Introduction

Worldwide, 2.7 million people are estimated to be diagnosed with, or have a history of, bladder cancer.[1] In the US there are 70,530 new cases and 14,680 deaths owing to bladder cancer per year.[2] Because of high recurrence rates, bladder cancer presents not only a significant medical problem, but also seems to be the most expensive form of cancer when cost is calculated from diagnosis to death.[3] Furthermore, Avritscher et al.[4] found that around 60% of these costs were related to treatment of recurrent disease.

Of all urothelial carcinomas, the majority (75-85%) present as non-muscle-invasive bladder cancer (NMIBC) confined to the mucosa (stage Ta in 70%; carcinoma in situ [CIS] in 10%) or to the submucosa (stage T1 in 20%).[5-7] These tumors range from benign low-risk, low-grade tumors to high-risk, high-grade tumors that are almost certain to recur and have a significant risk of progression to muscle-invasive or metastatic disease.[6] Therefore, the prognosis of NMIBC diverges and optimum treatment will depend on a number of tumor parameters. Low-risk bladder cancer—defined as pTa low-grade papillary tumors—is the type of NMIBC with the most favorable oncologic outcome.[6,8] Such cancers have a high risk of recurrence, but a very low risk of progression because they rarely invade the epithelial basement membrane. For low-risk bladder cancer, the risk of recurrence is 15% and 31% after 1 and 5 years respectively, with a risk of progression of <1% after both 1 and 5 years. Besides stage and grade, additional criteria to define low-risk tumors differ slightly between country or guideline. The American Urological Association (AUA) makes recommendations for ’index patients, where index patient 2 is in the lowest risk category and described as "a patient with small volume, low-grade Ta bladder cancer".[8] The National Comprehensive Cancer Network uses a similar definition for low-risk bladder cancer: a pTa grade 1-2 tumor. The European Association of Urology (EAU) defines a low-risk patient based on the European Organization for Research and Treatment of Cancer (EORTC) risk tables; a low-risk patient has a single, primary pTa grade 1 tumor of <3 cm.[5]

In this Review we will first discuss the development of bladder cancer, including risk factors and molecular markers that correlate with low-risk disease. Then we will follow the clinical pathway of low-risk bladder cancer based on current guidelines, from diagnosis using staging and grading classification systems, to treatment options and recommended follow-up.