Background Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs.Methods We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m²) or carboplatin (area under the curve [AUC]4•5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m²) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants.

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Plain English summaryBreast cancer is a diverse and varied disease. Recent research has shown that the collection of multiple biopsies before surgery can help researchers determine how the cancer is responding to treatment and can predict for long-term outcomes. However biopsies can be uncomfortable, and sometimes clinicians and research teams in hospitals may be reluctant to offer clinical trials requiring several biopsies to patients who have been recently diagnosed with breast cancer. The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) oversees a large number of breast cancer clinical trials where multiple biopsies are required. ICR-CTSU recognises that patient advocates (patients who have previously had, or cared for someone with, cancer) are key members of the trial design group and should be involved in the clinical trial throughout its lifespan. Patient advocates can provide reassurance regarding the acceptability of trial designs involving multiple biopsies from a patient perspective. This paper summarises patient advocate involvement in ICR-CTSU breast cancer trials activity and how this has benefited our research.AbstractThe importance of collecting tissue samples in breast cancer has become increasingly recognised, as the diversity of the disease has become better known. It has been documented in recent research that tumours may change in response to treatment prior to surgery (the neoadjuvant treatment setting). The collection of sequential biopsies over time can identify changes within tumours and potentially predict how the tumour may respond to certain treatments. However, the acceptability of multiple biopsies amongst patients, clinicians and other research staff in hospitals is variable and recruitment into clinical trials requiring multiple biopsies may be challenging.The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) is responsible for a portfolio of breast cancer trials where multiple biopsies are key to the trial design. Patient advocate involvement has been essential in helping us to design and deliver complex and innovative cancer trials which require multiple invasive tissue biopsies, often without any direct benefit to the trial participants. The views expressed by patient advocates involved in ICR-CTSU trials supports the published evidence that patients are willing to donate additional tissue for research and that clinicians’ concerns about approaching patients for trials involving multiple biopsies are often unfounded.Patient advocate involvement in ICR-CTSU trials activity takes various forms, from membership on protocol development groups and trial management groups, attendance at focus groups and forums, and presentations at trial development and launch meetings. This involvement has provided reassurance to research teams within the NHS and research ethics committees of the importance and acceptability of our trials from a patient perspective. Patient advocate involvement throughout the lifetime of our trials ensures that the ...