Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial.

Purpose: Transurethral resection of bladder tumor (TURBT) is the initial staging procedure for new bladder cancers (BCs). For muscle-invasive bladder cancers (MIBCs), TURBT may delay definitive treatment. We investigated whether definitive treatment can be expedited for MIBC using flexible cystoscopic biopsy and multiparametric magnetic resonance imaging (mpMRI) for initial staging.

Image directed redesign of bladder cancer treatment pathways: the BladderPath RCT.

Background: Transurethral resection of bladder tumour has been the mainstay of bladder cancer staging for > 60 years. Staging inaccuracies are commonplace, leading to delayed treatment of muscle-invasive bladder cancer. Multiparametric magnetic resonance imaging offers rapid, accurate and non-invasive staging of muscle-invasive bladder cancer, potentially reducing delays to radical treatment.

Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial.

Background: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies.

Methods: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies.

Selenium and Vitamin E for Prevention of Non-Muscle-Invasive Bladder Cancer Recurrence and Progression: A Randomized Clinical Trial.

Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.

Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.

Design, Setting, And Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK.

Recruiting women with ductal carcinoma in situ to a randomised controlled trial: lessons from the LORIS study.

Background: The LOw RISk DCIS (LORIS) study was set up to compare conventional surgical treatment with active monitoring in women with ductal carcinoma in situ (DCIS). Recruitment to trials with a surveillance arm is known to be challenging, so strategies to maximise patient recruitment, aimed at both patients and recruiting centres, were implemented.

Methods: Women aged ≥ 46 years with a histologically confirmed diagnosis of non-high-grade DCIS were eligible for 1:1 randomisation to either surgery or active monitoring.

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%).

Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study.

Background: Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit.

Cabazitaxel versus docetaxel for treatment of metastatic castrate refractory prostate cancer.

Objectives: To assess cabazitaxel versus docetaxel re-challenge for the treatment of metastatic castrate refractory prostate cancer (CRPC) patients previously treated with docetaxel at inception of primary hormone therapy.

Patients And Methods: The CANTATA trial was a prospective, two-arm, open-label, phase II study conducted in eight UK centres. Patients over the age of 18, with histologically proven, metastatic prostate cancer who had been previously treated with up to 6 cycles of docetaxel as part of the STAMPEDE trial (or treated with the same drug outside of the trial at primary diagnosis) and had a performance status (PS) of 0-2, were eligible.

TUXEDO: A phase I/II trial of cetuximab with chemoradiotherapy in muscle-invasive bladder cancer.

Objective: To assess feasibility and preliminary efficacy of adding cetuximab to standard chemoradiotherapy for muscle-invasive bladder cancer.

Patients And Methods: TUXEDO was a prospective, single-arm, open-label, phase I/II trial conducted in six UK hospitals. Cetuximab was administered with an initial loading dose of 400mg/m on day 1 of week -1, and then 7-weekly doses of 250mg/m .

A Study of Pazopanib Safety and Efficacy in Patients With Advanced Clear Cell Renal Cell Carcinoma and ECOG Performance Status 2 (Pazo2): An Open label, Multicentre, Single Arm, Phase II Trial.

Aim: Patients with advanced renal cell carcinoma and poor performance status (PS≥2) are often deemed unsuitable for treatment. The Pazo2 trial aimed to assess tolerability and efficacy of pazopanib as first-line treatment in renal cancer patients with ECOG PS2.

Methods: Pazo2 was a prospective, single arm, open label, multicentre, phase II trial, conducted in 26 UK centres.

Visualising harms in publications of randomised controlled trials: consensus and recommendations.

Objective: To improve communication of harm in publications of randomised controlled trials via the development of recommendations for visually presenting harm outcomes.

Design: Consensus study.

Setting: 15 clinical trials units registered with the UK Clinical Research Collaboration, an academic population health department, Roche Products, and .

Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells.

Comparing an Imaging-guided Pathway with the Standard Pathway for Staging Muscle-invasive Bladder Cancer: Preliminary Data from the BladderPath Study.

