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Abstract Introduction Platelet-derived growth factor receptor-α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel. Methods Patients were randomised to receive 21-d cycles of olaratumab (15 mg/kg, Days 1 and 8) plus mitoxantrone (12 mg/m2, Day 1) and prednisone (5 mg, twice daily) or M/P alone. Progression-free survival (PFS) was the primary end-point. Secondary end-points included overall survival (OS), safety, and circulating tumour cell (CTC) counts. Results A total of 123 patients were randomised, 63 to olaratumab + M/P and 60 to M/P. Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.87–1.90). Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P (HR = 1.08; 95% CI = 0.72–1.61). Both treatment arms had similar toxicity profiles; neutropenia (24% versus 15%), anaemia (13% versus 14%) and fatigue (11% versus 9%) (olaratumab + M/P versus M/P, respectively) were the most common grade ≥3 events. High CTC count was associated with poorer OS in both arms. Patients with very high cell counts (>37 cells/7.5 ml) exhibited improved OS with olaratumab + M/P (interaction P = 0.043). Conclusions Olaratumab + M/P had an acceptable safety profile but did not improve the efficacy of M/P chemotherapy. Further study with selected patient populations and earlier in the disease course might be considered. Highlights • The antibody, olaratumab, blocks the platelet-derived growth factor receptor alpha. • Olaratumab was added to mitoxantrone/prednisone to treat metastatic prostate cancer. • Olaratumab was safe but did not improve the efficacy of mitoxantrone/prednisone. • High circulating tumour cell counts were associated with poorer survival in both arms. • Patients with high circulating tumour cell counts appear to benefit from olaratumab. [ABSTRACT FROM AUTHOR]

Background Two-thirds of all cancer cases affect patients who are older than 65 years, yet the specific conditions of the treatment and supportive care in this age group are poorly studied. There are limited data on the specific psycho-oncological problems in elderly patients with genito-urinary cancers. The aim of this study was to investigate the psychosocial needs of elderly patients with genito-urinary tumors using screening questionnaires and to use such screening questionnaires for an in-patient psychosocial treatment program. Methods Patients (≥ 65 years, n = 319) who underwent surgical (n = 295) or medical treatment (n = 24) for genito-urinary malignancies between 06/2014 and 11/2015 in our institution were included for prospective stress assessment. This was done with standardized questionnaires for stress screening and for the identification of need for care (NCCN Distress Thermometer and Hornheider Screening Instrument, HSI). Results The patients scored an average of 4.4 on the Distress Thermometer. According to the survey evaluation, 28% of patients had need for psychosocial care. However, only a minority of patients (4%) did actually communicate any need for psychosocial care. We also assessed the actual utilization of inpatient psychosocial support which is offered to all patients. Conclusion There is a significant number of elderly patients with genito-urinary cancer with increased psychological stress and a consecutive need of psychosocial care. This is underreported and underused by the patients. Therefore, an easy low-threshold access system with an interdisciplinary and inter-professional collaborative support system would be desirable. Measuring psychological distress systematically can be helpful in treating older patients with malignant diseases. [ABSTRACT FROM AUTHOR]

Abstract: Context: High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.” Objective: To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment. Evidence acquisition: A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained. Evidence synthesis: The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment. Conclusions: Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the value of urine tests based on the detection of cytokeratins 8 and 18 for the diagnosis of bladder cancer compared with urine cytology. Methods: Samples from 112 patients before transurethral resection (group 1), 40 patients before secondary surgical treatment (group 2), 29 healthy control subjects (group 3, controls), and 10 women with acute urinary tract infection (group 4, controls) were examined with the UBC Rapid and UBC II enzyme-linked immunosorbent assay (ELISA) tests and voided urine cytology. Results: Of the 112 patients in group 1, 90 had transitional cell carcinoma. For the UBC Rapid, UBC ELISA, and cytology, the sensitivity and specificity was 64.4%, 46.6%, and 70.5% and 63.6%, 86.3%, and 79.5%, respectively. The cytology had the greatest accuracy (72.3%) compared with both cytokeratin tests (54.4% and 64.2%). For all three tests, sensitivity increased with tumor grade and stage. In group 2, 16 of 40 patients had residual carcinoma. The sensitivity was similar for all three tests, and the specificity of cytology was lower compared with its specificity in group 1 (47.9% versus 70.5% in group 1). In the controls with or without urinary tract infection, the specificity of cytology was greater than that of both other tests. The combination of the UBC ELISA test with cytology increased the sensitivity to 83% (specificity 68%). Conclusions: Both cytokeratin tests detected patients with transitional cell carcinoma, but were inferior to voided urine cytology in test quality. [Copyright &y& Elsevier]

