIMITATIONS: The estimated cost per scan for PSMA PET/CT was AUD$1203, which was less than the conventional imaging cost at AUD$1412. PSMA PET/CT was thus dominant, having both better accuracy and a lower cost. This resulted in a cost of AUD$959 saved per additional accurate detection of nodal disease, and AUD$1412 saved for additional accurate detection of distant metastases. The results were most sensitive to variations in the number of men scanned for each 68Ga-PSMA-11 production run. Subsequent research is required to assess the long-term costs and benefits of PSMA PET/CT-directed care. CONCLUSIONS: PSMA PET/CT has lower direct comparative costs and greater accuracy compared to conventional imaging for initial staging of men with high-risk prostate cancer. This provides a compelling case for adopting PSMA PET/CT into clinical practice. PATIENT SUMMARY: The proPSMA study demonstrated that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) better detects disease that has spread beyond the prostate compared with conventional imaging. Our analysis shows that PSMA PET/CT is also less costly than conventional imaging for the detection of disease spread. This research was presented at the European Association of Nuclear Medicine Scientific Meeting in October 2020.
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    Large variation in conservative management of low-risk prostate cancer in Australia and New Zealand
    Ong, WL ; Thangasamy, I ; Murphy, D ; Pritchard, E ; Evans, S ; Millar, J ; Chalasani, V ; Rashid, P ; Winter, M ; Vela, I ; Pryor, D ; Mark, S ; Lawrentschuk, N (WILEY, 2022-02-21)
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    High prostate-specific membrane antigen (PSMA) positron emission tomography (PET) maximum standardized uptake value in men with PI-RADS score 4 or 5 confers a high probability of significant prostate cancer
    Ptasznik, G ; Papa, N ; Kelly, BD ; Thompson, J ; Stricker, P ; Roberts, MJ ; Hofman, MS ; Buteau, J ; Murphy, DG ; Emmett, L ; Moon, D (WILEY, 2022-04-20)
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    Review of the use of prophylactic drain tubes post-robotic radical prostatectomy: Dogma or decent practice?
    Nzenza, TC ; Ngweso, S ; Eapen, R ; Rajarubendra, N ; Bolton, D ; Murphy, D ; Lawrentschuk, N (Wiley, 2020-09)
    OBJECTIVE: To assess the necessity of routine prophylactic drain tube use following robot-assisted radical prostatectomy (RARP). METHOD: We performed a literature review using the Medline, Scopus, and Web of Science databases with no restriction of language from January 1900 to January 2020. The following terms we used in the literature search: prostatectomy, radical prostatectomy, robot assisted, drainage, and drain tube. RESULTS: We identified six studies that examined the use of routine prophylactic drain tubes following RARP. One of these studies was a randomized study that included 189 patients, with 97 in the pelvic drain (PD) arm and 92 in the no pelvic drain (ND) arm. This non-inferiority showed an early (90-day) complication rate of 17.4% in the ND arm versus 26.8% in the PD arm (P < .001). Another non-inferiority randomized control trial (RCT) showed a complication rate of 28.9% in the PD group versus 20.4% in the ND group (P = .254). Similarly, the other studies found no benefit of routine use of prophylactic drain tube after RARP. CONCLUSION: Drain tubes play a role during robotic-assisted radical prostatectomy, however, following a review of the current available literature, they can be safely omitted and we suggest that clinicians may be selective in their use.
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    Subinguinal orchiectomy-A minimally invasive approach to open surgery.
    Anderson, E ; Pascoe, C ; Sathianathen, N ; Katz, D ; Murphy, D ; Lawrentschuk, N (Wiley, 2020-11)
    OBJECTIVES: To determine the rate of morbidity and assess the oncological outcomes for the subinguinal orchidectomy technique. BACKGROUND: Radical inguinal orchiectomy is the definitive management for a testicular mass suspicious for malignancy. The standard approach involves the division of the spermatic cord at the internal inguinal ring. In addition to the morbidity of a significant incision through skin and fascia, a known complication is damage to the nerves within the canal leading to local hypoesthesia or persistent inguinal and scrotal neuralgia. The subinguinal orchiectomy technique avoids opening the inguinal canal by excising the spermatic cord at the external inguinal ring. METHODS: Patient data from three urologists who routinely perform subinguinal orchiectomies for suspected testicular malignancy was collected. A retrospective analysis between March 2011 and March 2019 was undertaken evaluating demographic, clinical, and histological data points. Descriptive analysis of oncological and surgical outcomes of subinguinal orchiectomy for testicular mass was performed. Descriptive analysis of oncological and surgical outcomes of subinguinal orchiectomy for testicular mass was performed. RESULTS: About 42 orchiectomies performed via the subinguinal approach were identified. The median age was 38 years (range 22-72) and mean follow-up time was 18.4 months (range 0.59-61). Of the 38 patients with testicular cancer, histopathology showed 26 with pT1, 9 with pT2, and 3 with pT3 disease. Three patients had involvement of the cord, with one patient having a positive surgical margin secondary to venous invasion. No patients experienced neuropathic complications, hernia, or wound break down. CONCLUSION: These data suggest that subinguinal orchiectomy provides acceptable oncological outcomes, comparable to a traditional technique, and may decrease the risk of neuropathic injury and incisional/inguinal hernia. Further investigation with a larger, prospective series is required.
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    Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells
    Porter, LH ; Hashimoto, K ; Lawrence, MG ; Pezaro, C ; Clouston, D ; Wang, H ; Papargiris, M ; Thorne, H ; Li, J ; Ryan, A ; Norden, S ; Moon, D ; Bolton, DM ; Sengupta, S ; Frydenberg, M ; Murphy, DG ; Risbridger, GP ; Taylor, RA (WILEY, 2018-06-01)
    OBJECTIVE: To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer by first examining whether IDC-P was originally present in patients who later developed advanced prostate cancer and then using patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT). MATERIALS AND METHODS: We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan-Meier method. To demonstrate the response of IDC-P to ADT, we established PDXs from seven patients with familial and/or high-risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC-P within PDX grafts. RESULTS: We found that IDC-P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co-existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC-P. In the PDXs from all seven patients, IDC-P was identified and present at a similar volume to adenocarcinoma. Residual IDC-P lesions persisted after host castration and, similar to castrate-tolerant adenocarcinoma, testosterone restoration led to tumour regeneration. CONCLUSION: The study showed that IDC-P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC-P appears functionally relevant in advanced prostate cancer. The presence of IDC-P may be a trigger to develop innovative clinical management plans.
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    Changing face of robot-assisted radical prostatectomy in Melbourne over 12 years
    Sathianathen, NJ ; Lamb, AD ; Lawrentschuk, NL ; Goad, JR ; Peters, J ; Costello, AJ ; Murphy, DG ; Moon, DA (WILEY, 2018-03-01)
    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.