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Objectives This article presents the clinical trial protocol for a phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (NMIBC), the SUB-urothelial DUrvalumab injection-1 study (SUBDUE-1). The primary objectives of this study are to assess the safety of sub-urothelial injection of durvalumab using patient reported outcome measures and observed local or systemic adverse events. The secondary objectives are to examine the local immunological efficacy of sub-urothelial administration of durvalumab. Patients and methods The SUBDUE-1 trial will include adult patients with either high-risk NMIBC or MIBC, who are scheduled for radical cystectomy or who have refused or are unsuitable for systemic neoadjuvant chemotherapy. Three fixed total dose levels of durvalumab (25, 75, 150 mg) will be studied to identify a dose suitable to be taken forward into phase II trials. The primary endpoint is to evaluate the safety and tolerability of the trial intervention in terms of the incidence and severity of adverse events and the potential establishment of dose-limiting toxicities. The secondary efficacy endpoints include rates of pT0 status at resection, lymph node status, as well as the change in distribution of tumour-infiltrating lymphocytes and tumour-activated macrophages between pre- and post-injection bladder biopsies. Translational studies will focus on bladder tumour molecular sub-typing, immune infiltrate characterisation, and immune checkpoint protein expression relative to efficacy end-points. Outcome and significance If proven safe and effective, this novel strategy comprising sub-urothelial durvalumab injections aimed at promoting an anti-tumour immune reaction, will provide additional treatment options for reducing tumour recurrence and progression in treatment-naive patients with high-risk NMIBC or in patients with bacille Calmette-Guerin-refractory NMIBC. Local administration of durvalumab may be associated with a reduced rate of immunological side-effects and lower costs when compared to systemic delivery.

Objective To assess the activity and safety of sequential lutetium-177 (Lu-177)-PSMA-617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone-naive prostate cancer (mHNPC).Patients and Methods UpFrontPSMA (NCT04343885) is an open-label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement; prostate-specific antigen (PSA) >10 ng/mL at diagnosis; 15; and absence of extensive discordant fluorodeoxyglcuose (FDG)-positive, PSMA-negative disease. Ga-68-PSMA-11 and F-18-FDG positron-emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A (Lu-177-PSMA-617 7.5GBq q6w x 2 cycles followed by docetaxel 75 mg/m(2) q3w x 6 cycles), or standard-of-care treatment, Arm B (docetaxel 75 mg/m(2) q3w x 6 cycles). All patients receive continuous ADT. Patients are stratified based on disease volume on conventional imaging and duration of ADT at time of registration. The primary endpoint is the proportion of patients with undetectable PSA (

Healthcare utilisation has changed due to the COVID-19 pandemic. Many studies have reported a reduction in services such as cancer detection and treatment, and a reduction in patient participation in cancer early detection programmes (1). As the pandemic continues, there are concerns that service disruptions due to the pandemic response may lead to reduced referrals, "missed" care and presentations of malignancies at more advanced stage.

OBJECTIVE To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Objective To assess the activity and safety of cabazitaxel chemotherapy vs that of treatment with 177 Lu-PSMA-617, a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), in men with metastatic castration-resistant prostate cancer (mCRPC) who have received prior docetaxel treatment. Patients and methods The TheraP trial (ANZUP 1603) is an open-label, randomized, stratified, two-arm multicentre phase 2 trial comparing the activity and safety of cabazitaxel chemotherapy vs 177 Lu-PSMA-617 therapy in the treatment of men with mCRPC. Key eligibility criteria include prior docetaxel chemotherapy, rising prostate-specific antigen (PSA) level, sufficient PSMA avidity, as defined by centrally reviewed 68 Ga-PSMA-11 and fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with no discordant FDG-avid PSMA-negative sites of disease. Patients in the control group receive standard treatment with cabazitaxel (20 mg/m2 ) i.v. every 3 weeks with prednisolone 10 mg daily orally, for a maximum of 10 cycles. Patients in the experimental group receive 177 Lu-PSMA-617 (8.5 GBq decreasing by 0.5 GBq per cycle) i.v. every 6 weeks, for up to a maximum of six cycles. In the event of an exceptional response as defined on centrally reviewed post-therapy single-photon emission CT imaging, treatment will be suspended but can recommence on progression. The trial aims to include 200 patients who will be centrally randomized to one of the two treatment groups, in a 1:1 ratio. The primary endpoint is PSA response. Secondary endpoints are overall survival, progression-free survival (PFS), radiographic PFS, PSA PFS, objective tumour response, pain response, pain PFS, health-related quality of life, and frequency and severity of adverse events. The treatment and outcomes of patients excluded on the basis of low PSMA avidity or discordant FDG-avid disease on screening 68 Ga-PSMA-11 and Fluorine-18 (18 F)-FDG-PET/CT scan will also be assessed. Enrolment in the study commenced on 29 January 2018. Results and conclusions 177 Lu-PSMA-617 offers a potential additional life-prolonging treatment option for men with mCRPC. The results of this trial will determine, for the first time in a randomized design, the activity and safety of 177 Lu-PSMA-617, as compared with cabazitaxel chemotherapy in men with progressive mCRPC.

