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5070 Background: IO combination therapies [including IOIO and IO/vascular endothelial growth factor inhibitor (IOVE) combinations] in mRCC have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of trial ineligible patients who are treated with first-line IOIO or IOVE combinations are unknown. Methods: Metastatic RCC patients treated with first-line IOIO or IOVE were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria in IO trials) if they had a Karnofsky performance status (KPS) < 70%, no clear-cell component, brain metastases, hemoglobin (Hb) < 9 g/dL, eGFR < 40 mL/min, platelet count of < 100,000/mm3, and/or neutrophil count < 1500/mm3. Time to treatment failure (TTF) and overall survival (OS) were calculated from time of starting first-line IO therapy. Results: Overall, 26% (155/592) of patients in the International mRCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Baseline characteristics are listed in Table. The reasons for ineligibility were: no clear-cell component (34%, 53/155), Hb < 9g/dL (28%, 44/155), eGFR < 40 mL/min (19%, 30/155), brain metastases (19%, 29/155), KPS < 70% (14%, 21/155), platelet < 100,000/mm3 (3%, 4/155) and neutrophil count < 1500/mm3 (0%, 0/155). Between ineligible versus eligible patients, the response rate, median TTF and median OS of first-line IOIO or IOVE was 34% vs 46% (p = 0.02), 4.2 vs 9.7 months (p < 0.01), and 25.3 vs 44.4 months (p < 0.01), respectively. When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.50 (95% CI 1.05-2.14). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. These data may guide patient counselling and specific trials addressing the unmet needs of protocol ineligible patients are warranted. [Table: see text]

5500 Background: LuPSMA is a radiolabeled small molecule that delivers therapeutic β-radiation to PSMA-expressing tumors. Encouraging efficacy and safety has been shown in non-randomized studies of mCRPC. TheraP is a randomized phase II trial comparing LuPSMA vs cabazitaxel in men with mCRPC progressing after docetaxel. Methods: Men with mCRPC, and imaging with 68Ga-PSMA-11 and 18F-FDG PET/CT that confirmed high PSMA-expression and no sites of FDG-positive/PSMA-negative disease, were randomly assigned (1:1) to LuPSMA (6-8GBq q6weeks up to 6 cycles) vs cabazitaxel (20mg/m2 q3weeks up to 10 cycles); stratified by disease burden (>20 vs ≤20 sites), prior novel antiandrogens (NAA; abiraterone or enzalutamide), and study site. The primary endpoint was PSA response rate (PSA50-RR) defined by ≥50% reduction. Secondary efficacy endpoints included PSA-progression-free survival (PSA-PFS) and overall survival (OS). Data cut-off was 31DEC19 at this first pre-specified analysis. Results: 200 (median age 72 y, prior NAA 91%, >20 lesions 78%) of 291 PET screened men were randomised to LuPSMA (N=99) or cabazitaxel (N=101). 17 patients withdrew or died before receiving study treatment (1 LuPSMA vs 16 cabazitaxel). The PSA50-RR was higher in those assigned LuPSMA than cabazitaxel (65/99 [66%; 95%CI 56-75] vs 37/101 [37%; 95%CI 27-46]; P

5011 Background: Tumor mutational burden (TMB), PD-L1 expression, T-effector gene expression (GE) and a fibroblast TGF-β–response signature (F-TBRS) are associated with clinical outcomes with atezo mono in mUC (Mariathasan, Nature, 2018). Here we explore the potential predictive role of these biomarkers and APOBEC mutagenesis in IMvigor130. Methods: Pts receiving first-line (1L) mUC treatment (tx) were randomized 1:1:1 to atezo + PBC, atezo mono, or placebo + PBC. Coprimary efficacy endpoints were PFS and OS. Planned exploratory biomarker analyses included PD-L1 expression, TMB (FoundationOne), and T-effector GE (RNA-seq). Results: The 851 biomarker-evaluable pts (BEP) were representative of the 1200 ITT pts. Biomarker results are shown in Table. PD-L1 IC2/3 was associated with significantly longer OS for atezo mono vs placebo + PBC and a combination of PD-L1 IC2/3, and high TMB (> 10 muts/Mb) identified a pt subset (≈ 14% of BEP) with particularly favorable outcomes with atezo mono vs placebo + PBC; similar results for PD-L1 and TMB were not seen with atezo + PBC vs placebo + PBC. APOBEC mutagenesis was associated with improved OS with atezo-containing regimens whereas high F-TBRS was associated with inferior OS with atezo mono. Conclusions: These results reinforce the potential predictive nature of biomarkers associated with response/resistance to atezo and highlight potentially distinct biology driving benefit with atezo and atezo + PBC. These findings suggest a possible biomarker-directed approach to 1L mUC tx that warrants mechanistic interrogation and prospective validation. Clinical trial information: NCT02807636 . [Table: see text]

e19126 Background: Functional assessment of oncology patients can be challenging and is often not performed, or is undertaken by the clinician with minimal direct input from the patient. The ELderly Functional Index (ELFI) is a 12-item composite measure of self-reported functioning in cancer patients. ELFI is derived from four scales from the European Organisation for Research and Treatment of Cancer (EORTC) health-related quality of life (HRQOL) suite: Physical, Role and Social Functioning, and Mobility. This study validated ELFI in patients attending oncology clinics. Methods: For evaluation of validity and internal consistency, 621 cancer patients (31% aged >70 years) fully self-completed the ELFI, cognitive functioning (CF) and emotional functioning (EF) scales of the EORTC QLQ-C30, ECOG-performance status (ECOG-PS), instrumental activities of daily living (IADL) and Clinical Frailty Scale (CFS). For evaluation of test-retest reliability, 278 participants self-completed ELFI, CF, EF, ECOG-PS and Global Rating of Change one week later. Results: ELFI demonstrated excellent internal consistency (Cronbach alpha 0.93, p< 0.001) and test-retest reliability (intraclass correlation coefficient 0.90, p< 0.001). Hypotheses regarding convergent and discriminant validity were confirmed (multitrait-scaling). ELFI was better than its component scales and other function measures at differentiating between participants with different function and frailty scores (known-groups validity, Table). Exploratory factor analysis provided empirical support to the structural validity of ELFI. Strong correlation was observed between ELFI, function and frailty scores. Conclusions: ELFI is a validated patient-reported outcome measure of functional status. ELFI captures broader dimensions of functioning compared to ECOG-PS or IADL. As a composite measure, ELFI has enhanced statistical efficiency, reducing the sample size required to detect a given effect. ELFI could be used as a clinical trial endpoint to assess the functional domains of HRQOL. [Table: see text]

