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Murphy D.G.,Peter MacCallum Cancer Center | Murphy D.G.,Australian Prostate Cancer Research Center | Murphy D.G.,University of Melbourne | Sweeney C.J.,Dana-Farber Cancer Institute | Tombal B.,Cliniques Universitaires Saint Luc
European Urology | Year: 2017

Metastasis-directed therapy is of interest for the management of oligometastatic prostate cancer. Improved imaging may help with patient selection, but the approach to metastatic prostate cancer of "catching 'em all", or "Pokemet", must be considered experimental. © 2017 European Association of Urology.


Evans S.M.,Monash University | Millar J.L.,Alfred Hospital | Frydenberg M.,Monash University | Frydenberg M.,Monash Health | And 13 more authors.
BJU International | Year: 2014

Objective To describe the characteristics of patients with and without positive surgical margins (PSMs) and to analyse the impact of PSMs on secondary cancer treatment after radical prostatectomy (RP), with short-term follow-up. Patients and Methods We analysed data from 2385 consecutive patients treated using RP, who were notified to the Prostate Cancer Registry by 37 hospitals in Victoria, Australia between August 2008 and February 2012. Independent and multivariate models were constructed to predict the likelihood of PSMs. Independent and multivariate predictors of secondary treatment after RP in the initial 12 months after diagnosis were also assessed. Results Data on PSM status were collected for 2219/2385 (93%) patients. In total 592/2175 (27.2%) RPs resulted in PSMs; 102/534 (19.1%) in the low-risk group, 317/1218 (26.0%) in the intermediate-risk group, 153/387 (39.5%) in the high-risk group, and 9/11 (81.8%) in the very-high-risk disease group of patients. Patients having surgery in a hospital where <10 RPs occur each year were significantly more likely to have a PSM (incidence rate ratio [IRR] 1.44, 95% confidence interval [CI] 1.07-1.93) and those in the intermediate-, high- or very-high-risk groups (IRR 1.34, 95% CI 1.09-1.65, P = 0.007, IRR 1.96, 95% CI 1.57-2.45, P < 0.001 and IRR 3.81, 95% CI 2.60-5.60, P < 0.001, respectively) were significantly more likely to have a PSM than those in the low-risk group (IRR 2.50, 95% CI 1.23-5.11, P = 0.012). Patients with PSMs were significantly less likely to have been treated at a private hospital than a public hospital (IRR 0.76, 95% CI 0.63-0.93, P = 0.006) or to have undergone robot-assisted RP (IRR 0.69, 95% CI 0.55-0.87; P = 0.002) than open RP. Of the 2182 patients who underwent RP in the initial 12 months after diagnosis, 1987 (91.1%) received no subsequent treatment, 123 (5.6%) received radiotherapy, 47 (2.1%) received androgen deprivation therapy (ADT) and 23 (1.1%) received a combination of radiotherapy and ADT. Two patients (0.1%) received chemotherapy combined with another treatment. At a multivariate level, predictors of additional treatment after RP in the initial 12 months included having a PSM compared with a negative surgical margin (odds ratio [OR] 5.61, 95% CI 3.82-8.22, P < 0.001); pT3 compared with pT2 disease (OR 4.72, 95% CI 2.69-8.23, P < 0.001); and having high- or very-high-risk disease compared with low-risk disease (OR 4.36, 95% CI 2.24-8.50, P < 0.001 and OR 4.50, 95% CI 1.34-15.17, P = 0.015, respectively). Patient age, hospital location and hospital type were not associated with secondary treatment. Patients undergoing robot-assisted RP were significantly less likely to receive additional treatment than those receiving open RP (OR 0.59, 95% CI 0.39-0.88, P = 0.010). Conclusions These data indicate an important association between hospital status and PSMs, with patients who underwent RP in private hospitals less likely than those in public hospitals to have a PSM. Patients treated in lower-volume hospitals were more likely to have a PSM and less likely to receive additional treatment after surgery in the initial 12 months, and robot-assisted RP was associated with fewer PSMs than was open RP in this non-randomized observational study. PSM status and pathological T3 disease are both important and independent predictors of secondary cancer treatment for patients undergoing RP. A robot-assisted RP approach appears to decrease the likelihood of subsequent treatment, when compared with the open approach. © 2013 The Authors. BJU International © 2013 BJU International.


Evans S.M.,Monash University | Millar J.L.,Alfred Hospital | Davis I.D.,Monash University | Murphy D.G.,Australian Prostate Cancer Research Center | And 10 more authors.
Medical Journal of Australia | Year: 2013

