Matthew A. Young, MD
Sandip M. Prasad, MD, MPhil
BASICS
DESCRIPTION
• Adenocarcinoma of the bladder is an uncommon and frequently aggressive nonurothelial cancer.
• It is frequently muscle-invasive or metastatic at the time of diagnosis and therefore carries a poor prognosis.
• A common site is the urachus.
EPIDEMIOLOGY
• 0.5–2.0% of all primary bladder malignancies, making it the 3rd most common epithelial tumor of the bladder
• Can arise from the urachus or nonurachal epithelium, or in association with exstrophy of the bladder
• Most common tumor arising in the bladder of exstrophy patients, who have a 4% lifetime risk
• A majority of nonurachal, nonexstrophy-associated adenocarcinomas occur in men and are frequently associated with long-term inflammation or infection
• Occurs more frequently in areas where Schistosoma is endemic
• Urachal cancer: <1% of primary bladder cancer; 1/3 of bladder adenocarcinomas
RISK FACTORS
In tissue recombinant studies, adenocarcinoma can be produced from bladder urothelium under the appropriate hormonal and mesenchymal stimuli.
Genetics
Associated with gain of function in regions 20q and 8q, or loss of function at regions 5q and 8p (1)
PATHOPHYSIOLOGY
• Classification: Three groups related to site of tumor origin (2,3)
– Primary adenocarcinoma of bladder
– Urachal adenocarcinoma
– Extravesical adenocarcinoma (metastatic)
• Primary vesical adenocarcinoma: Can occur anywhere in the bladder, but the dome and the trigone of the bladder are common
– Most common type of cancer in bladder exstrophy
– All histologic variants of enteric carcinoma may occur in the bladder
– Papillary or solid; most are mucin-producing
– Most are poorly differentiated and invasive at the time of diagnosis
– Poor response to radiotherapy and chemotherapy
• Urachal carcinoma
– For classification as a urachal carcinoma, there must be:
Presence of a urachal remnant
Clear demarcation between the tumor and adjacent bladder mucosa
Predominant invasion of the muscularis propria or deeper structures of the bladder or extension to the space of Retzius, anterior abdominal wall, or umbilicus
Possible production of mucoid drainage from the umbilicus
• M.D. Anderson Cancer Center Diagnostic Criteria for Urachal Carcinoma
– Location in bladder dome or elsewhere in the midline of the bladder
– Sharp demarcation between tumor and normal surface epithelium
– Supportive criteria
Enteric-type histology
Absence of urothelial dysplasia
Absence of cystitis cystica or cystitis glandularis transitioning to the tumor
Absence of primary adenocarcinoma of another organ
• May produce stippled calcifications on plain films
• Prognosis is worse for urachal carcinoma than for primary adenocarcinoma of the bladder
• Urachal carcinoma demonstrates more extensive infiltration of the bladder wall, and for this reason, radical cystectomy is preferred over partial cystectomy, although the latter is still an option
• Urachal carcinomas are not always adenocarcinomas (most common type); others include transitional cell carcinoma, squamous cell carcinoma, and rarely sarcoma
• Metastatic lesions are very rare
– Adenocarcinomas from the colon, stomach, breast, ovary, endometrium, and prostate can metastasize to the bladder
– Local invasion of a colonic primary tumor is more common than metastasis
– Bladder adenocarcinoma is histologically indistinguishable from adenocarcinoma of the colon
• Sheldon Staging System for Urachal Carcinoma
– Stage I: No invasion beyond the urachal mucosa
– Stage II: Invasion confined to the urachus
– Stage III: Local extension into the
bladder (IIIA)
abdominal wall (IIIB)
peritoneum (IIIC)
viscera other than bladder (IIID)
– Stage IV: Metastases to the
regional lymph nodes (IVA)
distant site (IVB)
ASSOCIATED CONDITIONS
• Bladder exstrophy
• Schistosomiasis
GENERAL PREVENTION
Elimination of factors leading to chronic bladder inflammation
DIAGNOSIS
HISTORY
• Hematuria, mucosuria (uncommon)
– Usually painless
• Irritative voiding symptoms (frequency, urgency, dysuria)
• Foreign travel: Schistosomiasis
• Weight loss, flank pain, umbilical discharge (rare)
• Chronic infection
• History of exstrophy or other bladder pathology
• History of colon cancer or other malignancy; risk of metastatic lesion
PHYSICAL EXAM
• Pelvic mass by bimanual/rectal exam
• Bloody or mucoid umbilical discharge or umbilical mass
• Digital rectal exam; presence of blood in stool
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urine studies: Urinalysis, culture and sensitivity, urine cytology
• Serum electrolytes: BUN/Creatinine, liver function tests
• Carcinoembryonic antigen (CEA), CA125, and CA 19-9 may be elevated in 40–60% of patients presenting with peritoneal carcinomatosis
Imaging
• Urachal cancers may show stippled calcifications on plain x-ray films
• 60% of bladder tumors are detected with IVP, which has been largely replaced with the CT scan
• CT scan: Imaging method of choice for staging of bladder tumors; useful for detecting presence of pelvic lymphadenopathy and extravesical tumor extension
– Sensitivity: 64–94%, specificity: 62–100%
• Other investigations: CXR (staging), bone scan (staging, if bone pain is present), GI endoscopy, and breast exam (to exclude primary tumor) if clinically indicated
Diagnostic Procedures/Surgery
• Diagnostic cystoscopy and biopsy
– Essential for definitive diagnosis
– Bloody efflux from ureteral orifices suspicious for upper tract pathology
Pathologic Findings
• All histologic variants of enteric carcinoma may occur in the bladder
• Adenocarcinoma can have glandular, mucinous, or signet ring patterns
• Most produce mucin
• Primary adenocarcinoma of the bladder is associated with cystitis glandularis and is thought to arise from glandular metaplasia of the urothelium. These tumors can be papillary or solid
• Signet ring tumors produce linitis plastica of the bladder. They are aggressive and radical surgical excision should be considered
DIFFERENTIAL DIAGNOSIS
• Metastasis from colon, prostate, or other adenocarcinoma
• Benign or malignant urothelial tumors
TREATMENT
GENERAL MEASURES
• Site of origin and tumor behavior are factors important in determining treatment
• Adenocarcinoma of the bladder is generally unresponsive to radiation and chemotherapy.