485 Background: In patients (pts) with muscle invasive bladder (MIBC) suitable for curative definitive chemoradiotherapy (CRT), we hypothesise that the addition of pembrolizumab may be safe and improve efficacy. A pre-planned safety analysis was performed after the first 10 of planned 30 pts were enrolled and completed treatment. Methods: Patients with maximally resected non-metastatic MIBC and ECOG 0-1, who desire bladder preservation or are ineligible for cystectomy were treated with 64Gy in 32 daily radiation fractions to the whole bladder alone over 6.5 weeks in combination with 6 concurrent doses of weekly cisplatin at 35mg/m2 IV. Pembrolizumab was commenced concurrently with radiation and given flat-dose 200mg IV q21 days for 7 doses. Surveillance cystoscopy, urine cytology and CT chest-abdomen-pelvis were performed 12 & 24 weeks post CRT. The primary endpoint is feasibility, defined by a satisfactory low rate of unacceptable toxicity of a) G3-4 non-urinary adverse events (AE) or b) failure of completion of planned CRT according to defined parameters. Secondary endpoints include complete cystoscopic response without metastatic disease at 12 & 24 weeks, loco-regional PFS, metastatic DFS, and overall survival. A 2-stage design was planned, with accrual to be halted if >5 of the first 10 pts experienced unacceptable toxicity up to 12 weeks post treatment. Results: All 10 pts completed the course of CRT and pembrolizumab without alteration in radiation dose or schedule. 1 patient had a dose of cisplatin withheld. 4/10 pts experienced G3-4 non-urinary adverse events within 12 weeks of completing treatment. One immune related AE interrupted pembrolizumab delivery (G2 nephritis). By week 24, 9/10 pts achieved a complete cystoscopic response to treatment post CRT and were free of distant metastatic disease. Conclusions: Interim results indicate that pembrolizumab and CRT shows satisfactory safety, and promising efficacy. There were no unexpected safety signals. Follow up of these and additional pts will better define the efficacy and safety of the combination. Enrolment is ongoing with 20 pts recruited out of a planned total of 30. Clinical trial information: NCT02662062.

TPS385 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) for at least one year, is standard of care for men with very high-risk localised prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high risk features. Darolutamide is an androgen receptor antagonist with favourable tolerability. Our aim is to determine the efficacy of adding darolutamide to ADT and RT given in the setting of either primary definitive therapy (RP or RT), or adjuvant therapy for very high-risk PC. Methods: This study is a randomised (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localised PC, or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: use of adjuvant docetaxel; pelvic nodal involvement; RP. 1100 participants will be randomised to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival, with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.

608 Background: The role of CN for mRCC treated with ICI is not well defined. Our aim was to evaluate the role of CN for mRCC treated by ICI or TT using a propensity score-based analysis. Methods: We retrospectively assessed patients who were diagnosed with de novo mRCC and who had started first line systemic therapy (ICI or TT) between 2009 and 2019 using the International Metastatic RCC Database Consortium (IMDC). Overall Survival (OS) was compared between patients receiving CN and those treated by systemic therapies alone, using the Kaplan-Meier method and Cox regressions, in the TT and ICI arms separately. In order to account for treatment selection bias, inverse probability of treatment weighting (IPTW) of propensity scores, based on 14 confounding variables, was used and variables were considered balanced if standardized mean difference (SMD) < 0.1. For variables with SMD≥0.1, residual confounding was adjusted for using multivariable models. Results: 3856 patients had been treated by TT (2470 CN+ & 1386 CN-) and 198 by ICI (143 CN+ & 55 CN-). Median follow-up was 38.5 months. After IPTW, baseline characteristics were largely balanced between the CN+ and CN- arms, in the TT and ICI groups (14/14 and 12/14 with SMD < 0.1, respectively). CN was associated with significantly improved OS in both the ICI (Hazard Ratio [HR] = 0.39 [0.19-0.83]) and TT (HR = 0.56 [0.51-0.62]) groups. The interaction term between CN and therapy type (ICI vs TT) was not statistically significant (p = 0.43). The point estimates of the HRs were consistent in sensitivity analyses using multivariable models. Conclusions: In a propensity score-based analysis, CN was found to be associated with a significant OS benefit in patients treated by either ICI or TT. While this study is not a substitute for randomized controlled trials (e.g. CARMENA), the results suggest that CN may still play a role in selected patients in the ICI era.[Table: see text]

TPS768 Background: Renal cell carcinomas (RCC) are predominantly the clear cell (cc) subtype, with a unique biology, characterized by sensitivity to angiogenesis inhibition. However vascular endothelial growth factor-tyrosine kinase inhibitors elicit modest responses in people with rare variant non-clear cell (ncc) RCC. Immune checkpoint inhibitors (ICI) are active against many cancers, but people with rare variant nccRCC have been excluded from frontline trials despite experiencing a more aggressive disease course and poorer prognosis compared to those with ccRCC. UNISON (NCT03177239) aims to test 2 ideas; the activity of ICI in nccRCC, and the novel sequencing strategy of anti-programmed cell death protein (PD)1 immunotherapy, followed by the combination of anti-PD1 and anti-cytotoxic T-lymphocyte-associated protein (CTLA)4 blockade, in people failed by single agent treatment. Methods: This single-arm, two-part trial recruits people of good performance status suffering metastatic or locally advanced unresectable rare variant nccRCC, including but not limited to papillary (type 1/2), chromophobe, sarcomatoid, Xp11 translocation, collecting duct, and unclassified histological subtypes. Participants are offered fixed dose nivolumab at 240mg every two weeks in Part 1 of the trial. If they experience progressive disease, eligible participants may proceed to Part 2 consisting of nivolumab (3mg/kg) plus ipilimumab (1mg/kg) every 3 weeks for up to 4 doses. People experiencing disease control after single-agent or combined ICI are eligible to continue treatment for up to 1 year. UNISON is powered to distinguish a clinically non-relevant objective tumor response rate (OTRR) of 15% in people taking combination ICI whose cancers are refractory to single-agent PD1, versus a clinically-relevant OTRR of 30% at 5% level of significance with 80% power. 85 participants were recruited in Part 1, on the assumption that 55% of those entering Part 1 will be eligible for inclusion in Part 2. Enrolment commenced in November 2017 and was completed ahead of schedule in September 2019. Of the 48 participants projected to experience progression on anti-PD1 immunotherapy, 36 have so far commenced combination ICI in Part 2. Clinical trial information: NCT03177239.