Objective: To describe patterns of care for men diagnosed with prostate cancer in Victoria, Australia, between 2008 and 2011. Design, setting and patients: Men who were diagnosed with prostate cancer at 11 public and six private hospitals in Victoria from August 2008 to February 2011, and for whom prostate cancer notifications were received by the Prostate Cancer Registry. Main outcome measures: Characteristics of men diagnosed with prostate cancer; details of treatment provided within 12 months of diagnosis, according to National Comprehensive Cancer Network risk categories; and characteristics of men who did not receive active treatment within 12 months of diagnosis. Results: Treatment details were collected for 98.1% of men who were assessed as eligible to participate in the study (2724/2776) and were confirmed by telephone 12 months after diagnosis for 74.4% of them (2027/2724). Most patients (2531/2724 [92.9%]) were diagnosed with clinically localised disease, of whom 1201 (47.5%) were at intermediate risk of disease progression. Within 12 months of diagnosis, 299 of the 736 patients (40.6%) who had been diagnosed as having disease that was at low risk of progression had received no active treatment, and 72 of 594 patients (12.1%) who had been diagnosed as having disease that was at high risk of progression had received no active treatment. Of those diagnosed as having intermediate risk of disease progression, 54.5% (655/1201) had undergone radical prostatectomy. Those who received no active treatment were more likely than those who received active treatment to be older (odds ratio [95% CI], 2.96 [2.01-4.38], 10.94 [6.96-17.21] and 32.76 [15.84- 67.89], respectively, for age 65-74 years, 75-84 years and ≥85 years, compared with < 55 years), to have less advanced disease (odds ratio [95% CI], 0.20 [0.16-0.26], 0.09 [0.06-0.12] and 0.05 [0.02-0.90], respectively, for intermediate, high and very high-risk [locally advanced] or metastatic disease, compared with lowrisk disease) and to have had their prostate cancer notified by a private hospital (odds ratio [95% CI], 1.35 [1.10-1.66], compared with public hospital). Conclusion: Our data reveal a considerable "stage migration" towards earlier diagnosis of prostate cancer in Victoria and a large increase in the use of radical prostatectomy among men with clinically localised disease.


Lai J.,Queensland University of Technology | Lai J.,Australian Prostate Cancer Research Center | An J.,Queensland University of Technology | An J.,Australian Prostate Cancer Research Center | And 8 more authors.
Biological Chemistry | Year: 2014

We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance. © 2014, WDG. All rights reserved.


Yao H.H.I.,Royal Melbourne Hospital | Hong M.K.H.,Royal Melbourne Hospital | Corcoran N.M.,Royal Melbourne Hospital | Corcoran N.M.,Australian Prostate Cancer Research Center | And 2 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2014

Oligometastasis is a state of limited metastatic disease that may be amenable to aggressive local therapy to achieve long-term survival. This review aims to explore the role of ablative radiotherapy and surgical management of prostate cancer (CaP) patients with oligometastasis. We performed a systematic review of the literature from November 2003 to November 2013 in the PubMed and EMBASE databases using structured search terms. From our literature search, we identified 13 cases of oligometastatic CaP managed by surgery. The longest disease-free survival documented was 12 years following pulmonary metastasectomy. We also found 12 studies using radiotherapy to treat oligometastatic CaP with median follow-up ranging from 6 to 43 months. Local control rates and overall survival at 3 years range from 66 to 90% and from 54 to 92%, respectively. Most patients did not report any significant toxicity. The limited current literature suggests oligometastatic CaP may be amenable to more aggressive local ablative therapy to achieve prolonged local control and delay to androgen deprivation therapy (ADT). There is a larger body of evidence supporting the use of radiotherapy than surgery in this disease state. However, no direct comparison with ADT is available to suggest an improvement in overall survival. Further studies are required to determine the role of aggressive-targeted local therapy in oligometastatic CaP. © 2014 Wiley Publishing Asia Pty Ltd.


Murphy D.G.,Peter MacCallum Cancer Center | Murphy D.G.,Australian Prostate Cancer Research Center | Murphy D.G.,Royal Melbourne Hospital | Walton T.J.,Royal Melbourne Hospital | And 4 more authors.
BJU International | Year: 2012

The goals of focal therapy are laudable, namely reducing morbidity of treatment while ensuring at least equivalent oncological outcomes when compared with established interventions for localised prostate cancer, e.g. RP and external beam radiotherapy. While progress has been made towards better identifying the index lesion in these patients, there is much yet to be done to establish the validity of the index lesion theory as the metastatic focus and to establish that current targeting and ablative platforms are adequate to deliver the goals outlined above. The correct research questions have not yet been asked to establish either of these key principles underpinning focal therapy for localised prostate cancer. © 2011 The Authors.


PubMed | Australian Prostate Cancer Research Center and Peter MacCallum Cancer Center
Type: Journal Article | Journal: BJU international | Year: 2016

To assess the impact of the United States Preventive Services Task Force (USPTSTF) recommendations on prostate-specific antigen (PSA) testing, prostate biopsy, and prostatectomy in Australian men based on the available Medicare data.Events were identified using Medicare item numbers for PSA testing (66655, 66659), prostate biopsy (37219), prostatectomy (37210), and prostatectomy with lymph node dissection (37211). The occurrences of each procedure was queried per 100 000 capita for consecutive financial years over the period 2000-2015. For each item number, reports were also generated for all Australian States. For PSA testing the data was stratified into three age groups of 45-54, 55-64, and 65-74 years. For assessing the rate of prostatectomy the capita rate values for two item numbers of prostatectomy (37210) and prostatectomy with lymph node dissection (37211) were combined.Steady declines in per capita incidences of all five item numbers assessed were seen for the three consecutive financial years (2013-2015) since the publication of the USPTSTF recommendation statement. These declines were seen across all Australian States. When examining the rate of PSA testing for the three age brackets 45-54, 55-64, and 65-74 years, similar trends were identified.Since the introduction of the USPTSTF recommendation statement there has been a steady nationwide decline in per capita incidences of PSA testing, prostate biopsy, and prostatectomy based on the Australian Medicare data. Whether these declines are in the right direction toward reduction in over-diagnosis and overtreatment of clinically insignificant prostate cancer or stage migration toward more locally advanced disease due to lost opportunity in diagnosing and treating early clinically significant prostate cancer will remain to be seen.