Objective To characterize circulating oestrogen receptor ( ER) mutants and splice variants in men with advanced prostate cancer. Materials and methods Sequential blood samples were obtained from men with advanced prostate cancer, and from healthy controls. Blood-derived RNA samples were analysed using droplet digital PCR for the presence of six ERα mutations (E380Q, L536Q, Y537C, Y537S, Y537N and D538G), and six ERα and ERβ splice variants (ERα-66, ERα-36, ERβ1, ERβ2, ERβ4 & ERβ5). Results A total of 94 samples were collected from 42 men with advanced prostate cancer. Four mutations (E380Q, L536Q, Y537S and D538G) and all six splice variants were detected in patient samples. Splice variants were detectable in non-cancer control samples. The presence of ER mutations was associated with bone metastases and castration resistance. ERβ splice variant concentrations decreased after successive lines of treatment. Conclusions The ER mutations were detectable in plasma from patients with advanced prostate cancer. ER splice variants were frequently detected in both men with and without prostate cancer.

To describe the use of partial nephrectomy (PN) for patients with stage T1a renal cell carcinoma (RCC) by age group (65 and ≥65 years) in two Australian states.All adults diagnosed with RCC in 2012 and 2013 were identified through population-based cancer registries in the Australian states of Queensland and Victoria. For each patient, research assistants extracted patient, tumour and treatment data from medical records. Percentages of patients treated by PN were determined for the two age groups. Multivariable logistic regression analyses examined factors associated with PN. Clinicians treating RCC were sent surveys to assess attitudes towards PN.Data were collected on 956 patients (Victoria: n = 548; Queensland: n = 404) with stage T1a RCC. Of those undergoing surgery (n = 865), PN was more common for those aged65 years (61%) than for those aged ≥65 years (44%), with this difference significant after adjusting for patient, tumour (odds ratio 0.50, 95% confidence interval 0.36-0.70). There were significant interactions between age and treatment centre volume (P0.05) and residential state (P0.05). PN was less likely for younger patients treated at lower-volume hospitals (24 patients a year) but hospital volume was not associated with PN for older patients. PN was less likely for older patients in Queensland than Victoria. In multivariable analyses, age was not related to laparoscopic surgery. Queensland clinicians were less likely than those from Victoria to agree that PN was the treatment of choice for most T1aN0M0 tumours (P0.001).In Australia, patients aged65 years with small renal cancers were less likely to be treated by PN than younger patients. The variation in the surgical procedure used to treat older T1a RCC patients by state and hospital volume indicates that better evidence is needed to direct practice in this area.

Objective To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways. Patients and methods We collected malignant and matched non-malignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. Epithelial cell adhesion molecule-positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA sequencing analysis was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells. Results From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82% of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signalling, however, only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients. Conclusions Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4 and CLDN3. No consistent mutations or splice variants were observed, but upregulation of ERG signalling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement.