551 Background: IMvigor130 demonstrated a statistically significant improvement in PFS in pts receiving atezolizumab (atezo; anti–PD-L1) + platinum-based chemotherapy (plt/gemcitabine [gem]; Arm A) vs placebo + plt/gem (Arm C) as first-line treatment for mUC (Grande et al. 2019). Exploratory analyses examined efficacy outcomes in UT and LT mUC subgroups. Methods: Pts with UT and LT mUC from Arm A and Arm C were included. Chemotherapy was gem + investigator choice of plt (cisplatin or carboplatin). Tumors were assessed at baseline and every 9 wk until investigator-assessed PD per RECIST 1.1 or other events. PFS, OS and ORR in UT and LT subgroups are shown. Results: Baseline characteristics were comparable between Arm A and Arm C in the UT and LT subgroups; however, slight imbalances were noted, such as higher PD-L1–positive status (IC2/3) and lower Bajorin risk score in UT Arm A pts. With a median follow-up of 11.8 mo, median PFS was8.2 vs 6.2 mo in Arm A vs Arm C in UT pts (HR, 0.69 [95% CI: 0.51, 0.94]) and 8.1 vs 6.5 mo, respectively, in LT pts (HR, 0.85 [95% CI: 0.70, 1.02]). Interim median OS was 16.9 vs 13.5 mo in Arm A vs Arm C in UT pts (HR, 0.78 [95% CI: 0.54, 1.12]) and 15.8 vs 13.4 mo, respectively, in LT pts (HR, 0.87 [95% CI: 0.70, 1.08]). See table for additional efficacy results. Conclusions: Exploratorysubgroup analyses suggest activity of atezo + plt/gem in both UT and LT mUC, with outcomes in UT pts comparable to those seen in the LT and ITT populations. Clinical trial information: NCT02807636. [Table: see text]

TPS602 Background: Adjuvant intravesical bacillus Calmette-Guérin (BCG) decreases disease recurrence and progression in people with high-risk, non-muscle invasive urothelial bladder cancer (NMIBC), however recurrence occurs in 30% despite optimal therapy. Recent meta-analyses evaluating addition of intravesical mitomycin (MM) to BCG showed lower rates of recurrence and cancer-specific mortality in people with NMIBC who received combination regimens. Good quality randomized trials to definitively test this combination are lacking. The BCGMM trial (NCT02948543) will be the largest study to date evaluating this approach in people with high-risk NMIBC. Methods: This open-label phase 3 trial aims to randomize 500 participants, stratified by stage, site of disease, and presence of carcinoma in-situ, to Arm A (BCG induction weekly x6 then monthly x10) or Arm B (BCG + MM weekly x9 then monthly x9). This study is powered to detect a 10% improvement in 2-year disease free survival (DFS) at 5% level of significance with 85% power. Stage 1 of this study, designed to recruit 130 patients to determine rates of treatment completion, activity reflected by cystoscopic findings at 3 months, adverse events, resource use, and health related quality of life, has completed enrolment and successfully established feasibility of this trial protocol. Stage 2, aiming for a further 370 patients, will inform on additional endpoints including differences in DFS, time to recurrence and progression, overall survival, and potential predictive biomarkers, is estimated to complete accrual in December 2020. Successful treatment completion, defined as 75% or more of planned treatment doses, has been achieved in 76% of patients treated in the experimental arm of Stage 1, compared to 60% in those allocated BCG alone. Clinical trial information: NCT02948543.

(18)F-fluorodihydrotestosterone ((18)F-FDHT) is a radiolabeled analog of the androgen receptor’s primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. Methods: We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest) (18)F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor–positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland–Altman plots were used to evaluate repeatability of (18)F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Results: Twenty-seven patients with 140 (18)F-FDHT–avid regions were included. The best repeatability among (18)F-FDHT uptake metrics was found for SUV metrics (SUV(max,) SUV(mean), and SUV(peak)), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics (R(2) ≥ 0.92; ICC ≥ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUV(peak)) to 24.6% (SUV(max)). The test and retest androgen receptor–positive tumor volumes and TLU, respectively, were highly correlated (R(2) and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs > 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration–time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%–10.8%). Conclusion: Uptake metrics derived from (18)F-FDHT PET/CT show high repeatability and interobserver reproducibility.

Recent clinical trials have changed the treatment landscape for metastatic castration-sensitive prostate cancer. Ongoing and future studies using new therapeutic approaches hold the promise of further improving outcomes for patients with advanced prostate cancer.

ObjectiveTo evaluate the different methods of data visualisation and how it affects preference and data interpretation.DesignA cross-sectional survey, assessing interpretation and preference for four methods of data presentation, was distributed to participants.SettingMelbourne, VictoriaParticipantsMembers of Prostate Cancer Outcome Registry-Victoria (PCOR-Vic) and senior hospital staff in three metropolitan Victorian hospitals.InterventionsDifferent methods of data visualisation. Mainly, funnel plots, league charts, risk adjusted sequential probability ratio test (RASPRT) charts and dashboard.Main Outcome MeasureInterpretation scores assessed capacity by participants to identify outliers and poor performers. Preference was based on a 9-point Likert-scale (0 – 9).ResultsIn total, 113 participants responded to the online survey (16/58 urologists and 97/297 senior hospital staff, response rate 32%). Respondents reported that funnel plots were easier to interpret compared to league charts (mean interpretability score difference of 28% (95% CI: 19.2% - 37.0%, PConclusionWhen developing reports for clinicians and hospitals, consideration should be given to preference of end-users and ability of groups to interpret the graphs.

