Bladder cancer
Anju Sahdev, Sarah J. Vinnicombe in Husband & Reznek's Imaging in Oncology, 2020
The urothelium is the lining epithelium of the urinary collecting system, including the renal pelvis, ureters, bladder, and part of the urethra. Depending on the state of distension of the bladder, its thickness varies from three to seven cell layers. Under normal circumstances, these cells have a slow turnover rate, in the region of 3–6 months and will desquamate, but very few cells are seen in normal urine cytology specimens. When malignant transformation takes place, shedding of cells and haematuria will occur. Urothelial cancer can be classified according to its biological behavioural or morphological features. Behavioural features divide bladder cancer into non–muscle-invasive low-grade lesions or high-grade muscle-invasive lesions with risk of metastasis, and carcinoma in situ with propensity for muscle invasion. Non-invasive tumours can be divided into two morphological categories: papillary or flat. Carcinoma devoid of papillary structures is called carcinoma in situ (CIS) and is, by definition, high grade. Papillary lesions have delicate frond-like projections into the bladder lumen, non-papillary, or mixed papillary and infiltrative tumours. Papillary tumours are usually solitary intraluminal masses; non-papillary tumours may be infiltrative, ulcerative, or polypoid. These patterns of tumour growth are well demonstrated on imaging with CT and MR (Figure 16.1).
Bladder Cancer
Pat Price, Karol Sikora in Treatment of Cancer, 2020
The development of multi-drug combinations increased response rates and survival. MVAC and CMV regimes102 incorporate methotrexate, vinblastine, and cisplatin (with or without doxorubicin), described in Table 13.5. Both attain high response rates, including a significant complete response rate. Typically in an average patient population response rates of 40–50% with a 10% complete response rate were more common.103 These schedules improve median survival of patients with metastatic urothelial cancer from around 3–6 months, to around 9–12 months with treatment.102,104,105 Though not tested against best supportive care, there is improved survival compared to single-agent or less intensive schedules.104,105 Toxicities include significant rates of mucositis (40%), renal toxicity (31%), and neutropenic sepsis (20%), with a toxic death rate of 4%.102 An accelerated MVAC schedule administered on a 2-week cycle supported by granulocyte colony-stimulating factor (GCSF) was shown to achieve more complete responses (21% versus 12%) with some borderline evidence of benefit in long-term survival (24.6% versus 13.2%, borderline statistical significance) in EORTC randomized trial.106 As there were similar or lower levels of toxicity and treatment is completed more quickly this would be the preferred way to administer MVAC.
The urinary bladder
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
A series of genetic events has been clearly implicated in cancer formation but is outside the remit of this chapter. Activation of dominantly acting oncogenes such as ras and c-erbB-1 and -2, and transcription factors such as E2F3, have been reported in bladder cancer, as has the inactivation of tumour-suppressor genes such as p53, p21, p16 and the retinoblastoma gene. Activation of many other genes occurs including: those coding for enzymes that dissolve the basement membrane, such as the metalloproteinases (strome- lysin, collagenases and elastase), lysosomal enzymes such as the cathepsins and others including urinary plasminogen activators; angiogenic factors (e.g. vascular endothelial growth factor (VEGF]) and other peptide growth factors such as the epidermal growth factor (EGF) and its receptor (EGFR) also have a role to play, as well as the fibroblast growth factor (FGF) and its receptor-3 (FGFR-3) which was found to be altered mostly in non-muscle invasive disease. These changes are common to several tumour types, including prostate cancer. More recently, new approaches through genome-wide association studies allowed the investigation of genetic susceptibility for urothelial cancer. Several new loci were identified, but, to date, only two, NAT2 (N-acetyltransferase 2) and GSTM1 (glutathione S-transfer- ase Mu 1) have been demonstrated to be consistent germline susceptibility markers. These genetic markers do not yet have sufficient discriminatory ability to be used for clinical decision-making.
The emerging role of antibody-drug conjugates in urothelial carcinoma
Published in Expert Review of Anticancer Therapy, 2020
Michael Lattanzi, Jonathan E. Rosenberg
Urothelial cancer is the 4th most common cancer among men in the United States and the 8th leading cause of cancer-associated deaths among American males [15]. Most urothelial cancers begin in the bladder and are non-muscle invasive at diagnosis [16]. Non-muscle invasive bladder cancer (NMIBC) is typically managed by TURBT and usually followed by intravesical therapy such as bacillus Calmette-Guérin (BCG) [17]. Although the majority of these patients respond to available therapies, some high-risk patients will go on to develop locally-recurrent disease, at which point the standard of care has been radical cystectomy [18], a procedure associated with significant morbidity, quality of life and lifestyle changes, and a nontrivial mortality [19]. While non-muscle invasive bladder cancer has historically been the purview of urologic surgical oncologists, checkpoint blockade immunotherapy has recently demonstrated encouraging activity [20], and in January, 2020, pembrolizumab was FDA-approved for high-risk BCG-unresponsive NMIBC. The role for medical oncologists in the management of NMIBC may very well continue to evolve in the coming years.
Current and emerging bladder cancer biomarkers with an emphasis on urine biomarkers
Published in Expert Review of Molecular Diagnostics, 2020
Antonio Lopez-Beltran, Liang Cheng, Thomas Gevaert, Ana Blanca, Alessia Cimadamore, Matteo Santoni, Francesco Massari, Marina Scarpelli, Maria R. Raspollini, Rodolfo Montironi
demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new noninvasive approach for detection of urothelial cancer [108]. The UroMuTERT is simple, sensitive, and specific urine test capable of detecting urothelial cancer (carcinoma of the bladder and of the upper urinary tract. The test builds on the discovery of two highly recurrent mutations in the telomerase reverse transcriptase (TERT) gene; these mutations are present in any kind of urothelial tumor and can be detected in cells shed into the urine of patients with urothelial cancer. The UroMuTERT test was developed specifically for the detection of low levels of TERT mutations in bodily fluids. The UroMuTERT test demonstrated excellent sensitivity and specificity for the detection of all forms of urothelial cancer. The test, which detects TERT mutations in the urine, was found to significantly outperform urine cytology for the detection of low-grade early-stage tumors [109] (Table 3).
The cost effectiveness of pembrolizumab versus chemotherapy or atezolizumab as second-line therapy for advanced urothelial carcinoma in the United States
Published in Journal of Medical Economics, 2020
Rachael Louise Slater, Yizhen Lai, Yichen Zhong, Haojie Li, Yang Meng, Blanca Homet Moreno, James Luke Godwin, Tara Frenkl, Guru P. Sonpavde, Ronac Mamtani
Immunotherapy has revolutionized cancer care, particularly among patients with urothelial cancer. One concern about the adoption of novel therapeutics is that they are usually associated with high treatment costs. This US-based economic analysis suggests that pembrolizumab improves both survival and QALYs and is a cost-effective treatment compared with chemotherapy at a WTP threshold of $100,000 or $180,000 per QALY gained and dominates atezolizumab with cost savings. The use of individual patient longer follow-up data from the Phase III KEYNOTE-045 trial further mitigate the uncertainty of the projected survival of pembrolizumab and chemotherapy. To our knowledge, this is the first analysis which evaluates the cost-effectiveness of pembrolizumab vs. atezolizumab in the 2L mUC setting using the best available evidence from ITC. This analysis contributes to the value assessment for these important oncology drugs.