Objective The Asia Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2018) brought together 20 experts from 15 APAC countries to discuss the real-world application of consensus statements from the second APCCC held in St Gallen in 2017 (APCCC 2017). Findings Differences in genetics, environment, lifestyle, diet and culture are all likely to influence the management of advanced prostate cancer in the APAC region when compared with the rest of the world. When considering the strong APCCC 2017 recommendation for the use of upfront docetaxel in metastatic castration-naive prostate cancer, the panel noted possible increased toxicity in Asian men receiving docetaxel, which would affect this recommendation in the APAC region. Although androgen receptor-targeting agents appear to be well tolerated in Asian men with metastatic castration-resistant prostate cancer, access to these drugs is very limited for financial reasons across the region. The meeting highlighted that cost and access to contemporary treatments and technologies are key factors influencing therapeutic decision-making in the APAC region. Whilst lower cost/older treatments and technologies may be an option, issues of culture and patient or physician preference mean, these may not always be acceptable. Although generic products can reduce cost in some countries, costs may still be prohibitive for lower-income patients or communities. The panellists noted the opportunity for a coordinated approach across the APAC region to address issues of access and cost. Developments in technologies and treatments are presenting new opportunities for the diagnosis and treatment of advanced prostate cancer. Differences in genetics and epidemiology affect the side-effect profiles of some drugs and influence prescribing. Conclusions As the field continues to evolve, collaboration across the APAC region will be important to facilitate relevant research and collection and appraisal of data relevant to APAC populations. In the meantime, the APAC APCCC 2018 meeting highlighted the critical importance of a multidisciplinary team-based approach to treatment planning and care, delivery of best-practice care by clinicians with appropriate expertise, and the importance of patient information and support for informed patient choice.

Androgen deprivation and androgen targeted therapies (ATT) are established treatments for prostate cancer (PCa). Although initially effective, ATT induces an adaptive response that leads to treatment resistance. Increased expression of relaxin-2 (RLN2) is an important alteration in the adaptive response. RLN2 has a well described role in PCa cell proliferation, adhesion and tumour growth. The objectives of this study were to develop cell models for studies of RLN2 signalling and to implement in vitro assays for evaluating the therapeutic properties of the unique RLN2 receptor (RXFP1) antagonist

Objectives To determine whether use of nephron sparing surgery (NSS) for treatment of stage 1 renal cell carcinomas changed between 2009 and end 2013 in Australia. Patients and Methods All adult cases of renal cell carcinoma diagnosed in 2009, 2012, and 2013 were identified through the population-based Victorian Cancer Registry. For each identified patient, trained data-abstractors attended treating hospitals or clinician rooms to extract tumour and treatment data through medical record review. Multivariable logistic regression analyses examined significance of change in use of NSS over time, after adjusting for potential confounders. Results A total of 1836 patients with renal cell carcinoma were identified. Of these, the proportion of cases with stage 1 tumours was 64% in 2009, 66% in 2012, and 69% in 2013. For T1a tumours, the proportion of patients residing in metropolitan areas receiving NSS increased from 43% in 2009 to 58% in 2012 (P

Objectives To analyse the impact of the uro-oncology multidisciplinary meeting (MDM) at an Australian tertiary centre on patient management decisions, and to develop criteria for patient inclusion in MDMs. Methods Over a 3-month period, all cases presented at our weekly uro-oncology MDM were prospectively assessed, by asking the presenting clinician to state their provisional management plans and comparing this with the subsequent consensus decision. The impact of the MDM was graded as high if there was a major change in the management plan or if a plan was developed where there was none. Results Over the study period, 120 discussions about 107 patients were recorded. Prostate, urothelial, kidney and testis cancer represented 46 (38.3%), 36 (30%), 26 (21.6%) and 12 (10%) of the discussions, respectively. The MDM made high impact changes to the original plan in 32 (26.7%) cases. High impact changes were nearly twice as likely to occur in patients with metastatic disease as in those without metastases (P < 0.05). Primary cross referral between disciplines occurred in 40 (33.3%) cases, including 66.7% of testicular and 42% of bladder cancers but only 26% of prostate and 19% of kidney cancers (P < 0.02). Conclusions The uro-oncology MDM alters management plans in about one-quarter of cases. Additionally, MDMs also serve other purposes, such as cross-referral or consideration for clinical trials. Patients should be discussed in MDMs if multimodal therapy may be required, clinical trial eligibility is being considered or if metastasis or recurrence is noted.

Objectives To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to ‘standard’ treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient-reported outcomes, adverse events, biochemical failure-free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation. Patients and Methods The Radiotherapy – Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at ≤4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of >0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs ± extraprostatic extension ± seminal vesicle involvement. The postoperative PSA level must be ≤0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients. Results Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta-analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho-oncology sub-study to investigate a patient decision aid resource. Conclusion On the current evidence available, it remains unclear if ART is equivalent or superior to observation with early SRT.

