Treatment of Locally Advanced Primary Urethral Carcinoma — Non-Squamous Cell Carcinoma Histology (Stage T3–T4, N0, M0)

This protocol applies to primary urethral carcinoma with non-squamous cell carcinoma histology at locally advanced stage T3–T4, N0, M0 — disease that has extended into surrounding structures but without nodal or distant metastasis. In this setting, histological subtype is a critical determinant of perioperative treatment strategy when surgery with curative intent is planned.

Treatment overview

Perioperative systemic therapy combined with surgery forms the basis of management. Cisplatin-based combination chemotherapy is a central component, and the timing relative to surgery — as well as any role for radiotherapy — depends on the specific histological subtype.

The complete sequencing, alternative pathways, and histology-specific regimen details are available in the full structured protocol.

References

  1. Determine perioperative treatment according to histology in locally advanced urethral carcinoma treated with curative intent.
  2. In locally advanced urethral carcinoma, cisplatin-based chemotherapy with curative intent prior to surgery might improve survival compared to chemotherapy alone or surgery followed by chemotherapy.
  3. Follow the European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer for the use of perioperative systemic therapy in patients with locally advanced urethral urothelial carcinoma.
  4. In an analysis of males with primary UC using the National Cancer Database, neoadjuvant chemotherapy (NAC) was reported to decrease the risk of all-cause mortality, while AC was not associated with an OS benefit.
  5. A large retrospective cohort study in patients with locally advanced urethral carcinoma treated with adjuvant RT and surgery versus surgery alone demonstrated that the addition of RT improved OS.
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