Review – Bladder CancerA Systematic Review of Neoadjuvant and Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer
Introduction
With radical cystectomy (RC) alone, the 5-yr survival rate for urothelial carcinoma of the bladder (UCB) can be up to 80% for organ-confined lymph node–negative disease. However, it decreases to 40–50% in patients with extravesical disease, with a further reduction to 15–35% if lymph node metastases are present. Distant recurrences have been observed to occur more frequently than locoregional recurrences (approximately 20–50% vs 5–15% of cases), suggesting that perioperative systemic therapy may improve outcomes [1], [2], [3]. Despite improvements in imaging and surgical techniques, the overall mortality for patients with bladder cancers remains unchanged [4]. Thus improvements in survival will likely come from the strategies aimed at early disease detection and/or integration of new systemic therapies.
Despite the accumulating body of data supporting neoadjuvant chemotherapy (NC) for muscle-invasive operable UCB (T2–T4aN0M0), the perioperative timing, dose, schedule, and specific agents have been controversial. The ultimate goal is to improve survival for those with a high risk of recurrence while minimizing toxicity to those that will have minimal benefit, but limited clinical acceptance of this therapeutic approach allied with the paucity of data currently available limit informed decision making in this area of oncology. For example, perioperative chemotherapy was administered to only 11.6% of patients with stage III urothelial cancer in 1998, with 1.2% receiving NC and 10.4% receiving adjuvant chemotherapy (AC) [5]. A small increase of perioperative chemotherapy was then noted: 11.3% in 1998 and 16.8% in 2003. A more recent study of North American academic referral institutions demonstrated that only 12% of T2–T4aN0M0 UCB patients received NC, 22% received AC, and only 9% of all patients received neoadjuvant cisplatin-based chemotherapy [6]. Although many patients with UCB are older with comorbidities and poor renal function and performance status, we need a more comprehensive understanding of the barriers to the use of perioperative cisplatin-based multiagent chemotherapy. The goal of this systematic review is to describe the data currently supporting NC and AC in association with RC for muscle-invasive UCB.
Section snippets
Evidence acquisition
A literature review searching Medline and major cancer conferences for prospective trials and major preclinical and retrospective studies in the last 5 yr was performed in March 2012. The search strategy included the terms bladder cancer, urothelial carcinoma, radical cystectomy, neoadjuvant chemotherapy, and adjuvant chemotherapy.
Identifying the high-risk patient: baseline staging and prognosis
Clinical staging involves a complete physical examination, transurethral resection of bladder tumor (TURBT) with pre- and postresection bimanual examination, and cross-sectional imaging of the bladder and upper urinary tracts. Despite advances in technology, a large disparity remains between clinical and pathologic staging. Bimanual examination, for example, is accurate in only 57% of patients, with overstaging in 11% and understaging in 31%, with only 41% accuracy of predicting organ-confined
Conclusions
Data support the use of cisplatin-based combinations as NC preceding RC for patients with muscle-invasive resectable UCB. Despite the lack of robust data, high-risk patients who qualify for cisplatin may be offered AC in the absence of a trial. Future studies using the neoadjuvant paradigm and integrating biologic agents may improve the efficacy of systemic therapy and improve outcomes.
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