Objective To review time-trends in the use of perioperative chemotherapy and its impact on oncological outcomes in patients with bladder urothelial cancer (UC) at a single tertiary institution. Patients and Methods Using electronic and paper medical records, 89 patients were identified who underwent radical cystectomy with or without perioperative chemotherapy between 2004 and 2011 at Austin Health in Melbourne, Australia. Patient demographics, clinico-pathological characteristics and details of recurrence and death were assessed by retrospective chart review. Survival analysis was carried out using the Kaplan Meier method, with the impact of predictors assessed using Cox proportional hazard models. Results The median (range) age of this cohort was 65 (37–84) years, and 66 (74%) patients were male. Pathologic features included 68 (76%) pure UC, 21 (24%) mixed UC and 84 (94%) high grade tumours. On clinical staging, 63 (71%) patients had muscle-invasive bladder cancer (cT-stage ≥T2), of whom 11 (17%) received neoadjuvant chemotherapy, with an increasing trend in use over time. Following radical cystectomy, pT-stage ≥T3 and/or node positive were identified in 35 (39%) patients, of whom 16 (46%) received adjuvant chemotherapy. In addition, five patients with stage pT2 received adjuvant chemotherapy. Of the total cohort of patients, 31 (35%) suffered recurrences, and 33 died, 27 from urothelial carcinoma. On multivariate analysis, after adjusting for age, pT-stage and pN-stage, perioperative chemotherapy was associated with a significantly lower risk of recurrence [relative risk (RR) 0.41, p < 0.05], but not death from cancer or all causes. Conclusions Perioperative chemotherapy, and in particular neoadjuvant chemotherapy, remains relatively under-utilised at our institution despite recent increases. The significant reduction in the risk of recurrence following treatment with perioperative chemotherapy with radical cystectomy highlights the importance of multi-modality treatment in bladder UC. Identifying barriers to more widespread implementation of perioperative chemotherapy is critical for enhancing outcomes in patients with bladder UC.

Objective To describe the contemporary patterns of care for renal cell carcinoma (RCC) using a whole of population series from Victoria. Patients and methods Retrospective review of medical records of all patients diagnosed and treated for RCC in Victoria in 2009. Patients were identified via the State-wide Victorian Cancer Registry. Patient demographic characteristics, symptoms, stage, and first-line treatment were assessed. Associations between case residential location (metropolitan or rural) and treatment were examined using multivariate logistic regression after adjusting for age, sex, socioeconomic status, treatment in private or public hospital and comorbidity. Results Data were obtained for 499 of 577 eligible patients. In all, 413 patients (83%) underwent surgery. Laparoscopic radical nephrectomy (RN) was the most common procedure for Stage I pT1a/pT1b tumours (51.2%); partial nephrectomy (PN) was performed for 27% of Stage I RCC In multivariate analysis, regional patients were less likely to receive PN (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18–0.85) for Stage I RCC, and less likely to receive systemic therapy for Stage IV RCC (OR 0.06, 95% CI 0.01–0.41). Multidisciplinary team meetings were recorded for only 25% of patients and 3% were enrolled in a clinical trial. Conclusion Most contemporary patients diagnosed with RCC are still treated with RN, including those with smaller tumours amenable to PN. This may impact future outcomes, including increased risk of chronic kidney disease and its potential financial healthcare burden. Patterns of treatment also appear to differ between metropolitan and regional populations.

Objective To determine the patterns of management and surveillance imaging amongst medical oncologists in Australia for stage I testicular cancer during 2010. Methods We conducted a survey comprising 14 questions about the management strategy and surveillance imaging for all patients with stage I testicular cancer treated over the previous 12 months. Results A total of 52 medical oncologists documented the management for an estimated 470 patients. For seminoma, management was in the form of surveillance in 33%, radiotherapy in 5% and adjuvant carboplatin in 62% of patients. For non-seminoma, management was surveillance in 73%, adjuvant chemotherapy in 23% and retroperitoneal lymph node dissection in 4% of patients. The frequency of surveillance imaging was highly variable, and ≥10 computed tomography (CT) scans were used by 38% of clinicians for seminoma and 46% of clinicians for non-seminoma. Conclusion We found considerable variation in management patterns. The infrequent use of surveillance and frequent use of carboplatin for seminoma differs from international guidelines. Radiation exposure from CT imaging should be reduced through standardized follow-up protocols, and possibly by alternate imaging methods if validated in appropriate studies.