Murphy D.G.,The Peter MacCallum Cancer Center | Murphy D.G.,Australian Prostate Cancer Research Center | Bjartell A.,Lund University | Ficarra V.,University of Padua | And 9 more authors.
European Urology | Year: 2010

Context: Robot-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in widespread use for the management of localised prostate cancer (PCa). Many reports of the safety and efficacy of this procedure have been published. However, there are few specific reports of the limitations and complications of RALP. Objective: The primary purpose of this review is to ascertain the downsides of RALP by focusing on complications and limitations of this approach. Evidence acquisition: A Medline search of the English-language literature was performed to identify all papers published since 2001 relating to RALP. Papers providing data on technical failures, complications, learning curve, or other downsides of RALP were considered. Of 412 papers identified, 68 were selected for review based on their relevance to the objective of this paper. Evidence synthesis: RALP has the following principal downsides: (1) device failure occurs in 0.2-0.4% of cases; (2) assessment of functional outcome is unsatisfactory because of nonstandardised assessment techniques; (3) overall complication rates of RALP are low, although higher rates are noted when complications are reported using a standardised system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a steep learning curve exists, and although acceptable operative times can be achieved in <20 cases, positive surgical margin (PSM) rates may require experience with >80 cases before a plateau is achieved; (6) robotic assistance does not reduce the difficulty associated with obese patients and those with large prostates, middle lobes, or previous surgery, in whom outcomes are less satisfactory than in patients without such factors; (7) economic barriers prevent uniform dissemination of robotic technology. Conclusions: Many of the downsides of RALP identified in this paper can be addressed with longer-term data and more widespread adoption of standardised reporting measures. The significant learning curve should not be understated, and the expense of this technology continues to restrict access for many patients. © 2009 European Association of Urology.


Crowe J.,Australian Prostate Cancer Research Center | Wootten A.C.,Australian Prostate Cancer Research Center | Howard N.,Australian Prostate Cancer Research Center
Australian Journal of Primary Health | Year: 2015

The role of the General Practitioner (GP) in testing for and managing men with prostate cancer (PCa) is significant. Very few studies have explored the attitudes and practices of Australian GPs in the context of the role of PCa testing. In this study, a 46-item web-based questionnaire was used to assess self-reported PCa testing attitudes and practices of GPs. This questionnaire was circulated to divisions of general practice and Medicare locals for further distribution to their GP members across Australia. GPs from all states and territories participated, and a total of 136GPs completed the survey. Of the responding GPs, 57% always or usually offered PCa testing to asymptomatic men ≤70 years of age and 60% of GPs always or usually included a digital rectal examination (DRE). Many (80%) of the GPs stated that the current PCa testing guidelines were not clear. PCa testing was offered opportunistically by 56% while 39% offered testing at the patient's request. The results captured in this study represent a snapshot of GP attitudes and practices from across Australia. The results presented indicate a wide variation in the approaches to PCa testing in general practice across Australia, which in most part appear to be related to the lack of clarity of the current prostate cancer testing guidelines. © La Trobe University 2015


PubMed | Australian Prostate Cancer Research Center
Type: Journal Article | Journal: Minerva urologica e nefrologica = The Italian journal of urology and nephrology | Year: 2016

The aim of this paper is to provide a systematic examination of the available evidence identifying factors that predict the detection of occult nodal metastatic disease at the time of radical cystectomy in patients with urothelial cancer of the bladder (BCa).A systematic literature search of the PubMed database was performed in August 2015 using medical subject headings and free-text protocol. The search was conducted by applying keywords: bladder cancer, urothelial cancer, lymph node metastasis, node positive, micrometastasis and occult metastasis.High-quality evidence assessing clinical factors that predict the discovery of occult nodal disease at the time of radical cystectomy is sparse. Despite the large number of studies examining this topic, there is a vast heterogeneity across the publications in patient selection, extent of lymph node dissection, and pathological assessment. The majority of studies reporting clinical and molecular characteristics associated with positive nodal status are based on univariable analysis and not corrected for known markers of tumor biology (stage, grade, lymphovascular invasion).Identifying BCa with occult lymph node metastasis holds the promise of facilitating patient selection for neoadjuvant medical therapy and tailoring surgical interventions, potentially improving clinical outcomes for BCa patients. Molecular markers need to be externally validated in prospectively well-designed trials and need to prove clinical utility. Image-guided surgical technologies need further development before being adopted in routine practice.

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