Bladder cancer (BC) is the most common neoplasm affecting the urinary tract, ranks seventh in frequency among malignant tumors in men and seventeenth place — among women. The risk of bladder cancer in different countries varies from 9 to 27 and from 2 to 6 per 100,000 population in men and women, respectively [1]. The risk of death from bladder cancer also differs in men and women, and in European countries it is 8 and 3 per 100,000 population, respectively [1].

Modern methods of diagnosing bladder cancer

According to modern concepts, in about three-quarters of patients with newly diagnosed bladder cancer, the neoplasm is superficial — that is, it does not extend beyond the mucosa (stages Ta, T1 and Tis). Despite belonging to the same classification category, the biological potential of tumors varies significantly. Neoplasms with exophytic growth, having a papillary structure, develop slowly and rarely become a threat to the life of the patient. Carcinomas with initial signs of growth towards the muscle wall, especially at a low degree of differentiation, tend to recur and progress, leading to local spread and distant metastasis. Carcinoma in situ is also a potentially aggressive low-grade neoplasm.

Hematuria is the most common symptom of bladder cancer. Pain and dysuria are less common in superficial bladder carcinomas, however, they may indicate the presence of carcinoma in situ or associated cystitis. When taking an anamnesis, attention should be paid to the risk factors for the development of bladder cancer — smoking, occupational hazards, and in patients with a recurrent course of the disease — carefully record all previous therapeutic measures, examination results and protocols of histopathological findings [1].

Modern methods of diagnosing bladder cancer

An objective examination for superficial bladder cancer is performed in all patients to obtain a complete picture of the state of the organs and systems of the body, however, it may not provide valuable information specific to the tumor process [1].

Imaging techniques are widely used in the examination of patients with suspected bladder cancer. Intravenous urography makes it possible to identify filling defects in the pyelocaliceal system of the kidneys and in the ureters corresponding to a tumor lesion, which are detected in 1.8% of patients with bladder cancer and 7.5% of patients with transitional cell carcinomas located in the vesical triangle. In recent years, this study has been replaced by computed tomography (CT), which is characterized by a higher sensitivity for detecting small tumors and the ability to obtain information about the degree of their local spread and the state of regional lymph nodes [3, 4].

Ultrasound scanning is often used as the primary imaging modality for the urinary tract. Recently, the sensitivity of this study in the diagnosis of bladder carcinomas has increased significantly due to the advent of high-precision modern devices that can image small tumors. Transabdominal ultrasound, as well as X-ray diagnostic methods, gives an idea of ​​the state of the cavitary systems of the kidneys and the presence of tumors of the renal pelvis and upper ureters [5].

Cytological examination of urine allows you to find out with a high probability about the lesion of the urothelium lining the urinary tract, low-grade squamous tumor — carcinoma in situ. Due to the fact that the sensitivity of this study increases as the degree of differentiation of bladder cancer decreases, a negative result does not rule out the presence of carcinoma. The disadvantages of this method are also a high degree of subjectivity in the interpretation of the belonging of the cells obtained during the sampling of the material to classification categories, as well as a pronounced dependence of the quality of the material obtained for the study on the thoroughness of all stages of drug preparation. Urine for research should be taken during the day, it is also possible to prepare preparations from washings from the walls of the bladder, The molecular markers of urinary bladder cancer (NMP‑22, Immunocyt, BTA stat, BTA TRACK, etc.) proposed by various researchers, despite great expectations, did not allow abandoning urine cytology or cystoscopy. In general, the sensitivity of these new tests is higher than that of a cytological study, but they lose in specificity, since the results obtained depend on many factors — concomitant inflammation, treatment with BCG vaccine, differ in the presence of primary and recurrent tumors, etc. [7]. The UroVision test, based on the identification of chromosome microsatellites, is the most promising to date [8].

Cystoscopy with transurethral resection

(TUR) of a papillary neoplasm of the bladder and subsequent histological examination of the removed tumor tissue is the "gold standard"; diagnosis of papillary forms of BC. During the examination of the bladder, it is required to carefully examine all the walls and note the locations of the identified tumors on the schematic image — bladder diagram. In patients in whom a presumptive diagnosis of bladder cancer was made on the basis of clear signs on x-ray or ultrasound, cystoscopy on an outpatient basis can be omitted and performed in an endoscopic operating room, immediately before TUR. The goal of TUR in neoplasms of categories Ta and T1 is to clarify the diagnosis and remove all visible neoplasms. Before TUR, bimanual palpation of the bladder under anesthesia should also be performed, and the introduction of a resectoscope should be carried out under visual control, in which it is necessary to examine the urethra throughout. Examination of the bladder can, if indicated, be supplemented by taking sections of the epithelial lining of the bladder and the prostatic urethra and complete with transurethral resection of the tumor. Small neoplasms should be removed as a single block, in which the area of ​​the bladder wall subject to the tumor must be presented. Large neoplasms can be resected fragmentarily, however, in this case, the section of the muscular wall of the bladder located under the tumor should be presented separately for pathoanatomical conclusion. In cases where a mass was detected during bimanual palpation before surgery, this study should be repeated after the operation is completed. Careful implementation of TUR is the key to a successful prognosis in bladder cancer, and the absence of muscle tissue in the material sent for histopathological conclusion is a risk factor for the progression of the residual tumor [9, 10] Indications for randomized biopsy in BC are suspicion of carcinoma in situ of the bladder, discrepancy between the results of cytological and post-surgical histopathology in relation to category G, detection of a T1G3 neoplasm [11].

In recent years, advanced technologies have been proposed to improve the visualization of bladder tumors — fluorescence cystoscopy, narrow spectrum cystoscopy, optical coherence tomography, confocal scanning laser microscopy.

Photodynamic Diagnostics

— fluorescent cystoscopy, which is performed in blue light after prior exposure of the bladder mucosa to 5-aminolevulinic acid or hexaminolevulic acid. Researchers have shown that such preparation allows visualization of malignantly transformed areas of the urothelial lining and, in particular, carcinoma in situ with higher sensitivity. At the same time, the specificity of such a study turned out to be low and, in the long-term follow-up period, it turned out that, unlike standard white light TUR, fluorescent-guided TUR leads to a decrease in recurrence by only 9% within 9 months and does not affect cancer progression and survival. patients [12].

First experience with narrow spectrum cystoscopy using 415nm and 540nm filters offers an opportunity to increase the detection rate of bladder cancer, which, however, should be confirmed by subsequent observations [13]. Optical coherence tomography (OCT) is a promising area of ​​research that allows obtaining high image quality, similar to the picture obtained when examining bladder preparations under microscope magnification. With OCT, light with a wavelength of 1300 nm penetrates 4 mm deep into the bladder wall and is displayed in the receiver as a transverse layered image with a resolution of 15 nm. The combination of this method with confocal scanning laser microscopy, in which the degree of differentiation of bladder cancer can be identified, is called optical biopsy. At the same time, the key diagnostic features that play a leading role in predicting the clinical course of the disease can be judged even at the diagnostic stage [14].

Due to the fact that there is a significant risk of residual fragments of superficial neoplasms after TUR, which is especially common (33-53% of cases) at stage T1, and also taking into account the fact that at primary diagnosis in 4-50 In % of patients, invasive transitional cell carcinoma was mistakenly regarded as superficial cancer, all patients in whom post-surgical histopathological examination revealed carcinomas of stage T1, grade G3 (with the exception of carcinoma in situ) are shown to perform a second TUR 2–6 weeks after the primary resection. This should also be done in cases where the primary TUR was not fully performed, as well as in the absence of a fragment of the muscle wall in the resected material [15].

The pathoanatomical conclusion plays a leading role in the diagnosis of bladder cancer. The study protocol for each fragment sent for study should describe the depth of invasion and the degree of cancer differentiation, the presence of carcinoma in situ or anomalies in the histological structure of the bladder epithelium adjacent to the tumor, the presence of detrusor fragments and perivascular invasion. Most of the leading urological clinics hold joint conferences with representatives of the pathoanatomical service, where they jointly discuss the operated patients to determine the tactics of their subsequent treatment and the regimen of postoperative observation [16].

Patients at risk of recurrence and progression of bladder cancer have recently been increasingly assessed according to the scoring system proposed by the European Organization for Research and Treatment of Cancer, which takes into account the depth of invasion, the degree of differentiation, the number, size and previous recurrence, as well as the presence of concomitant carcinoma in situ [17].

Thus, at present, the leading professional organizations, based on the principles of evidence-based medicine, have developed and introduced into medical practice a diagnostic algorithm that allows to detect bladder cancer. The search continues for new methods with high sensitivity and specificity to provide an early and better understanding of the classification categories and prognosis of bladder carcinomas.

References

Al-Shukri S. Kh., Tkachuk V. N. Tumors of the genitourinary organs. St. Petersburg: Piter, 2000. S. 309.

Korneev IA Prediction of the clinical course of superficial and locally advanced urothelial cancer: Abstract of the thesis. dis. Dr. med. Sciences: 14.00.40 / St. Petersburg State. honey. un-t im. acad. I. P. Pavlova. S‑Pb., 2006. S. 34.
  1. Palou J., Rodriguez-Rubio F., Huguet J. et al. Multivariate analysis of clinical parameters of synchronous primary superficial bladder cancer and upper urinary tract tumours // J. Urol. 2005. Vol.174(3). P. 859–861.
  2. Nolte-Ernsting C., Cowan N. Understanding multislice CT urography techniques: many roads leading to Rome // Eur. Radiol. 2006. Vol.16(12). P. 2670–2686.
  3. Goessl C., Knispel HH, Millar K. et al. Is routine excretory urography necessary at first diagnosis of bladder cancer? // J. Urol. 1997. Vol.157(2). P. 480–481.
  4. Têtu B. Diagnosis of urothelial carcinoma from urine // Mod Pathol. 2009 Vol. 22 (Suppl 2). S. 53–59.
  5. Yutkin V., Nisman B., Pode D. Can urinary biomarkers replace cystoscopic examination in bladder cancer surveillance? // Expert Rev Anticancer. 2010 Vol. 10(6). P. 787–790.
  6. Schlomer BJ, Ho R., Sagalowsky A. et al. Prospective Validation of the Clinical Usefulness of Reflex Fluorescence In Situ Hybridization Assay in Patients With Atypical Cytology for the Detection of Urothelial Carcinoma of the Bladder // J. Urol. 2010 Vol. 183(1). P. 62–67.
  7. Aaronson DS, Walsh TJ, Smith JF et al. Meta-analysis: does lidocaine gel before flexible cystoscopy provide pain relief? // BJU Int. 2009 Vol. 104(4). P. 506–509; discussion 509–10.
  8. Blick CG, Nazir SA, Mallett S. et al. Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cyst and voided urine cytology: results for 778 patients from a hospital haematuria clinic // BJU Int. 2012. Vol. 110(1). P. 84–94.
  9. Mungan MU, Canda AE, Tuzel E. et al. Risk factors for mucosal prostatic urethral involvement in superficial transitional cell carcinoma of the bladder // Eur. Urol. 2005 Vol. 48(5). P. 760–763.
  10. Grossman HB, Stenzl A., Fradet Y. et al. Long-term decrease in bladder cancer recurrence with examinolevulinate enabled fluorescence cyst // J. Urol. 2012. Vol. 188(1). P. 58–62.
  11. Cauberg EC, Kloen S., Visser M. et al. Narrow band imaging cystoscopy improves the detection of non-muscle-invasive bladder cancer // Urology. 2010 Vol. 76(3). P. 658–663.
  12. Danilchenko D. I., Koenig F., Kastein A. et al. Intravital optical biopsy of bladder cancer: reality and development prospects. Abstracts of the fourth international urological symposium "Diagnostics and treatment of bladder cancer", Nizhny Novgorod, 2005. S. 24.
  13. Divrik RT, Yildirim Ü., Zorlu F. et al. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial // J. Urol. 2006 Vol. 175(5). P. 1641–1644.
  14. Lopez-Beltran A., Bassi P., Pavone-Macaluso M. et al. Handling and pathology reporting of specimens with carcinoma of the urinary bladder, ureter, and renal pelvis // Eur. Urol. 2004. Vol.45(3). P. 257–266.
  15. Sylvester RJ, van der Meijden AP, Oosterlinck W. et al. Predicting recurrence and progression in individual patients with stage TaT1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials // Eur. Urol. 2006 Vol. 49(3). P. 466–465.
    17. Authors: S. Kh. Al-Shukri, I. A. Korneev
    18. Department of Urology, First St. Petersburg State Medical University named after I.I. acad. I. P. Pavlova

Source: Urological Gazette 2013 No.2

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