What's known on the subject? and What does the study add? Non-muscle-invasive bladder cancer has a significant recurrence and progression rate despite transurethral resection. The current standard of care to lower the risk of recurrence and progression is adjuvant BCG followed by maintenance BCG. Despite this, a significant number of patients experience recurrence and progress to invasive cancer. Several randomized trials have studied combination therapy (BCG with chemotherapy) to try to reduce the recurrence and progression rate. We performed a systematic review with meta-analysis and found that adjuvant BCG followed by maintenance therapy is the appropriate standard of care when compared with combination therapy. We conclude that further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone. Objective To determine if the combination of intravesical chemotherapy and maintenance bacille Calmette-Guerin (BCG), used in sequence, is superior to maintenance BCG alone in the treatment of non-muscle-invasive bladder cancer (NMIBC). Methods We searched biomedical literature databases for randomized controlled trials that compared sequential, intravesical chemotherapy added to maintenance BCG with maintenance BCG alone. Studies that did not use maintenance BCG were excluded. The meta-analysis was performed using the fixed effects model. Results Four trials were identified, including 801 patients. Adding chemotherapy to maintenance BCG did not result in a significant reduction in recurrence (relative risk [RR] 0.92; 95% confidence interval [CI] 0.79–1.09; P = 0.32) or progression (RR 0.88; 95% CI 0.61–1.27; P = 0.5). The risk of recurrence (RR 0.75; 95% CI 0.61–0.92; P = 0.006) and progression (RR 0.45; 95% CI 0.25–0.81; P = 0.007) were reduced when the single trial that included isolated Tis was excluded. Toxicity was similar for both groups. Conclusions Adjuvant therapy with induction BCG followed by maintenance BCG is the appropriate standard of care for patients with resected NMIBC at high risk of recurrence. Further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.

What's known on the subject? and What does the study add? Operating principles exist both within Australia and internationally to provide guidance on how to establish clinical registries. In establishing a registry, consideration needs to be given to its purpose, the stakeholders and the output it will generate and to whom output will be disseminated The present study describes how a prostate cancer-specific registry was developed that aligns with generic operating principles. We describe the governance model, the data items collected, the collection methodology clinical indicators selected for reporting and the reporting framework. OBJECTIVE • To establish a pilot population-based clinical registry with the aim of monitoring the quality of care provided to men diagnosed with prostate cancer. PATIENTS AND METHODS • All men aged >18 years from the contributing hospitals in Victoria, Australia, who have a diagnosis of prostate cancer confirmed by histopathology report notified to the Victorian Cancer Registry are eligible for inclusion in the Prostate Cancer Registry (PCR). • A literature review was undertaken aiming to identify existing quality indicators and source evidence-based guidelines from both Australia and internationally. RESULTS • A Steering Committee was established to determine the minimum dataset, select quality indicators to be reported back to clinicians, identify the most effective recruitment strategy, and provide a governance structure for data requests; collection, analysis and reporting of data; and managing outliers. • A minimum dataset comprising 72 data items is collected by the PCR, enabling ten quality indicators to be collected and reported. • Outcome measures are risk adjusted according to the established National Comprehensive Cancer Network and Cancer of the Prostate Risk Assessment Score (surgery only) risk stratification model. Recruitment to the PCR occurs concurrently with mandatory notification to the state-based Cancer Registry. • The PCR adopts an opt-out consent process to maximize recruitment. • The data collection approach is standardized, using a hybrid of data linkage and manual collection, and data collection forms are electronically scanned into the PCR. • A data access policy and escalation policy for mortality outliers has been developed. CONCLUSIONS • The PCR provides potential for high-quality population-based data to be collected and managed within a clinician-led governance framework. • This approach satisfies the requirement for health services to establish quality assessment, at the same time as providing clinically credible data to clinicians to drive practice improvement.

A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the first immunotherapeutic agent to obtain approval for CaP treatment. This short review will focus on the growing body of evidence suggesting an immunity-based link between CaP and inflammation and infection.