A significant proportion of men with rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP) fail prostate fossa (PF) salvage radiation treatment (SRT). This study was done to assess the ability of (18)F-fluoromethylcholine ((18)F-FCH) PET/CT (hereafter referred to as (18)F-FCH), (68)Ga-HBED-CC PSMA-11 PET/CT (hereafter referred to as PSMA), and pelvic multiparametric MRI (hereafter referred to as pelvic MRI) to identify men who will best benefit from SRT. Methods: Prospective, multisite imaging studies were carried out in men who had rising PSA levels after RP, high-risk features, and negative/equivocal conventional imaging results and who were being considered for SRT. (18)F-FCH (91/91), pelvic MRI (88/91), and PSMA (31/91) (Australia) were all performed within 2 wk. Imaging was interpreted by experienced local/central interpreters who were masked with regard to other imaging results, with consensus being reached for discordant interpretations. Expected management was documented before and after imaging, and data about all treatments and PSA levels were collected for 3 y. The treatment response to SRT was defined as a reduction in PSA levels of >50% without androgen deprivation therapy. Results: The median Gleason score, PSA level at imaging, and PSA doubling time were 8, 0.42 (interquartile range, 0.29–0.93) ng/mL, and 5.0 (interquartile range, 3.3–7.6) months. Recurrent prostate cancer was detected in 28% (25/88) by pelvic MRI, 32% (29/91) by (18)F-FCH, and 42% (13/31) by PSMA. This recurrence was found within the PF in 21.5% (19/88), 13% (12/91), and 19% (6/31) and at sites outside the PF (extra-PF) in 8% (7/88), 19% (17/91), and 32% (10/31) by MRI, (18)F-FCH, and PSMA, respectively (P < 0.004). A total of 94% (16/17) of extra-PF sites on (18)F-FCH were within the pelvic MRI field. Intrapelvic extra-PF disease was detected in 90% (9/10) by PSMA and in 31% (5/16) by MRI. (18)F-FCH changed management in 46% (42/91), and MRI changed management in 24% (21/88). PSMA provided additional management changes over (18)F-FCH in 23% (7/31). The treatment response to SRT was higher in men with negative results or disease confined to the PF than in men with extra-PF disease ((18)F-FCH 73% [32/44] versus 33% [3/9] [P < 0.02], pelvic MRI 70% [32/46] versus 50% [2/4] [P was not significant], and PSMA 88% [7/8] versus 14% [1/7] [P < 0.005]). Men with negative imaging results (MRI, (18)F-FCH, or PSMA) had high (78%) SRT response rates. Conclusion: (18)F-FCH and PSMA had high detection rates for extra-PF disease in men with negative/equivocal conventional imaging results and rising PSA levels after RP. These findings affected management and treatment responses, suggesting an important role for PET in triaging men being considered for curative SRT.

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.

Background The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations. Methods Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off). Results Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmar-plantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most non-hematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%). Conclusions A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations. Trial registration ClinicalTrials.gov, NCT00720941, Registered July 22, 2008 ClinicalTrials.gov, NCT01147822, Registered June 22, 2010 Electronic supplementary material The online version of this article (10.1186/s13045-018-0617-1) contains supplementary material, which is available to authorized users.

Background: In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics. Objective: To present the report of APCCC 2017. Design, setting, and participants: Ten important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; "oligometastatic" prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process. Results and limitations: Voting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data. Conclusions: The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them. Patient summary: The second Advanced Prostate Cancer Consensus Conference APCCC 2017 did provide a forum for discussion and debates on current treatment options for men with advanced prostate cancer. The aim of the conference is to bring the expertise of world experts to care givers around the world who see less patients with prostate cancer. The conference concluded with a discussion and voting of the expert panel on predefined consensus questions, targeting areas of primary clinical relevance. The results of these expert opinion votes are embedded in the clinical context of current treatment of men with advanced prostate cancer and provide a practical guide to clinicians to assist in the discussions with men with prostate cancer as part of a shared and multidisciplinary decision-making process. At the Advanced Prostate Cancer Consensus Conference, 10 important areas of controversy in advanced prostate cancer management were identified, discussed, and the experts voted on 150 predefined consensus questions. The full report of the results is summarised here.

ObjectiveTo explore men’s lived experience of advanced prostate cancer (PCa) and preferences for support.DesignCross-sectional qualitative study applying open-ended surveys and interviews conducted between June and November 2016. Interviews audio-recorded and transcribed verbatim and analysed from an interpretive phenomenological perspective.SettingAustralia, nation-wide.Participants39 men diagnosed with advanced PCa (metastatic or castration-resistant biochemical progression) were surveyed with 28 men subsequently completing a semistructured in depth telephone interview.ResultsThematic analysis of interviews identified two organising themes: lived experience and supportive care. Lived experience included six superordinate themes: regret about late diagnosis and treatment decisions, being discounted in the health system, fear/uncertainty about the future, acceptance of their situation, masculinity and treatment effects. Supportive care included five superordinate themes: communication, care coordination, accessible care, shared experience/peer support and involvement of their partner/family.ConclusionsLife course and the health and social context of PCa influence men’s experiences of advanced disease. Multimodal interventions integrating peer support and specialist nurses are needed that more closely articulate with men’s expressed needs.

