Surgery (Austin & Northern Health) - Research Publications
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ItemDistant Nodes Seen on PSMA PET-CT Staging Predicts Post-Treatment Progression in Men with Newly Diagnosed Prostate Cancer-A Prospective Cohort Study(MDPI, 2022-12)PSMA PET-CT scans are now recommended in international urological guidelines for primary staging and re-staging of prostate cancer. However, there is little published literature on the clinical outcomes for patients after treatment decisions made using PSMA PET-CT results. This is a multisite, prospective cohort study investigating the clinical outcomes of men who received treatment plans based on PSMA PET-CT results for primary staging. Men with biopsy proven prostate cancer received a PSMA PET-CT scan for primary staging. Treatment plans were recommended by multidisciplinary teams (MDT). After treatment, these men were followed with 6 monthly PSA tests and imaging or biopsies if recommended by MDT. The primary outcome was treatment progression defined as the addition or change of any treatment modalities such as androgen deprivation therapy, radiation therapy or chemotherapy. In total, 80% of men did not have any treatment progression after enactment of treatment based on PSMA PET-CT primary staging results at 29 months of follow up. Men who had distant nodes seen on PSMA PET-CT had a 5 times increased risk of treatment progression. Larger studies with longer follow up are needed to validate our results and optimise the way clinicians use PSMA PET-CT results to guide management.
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ItemPSMA PET-CT Imaging Predicts Treatment Progression in Men with Biochemically Recurrent Prostate Cancer-A Prospective Study of Men with 3 Year Follow Up(MDPI, 2022-06)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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ItemIntraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells(WILEY, 2018-06)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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ItemImplementation rates of uro-oncology multidisciplinary meeting decisions(WILEY, 2017-11)OBJECTIVES: To assess implementation rates of the consensus plans made at the uro-oncology multidisciplinary meeting (MDM) of an Australian tertiary centre, and analyse obstacles to implementation. METHODS: A retrospective review was performed of all patients discussed at the uro-oncology MDM at our institution between 1 January and 30 June 2015. Rates of referral for MDM discussion after a new histological diagnosis of malignancy, categorised by tumour type, were assessed. Patient records were interrogated to confirm MDM plan implementation, with the outcomes examined being completion of MDM plan within 3 months and factors preventing implementation. RESULTS: During the enrolment period, from 291 uro-oncological procedures, 240 yielded malignant histology of which 160 (67%) were discussed at the MDM. Overall, 202 patients, including 32 females, were discussed at the uro-oncology MDM. MDM consensus plans were implemented in 184 (91.1%) patients. Reasons for deviation from the MDM plan included delay in care, patient deterioration or comorbidities, patient preference, consultant decision, loss to follow-up, and change in patient scenario due to additional new information. CONCLUSION: The MDM is increasingly important in the care of uro-oncology patients, with about two-thirds of new diagnoses currently captured. There appear to be few barriers to the implementation of consensus plans, with nearly all patients undergoing the recommended management.
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ItemTrends in the surgical treatment of benign prostatic hyperplasia in a tertiary hospital(WILEY, 2018-01)BACKGROUND: To assess current treatment trends and perioperative outcomes of transurethral resection of the prostate (TURP) and photoselective vaporization of the prostate (PVP) in a tertiary institution. METHODS: We prospectively collected a database of all patients undergoing TURP and PVP for benign prostatic hyperplasia (BPH) at a tertiary hospital between January 2011 and December 2013. Patient characteristics such as length of stay, readmission, anticoagulation status, American Society of Anesthesiologists (ASA) score and need for blood transfusion were recorded and analysed. RESULTS: In total, 560 cases were included: 204 (36.4%) underwent TURP and 356 (63.6%) PVP. Patients undergoing PVP had higher ASA scores (P < 0.001) and were more frequently on continuing anticoagulant therapy (P < 0.001). With regards to non-aspirin/asasantin coagulation therapy, 61 (17.1%) patients underwent PVP with their anticoagulants continued while no patients who received TURP continued anticoagulation. Blood transfusion percentages were similar at 1.0% for TURP and 1.7% for PVP but readmission proportions were higher after PVP (32 patients, 9.0%) compared to TURP (10 patients, 4.9%). These differences were attenuated when excluding patients continuing anticoagulation during the procedure. CONCLUSION: At our institution, the use of PVP has been increasing on a year-by-year basis. The results of the current study demonstrated that PVP is safe in patients with increased anaesthetic risk or on active anticoagulation when compared to traditional TURP. While this makes PVP an attractive alternative to TURP in high-risk anticoagulated patients, these patients may have complex post-discharge issues that should be addressed during the informed consent process.