F-FDG-6-phosphate. This metabolite becomes trapped and cannot proceed along the normal pathway of glucose metabolism. Eventually, increased amounts accumulate within malignant cells. This abnormal concentration of 18 F-FDG in tumour cells produces a detectable signal greater than the background, allowing the isolation of tumour deposits [3]. The signal detected by the PET camera arises from the emission of radiation in the form of γ -photons when a positron collides with an electron within the radioisotope. Quantitative analysis of accumulated radioisotope within different tissues forms the basis of reporting PET studies. A standardized uptake value for normal tissue is established based on radioisotope uptake, and areas of interest within the same tissue are compared to this index for reduced or increased uptake. Tumours typically have a greater standardized uptake value than normal, indicating radioisotope accumulation.

To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to 'standard' treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient-reported outcomes, adverse events, biochemical failure-free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation.The Radiotherapy - Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at ≤4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs ± extraprostatic extension ± seminal vesicle involvement. The postoperative PSA level must be ≤0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients.Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta-analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho-oncology sub-study to investigate a patient decision aid resource.On the current evidence available, it remains unclear if ART is equivalent or superior to observation with early SRT.

Objective To determine the validity of using an historical maximum spontaneous regression rate (reportedly 0–1.1% in those with lung metastases after nephrectomy) in clinical trials of treatments for patients with metastatic renal cell carcinoma (RCC), as the eligibility criteria for most studies will select patients with better performance status (and thus excluding those who are unlikely to respond) and more modern staging methods would potentially reduce the number of false-positives. Patients and methods A multicentre randomized,placebo-controlled, double-blind trial was recently completed in which 197 patients with metastatic RCC from 17 study centres across Canada were randomized to receive placebo or recombinant interferonγ-1b (60 µg/m2) subcutaneously once every 7 days until disease progression. All tumour responses were validated by an independent response committee unaware of the treatment. Results The median (95% confidence interval) overall response rate (complete, CR, and partial, PR) for those on interferon-γ was 4 (1.4–11.5)% and for those on placebo was 6 (2.5–13.2)% (P = 0.75). In the six patients who were receiving placebo the CR and PR (three each) was considered to represent spontaneous remission. Of these six patients (aged 44–64 years) five had undergone nephrectomy, one a tumour embolization, four had clear cell carcinoma and one an adenocarcinoma, and all had regression of lung and/or lymph node metastases. Conclusion The lack of efficacy of interferon-γ in this trial underlines the importance of continued research to identify alternative therapeutic agents or combinations of agents in phase II studies. However, the threshold response rate for initiating phase III trials should be increased to 18% in the phase II trials, i.e. three times the response rate on placebo.

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.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.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 where10 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, P0.001 and IRR 3.81, 95% CI 2.60-5.60, P0.001, 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, P0.001); pT3 compared with pT2 disease (OR 4.72, 95% CI 2.69-8.23, P0.001); and having high- or very-high-risk disease compared with low-risk disease (OR 4.36, 95% CI 2.24-8.50, P0.001 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).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.

To describe the contemporary patterns of care for renal cell carcinoma (RCC) using a whole of population series from Victoria.Retrospective review of medical records of all patients diagnosed and treated for RCC in Victoria in 2009. Patients were identified via the State-wide Victorian Cancer Registry. Patient demographic characteristics, symptoms, stage, and first-line treatment were assessed. Associations between case residential location (metropolitan or rural) and treatment were examined using multivariate logistic regression after adjusting for age, sex, socioeconomic status, treatment in private or public hospital and comorbidity.Data were obtained for 499 of 577 eligible patients. In all, 413 patients (83%) underwent surgery. Laparoscopic radical nephrectomy (RN) was the most common procedure for Stage I pT1a/pT1b tumours (51.2%); partial nephrectomy (PN) was performed for 27% of Stage I RCC In multivariate analysis, regional patients were less likely to receive PN (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18-0.85) for Stage I RCC, and less likely to receive systemic therapy for Stage IV RCC (OR 0.06, 95% CI 0.01-0.41). Multidisciplinary team meetings were recorded for only 25% of patients and 3% were enrolled in a clinical trial.Most contemporary patients diagnosed with RCC are still treated with RN, including those with smaller tumours amenable to PN. This may impact future outcomes, including increased risk of chronic kidney disease and its potential financial healthcare burden. Patterns of treatment also appear to differ between metropolitan and regional populations.