Background We previously reported that treatment with enzalutamide (ENZA) rather than an older non-steroidal anti-androgen (NSAA: bicalutamide, nilutamide, or flutamide), resulted in longer overall survival when added to standard first-line treatment, with or without concurrent early docetaxel, in mHSPC (hazard ratio 0.67, 95% CI 0.52 to 0.86, p = 0.002, NEJM 2019). Here we report effects on HRQL. Methods HRQL was measured with the EORTC QLQ-C30 and PR25 at weeks 0, 4, 12, and then 12-weekly until clinical progression. We used mixed models for repeated measures to calculate the least squares mean difference (LSMD), 95% CI, and p-value for comparisons of the randomly assigned groups for all assessments from week 4 to 156. For each analysis of deterioration-free survival, the endpoint was defined a-priori as the earliest of death, clinical progression, cessation of study treatment, or a 10-point worsening from baseline (minimum clinically important difference on scales scored from 0 to 100) in the pertinent HRQL sub-scale: physical functioning (PF), global health and quality of life (GHQL), cognitive functioning (CF), and fatigue; p-values were based on the log-rank test. Results Completion of HRQL forms in 1016 men with a baseline assessment of HRQL (1125 randomised) ranged from 94% at week 12 to 78% at week 156. Random assignment to ENZA v NSAA was associated with modest impairments (LSMD, 95% CI) from week 4 to 156 in fatigue (5.0, 3.3 to 6.7, p Conclusions The addition of ENZA maintained GHQL and improved deterioration-free survival because early impairments in specific aspects of HRQL were insufficient to outweigh the subsequent benefits of delayed clinical progression. Clinical trial identification ACTRN12614000110684, NCT02446405; EUCTR2014-003190-42-IE. Legal entity responsible for the study ANZUP Cancer Trials Group and the NHMRC Clinical Trials Centre, University of Sydney. Funding Astellas Pharma. Disclosure M.R. Stockler: Research grant / Funding (institution): Astellas; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Bayer. A.J. Martin: Research grant / Funding (institution): Astellas. I.D. Davis: Research grant / Funding (institution): Astellas. K.N. Chi: Research grant / Funding (institution): Astellas. S. Chowdhury: Research grant / Funding (institution): Astellas. L.G. Horvath: Research grant / Funding (institution): Astellas. N.J. Lawrence: Research grant / Funding (institution): Astellas. G.M. Marx: Research grant / Funding (institution): Astellas. J. Mc Caffrey: Research grant / Funding (institution): Astellas. R. McDermott: Research grant / Funding (institution): Astellas. S.A. North: Research grant / Funding (institution): Astellas. F. Parnis: Research grant / Funding (institution): Astellas. D.W. Pook: Research grant / Funding (institution): Astellas. M.N. Reaume: Research grant / Funding (institution): Astellas. S.K. Sandhu: Research grant / Funding (institution): Astellas. T.H. Tan: Research grant / Funding (institution): Astellas. A. Thomson: Research grant / Funding (institution): Astellas. R. Zielinski: Research grant / Funding (institution): Astellas. C.J. Sweeney: Research grant / Funding (institution): Astellas. All other authors have declared no conflicts of interest.

Background SORCE is a randomised, double-blind trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) at intermediate or high risk of recurrence (Leibovich classification). Methods We recruited patients from 147 sites in the UK, Australia, France, Belgium, Denmark, The Netherlands and Spain and randomised them (2:3:3) between three years of placebo (A), one year of sorafenib followed by two years of placebo (B) and three years of sorafenib (C). The initial sorafenib dose was 400mg twice per day orally, amended during trial recruitment to a reduced starting dose of 400mg daily. The primary outcome is investigator-reported disease-free survival (DFS). Given the results of the ASSURE and S-TRAC trials, and blinded to SORCE outcomes, we revised the primary analysis to compare three years of sorafenib (arm C) vs placebo (arm A) to focus on the question of longer exposure to sorafenib. Results Between July 2007 and April 2013, we randomised 1711 patients; 430, 642, and 639 to arms A, B, and C respectively. Median age was 58 years; 71% male, 84% clear cell histology, 53% at intermediate risk of recurrence and 47% at high risk of recurrence. We observed no differences in DFS or OS in any of our pre-planned and pre-powered analyses: all randomised patients, high-risk patients only, and patients with clear cell RCC only. Median DFS was not reached for three years sorafenib or for placebo (HR 1.01, 95% CI 0.83 -1.23, p=0.95). We observed non-proportional hazards: restricted mean survival time (RMST) was 6.81 years for three years of sorafenib and 6.82 years for placebo, RMST difference 0.01, 95% CI -0.49 – 0.48, p=0.99. Despite offering treatment adaptations, over half of patients stopped treatment early. Grade 3 hand-foot syndrome was reported in 24% of patients on sorafenib. Conclusions Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence following nephrectomy; it is the appropriate control of our current international adjuvant RCC trial, RAMPART. Clinical trial identification ISRCTN38934710; EudraCT: 2006-006079-19; NCT00492258. Legal entity responsible for the study University College London (UCL). Funding Cancer Research UK, UK Medical Research Council, Educational Grants and Drug Supply from Bayer, Cancer Australia Support for Cancer Clinical Trials Program and University College London. Disclosure T.Q.G. Eisen: Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Research grant / Funding (self): Pfizer; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): GSK; Honoraria (self): AVEO; Honoraria (self): Astellas; Honoraria (self): Boehringer Ingelheim. I.D. Davis: Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche / Genentech; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bristol-Myers Squibb. M.R. Stockler: Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Binomics; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Tilray. J.M.G. Larkin: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Achilles Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Covance; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Aveo; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: Eisai; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Imugene; Advisory / Consultancy: Incyte; Advisory / Consultancy: iOnctura. A. Bex: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy, Non-remunerated activity/ies: BMS; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Non-remunerated activity/ies: Roche. S. Joniau: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas ; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ferring; Speaker Bureau / Expert testimony: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MDX Health; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: Sanofi. J. Bellmunt: Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Takeda; Shareholder / Stockholder / Stock options: Biocline. All other authors have declared no conflicts of interest.