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ItemMetformin may offer no protective effect in men undergoing external beam radiation therapy for prostate cancer(WILEY, 2019-05)OBJECTIVES: To assess whether metformin reduces radio-resistance and increases survival in men undergoing external beam radiation therapy (EBRT) for prostate cancer (PCa), and to determine its effect on hypoxia inducible factor 1-α (HIF1α). PATIENTS AND METHODS: All patients treated with curative intent with EBRT for PCa at a major cancer centre between 2000 and 2007 were included in this study. The outcome measures of time to biochemical failure (BF), metastasis, PCa-specific mortality and overall survival (OS) were analysed in those taking metformin vs those not, using competing risk and Cox regression models. To determine metformin's effect on HIF1α expression and survival in vitro, PC3 cells with high basal HIF1α levels were subjected to increasing doses of metformin after H2 O2 -induced oxidative stress. RESULTS: A total of 2055 eligible cases, including 113 who were on metformin, were identified, with a median follow-up of 95.7 months. There were no differences in age, initial prostate-specific antigen level, Gleason score, T-stage, D'Amico risk class or duration of androgen deprivation therapy (ADT) between patients who were or were not on metformin. Treatment with metformin did not result in any apparent improvement in time to BF, time to metastasis detection or OS, but there was a 1.5-fold increase in PCa-specific deaths (P = 0.045) in patients on metformin and ADT when adjusted for cancer risk and comorbidities. When comparing patients on high-dose metformin (>1 g/d) with those on low-dose metformin (≤1 g), there was no difference in either time to metastases or time to BF. In vitro metformin at a high concentration of 100 μM did not reduce HIF1α expression, nor did metformin affect the PC3 cell survival when exposed to oxidative stress (H2 O2 ). CONCLUSIONS: No association was found between the use of metformin and time to metastasis detection, time to BF or OS in patients undergoing radiation therapy with or without ADT for PCa. In vitro, low therapeutic concentrations of metformin had no effect on HIF1α, and this observation could explain the conflicting evidence for the effectiveness of metformin in men undergoing EBRT for PCa. Higher, more toxic doses of metformin may be required to inhibit the mammalian target of rapamycin-HIF1α pathway in this patient group.
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ItemProspective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy(WILEY, 2018-09)OBJECTIVE: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). PATIENTS AND METHODS: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. RESULTS: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. CONCLUSION: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.
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ItemProstate cancer screening in Primary Health Care: the current state of affairs(SPRINGER INTERNATIONAL PUBLISHING AG, 2015-02-13)This study aims to examine the current practice of General practitioners (GPs)/primary care physicians in opportunistic screening for prostate cancer (PC) by digital rectal examination(DRE) and Prostate Specific Antigen(PSA) testing and identify any difference in screening practice. Printed copies and/or electronic versions of a survey was distributed amongst 438 GPs throughout Australia in 2012. Statistical analyses (Wilcoxon rank-sum test, Fisher's exact test or Pearson chi-square test)were performed by outcomes and GP characteristics.There were a total of 149 responses received (34%), with similar gender distribution in rural and metropolitan settings. 74% GPs believed PSA testing was at least 'somewhat effective' in reducing PC mortality with annual PSA screening being conducted by more GPs in the metropolitan setting compared to the rural GPs (35% vs 18.4%), while 25% of rural GPs would not advocate routine PSA screening. When examining the concordance between DRE and PSA testing by gender of GP, the male GPs reported performing PSA testing more frequently than DRE in patients between ages 40 to 69 (p = 0.011). Urology Society guidelines (77.2%) and College of GPs (73.2%) recommendations for PC screening were thought to be at least 'somewhat useful'. Although reference ranges for PSA tests were felt to be useful, the majority (65.8%) found it easier to refer to an urologist due to the disagreements in guidelines. In conclusion, the current guidelines for PSA screening appear to cause more confusion due to their conflicting advice, leaving GPs to formulate their own practice methods, calling for an urgent need for uniform collaborative guidelines.