To determine the patterns of management and surveillance imaging amongst medical oncologists in Australia for stage I testicular cancer during 2010.We conducted a survey comprising 14 questions about the management strategy and surveillance imaging for all patients with stage I testicular cancer treated over the previous 12 months.A total of 52 medical oncologists documented the management for an estimated 470 patients. For seminoma, management was in the form of surveillance in 33%, radiotherapy in 5% and adjuvant carboplatin in 62% of patients. For non-seminoma, management was surveillance in 73%, adjuvant chemotherapy in 23% and retroperitoneal lymph node dissection in 4% of patients. The frequency of surveillance imaging was highly variable, and ≥10 computed tomography (CT) scans were used by 38% of clinicians for seminoma and 46% of clinicians for non-seminoma.We found considerable variation in management patterns. The infrequent use of surveillance and frequent use of carboplatin for seminoma differs from international guidelines. Radiation exposure from CT imaging should be reduced through standardized follow-up protocols, and possibly by alternate imaging methods if validated in appropriate studies.

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Non-muscle-invasive bladder cancer has a significant recurrence and progression rate despite transurethral resection. The current standard of care to lower the risk of recurrence and progression is adjuvant BCG followed by maintenance BCG. Despite this, a significant number of patients experience recurrence and progress to invasive cancer. Several randomized trials have studied combination therapy (BCG with chemotherapy) to try to reduce the recurrence and progression rate. We performed a systematic review with meta-analysis and found that adjuvant BCG followed by maintenance therapy is the appropriate standard of care when compared with combination therapy. We conclude that further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.To determine if the combination of intravesical chemotherapy and maintenance bacille Calmette-Guérin (BCG), used in sequence, is superior to maintenance BCG alone in the treatment of non-muscle-invasive bladder cancer (NMIBC).We searched biomedical literature databases for randomized controlled trials that compared sequential, intravesical chemotherapy added to maintenance BCG with maintenance BCG alone. Studies that did not use maintenance BCG were excluded. The meta-analysis was performed using the fixed effects model.Four trials were identified, including 801 patients. Adding chemotherapy to maintenance BCG did not result in a significant reduction in recurrence (relative risk [RR] 0.92; 95% confidence interval [CI] 0.79-1.09; P = 0.32) or progression (RR 0.88; 95% CI 0.61-1.27; P = 0.5). The risk of recurrence (RR 0.75; 95% CI 0.61-0.92; P = 0.006) and progression (RR 0.45; 95% CI 0.25-0.81; P = 0.007) were reduced when the single trial that included isolated Tis was excluded. Toxicity was similar for both groups.Adjuvant therapy with induction BCG followed by maintenance BCG is the appropriate standard of care for patients with resected NMIBC at high risk of recurrence. Further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.

To establish a pilot population-based clinical registry with the aim of monitoring the quality of care provided to men diagnosed with prostate cancer.All men aged18 years from the contributing hospitals in Victoria, Australia, who have a diagnosis of prostate cancer confirmed by histopathology report notified to the Victorian Cancer Registry are eligible for inclusion in the Prostate Cancer Registry (PCR). A literature review was undertaken aiming to identify existing quality indicators and source evidence-based guidelines from both Australia and internationally.A Steering Committee was established to determine the minimum dataset, select quality indicators to be reported back to clinicians, identify the most effective recruitment strategy, and provide a governance structure for data requests; collection, analysis and reporting of data; and managing outliers. A minimum dataset comprising 72 data items is collected by the PCR, enabling ten quality indicators to be collected and reported. Outcome measures are risk adjusted according to the established National Comprehensive Cancer Network and Cancer of the Prostate Risk Assessment Score (surgery only) risk stratification model. Recruitment to the PCR occurs concurrently with mandatory notification to the state-based Cancer Registry. The PCR adopts an opt-out consent process to maximize recruitment. The data collection approach is standardized, using a hybrid of data linkage and manual collection, and data collection forms are electronically scanned into the PCR. A data access policy and escalation policy for mortality outliers has been developed.The PCR provides potential for high-quality population-based data to be collected and managed within a clinician-led governance framework. This approach satisfies the requirement for health services to establish quality assessment, at the same time as providing clinically credible data to clinicians to drive practice improvement.