Abstract: The case of a 74-year-old man is reported who suffered from a locally advanced prostate cancer treated by neoadjuvant hormonal ablation, followed by prostatectomy. Histological examination of the prostatectomy specimen disclosed an adenocarcinoma with partial, Paneth-like, neuroendocrine differentiation. Extensive perineural tumor invasion was found with a total of 921 perineural tumor foci. Neuroendocrine differentiation of tumor cells was accentuated in perineural locations and was associated with an elevated expression of N-CAM and vimentin, and a reduced expression of E-Cadherin and Ki-67. We hypothesize that neuroendocrine differentiation may promote perineural invasion of prostate cancer cells by a “catherin-switch” and by mechanisms involving epithelial-mesenchymal transition. [Copyright &y& Elsevier]

BK polyomavirus (BKPyV) associated nephropathy (BKVAN) is seen in about 5% of renal transplant patients and can lead to chronic graft failure or graft loss. No effective therapy is available. Leflunomide has shown promising results in BKVAN. We performed a systematic review about the use of leflunomide for the treatment of BKVAN. The recommendations of the Cochrane Handbook of systematic Reviews were followed. Due to different study designs and endpoints no meta-analysis was performed. The literature search for primary studies yielded 274 results. Finally, twelve studies were included with a total of 267 patients. Clearance of BKPyV viremia was reported in 33.3% to 92.3% of cases and 27 graft losses (10.1%). The included studies were very heterogeneous, especially in terms of leflunomide dosing. Pharmacokinetics seem to have an important impact on the efficacy of leflunomide in BKVAN. There was no correlation between leflunomide serum levels and virus reduction. New adverse events of leflunomide have been described, e.g. haemolytic anaemia and thrombotic microangiopathy. Overall, the risk of bias in the studies was assessed as high and the quality of evidence was rated low. The role of leflunomide in BKVAN remains unclear, but further studies seem reasonable and should address pharmacokinetic aspects. • Newest systematic review about the use of leflunomide in BK polyomavirus associated nephropathy • Importance to summarize evidence for planning proper RCTs • First description of adverse events which might lead to atypical hemolytic uremic syndrome [ABSTRACT FROM AUTHOR]

• Follow-up of non-muscle-invasive bladder cancer (NMIBC) is based on cystoscopy • The relevance of urine markers in the surveillance of NMIBC is obscure. • This study intends to identify scenarios for the use of urine markers high-risk NMIBC. • The simulation suggests that marker-supported follow-up in high-risk NMIBC is safe. • Marker-supported follow-up will significantly reduce the number of cystoscopies. A plethora of urine markers for the management of patients with bladder cancer has been developed and studied in the past. However, the clinical impact of urine testing on patient management remains obscure. The goal of this manuscript is to identify scenarios for the potential use of molecular urine markers in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. Information on the course of disease of patients with high-risk NMIBC and performance data of a point-of-care test (UBC rapid™), an MCM-5 directed ELISA (ADXBLADDER™), and 2 additional novel assays targeting alterations of mRNA expression and DNA methylation (Xpert bladder cancer monitor™, Epicheck™) were retrieved from high-quality trials and/or meta-analyses. In addition, the sensitivity of white light cystoscopy (WLC) and the impact of a urine marker result on the performance of WLC were estimated based on fluorescence cystoscopy data and information from the CeFub trial. This information was applied to different scenarios in patient follow-up and sensitivity, estimated number of cystoscopies, and the numbers needed to diagnose were calculated. The sensitivity of guideline-based regular follow-up (SOC) at 1 year was calculated at 96%. For different marker-supported strategies sensitivities ranging from 77% to 97.9% were estimated. Calculations suggest that several strategies are effective for the SOC. While for the SOC 24.6 WLCs were required to diagnose 1 tumor recurrence (NND), this NND dropped below 5 in some marker-supported strategies. Based on the results of this simulation, a marker-supported follow-up of patients with HR NMIBC is safe and offers the option to significantly reduce the number of WLCs. Further research focusing on prospective randomized trials is needed to finally find a way to implement urine markers into clinical decision-making. [ABSTRACT FROM AUTHOR]

Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit. Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT). A multivariable Cox proportional hazards model for overall survival (OS) was developed using the NCDB and applied to the INT dataset. Parameters were used to make receiver operating characteristic (ROC) curves. ROC-related criteria were optimized to identify a predictive probability cut point and dichotomize patients from INT into risk groups for limited OS of <6 and <12 months. NCDB had 860 deaths; 105 (5%) at 6 months and 296 (15%) at 12 months. INT had 257 deaths; 56 (8%) at 6 months and 124 (18%) at 12 months. Limited OS was associated with older age, greater T and N stage, and fewer lymph nodes removed. Optimized ROC criteria using the OS <6 months curve best dichotomized INT patients into high-risk group with median OS of 24 months (95% CI 18-34) and low-risk group with median OS of 174 months (95% CI 120-NE). We developed a simple model that could be used as a screening tool for early palliative care referral. [ABSTRACT FROM AUTHOR]