Cancer cell lines can be useful to model cancer stem cells. Infection with Mycoplasma species is an insidious problem in mammalian cell culture. While investigating stem-like properties in early passage melanoma cell lines, we noted poorly reproducible results from an aliquot of a cell line that was later found to be infected with Mycoplasma hyorhinis. Deliberate infection of other early passage melanoma cell lines aliquots induced variable and unpredictable effects on expression of putative cancer stem cell markers, clonogenicity, proliferation and global gene expression. Cell lines established in stem cell media (SCM) were equally susceptible. Mycoplasma status is rarely reported in publications using cultured cells to study the cancer stem cell hypothesis. Our work highlights the importance of surveillance for Mycoplasma infection while using any cultured cells to interrogate tumor heterogeneity.

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

The purpose of this study was to compare the accuracy of [(11)C]choline positron emission tomography (CHOL-PET) with that of the combination of T2-weighted and diffusion-weighted (T2W/DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET.This study included 21 patients who underwent CHOL-PET and T2W/DW MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), and sensitivity and specificity values. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models.The best automatic contouring method, 60% of the maximum SUV (SUV60) , had similar correlations (DSC: 0.59) with the manual PET contours (DSC: 0.52, P=.127) and significantly better correlations than the manual MRI contours (DSC: 0.37, P.001). The sensitivity and specificity values were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET.CHOL-PET is superior to the combination of T2W/DW MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies but may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict how well CHOL-PET delineates IPLs.

Ipilimumab is a human anti-CTLA-4 monoclonal antibody recently approved for the treatment of advanced melanoma. Stimulation of T-cell activity unmasks antitumor activity, but can cause immune-related adverse events. Autoimmune hypophysitis is of particular importance because its presentation can be subtle but life threatening. We present two cases where early recognition of ipilimumab-related autoimmune hypophysitis led to timely intervention and low subsequent morbidity, without compromise of antitumor effects. We provide recommendations for detection and management of this potentially life-threatening complication of ipilimumab.

Posterior reversible encephalopathy syndrome (PRES) has been described in the context of uncontrolled hypertension, eclampsia, renal disease and autoimmune conditions, or in patients treated with chemotherapy or immunosuppressive agents. In contrast, we report the occurrence of PRES in a patient with untreated metastatic transitional cell carcinoma. The case emphasizes important diagnostic challenges associated with atypical presentations without "typical" risk factors and the limitations of common diagnostic imaging modalities. It highlights the ability of nonmalignant conditions like PRES to mimic brain metastases and the importance of magnetic resonance imaging as a diagnostic tool. A high index of suspicion is warranted in atypical presentations, as prompt treatment is imperative to ensure full neurological recovery.

Background We sought to determine the survival benefits that patients judged sufficient to warrant adjuvant therapy with sorafenib for 1 year, or for 3 years after resection of renal cell carcinoma in the SORCE trial. Methods SORCE participants from all sites in Australia and New Zealand, and selected sites in the UK, completed a validated preferences questionnaire at months 0, 3, 15, and 42 to elicit the minimum survival benefits they judged sufficient to warrant adjuvant sorafenib for 1 year (versus observation), or for 3 years (versus 1 year). The questionnaires used reference survival times of 5 and 15 years; and reference survival rates at 5 years of 65% and 85%. Results The 233 participants had a median age of 57 years (range 29–78) and 71% were male. For 1 year of sorafenib versus no adjuvant therapy, the median benefits in survival times judged sufficient to warrant treatment were an extra 9 months beyond 5 years and an extra 1 year beyond 15 years; the median benefit in survival rates were an extra 4% beyond 65% and an extra 3% beyond 85% at 5 years. For 3 years of sorafenib versus 1 year of sorafenib, the median benefit in survival time judged sufficient to warrant extended treatment was an extra 1 year beyond both 5 and 15 years. Participants randomly allocated to treatment with sorafenib judged larger benefits necessary than those allocated to placebo. Participants' preferences were not associated with their baseline characteristics or the interval from randomisation. Conclusion Most participants judged an extra year of survival necessary to warrant 1 year of adjuvant sorafenib worthwhile, and an additional year of survival to warrant extending the duration of sorafenib from 1 to 3 years. Patients' preferences are important in shared decision making. SORCE trial clinical trials number NCT00492258.

OBJECTIVE To characterise the practice of active surveillance (AS) for men with low risk prostate cancer by examining the characteristics of those who commence AS, the rate of adherence to accepted AS follow-up protocols over 2 years, and factors associated with good adherence. Design, setting: Retrospective cohort study; analysis of data collected from 38 sites participating in the Prostate Cancer Outcomes Registry-Victoria. PARTICIPANTS Men diagnosed with prostate cancer between August 2008 and December 2014 aged 75 years or less at diagnosis, managed by AS for at least 2 years, and with an ISUP grade group of 3 or less (Gleason score no worse than 4 + 3 = 7). MAIN OUTCOME MEASURES Adherence to an AS schedule consisting of at least three PSA measurements and at least one biopsy in the 2 years following diagnosis. RESULTS Of 1635 men eligible for inclusion in the analysis, 433 (26.5%) adhered to the AS protocol. The significant predictor of adherence in the multivariate model was being diagnosed in a private hospital (v public hospital: adjusted odds ratio [aOR], 1.83; 95% CI, 1.42-2.37; P < 0.001). Significant predictors of non-adherence included being diagnosed by transurethral resection of the prostate (v transrectal ultrasound biopsy [TRUS]: OR, 0.54; 95% CI, 0.39-0.77; P < 0.001) or transperineal biopsy (v TRUS: OR, 0.32; 95% CI, 0.19-0.52; P < 0.001), and being 66 years of age or more at diagnosis (v < 55 years: OR, 0.65; 95% CI, 0.45-0.92; P = 0.015). CONCLUSION Almost three-quarters of men who had prostate cancer with low risk of disease progression did not have follow-up investigations consistent with standard AS protocols. The clinical consequences of this shortcoming are unknown.

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

Aim: Pilot clinical trial of NY-ESO-1 (ESO) protein in ISCOMATRIX™ adjuvant pulsed onto peripheral blood dendritic cells (PBDC), to ascertain feasibility, evaluate toxicity and assess induction of ESO-specific immune responses. Patients & methods: Eligible participants had resected cancers expressing ESO or LAGE-1 and were at high risk of relapse. PBDC were produced using CliniMACS®plus, with initial depletion of CD1c+ B cells followed by positive selection of CD1c+ PBDC. Patients received three intradermal vaccinations of ESO/IMX-pulsed PBDC at 4-week intervals. Results: The process was feasible and safe. No vaccine-induced immune responses were detected. Assays of immunomodulatory cells did not correlate with outcomes. One patient had a long lasting complete remission. Conclusion: This method was feasible and safe but was minimally immunogenic.

