Regarding bladder cancer, the following statements are true EXCEPT?
The estimated male: female ratio for bladder cancer incidence is 3.8:1. However, women are more likely to be diagnosed with primary muscle-invasive disease than men. In a series of patients undergoing radical cystectomy for de novo muscle-invasive TCC, women were more likely to be diagnosed with muscle invasion primarily than men (85.2% and 50.7% respectively), probably as a lot of these women present with UTI’s or irritative LUTS and are treated as such. Women are also more likely to be older than men when diagnosed, with a direct effect on their survival. In addition, delayed diagnosis is more likely in women after haematuria is observed because the differential diagnosis in women includes diseases more prevalent than bladder cancer.
The incidence rate of bladder cancer is highest in developed countries. 63% of all bladder cancer cases occur in developed countries with 55% from North America and Europe. There is a geographic difference in bladder cancer incidence rates across the world with the highest in Southern and Eastern Europe, parts of Africa, Middle East and North America and the lowest in Asia and underdeveloped areas in Africa. The incidence peaks in the seventh decade of life.
Superficial bladder cancer is much more common than muscle-invasive bladder cancer. However, among patients treated with radical cystectomy because of muscle-invasive disease, 57% had muscle invasion at presentation, while 43% had been initially diagnosed with non-muscle-invasive disease that progressed despite organ-preserving treatment.
Tobacco smoking is the most wellestablished risk factor for bladder cancer, causing 50%–65% of male cases and 20%–30% of female cases. Which of the following statements regarding smoking and bladder cancer is TRUE?
Smoking is responsible for 30%–50% of all bladder cancers in males, and smokers have a 2- to 6-fold greater risk of getting bladder cancer. A causal relationship has been established between an exposure to tobacco and cancer in studies in which chance, bias and confounding can be ruled out with reasonable confidence. A meta-analysis looked at 216 observational studies on cigarette smoking and cancer from 1961 to 2003, with reported estimates for current and/or former smokers. The pooled risk estimates for bladder cancer demonstrated a significant association for both current and former smokers. In an analysis of 21 studies, the overall relative risk calculated for current smokers was 2.77, while an analysis of 15 studies showed that the overall relative risk calculated for former smokers was 1.72.
Smoking cessation will decrease the risk of eventual urothelial cancer formation in a linear fashion. After 15 years of not smoking, the risk of cancer formation is the same as for a person who never smoked. The strong influence of smoking in bladder cancer formation prevents accurate determination of other less significant dietary, micronutrient, or lifestyle changes that may alter bladder cancer formation.
An immediate decrease in the risk of bladder cancer is observed in those who stopped smoking. The reduction was about 40% within 1–4 years of quitting smoking.
A 69-year-old male has undergone a radical cysto-prostatectomy for muscleinvasive bladder cancer with no histological evidence of peri-vesical invasion. Staging investigations included a CT of the chest and abdomen, which showed no metastasis. However, histology of the lymphadenectomy specimen showed that two lymph nodes in the external iliac group were positive for metastasis. What would be the correct TNM (2017) pathological staging?
The Tumour, Node, Metastasis (TNM) Classification of Malignant Tumours is the method most widely used to classify the extent of cancer spread. An eighth edition was published in 2017.
2017 TNM Classification of Urinary Bladder Cancer:
Both CT and MR imaging may be used for assessment of local invasion, but they are unable to detect microscopic invasion of perivesical fat (T3a). The aim of CT and MR imaging is therefore to detect T3b disease or higher. The assessment of nodal status based simply on size is limited by the inability of both CT and MR imaging to identify metastases in normal sized or minimally enlarged nodes. Pelvic nodes greater than 8 mm and abdominal nodes greater than 10 mm in maximum short axis diameter should be regarded as enlarged on CT and MR imaging.
Sensitivities for detection of lymph node metastases are low, ranging from 48% to 87%. Specificities are also low as nodal enlargement may be due to benign pathology. The pN (pathological Node) category is closely related to the number of lymph nodes studied by the pathologist. For this reason, some authors have observed that more than nine lymph nodes have to be investigated to reflect pN0 appropriately after cystectomy.
Regarding the molecular biology of bladder cancer pathogenesis, the following are true, EXCEPT:
Multiple genetic and epigenetic alterations have been described in bladder cancer, including those that affect signal transduction, the cell cycle, invasion, angiogenesis and apoptosis. Most genetic events to date have been identified in high-grade and muscle-invasive bladder cancer. Many of these events are also found in CIS, confirming the likely progression to muscle-invasive TCC via CIS.
Chromosome 9 loss of heterozygosity (LOH) is found in found in more than 50% of all bladder tumours regardless of stage and grade. Current evidence suggests that genetic alterations on chromosome 9q are an early event in bladder tumour formation. Other chromosomal alterations are loss of 17p, 3p, 13q, 18q and 10q. These are noted more frequently in high than in low grade and stage disease.
The key tumour suppressor genes altered in bladder cancer are TP53 and RB1, pathways that control the cell cycle. (P53 is a classic tumour suppressor gene and in its mutated form it is overtly stabilised and hence it is overexpressed in invasive TCC). TP53 gene is the most commonly mutated gene in high-grade muscle-invasive urothelial cancer. The TP53, retinoblastoma (RB), PTEN genes and loss of chromosome 17 are all associated with high-grade cancer. Alterations in TP53, RB and PTEN are poor prognostic indicators.
Several known oncogenes are altered in TCC. Activating point mutations of FGFR3 have been identified in approximately 40% of bladder tumours overall. Mutant FGFR3 is predicted to activate the RAS-MAP kinase pathway
Which of the following statements is FALSE regarding fluorescence-guided biopsy or photodynamic diagnosis (PDD) and resection?
Photodynamic diagnosis (PDD) is performed using filtered blue light after intravesical instillation of a photosensitiser 5-Aminolaevulinic acid (ALA) or hexa-aminolaevulinic acid (HAL). The additional detection rate with PDD for all tumours is about 20% and about 23% for CIS.
The EAU guidelines recommend that if the equipment is available, fluorescence guided (PDD) biopsy should be performed when bladder CIS is suspected (e.g., positive urine cytology, recurrent tumour with previous history of a high-grade lesion).
Kausch I, Sommerauer M, Montorsi F, et al. Photodynamic diagnosis in non-muscle-invasive bladder cancer: A systematic review and cumulative analysis of prospective studies. Eur Urol 2010; 57(4): 595–606.
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