A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the first immunotherapeutic agent to obtain approval for CaP treatment. This short review will focus on the growing body of evidence suggesting an immunity-based link between CaP and inflammation and infection.

OBJECTIVE To assess renal tumours for hypoxic regions using 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET), a recognized noninvasive method for detecting hypoxia in tumours, as renal cell carcinoma (RCC) can be potentially cured with nephrectomy but recurrence develops in most patients, who then respond poorly to treatments such as chemotherapy, and hypoxia is known to confer resistance to radiotherapy and chemotherapy in many solid tumours. PATIENTS AND METHODS In all, 17 patients had 18F-FMISO PET scans before nephrectomy for presumed RCC. Specimens were examined histologically, and immunohistochemistry was used to compare the microvessel density (MVD) as an indicator of angiogenesis in the tumour and normal parenchyma, in 15 patients. Tumour oxygenation was measured invasively in three patients using a polarographic oxygen sensor probe. RESULTS Of the 15 patients with histological results, 11 had RCC and four had other tumours. Although there was a trend there was no statistically significant (P = 0.14) difference in the maximum standardized uptake value (SUVmax) when comparing the region of the kidney involved with RCC; the mean (95% confidence interval) SUVmax in the tumours was 1.3 (0.15), whilst that in the normal contralateral kidney was 1.1 (0.22). The MVD was greater in RCC, at 13.7 (3.1) mean vessels per high-power field than in normal tissue, at 6.9 (1.9). Hypoxia as measured polarographically was detected in three RCCs (median pO2 9.6 mmHg) compared to normal parenchyma at 37.6 mmHg. CONCLUSIONS Although 18F-FMISO scans showed significant uptake in other solid tumours, there was only mild 18F-FMISO uptake in the present RCCs. The invasive measurements indicated that there was hypoxia in RCC, but the median pO2 did not fall below 9.5 mmHg. Further direct studies of renal tumour oxygenation combined with therapies directed towards hypoxia may allow a better understanding of the relationship between 18F-FMISO results and the biological significance of hypoxia in RCC.

Introduction: Hypoxia stimulates angiogenesis and has been demonstrated in tumours where it correlates with resistance to treatment and poor prognosis. We have previously demonstrated hypoxia in human Renal Cell Carcinoma (RCC). The purpose of animal models was to further evaluate oxygen levels within RCC whilst also focusing on expression of the protein carbonic anhydrase IX (CA IX). This protein is stimulated by hypoxia and involved in angiogenesis and may be a potential tumour target for imaging and future therapies. Methods: Balb/c nude mice had human RCC (SK-RC-52) xenografted subcutaneously. Tumours were grown to different volumes with oxygen levels measured. Further groups then had the radiolabelled monoclonal antibody 124I-G250 (that binds to CA IX) injected intravenously and had Positron Emission Tomography (PET), gamma counting and oxygen studies performed on days 0,1,2,3,5,7,10 and 14 post injection. Immunohistochemistry and autoradiography was also performed. Results: An inverse relationship between tumour volume and hypoxia within the model was established (P

Introduction: The growth of human tumours under the renal capsule in animal models has been performed successfully for many years. However, the use of modern surgical equipment has not always been translated into the animal laboratory. We report on a novel method for human renal tumour transplants using an automated biopsy gun to obtain tumour tissue and an epidural needle with introducer to easily deploy the grafts under the renal capsule. Methods: Nude mice had human xenografted tumours grown subcutaneously after implantation of cells from culture. Tumours were then biopsied using a 16 gauge automated biopsy gun. Digital callipers were used to measure a 2 mm segment of the biopsy core that was cut and placed inside a hollow needle (epidural needle). The needle was placed under the renal capsule and the trochar introduced to deploy the graft beneath the capsule with minimal trauma. Results: Tumour grafts were be established in ninety percent of grafted kidneys in this renal subcapsular model. Grafts were confirmed by direct observation and histology. Conclusion: Modern surgical equipment may be utilised to allow tumour transplantation to be undertaken in a more precise fashion than has previously been possible, with the volume of deployed tumour able to be identified and reliably reproduced. Surgical researchers and laboratory-based scientists need to embrace new techniques and utilise them where appropriate in order to allow for a more objective comparison of results of xenograft transplantation.