BACKGROUND: The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS: In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS: A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS: In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).

• MeSH
• Chemotherapy, Adjuvant MeSH
• Intention to Treat Analysis MeSH
• B7-H1 Antigen metabolism   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Neoplasm Invasiveness MeSH
• Carcinoma, Transitional Cell drug therapy   pathology   surgery   MeSH
• Quality of Life MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder Neoplasms drug therapy   pathology   surgery   MeSH
• Nivolumab adverse effects   therapeutic use   MeSH
• Placebos therapeutic use   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Agents, Immunological adverse effects   therapeutic use   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Research Support, N.I.H., Extramural MeSH
• Comparative Study MeSH

The article will briefly explain the processes of organized screening in the NHS Cervical Screening Programme (NHSCP). Quality control is well established and monitored by regional quality assurance reference centres. The final outcome of screening is also monitored by national cervical cancer mortality and incidence rates: data will be presented for rates of in situ and invasive cervical carcinoma before and after the introduction of organized screening. The NHSCSP is using the introduction of liquid-based cytology as a platform for modernization, which is planned to include high-risk human papillomavirus (HR HPV) testing for low-grade cytology triage as well as a test of cure after treatment. Trials of computer-assisted screening are also in progress. High standards of quality control will be needed in the era of vaccination, when prevalence of preinvasive and invasive cervical cancer will decline. The NHSCSP is well placed to take on these challenges, if necessary by introducing primary HR HPV testing so that cytology screening can be concentrated on women who are genuinely at risk.

• MeSH
• Cytological Techniques methods   trends   utilization   MeSH
• Epidemiology MeSH
• Humans MeSH
• Uterine Cervical Neoplasms diagnosis   MeSH
• Mass Screening methods   standards   utilization   MeSH
• Sensitivity and Specificity MeSH
• Statistics as Topic MeSH
• Government Programs methods   organization & administration   statistics & numerical data   MeSH
• Outcome and Process Assessment, Health Care MeSH
• Check Tag
• Humans MeSH
• Geographicals
• England MeSH