Purpose Advanced prostate cancer (PC) is associated with substantial psychosocial morbidity. We sought to determine whether mindfulness-based cognitive therapy (MBCT) reduces distress in men with advanced PC. Methods Men with advanced PC (proven metastatic and/or castration-resistant biochemical progression) were randomly assigned to an 8-week, group-based MBCT intervention delivered by telephone (n = 94) or to minimally enhanced usual care (n = 95). Primary intervention outcomes were psychological distress, cancer-specific distress, and prostate-specific antigen anxiety. Mindfulness skills were assessed as potential mediators of effect. Participants were assessed at baseline and were followed up at 3, 6, and 9 months. Main statistical analyses were conducted on the basis of intention to treat. Results Fourteen MBCT groups were conducted in the intervention arm. Facilitator adherence ratings were high (> 93%). Using random-effects mixed-regression models, intention-to-treat analyses indicated no significant changes in intervention outcomes or in engagement with mindfulness for men in MBCT compared with those receiving minimally enhanced usual care. Per-protocol analyses also found no differences between arms in outcomes or engagement, with the exception of the mindfulness skill of observing, which increased over time for men in MBCT compared with usual care ( P = .032). Conclusion MBCT in this format was not more effective than minimally enhanced usual care in reducing distress in men with advanced PC. Future intervention research for these men should consider approaches that map more closely to masculinity.

Abiraterone improves survival, relieves pain, improves quality of life and extends time to prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC). A consensus-based guide for using abiraterone in patients with mCRPC has been developed by Australian clinicians with expertise in prostate cancer, based on their experience and supported by published data. Recommendations were developed for eight key topics: abiraterone administration; steroid administration and duration of use; concomitant medications and drug interactions; timing of testing and monitoring response; safety in different populations; potential toxicities; precautions and contraindications; and referral and multidisciplinary care. Abiraterone is taken orally in a fasting state. Symptoms associated with mineralocorticoid excess are managed by coadministration of low-dose prednisone or prednisolone. Potassium levels, blood pressure and liver function need to be tested frequently during the early treatment phase. Response to treatment is monitored based on symptoms, radiological imaging and PSA levels. Potential adverse consequences of long-term steroid therapy on bone and metabolic health need to be screened for and managed. Advanced prostate cancer is best managed by a multidisciplinary team and early referral should be considered. Questions about the potential use of abiraterone in early disease and in combination with other therapies are being addressed in ongoing clinical trials.

This is the first prospective study in a contemporary Australian/New Zealand population to determine the prevalence of testosterone deficiency in testicular cancer survivors at 12 months from treatment, and any association with poorer quality of life. Hormone assays from 54 evaluable patients in a prospective cohort study revealed biochemical hypogonadism in 18 patients (33%) and low-normal testosterone in 13 patients (24%). We found no association between testosterone levels and quality of life (all P > 0.05). Hypogonadal patients should be considered for testosterone replacement to prevent long-term morbidity.

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.

Population screening with prostate-specific antigen (PSA) for detection of prostate cancer is a topic associated with ongoing dissent and confusion within the oncology and wider medical community. The PSA blood test has been used in various stages of prostate cancer management, including screening and the assessment of future risk of prostate cancer development, detection of recurrent disease after local therapy and in the management of advanced disease. However, PSA-based decision-making in prostate cancer has significant shortcomings. This review will summarise the evidence and current recommendations for the use of PSA in detection and management of prostate cancer.

Summary Background An unmet medical need exists for patients with metastatic renal cell carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. Fibroblast growth factor (FGF) pathway activation has been proposed as a mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors. We therefore compared dovitinib with sorafenib as third-line targeted therapies in patients with metastatic renal cell carcinoma. Methods In this multicentre phase 3 study, patients with clear cell metastatic renal cell carcinoma who received one previous VEGF-targeted therapy and one previous mTOR inhibitor were randomly assigned through an interactive voice and web response system to receive open-label dovitinib (500 mg orally according to a 5-days-on and 2-days-off schedule) or sorafenib (400 mg orally twice daily) in a 1:1 ratio. Randomisation was stratified by risk group and region. The primary endpoint was progression-free survival (PFS) assessed by masked central review. Efficacy was assessed in all patients who were randomly assigned and safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01223027. Findings 284 patients were randomly assigned to the dovitinib group and 286 to the sorafenib group. Median follow-up was 11·3 months (IQR 7·9–14·6). Median PFS was 3·7 months (95% CI 3·5–3·9) in the dovitinib group and 3·6 months (3·5–3·7) in the sorafenib group (hazard ratio 0·86, 95% CI 0·72–1·04; one-sided p=0·063). 280 patients in the dovitinib group and 284 in the sorafenib group received at least one dose of study drug. Common grade 3 or 4 adverse events included hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), fatigue (24 [8%]), dyspnoea (21 [7%]), and palmar-plantar erythrodysaesthesia (18 [6%]) in the sorafenib group. The most common serious adverse event was dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, respectively). Interpretation Dovitinib showed activity, but this was no better than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGF-targeted therapies and mTOR inhibitors. This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting. Funding Novartis Pharmaceuticals Corporation.

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.