– Radical cystectomy is treatment of choice.
– Excision of the urachus and umbilicus is usually required if a urachal primary is suspected
• Adjuvant chemotherapy or radiotherapy may be used, but surgery remains the most consistently effective treatment (4,5,6)
MEDICATION
First Line
• Generally unresponsive to radiation and cytotoxic chemotherapy (7)
• Some response to standard regimens such as combination methotrexate, vinblastine, adriamycin, cisplatin (MVAC)
• Recently, 5-FU and cisplatin-based chemotherapy have demonstrated a modest response rate
• A clinical trial at M.D. Anderson using gemcitabine, 5-FU, leucovorin, and cisplatin (Gem-FLP) reported a clinical response rate in 30–40% of patients
• Currently there is no role for neoadjuvant chemotherapy for clinically node-negative resectable disease
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Radical cystectomy with pelvic lymph node dissection remains the gold standard
• Adjuvant chemotherapy or radiotherapy has not improved survival significantly
• Partial cystectomy (with bladder mucosal sampling) with en bloc removal of the urachus and umbilicus is an option for low-volume, low-stage urachal carcinoma
ADDITIONAL TREATMENT
Radiation Therapy
Urachal adenocarcinoma is radio resistant
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Signet cell variant has a 50% mortality at 1 yr
• Urachal adenocarcinoma: Overall 11–55% 5-yr survival, but early-stage disease may have up to 93% 5-yr survival
• Nonurachal adenocarcinoma: 27–61% 5-yr survival
• Recurrence risk for urachal carcinoma
– Positive margin
– Umbilicus sparing resections are associated with a higher risk of relapse
– Tumor involving the peritoneal surfaces or the abdominal wall
– Occult lymph node metastases
COMPLICATIONS
• Ureteral obstruction from local spread of tumor
• Metastasis to pelvic lymph nodes, liver, lung, mediastinum, and bone
• Surgical complications: Bleeding, infection, rectal injury
FOLLOW-UP
Patient Monitoring
• Abdominal imaging (CT)
• Metastatic workup if suspected
Patient Resources
• American Cancer Society:
– www.cancer.org
• National Cancer Institute
– www.nci.nih.gov
• United Ostomy Association:
– www.uoa.org
REFERENCES
1. Vauhkonen H, Böhling T, Eissa S, et al. Can bladder adenocarcinomas be distinguished from schistosomiasis-associated bladder cancers by using array comparative genomic hybridization analysis? Cancer Genet Cytogenet. 2007;177(2):153–157.
2. El-Mekresh MM, el-Baz MA, Abol-Enein H, et al. Primary adenocarcinoma of the urinary bladder: A report of 185 cases. Br J Urol. 1998;82(2):206–212.
3. Dahm P, Gschwend JE. Malignant non-urothelial neoplasms of the urinary bladder: A review. Eur Urol. 2003;44:672–681.
4. Siefker-Radtke AO, Gee J, Shen Y, et al. Multimodality management of urachal carcinoma: The MD Anderson Cancer Center experience. J Urol. 2003;169:1295–1298.
5. Herr HW, Bochner BH, Sharp D, et al. Urachal carcinoma: Contemporary surgical outcomes. J Urol. 2007;178:74–78.
6. Siefker-Radtke A. Urachal Adenocarcinoma: A Clinician’s Guide for Treatment. Sem Oncol. 2012;39(5):619–624.
7. Siefker-Radtke A. Systemic chemotherapy options for metastatic bladder cancer. Expert Rev Anticancer Ther. 2006;6:877–885.
ADDITIONAL READING
Zhong M, Gersbach E, Rohan SM, et al. Primary adenocarcinoma of the urinary bladder: Differential diagnosis and clinical relevance. Arch Pathol Lab Med. 2013;137(3):371–381.
See Also (Topic, Algorithm, Media)
• Bladder Cancer, Adenocarcinoma Image 
• Bladder Cancer, General
• Urachal Carcinoma
CODES
ICD9
• 188.1 Malignant neoplasm of dome of urinary bladder
• 188.7 Malignant neoplasm of urachus
• 188.9 Malignant neoplasm of bladder, part unspecified
ICD10
• C67.1 Malignant neoplasm of dome of bladder
• C67.7 Malignant neoplasm of urachus
• C67.9 Malignant neoplasm of bladder, unspecified
CLINICAL/SURGICAL PEARLS
• Umbilicus may be involved in up to 7% of patients with adenocarcinoma of the bladder.
• Most common tumor arising in the bladder of exstrophy patients, who have a 4% lifetime risk.
• Adenocarcinoma of the bladder is generally unresponsive to radiation and chemotherapy.