We searched MEDLINE, PubMed, and the Cochrane Library for manuscripts published in English from database inception to Aug 31, 2015. We searched for all articles with the search terms “urothelial carcinoma” or “bladder cancer” in combination with any of the following terms: “epidemiology”, “genetics”, “pathophysiology”, “diagnosis”, “urinary markers”, “biopsy”, “treatment”, “surgery”, “radiation therapy”, “chemotherapy”, “medical therapy”, “chemoradiation”, “trimodality therapy”,
SeminarBladder cancer
Introduction
Each year, bladder cancer is diagnosed in about 74 000 patients in the USA and in more than 430 000 patients worldwide, making it the fourth most common cancer in men and the 11th most common cancer in women.1 However, even though bladder cancer is common, it is often mismanaged. A 2012 analysis of Surveillance, Epidemiology, and End Results Program data suggested that of 4790 patients with high-grade non-muscle-invasive disease diagnosed between 1992 and 2002, only one patient received treatment according to formal recommendations.2 To promote improved adherence to best practices for bladder cancer treatment, we present a state-of-the-art, updated review of diagnosis and management of this disease.
Section snippets
Overview
Most bladder cancers are urothelial carcinomas. At presentation, roughly 75% of patients have non-muscle-invasive bladder cancer and 25% have muscle-invasive or metastatic disease. About 50% of non-muscle-invasive bladder cancers are low grade, whereas most muscle-invasive or metastatic tumours are high grade.3 Morphologically, bladder tumours can be divided into papillary, solid, and mixed types. The papillary type is predominant, especially in non-muscle-invasive bladder cancer.
Grading of urothelial carcinoma
In
Histological variants of urothelial carcinoma
Although urothelial carcinoma accounts for most bladder cancers, other histological types can also be found in the bladder, albeit at far lower frequencies.6, 20 Urothelial carcinomas frequently undergo divergent differentiation, resulting in a wide range of histological variants.6, 21, 22 These histological variants are generally not limited to the bladder; they can also be present in other sites. Therefore, when a histological variant is encountered in the bladder, metastasis from other
Papillary and non-papillary disease
Bladder tumours can be categorised as papillary or non-papillary on the basis of distinct genetic alterations, the most notable of which are activating mutations in FGFR3 in papillary tumours and inactivating mutations involving major tumour suppressors TP53 and RB1 in non-papillary tumours.41 More recently, in 2014, The Cancer Genome Atlas (TCGA)42 and other groups43, 44, 45, 46, 47, 48 have identified additional mutations that distinguish papillary and non-papillary bladder cancers. Both
Clinical presentation
Most patients with bladder cancer are diagnosed during diagnostic testing prompted by haematuria. Visible haematuria is one of the symptoms most strongly correlated with bladder cancer diagnosis; 3 year positive predictive values are 7·4% (95% CI 6·8–8·1) in men and 3·4% (2·9–4·0) in women.66 Patients without haematuria typically have a longer time from onset of symptoms (eg, urgency or recurrent infections) to diagnosis.67 At presentation, most patients present with a solitary lesion smaller
Risk stratification
Reported 5 year rates of non-muscle-invasive bladder cancer recurrence range from 50% to 70%, and reported 5 year rates of progression range from 10% to 30%. Factors associated with recurrence and progression include high stage, high grade, large tumour size, multifocality, high number of previous recurrences, and presence of concomitant carcinoma in situ.86, 87, 88, 89 Other negative prognostic factors include the presence of lymphovascular invasion, histological variants (eg, micropapillary
Radical cystectomy and pelvic lymphadenectomy
Radical cystectomy and bilateral pelvic lymphadenectomy, often preceded by neoadjuvant cisplatin-based chemotherapy, is the gold-standard definitive surgical treatment for bladder cancer.111, 112 Although nerve-sparing radical cystectomy is appropriate in men and women, except when sparing nerves would compromise tumour control (eg, in patients with T3–T4 [advanced] tumours),113 the long-term safety of prostate or seminal vesicle sparing (proposed to optimise sexual function and continence), or
Bladder-sparing trimodality treatment
Patients who want to preserve their native bladder could be candidates for bladder-sparing trimodality treatment, which consists of visibly complete transurethral resection followed by conformal radiotherapy and concurrent radiosensitising chemotherapy (figure 4).134 This approach is supported by completed prospective trials and international consensus guidelines.111, 135, 136, 137
Trimodality treatment for non-muscle-invasive bladder cancer
For Ta or Tis (flat in situ) tumours, trimodality treatment is generally not supported by available evidence. In T1
Muscle-invasive bladder cancer standards of care
The key systemic treatment regimens for muscle-invasive bladder cancer are summarised in table 2.144, 145, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172 At present, the data supporting a benefit for chemotherapy are strongest for neoadjuvant chemotherapy before radical surgery or radiotherapy; data for adjuvant chemotherapy are less robust. In the neoadjuvant setting, cisplatin-based regimens, including MVAC and CMV (cisplatin, methotrexate, and vinblastine), have shown
Follow-up after treatment of urothelial carcinoma
Surveillance for bladder cancer is important because of the high rate of recurrence of both non-muscle-invasive and muscle-invasive disease and the short time to progression and death in patients with metastatic disease. Surveillance strategies are driven by the stage and grade of the tumour and are designed to minimise overtesting while optimising early detection of recurrences.
For non-muscle-invasive bladder cancer, the risk of recurrence after 5 years ranges from 50% to 90%, with higher
Controversies and uncertainties and outstanding research questions
Bladder cancer is a complex disease, and its biology has only begun to be understood. Further research into urinary markers for diagnosis is needed. However, for maximum positive effect on patient care, research should focus on response prediction and monitoring patients during treatment rather than diagnostic evaluation of haematuria. An example of a tool for response prediction is the CyPRIT (Cytokine Panel for Response to Intravesical Therapy), which could potentially allow for real-time
Search strategy and selection criteria
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Cancer facts and figures 2015
Quality of care in patients with bladder cancer: a case report?
Cancer
Tumours of the urinary tract
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