Treating Bladder Ca with Sunitinib

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The medication is being tested as adjuvant therapy in patients with locally advanced urothelial cancer.

Locally advanced urothelial cancer (UC), variably defined as muscle-invasive UC with a large or palpable mass, local extension or fixation, or lymph-node enlargement, represents a challenging clinical dilemma.

These patients are at high risk for systemic progression and occult micrometastasis and mandate a careful metastatic evaluation. Many are symptomatic with disabling voiding symptoms, incontinence, or refractory hematuria. Hydronephrosis is common and represents yet another poor prognostic parameter, particularly if bilateral.

Clinical understaging is common, with the majority of patients having extravesical extension, substantial lymph-node involvement, or other adverse pathologic findings. Aggressive histologic subtypes tend to congregate in this population, necessitating careful pathologic review and, occasionally, alternative management strategies.

Given all these considerations, the prognosis for patients with locally advanced UC is compromised; systemic recurrences are relatively common if managed with definitive local therapies alone, and most patients must consider a multimodal approach using either neoadjuvant or adjuvant strategies. The relative merits of these two strategies for invasive

UC patients taken as a whole remain controversial; however, for locally advanced disease, in which systemic therapy is almost universally required, it is best administered prior to surgery.

The neoadjuvant approach optimizes the likelihood that the patient will receive all required treatments. In addition, recent studies have shown that radical cystectomy is well tolerated after neoadjuvant chemotherapy, with no substantial increase in perioperative complications. At cystectomy, about 30%-40% of patients will have no evidence of disease (pT0), which can facilitate surgery.

Clearly, some highly symptomatic patients with locally advanced UC will require surgery up front to address disabling symptoms, but most are best managed with a neoadjuvant approach.

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