Urothelial cancer

Urothelial cancer, most commonly bladder cancer, arises from the transitional epithelium lining the urinary tract. GLOBOCAN 2022 estimated 614,298 new cases and 220,596 deaths worldwide, with roughly 75% of the burden occurring in men, while the newer GLOBOCAN 2024 release put incidence at 635,264 cases, ranked eighth worldwide, and mortality at 227,626 deaths, ranked thirteenth. In the United States, SEER projects 84,530 new cases and 17,870 deaths for 2026, with an incidence rate of 17.9 per 100,000 and a death rate of 4.1 per 100,000. Five-year relative survival is 79.1% overall, but this conceals a very wide stage gradient: 98.0% for in situ disease, which makes up half of cases, 73.0% for localised disease, 41.8% for regional disease, and only 9.6% for distant disease.

Treatment is stratified by depth of invasion and risk. Non-muscle-invasive disease is treated with transurethral resection followed by intravesical chemotherapy and, for higher-risk tumours, bacillus Calmette-Guerin; BCG-unresponsive disease now has three FDA-approved options, pembrolizumab, the intravesical gene therapy nadofaragene firadenovec, and radical cystectomy for those fit for surgery. Muscle-invasive disease is treated with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy, or with bladder-sparing trimodal chemoradiation, and since 2025 with perioperative pembrolizumab plus enfortumab vedotin, an approval extended in 2026 to cisplatin-eligible patients based on KEYNOTE-B15/EV-304. Adjuvant nivolumab is standard after cystectomy in patients at high recurrence risk. Metastatic disease is now led by enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4, combined with pembrolizumab as first-line therapy regardless of cisplatin eligibility, with erdafitinib reserved for the roughly 20% of patients whose tumours carry an actionable FGFR2/3 alteration.

Nuclear medicine's role in staging urothelial cancer remains unsettled and is limited chiefly by physiology. FDG accumulates in urine and is excreted through the collecting system, obscuring the primary tumour and adjacent pelvic nodes on FDG PET/CT, the exact anatomical region that matters most for surgical planning. AUA, EAU, ESMO and NCCN guidelines diverge as a result: the US-oriented consensus is to avoid routine PET in initial staging and consider it only in selected or indeterminate cases, while ESMO and EAU jointly recommend systematic FDG PET/CT staging in oligometastatic patients being considered for radical treatment, to avoid overtreatment. Meta-analysis nodal-staging accuracy is modest across all modalities, with pooled sensitivity of about 0.40 for CT, 0.60 for MRI and 0.56 for FDG PET/CT against specificities around 0.91 to 0.92, leaving occult nodal disease a persistent blind spot before radical cystectomy.