Transurethral resection of bladder tumour (TURBT) is central to the diagnosis of muscle-invasive bladder cancer (MIBC). With the oncological safety of TURBT unknown, staging inaccuracies commonplace, and correct treatment of MIBC potentially delayed, multiparametric magnetic resonance imaging (mpMRI) may offer rapid, accurate, and noninvasive diagnosis of MIBC. BladderPath is a randomised trial comparing risk-stratified (5-point Likert scale) image-directed care with TURBT for patients with newly diagnosed BC.

Results of a UK National Cancer Research Institute Phase II study of brentuximab vedotin using a response-adapted design in the first-line treatment of patients with classical Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or comorbidity (BREVITY).

Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was complete metabolic response (CMR) by positron emission tomography/computed tomography after four BV cycles (PET4).

Overall Survival in Men With Bone Metastases From Castration-Resistant Prostate Cancer Treated With Bone-Targeting Radioisotopes: A Meta-analysis of Individual Patient Data From Randomized Clinical Trials.

Importance: Both α-emitting and β-emitting bone-targeted radioisotopes (RIs) have been developed to treat men with metastatic castration-resistant prostate cancer (CRPC). Only 1 phase 3 randomized clinical trial has demonstrated an overall survival (OS) benefit from an α-emitting RI, radium 223 (223Ra), vs standard of care. Yet no head-to-head comparison has been done between α-emitting and β-emitting RIs.

Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial.

Background: Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial.

Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23-gene panel with utility for non-invasive diagnosis and risk stratification.

Objectives: To develop a focused panel of somatic mutations (SMs) present in the majority of urothelial bladder cancers (UBCs), to investigate the diagnostic and prognostic utility of this panel, and to compare the identification of SMs in urinary cell-pellet (cp)DNA and cell-free (cf)DNA as part of the development of a non-invasive clinical assay.

Patients And Methods: A panel of SMs was validated by targeted deep-sequencing of tumour DNA from 956 patients with UBC. In addition, amplicon and capture-based targeted sequencing measured mutant allele frequencies (MAFs) of SMs in 314 urine cpDNAs and 153 urine cfDNAs.

Total Fluid Intake and the Risk of Recurrence in Patients With Non-Muscle Invasive Bladder Cancer: A Prospective Cohort Study.

Objectives: To investigate the role of fluid intake from beverages before and after a diagnosis of bladder cancer in relation to the risk of developing bladder cancer recurrence.

Study Design: Prospective cohort study.

Methods: 716 patients with non-muscle invasive bladder cancer (NMIBC), who received transurethral resection of a primary bladder tumour (TURBT) and completed self-administrated questionnaires on usual fluid intake from beverages at time of diagnosis (over the year before diagnosis) and during follow-up (over the year after diagnosis), were included.

The association between smoking cessation before and after diagnosis and non-muscle-invasive bladder cancer recurrence: a prospective cohort study.

Background: Smoking is a major risk factor for bladder cancer, but the relationship between smoking cessation after initial treatment and bladder cancer recurrence has been investigated less frequently and not prospectively yet.

Methods: 722 non-muscle-invasive bladder cancer (NMIBC) patients (pTa, pT1, and CIS) from the prospective Bladder Cancer Prognosis Programme (BCPP) cohort, selected in the UK between 2005 and 2011, provided complete data on smoking behavior before and up to 5 years after diagnosis. The impact of smoking behavior on NMIBC recurrence was explored by multivariable Cox regression models investigating time-to-first NMIBC recurrence.

Fruit and vegetable intake and the risk of recurrence in patients with non-muscle invasive bladder cancer: a prospective cohort study.

Introduction: There is some evidence that greater consumption of fruit and vegetables decreases the risk of bladder cancer. The role of fruit and vegetables in bladder cancer recurrence is still unknown.

Objective: The role of total fruit and vegetable intake in relation to the risk of developing bladder cancer recurrence in a prospective cohort study.

A Study of Angiogenesis Markers in Patients with Renal Cell Carcinoma Undergoing Therapy with Sunitinib.

Background: Sunitinib is a tyrosine kinase inhibitor (TKI) targeting tumour angiogenesis in patients with advanced renal cell carcinoma (RCC). Currently no universally agreed model exists correlating the expression of angiogenesis markers with the success of treatment.

Patients And Methods: We retrospectively analysed archival tissue for 59 RCC patients treated with sunitinib.