What is the recommended diagnostic work‑up and management for a bladder tumor to distinguish pure adenocarcinoma from urothelial carcinoma?

Distinguishing Pure Adenocarcinoma from Urothelial Carcinoma in Bladder Tumors

For bladder adenocarcinoma, proceed directly to radical cystectomy or segmental cystectomy with bilateral pelvic lymphadenectomy, as conventional chemotherapy regimens effective for urothelial carcinoma (such as MVAC) are not effective for pure adenocarcinoma. 1

Diagnostic Work-Up

Initial Tissue Diagnosis

• Perform transurethral resection of bladder tumor (TURBT) with examination under anesthesia to obtain adequate tissue for histologic diagnosis. 1 The pathology report must specify:

  • Presence of muscularis propria (detrusor muscle) in the specimen and whether it is invaded 1
  • Presence or absence of lymphovascular space invasion 1
  • Presence or absence of carcinoma in situ 1
  • The percentage of any variant histology component 1

• If squamous or adenocarcinoma component comprises >95% of the tumor, classify it as pure squamous cell carcinoma or pure adenocarcinoma rather than urothelial carcinoma with divergent differentiation. 1

Pre-Operative Imaging

• Obtain CT or MRI of abdomen and pelvis before TURBT if the tumor appears solid (sessile), high-grade, or suggests muscle invasion on cystoscopy. 1

• Perform upper tract imaging with CT urography (preferred), MRI urogram, or retrograde pyelography to exclude synchronous upper tract urothelial carcinoma. 1

Location-Specific Considerations for Adenocarcinoma

• Adenocarcinomas occurring in the bladder dome suggest urachal origin, while periurethral location or signet-ring cell histology indicate primary bladder adenocarcinoma. 1

• For suspected urachal carcinoma, plan for en-bloc resection of the urachal ligament with the umbilicus in addition to cystectomy. 1

Critical Management Distinctions

Pure Adenocarcinoma

• Proceed with radical cystectomy or segmental (partial) cystectomy as primary treatment. 1

• Do not use conventional urothelial chemotherapy regimens (MVAC, gemcitabine/cisplatin) as they are ineffective for pure adenocarcinoma. 1

• Individualize the use of chemotherapy or radiation therapy, recognizing these may provide potential benefit in select patients despite lack of proven efficacy. 1

• Consider alternative therapy or enrollment in clinical trials given the lack of established systemic treatment options. 1

Urothelial Carcinoma (Pure or Mixed)

• Treat urothelial carcinoma with mixed histologic features (containing adenocarcinoma component <95%) using the same approach as pure urothelial carcinoma, but recognize the generally worse prognosis. 1

• Mixed histology tumors (urothelial plus adenocarcinoma, squamous, micropapillary, nested, plasmacytoid, or sarcomatoid) should be identified due to their more aggressive natural history. 1

• Standard platinum-based chemotherapy regimens remain appropriate for urothelial carcinoma with mixed histology, though only the urothelial component may respond. 1

Surgical Approach

Radical Cystectomy Requirements

• Perform bilateral pelvic lymphadenectomy including at minimum the common iliac, internal iliac, external iliac, and obturator nodes. 1

Segmental (Partial) Cystectomy Criteria

• Reserve segmental cystectomy only for solitary lesions in locations amenable to resection with adequate margins and no carcinoma in situ present. 1

• Include bilateral pelvic lymphadenectomy with the same nodal stations as radical cystectomy. 1

Common Pitfalls

Inadequate Tissue Sampling

• Ensure muscle is present in the TURBT specimen—a small tumor fragment with few muscle fibers is inadequate for assessing invasion depth and guiding treatment. 1

• Repeat TURBT if no muscle is present in the specimen for high-grade disease, for any T1 lesion, or if initial resection does not allow adequate staging. 1

Misclassification of Mixed Histology

• Recognize that 25% of bladder cancers have mixed histologic features, which are uniformly high-grade and invasive (99%). 2, 3

• Mixed histologic features at TURBT independently predict extravesical disease and indicate locally aggressive disease requiring aggressive multimodality treatment. 2

Inappropriate Chemotherapy Selection

• Do not apply urothelial chemotherapy regimens to pure adenocarcinoma—systemic chemotherapy for urothelial carcinoma is generally ineffective for pure non-urothelial histology. 1, 4

• In mixed histology cases treated with systemic chemotherapy, only the non-urothelial component may remain after treatment, as it does not respond to standard regimens. 1

Prognostic Considerations

• All variant histologies, including adenocarcinoma differentiation, portend worse prognosis than pure urothelial carcinoma. 5, 3

• Pure adenocarcinoma and other non-urothelial bladder cancers demonstrate aggressive behavior and often present at advanced stages, necessitating radical treatment strategies. 6, 5

• The presence of any adenocarcinoma component (even in mixed tumors) is associated with muscle invasion at TURBT and extravesical disease at cystectomy. 2