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Urothelial carcinoma of the urethra is the type of urethral cancer that grows from the same lining as bladder cancer, usually in the part of the urethra nearest the bladder or running through the prostate. It is treated by borrowing from bladder cancer: surgery, and chemotherapy with cisplatin before surgery when the disease is advanced.
Primary urethral carcinoma is classified by the lining it arises from, and urothelial carcinoma arises in the proximal (bulbomembranous and prostatic) urethra in men and the proximal urethra in women, where the lining is urothelium continuous with the bladder (Gakis 2013). In the international collaboration on primary urethral carcinoma, 154 patients from ten referral centres between 1993 and 2012 had urothelial carcinoma in 47 percent, squamous cell carcinoma in 30 percent, adenocarcinoma in 11 percent and mixed or other histology in the rest; clinical nodal stage was the critical predictor of recurrence and survival (Gakis 2016). Two thirds of the patients in that series were men.
How it differs from its parent: the parent page covers all urethral cancers; this histology is the one closest to bladder cancer in behaviour and treatment, and it can be a first presentation of urothelial carcinoma of the prostatic ducts, which the EAU guideline treats with cystoprostatectomy pathways. A separate urethral urothelial carcinoma must also be distinguished from recurrence in the urethra after cystectomy for bladder cancer, which is staged as bladder disease.
How common: fewer than one case per million a year for all urethral cancer (parent page; Derksen 2013 gives 0.7 per million women in the Netherlands), and no registry counts the urothelial type alone.
Treatment follows the EAU guideline for the parent, with no randomised trial in this histology: urethra-sparing surgery for distal and superficial disease, and for locally advanced proximal disease cisplatin-based chemotherapy before surgery, borrowed from bladder cancer, with radiotherapy as an alternative; metastatic disease is treated as urothelial cancer of the bladder, so the enfortumab vedotin and pembrolizumab regimens linked from the parent page apply (EAU Guidelines: primary urethral carcinoma).
The commonest histology of primary urethral carcinoma: 72 of 154 patients (47 percent) in the international collaboration's ten-centre series, median age 66 (Gakis 2016). Urethral cancer as a whole affects about 650 people a year in the European Union (Visser 2012).
Renal cell carcinoma comes from the kidney's filtering cortex, urothelial cancer from the lining of the collecting system and bladder, and the adrenal on top hosts cortical and medullary (neuroblastoma) tumours.
Same organ: Collecting duct carcinoma of the kidney, Renal medullary carcinoma (SMARCB1-deficient), TFE3-rearranged (translocation) renal cell carcinoma, Fumarate hydratase-deficient renal cell carcinoma (HLRCC-associated), Succinate dehydrogenase-deficient renal cell carcinoma, Mucinous tubular and spindle cell carcinoma of the kidney, Eosinophilic solid and cystic renal cell carcinoma, Clear cell papillary renal cell tumour, Squamous cell carcinoma of the urethra, Adenocarcinoma of the urethra (including clear cell adenocarcinoma), Melanoma of the urethra, Non-muscle-invasive bladder cancer, Muscle-invasive and advanced bladder cancer, Bladder & urothelial cancer, Clear cell renal cell carcinoma, Papillary renal cell carcinoma, Chromophobe renal cell carcinoma, Renal cell carcinoma, Wilms tumour (nephroblastoma), Neuroblastoma (paediatric), Low-risk neuroblastoma (INRG very low and low risk, including stage MS), Intermediate-risk neuroblastoma, High-risk neuroblastoma, Adrenocortical carcinoma, Pheochromocytoma and paraganglioma (PPGL), Urethral cancer, Penile cancer, Localised penile cancer (organ-confined, node-negative), Node-positive and metastatic penile cancer, Localised adrenocortical carcinoma (ENSAT stage I to III, resectable), Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable), Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127), Metastatic pheochromocytoma and paraganglioma
Treated as the parent page describes, borrowing bladder cancer pathways: urethra-sparing surgery when distal, cisplatin-based chemotherapy before surgery or chemoradiation when locally advanced, bladder-cancer systemic therapy when metastatic.
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Query for this cancer: (TITLE:"Urothelial carcinoma of the urethra" OR ABSTRACT:"Urothelial carcinoma of the urethra" OR TITLE:"Urethral urothelial carcinoma" OR ABSTRACT:"Urethral urothelial carcinoma" OR TITLE:"Transitional cell carcinoma of the urethra" OR ABSTRACT:"Transitional cell carcinoma of the urethra" OR TITLE:"Urothelial carcinoma proximal and prostatic urethra" OR ABSTRACT:"Urothelial carcinoma proximal and prostatic urethra" OR TITLE:"Prostatic urethral carcinoma" OR ABSTRACT:"Prostatic urethral carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Urothelial carcinoma of the urethra, not a curated reading list.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Hyperglycaemia: hold if glucose above 13.9 mmol/L (250 mg/dL).
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
See all on the product pages:Enfortumab vedotinGemcitabine + cisplatinPembrolizumab·Printable cards in the navigator
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