Washington, DC USA (UroToday.com) Neoadjuvant chemotherapy has been widely accepted as part of the treatment algorithm for patients with surgically resectable ≥cT2 bladder urothelial carcinoma. Given the currently presumed pathogenesis of a pan-transitional cell field defect, the role of neoadjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is being increasingly investigated.
In this session, Dr. Jean Hoffman-Censits commenced by noting the challenges in utilizing neoadjuvant strategies in patients with UTUC. Namely, these are older patients with underlying renal insufficiency in whom the toxicities of chemotherapy are not trivial.
In addition, there is a lack of level 1 evidence to guide management. In retrospective studies, the pathologic complete response rate (pCRR) for patients receiving neoadjuvant chemotherapy ranges from 0-38% (Youssef et al., BJUI 2011). Moreover, many of these patients experience pathologic down staging and improved cancer-specific survival.
A recent metaanalysis concluded that there are apparent OS and DFS advantages for adjuvant cisplatin-based chemotherapy in UTUC. Through similar analyses in the neoadjuvant setting were promising, the authors concluded that more studies were needed to determine its utility (Leow et al, Eur Urol 2014).
Dr. Hoffman-Censits emphasized that due to the nature of extirpative surgery for UTUC and patient population with underlying baseline renal insufficiency, the neoadjuvant setting may be the only opportunity for patients to receive cisplatin-based systemic therapy. Thus, given these retrospective data, she argued in favor of neoadjuvant chemotherapy in UTUC, particularly in the clinical trial context.
There are 2 trials actively recruiting patients in this space: NCT02412670 (ECOG-ACRIN) and NCT01261728 (Mayo Clinic Arizona, Hartford Hospital). Primary endpoints are pCRR and response rate to ≤T2, respectively. Secondary endpoints include RFS, CSS, bladder cancer RFS, renal insufficiency, and chemotherapy toxicities. A prior trial (NCT01663285) was closed prematurely due to poor patient enrollment. The results of the currently open trials are eagerly awaited to help inform management in this challenging patients population.
Jean Hoffman-Censits, MD
Thomas Jefferson University Hospital
Benjamin T. Ristau, MD from the 2015 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" December 2 - 4 Washington, DC USA
Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA