I. Early detection and symptoms
Hematuria is the most common symptom of bladder cancer, especially intermittent painless hematuria, which can be manifested as carnal hematuria or microscopic hematuria.
Patients with bladder cancer also have urinary frequency, urinary urgency, urinary difficulty and pelvic pain as the first manifestation, which is another common symptom of bladder cancer and is often associated with diffuse carcinoma in situ or invasive bladder cancer, while early stage tumors do not have such symptoms.
Other symptoms include pain in the lumbar region due to ureteral obstruction, edema in the lower limbs, pelvic mass, and urinary retention. Some patients present with weight loss, renal insufficiency, abdominal pain or bone pain at the time of consultation, all of which are advanced symptoms.
Physical examination
Palpable pelvic masses in patients with bladder cancer are mostly evidence of locally progressive tumors. Physical examination also includes transrectal and transvaginal finger examination and double examination of abdomen under anesthesia, but physical examination has limited diagnostic value in early bladder cancer.
Imaging examination
Ultrasonography Ultrasonography can be performed by three routes (transabdominal, transrectal and transurethral) and can examine kidney, ureter, prostate and other organs (such as liver, etc.) at the same time. Transrectal ultrasound shows the bladder triangle, bladder neck and prostate more clearly. Transurethral ultrasound is less widely used and requires anesthesia, but the images are clear and the staging accuracy is higher [3]. Foreign reports of transurethral ultrasound determination of tumor staging, compared with pathologic staging, showed that the accuracy of non-muscle infiltrating tumors was 94% to 100%, and the accuracy of muscle infiltrating tumors was 63% to 96, 8%.
Color Doppler ultrasonography can also show blood flow signals at the base of the tumor, but blood flow signs of bladder tumors are not very helpful for preoperative tumor staging and grading [5].
In conclusion, ultrasonography can not only detect bladder cancer, but also help to stage bladder cancer and understand whether there is local lymph node metastasis and surrounding organ invasion, especially for those with contrast allergy [2].
2. Urological plain film and intravenous urography (KUB+IVU) Urological plain film and intravenous urography have been considered as routine examinations for patients with bladder cancer in order to detect coexisting upper urinary tract tumors. However, the need for this test at the time of initial diagnosis is currently questioned because of the small amount of important information obtained. CT imaging of the urinary tract (CTU) can be an alternative to conventional IVU, providing more information and a higher diagnostic accuracy for uroepithelial tumors, but with the disadvantage of more radiation exposure.
3. CT examination Traditional CT (plain scan + enhanced scan) has some value in diagnosing bladder tumors, which can detect larger tumors and can also be distinguished from blood clots. In recent years, the resolution of multi-row (64-128 row) spiral CT is greatly improved and can detect smaller tumors (1-5mm), but in situ cancer is still not easy to be detected, the ureteral situation cannot be understood, the staging accuracy is not high, the enlarged lymph nodes cannot be distinguished from metastasis or inflammation, and it cannot accurately distinguish whether the tumor is confined to the bladder or invaded outside the bladder. In addition, previous history of tumor resection may result in overstaging due to local inflammatory reaction. Therefore, CT can be performed if cystoscopy reveals a tumor that is substantial (non-tip), has the potential to infiltrate into the muscularis or to understand the presence or absence of liver lesions.
CT simulation cystoscopy can obtain visual information similar to that of cystoscopy, and although it cannot completely replace cystoscopy, it has its applications and is a better alternative and complementary method to cystoscopy.
When performing CT simulation cystoscopy, one method is to draw out the urine, fill the bladder with gas, and then perform a scan to reconstruct the data obtained in three dimensions. The accuracy rate with CT simulation cystoscopy is 88%, and CT simulation cystoscopy can accurately identify masses >5 mm and can show mucosal abnormalities as small as 2 mm. CT simulation cystoscopy can also be contrasted with intravenous or transcystic injection of contrast medium.
4. Chest examination Preoperative chest X-ray should be routinely taken to understand the presence of pulmonary metastases. The most sensitive examination method for lung metastasis is chest CT .
5. MRI examination Traditional MRI has no obvious superiority for bladder cancer examination. t1-weighted image of urine shows very low signal, low to moderate signal of bladder wall, and high signal of fat around the bladder. t1-weighted image is useful for examining tumor spread to adjacent fat, lymph node metastasis and bone metastasis, and can even evaluate the invasion of adjacent organs other than prostate. t2-weighted image T2-weighted images are high signal in the urine, low signal in the normal detrusor muscle, and moderate signal in most bladder cancers. Interruption of the tumor beneath the low-signal forced urinary muscle suggests muscle infiltration. Therefore, MRI helps in staging the tumor. Dynamic MRI is more accurate than CT or non-enhanced MRI in showing the presence of uroepithelial carcinoma and the extent of muscle invasion [19]. Because the mean apparent diffusion coefficient (ADC) of bladder tumors is lower than that of surrounding tissues, diffusion-weighted imaging (DWI) provides better preoperative assessment of tumor T-staging and may be valuable in assessing tumor invasion of surrounding tissues.
The application of MRI simulating cystoscopy is more effective in diagnosing tumors (including smaller tumors). The sensitivity and specificity of simulated cystoscopic reconstruction with multidimensional reconstruction is higher in patients with bladder cancer undergoing MRI cystography, using intraoperative or cystoscopic findings as a reference standard.
In terms of staging, the application of enhancers for MRI for staging can distinguish non-muscle infiltrating tumors from muscle infiltrating tumors and the depth of infiltration, and can also detect signs of metastasis in normal-sized lymph nodes. For example, the application of iron as an enhancer can identify lymph nodes with or without metastases: benign enlarged lymph nodes can engulf iron and show reduced signal intensity on T2-weighted images, whereas lymph node metastases do not show this sign. Recently, the accuracy of gadolinium-enhanced MRI for staging bladder cancer was evaluated and the MRI staging accuracy was 62%, with 32% showing overstaging, but the MRI staging accuracy improved to 85% and 82% for differentiating non-muscle-infiltrating tumors from muscle-infiltrating tumors or for differentiating tumors confined to the bladder, respectively.
The sensitivity of MRI is much higher than that of CT and even higher than that of nuclear bone scan in detecting the presence or absence of bone metastases.
Bone scans are generally not routinely used. It is only used in patients with infiltrative tumors who have bone pain and are suspected of having bone metastases [1].
7. PET (positron emission tomography) is generally not used for diagnosis because the tracer FDG (fluorodeoxyglucose) excreted into the bladder via the kidneys can interfere with the diagnosis of smaller tumors, and the high cost limits its application. Currently, PET/CT is mainly used for preoperative staging of muscle-invasive bladder cancer, but there are few studies and few cases regarding tumor staging, and thus results are variable. Although the use of novel tracers (e.g., choline, methionine) has been reported, limited data suggest that 11C-choline may be a promising tracer for detecting lymph node metastasis, but further confirmation is needed.
IV. Urine cytology
Urine cytology is one of the main methods for diagnosis and postoperative follow-up of bladder cancer. Urine specimens are usually collected by natural urination, or by bladder irrigation, which can get more cancer cells and help to improve the diagnosis rate. Positive urine cytology means that there is a possibility of uroepithelial cancer in any part of the urinary tract, including: calyces, pelvis, ureter, bladder and urethra. The sensitivity of urine cytology for detecting bladder cancer is 13% to 75% and the specificity is 85% to 100%. The sensitivity is closely related to the malignant grading of cancer cells. The lower sensitivity of bladder cancer with low grading is due to the fact that on the one hand, tumor cells are better differentiated and their characteristics are similar to normal cells, which are not easy to identify, and on the other hand, because of the relatively tight adhesion between cancer cells, not enough cancer cells are shed to urine to be detected, so a negative urine cytology does not exclude the existence of low-grade uroepithelial cancer; on the contrary, high-graded bladder cancer or carcinoma in situ has higher sensitivity and specificity [30-32]. Factors such as low number of cancer cells in urine specimens, atypical or degenerative changes of cells, urinary tract infections, stones, bladder perfusion therapy and technical differences of the examiner can affect the results of urine cytology [33, 34].
V. Urinary bladder cancer markers
In order to improve the non-invasive detection of bladder cancer, the study of urinary bladder cancer markers has received much attention, and the US FDA has approved the inclusion of BTAstat, BTAtrak
NMP22, FDP, ImmunoCyt and FISH for the detection of bladder cancer. It is believed that with the emergence of new technologies, the future of research and application of urine bladder cancer markers is bright.
VI. Cystoscopy and biopsy
Cystoscopy and biopsy are the most reliable methods to diagnose bladder cancer. Cystoscopy can clarify the number, size, morphology (papillary or broad-based), location and abnormalities of surrounding bladder mucosa of bladder tumors, and biopsy of tumors and suspicious lesions can be performed to clarify pathological diagnosis. If available, flexible cystoscopy is recommended. Compared with rigid cystoscopy, this method has the advantages of less injury, no blind field of view, and relative comfort.
Bladder tumors are usually multifocal and non-muscle invasive bladder cancer can be associated with carcinoma in situ or dysplasia and present as inflammation-like reddish villous mucosal changes or can appear completely normal.
Routine random or selective biopsy of the normal bladder mucosa in non-muscle-infiltrating bladder cancer is not recommended because the likelihood of finding carcinoma in situ is very low (less than 2%), especially for those with low-risk bladder cancer. However, when urine exfoliation cytology is positive or the bladder mucosa behaves abnormally, selective biopsy is recommended to clarify the diagnosis and understand the extent of the tumor. Random biopsy should be considered when the urine cytology is positive and the bladder mucosa is normal and in situ cancer is suspected. If the bladder tumor is carcinoma in situ, multiple carcinomas or if the tumor is located in the bladder triangle or neck, there is an increased risk of complicating urethral carcinoma of the prostate, and biopsy of the prostate is recommended.
VII. Diagnostic transurethral resection (TUR)
If imaging examination reveals a non-muscle infiltrating tumor occupying lesion in the bladder, cystoscopy can be omitted and TUR can be performed directly, which can achieve two purposes, one is to remove the tumor, and the other is to clarify the pathological diagnosis and grading and staging of the tumor, and provide a basis for further treatment as well as prognosis.
TUR method: if the tumor is small (less than 25 px), the tumor can be removed together with the basal part of the bladder wall and sent for pathological examination; if the tumor is large, a step-by-step resection is performed, starting with the excision of the protruding part of the tumor, followed by the excision of the basal part of the tumor, which should contain the muscular layer of the bladder wall, and finally the excision of the peripheral area of the tumor, and these three parts of the specimen are sent for pathological examination [41,42]. ]. cautery is avoided as much as possible during TUR to minimize the damage to the specimen tissue [43]. (Biopsy forceps can also be used to biopsy the base of the tumor as well as the surrounding mucosa, which can effectively protect the specimen tissue from damage and can be used in conjunction with TUR as appropriate.)
Fluorescence cystoscopy
Fluorescence cystoscopy is performed by instilling a photosensitizer, such as 5-aminoketovaleric acid (5-ALA), Hexaminolaevulinate (HAL) or Hypericin, into the bladder, which produces a fluorescent substance that accumulates highly selectively in the neoplastic bladder mucosa. In contrast, it can detect small tumors, dysplasia or carcinoma in situ that are difficult to detect with ordinary cystoscopy, and the detection rate can be increased by 14% to 25%. The European Society of Urology guidelines recommend that fluoroscopic cystoscopy should be considered for further investigation when in situ bladder cancer is suspected or when urine cytology is positive but normal on plain cystoscopy. Recently, it has been reported that electrosurgery of bladder tumors performed under fluorescence cystoscopy guidance can significantly reduce the postoperative recurrence rate of tumors compared with ordinary electrosurgery, but the effect on the progression rate of tumors and patient survival remains to be further clinically observed. The disadvantage of fluorescence cystoscopy is that the specificity of diagnosing bladder cancer is relatively low, and inflammation, recent bladder tumor electrosurgery and bladder perfusion therapy can lead to false positive results.
IX. Secondary transurethral resection (ReTUR)
After electrosurgery for non-muscle invasive bladder cancer, a considerable number of tumor recurrences are due to tumor remnants, especially for intermediate and high-grade stage T1 bladder cancer, the tumor remnant rate after the first electrosurgery can reach 33, 8% to 36%. In addition, due to the quality of electrosurgery technique and sent tumor specimens, the first electrosurgery can also cause deviation in pathological staging of some tumors. Some scholars suggested that ReTUR for non-muscle invasive bladder cancer within a short period of time after the first electrosurgery, especially for those high-risk stage T1 bladder cancer, can reduce the postoperative tumor recurrence and progression rates and can obtain more accurate pathological tumor staging.ReTUR can reduce the postoperative tumor recurrence rate from 63,24% to 25,68% and tumor progression rate in patients with stage T1 bladder cancer The tumor progression rate was reduced from 11,76% to 4,05%. As for when to perform ReTUR after the first electrosurgery is still inconclusive, most scholars suggest that it should be performed within 2 to 6 weeks after the first electrosurgery.
To summarize.
1.Patients with bladder tumor need to take medical history, do physical examination, urine routine, ultrasound, urine exfoliative cytology, IVU examination and chest X-ray.
2.Cystoscopy and pathological biopsy or diagnostic TUR should be performed for all patients considering bladder cancer.
3.Random biopsy should be considered for suspected carcinoma in situ and positive urinary exfoliative cytology without clear mucosal abnormalities.
4.Patients with muscle-infiltrating bladder cancer can choose pelvic CT/MRI and bone scan according to their needs.