LBA2 Background: Testosterone suppression (TS) is the backbone of treatment for mHSPC. OS is improved by the addition of early docetaxel (DOC) or abiraterone to TS. ENZAMET assessed the effects of enzalutamide (ENZA), a potent androgen receptor (AR) inhibitor, versus a nonsteroidal anti-androgen (NSAA: bicalutamide, nilutamide, or flutamide) in addition to SOC (TS with or without DOC) in mHSPC. Methods: Men with mHSPC were randomly assigned 1:1 to receive TS plus either ENZA or NSAA. Randomization was stratified by: volume of disease (high vs low, according to CHAARTED); planned early DOC; planned anti-resorptive therapy, comorbidity score (ACE-27), and study site. The primary endpoint was overall survival. Accrual of 1100 men provided 80% power to detect a 25% reduction in the hazard of death (HR 0.75) with up to 4 interim analyses (IA), the first planned to occur after 235 deaths (50% of total information with a critical p-value threshold

TPS332 Background: Lutetium-177 [177Lu]-PSMA-617 is a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), which is commonly overexpressed in prostate cancer. This treatment has demonstrated promising activity and tolerability in men progressing after multiple lines of chemotherapy and endocrine therapy. This trial will determine the activity and safety of 177Lu-PSMA-617 compared to cabazitaxel chemotherapy in men with progressive metastatic castrate resistant prostate cancer. Methods: TheraP is an open-label, randomised, two-arm, multi-centre, phase 2 trial comparing the activity and safety of experimental treatment with [177Lu]-PSMA-617 versus standard 2nd line chemotherapy with cabazitaxel. Key eligibility criteria include prior chemotherapy with docetaxel; rising serum PSA; sufficient PSMA avidity according to central reviewed of imaging with PSMA PET/CT and FDG PET/CT; no discordance between FDG PET and PSMA PET. The trial will include 200 participants randomised in a 1:1 ratio to either [177Lu]-PSMA-617 intravenously every 6 weeks, 8.5 GBq for cycle 1, decreasing by 0.5 GBq with each subsequent cycle, up to maximum 6 cycles (experimental group); or, chemotherapy with cabazitaxel (20 mg/m2) intravenously every 3 weeks, for 10 cycles (standard group). In the event of an exceptional response to [177Lu]-PSMA-617, according to centrally-reviewed, post-therapy SPECT imaging, treatment is suspended but can recommence subsequently on progression. The primary endpoint is a 50% or greater reduction from baseline in serum PSA. Secondary endpoints include overall survival, progression-free survival (PFS), PSA-PFS, pain-PFS, radiographic-PFS, health-related quality of life, pain response, and adverse events. The outcomes of patients excluded because of discordant disease on FDG PET and PSMA PET will be reported as a tertiary objective. The study has accrued 79 of 200 planned participants from 29 January 2018 to 23 October 2018. Clinical trial information: NCT03392428.

188 Background: Identifying predictive biomarkers for mCRPC patients receiving androgen receptor signalling inhibitors (ARSI) or chemotherapy remains an unmet clinical need. FOLH1 encodes for Prostate-Specific Membrane Antigen (PSMA), a type II glycoprotein highly expressed on prostate cancer cells. We designed a whole blood assay to detect FOLH1 mRNA, and correlated expression with clinical outcomes in patients commencing ARSI (abiraterone or enzalutamide) or chemotherapy (docetaxel or cabazitaxel). Methods: mCRPC patients commencing ARSI or chemotherapy were prospectively recruited at three Australian centres from June 2016 to July 2018. A quantitative reverse transcription polymerase chain reaction assay was used to detect FOLH1 transcript from whole blood samples collected in PAXgene® RNA tubes. Pre-treatment FOLH1 expression was correlated with PSA response rate (Fisher’s exact test) and PSA progression-free survival (PSA-PFS) (log-rank test). Results: Median follow-up was 13.6 months (IQR 9.7–19.3). In total, 88 pre-treatment samples were analysed, of which 75 (85%) were FOLH1-positive. In patients receiving ARSI, outcomes favoured FOLH1-positive patients compared to FOLH1-negative patients, with higher PSA response rates (39/60, 65% vs. 2/7, 29%; p = 0.1) and longer PSA-PFS (median 9.0 months [95% CI, 7.2-10.8] vs. 2.8 months [95% CI, 2.3-3.3]; p = 0.03). Conversely, in chemotherapy-treated patients, inferior outcomes were observed in FOLH1-positive patients compared to FOLH1-negative patients, with lower PSA response rates (4/15, 27% vs. 5/6, 83%, p = 0.05) and shorter PSA-PFS (median 2.9 months [95% CI, 2.8-3.0] vs. 4.1 months [95% CI, 3.7-4.5]; p = 0.32). Conclusions: Pre-treatment FOLH1 expression may differentiate between outcomes on ARSI vs. chemotherapy in mCRPC patients. The utility of FOLH1 as a predictive biomarker in mCRPC warrants further evaluation in larger, independent cohorts. [Table: see text]

Aim To assess the response rate and safety of sorafenib in different subpopulations of patients with advanced renal cell carcinoma (RCC). Methods Single-arm open access trial. Key eligibility: advanced RCC with either clear-cell or non-clear-cell histopathology; progression on prior systemic chemotherapy or treatment naive. Sorafenib was commenced at 400 mg twice daily continuously. Results A total 47 participants with metastatic RCC were treated with sorafenib. Overall, 1 participant experienced complete response, 6 (13%) had documented partial response (PR) and 29 (62%) had stable disease (SD) as the best response. Eight (17%) had non-clear-cell histopathology and five (10%) had sarcomatoid features. In the non-clear-cell histopathology cohort, five participants (62.5%) had SD. Twenty-three (49%) participants were treatment naive; of these, 1/23 showed CR, 5/23 experienced PR and 13/23 had SD (clinical benefit: 83%). Overall, 14 (30%) and 22 (47%) participants had high-risk status according to MSKCC (Memorial Sloan-Kettering Cancer Center) and Heng prognostic scores, respectively. In the MSKCC poor prognostic group (14 participants), one participant had CR, two participants showed PR and eight participants had SD (clinical benefit: 79%). In Heng poor prognostic group (22 participants), 1 participant experienced CR, 2 participants showed PR and 13 had SD (clinical benefit: 73%). Hand–foot syndrome (53%), rash (47%), fatigue (42%), nausea (40%), anorexia (34%) and diarrhea (32%) were the most common adverse events. Conclusions This study confirms the efficacy and tolerability of sorafenib in a different spectrum of advanced RCC patients including non-clear-cell histology, poor prognostic status and as first-line treatment.