1.Do you know about bladder cancer? Bladder cancer is a common malignant tumor of urinary system, and its incidence rate ranks the first among malignant tumors of urinary system. In China, the incidence rate of bladder cancer in men ranks the eighth among systemic tumors, and women rank after twelve. Bladder cancer can occur at any age, including children, but the main age of incidence is after middle age, and the incidence rate increases with age, and older people are more likely to suffer from bladder cancer than young people. Bladder cancer is a malignant overgrowth of bladder cells. The majority of bladder cancers are of the migrating epithelial cell type, 90-95% of bladder cancers are of this type, and they are most commonly seen in the wall and posterior wall of the bladder, followed by the deltoid region and the neck, and develop in multiple places at the same time. The surface of most of the body’s cavity organs consists of epithelial cells, such as the stomach, intestines, gallbladder and bladder. The cells on the surface of the bladder are called migratory epithelial cells. Bladder cancer can be accompanied by tumors of renal pelvis, ureter and urethra successively or simultaneously. 2.Natural course of bladder cancer Most bladder cancer patients are in well-differentiated or moderately differentiated non-muscle invasive bladder cancer at the time of diagnosis, and about 10% of them eventually develop into muscle invasive bladder cancer or metastatic bladder cancer. The size, number, stage and grading of bladder cancer are closely related to its progression, especially the stage and grading, with low-stage and low-grade tumors having a lower risk of disease progression than high-stage and high-grade tumors. Overall, the risk of muscle infiltration is much higher in stage T1 bladder cancer than in stage Ta. Studies have found that the risk of progression in G1 bladder cancer (6%) is only 1/5 of that in G3 bladder cancer (30%). a group of up to 20 years of follow-up data found that the risk of disease progression is higher in G3 bladder cancer, 14% in TaG1 bladder cancer and up to 45% in T1G3, but the risk of recurrence is the same, about 50%. 3. Which patients are at risk of developing bladder cancer? The two clearer risk factors for bladder cancer are smoking and long-term exposure to industrial chemicals. Among them, smoking is the biggest risk factor for bladder cancer. Bladder cancer caused by smoking accounts for 25%-65% of all bladder cancers, and the probability of bladder cancer in patients who smoke is four times higher than that of non-smokers. The risk of developing bladder cancer increases with the number of cigarettes smoked, the length of time, and the extent of each inhalation, in both men and women, but cessation of smoking reduces this risk. Exposure to fuels is the most common industrial risk factor for bladder cancer, and is commonly associated with the dyeing of wood and chemicals. Thus, long-term smokers and those involved in textiles, fuel manufacturing, rubber chemicals, pharmaceuticals and pesticides, as well as those involved in the production of paints, leather, aluminum, and steel, and those who regularly dye their hair, are more likely to develop bladder cancer. In addition, bladder’s own disease or chronic irritation, such as long-term use of catheter, schistosomiasis infection, chronic infection, pelvic irradiation, bladder stones and so on are also common susceptibility factors. 4.Can bladder cancer be hereditary or contagious? There is no conclusive evidence that bladder cancer can be inherited from parents to children. Family members are easily exposed to similar risk factors. In some cases, several people within a family develop bladder cancer at the same time, but there may also be different risk factors among family members, such as smoking or environmental factors. What is certain, however, is that most people with bladder cancer do not have a clear family history of bladder cancer. Bladder cancer is not a contagious disease, so it cannot be passed on to your family or friends. However, as mentioned above, family members of bladder cancer patients are prone to be exposed to similar risk factors such as smoking, environmental chemicals and other harmful substances. Therefore, their risk of developing bladder cancer may be higher than normal. 5. What are the first symptoms of bladder cancer? Sudden painless hematuria visible to the naked eye throughout is the most common first symptom of bladder cancer. Hematuria is intermittent and often disappears suddenly, which does not get patients’ attention and further exploration, which becomes an important reason for no early diagnosis of bladder cancer. Therefore, middle-aged and old men with high risk factors for bladder cancer should be alert to bladder cancer if painless hematuria occurs. Patients with recurrent urinary tract infections should also exclude the possibility of tumor. 6. What are the main diagnostic methods of bladder cancer? It is not difficult to diagnose bladder cancer. Any painless hematuria above 40 years old which is not obvious should be thought of the possibility of urinary tumor, among which bladder cancer is the most common. Patients should undergo further examination, including: urine exfoliative cytology, impactography, cystoscopy and tumor tissue biopsy, etc. Among them, cystoscopy is the most reliable method to diagnose bladder cancer. Cystoscopy and pathological biopsy or diagnostic transurethral electrolysis should be carried out for all patients considering bladder cancer. Nowadays, diagnostic transurethral electrolysis is more recommended as the main diagnostic method, which is safe, reliable, and accurate in pathological staging and grading of the tumor. 7. I heard that cystoscopy is very difficult and painful, can I not do it? If the doctor suspects that the bladder is occupied, cystoscopy must be done because it is the clearest and most intuitive way to find out whether there is any abnormality in the bladder, which cannot be replaced by any other inspection methods. According to the results of cystoscopy, doctors have to judge whether the patient needs surgical treatment, what kind of surgery is needed, and whether the bladder can be preserved, which is very important to the patient and relates to the patient’s quality of life after the surgery. Moreover, after receiving surgical treatment with bladder preservation for early-stage bladder cancer, regular cystoscopy is still needed to clarify whether there is any tumor recurrence. Therefore, cystoscopy is an indispensable test in the diagnosis and follow-up of bladder cancer. Cystoscopy does cause mild discomfort, especially when the patient is very nervous. Doctors will use anesthetics in advance before operation. As long as patients relax and cooperate with doctors, basically all patients can complete the examination successfully. 8.What is the stage and prognosis of bladder cancer? Bladder cancer can be divided into non-muscle invasive bladder cancer and muscle invasive bladder cancer. About 75% of bladder cancer patients are in well-differentiated or moderately differentiated non-muscle invasive bladder cancer at the time of diagnosis, and about 25% of patients have muscle invasive bladder cancer or metastatic bladder cancer. The size, number, stage and grade of bladder cancer are closely related to its pathogenesis, especially the stage and grade. The risk of disease progression is lower for low-stage, high-grade tumors than for high-stage, high-grade tumors. 9. What is the risk classification of non-muscle invasive bladder cancer? Low-risk NMIBC: primary, solitary, TaGl (low-grade uroepithelial carcinoma), diameter <3cm, no CIS.(Note: both of the above conditions must be present for low-risk non-dirty layer invasive bladder cancer) Intermediate-risk NMIBC: all NMIBC that are not included in the low-risk and high-risk classifications High-risk NMIBC any of the following: ① Stage T1 tumor ② G3 (or high-grade uroepithelial carcinoma ) ③ CIS ④ Simultaneous fulfillment: multiple, recurrent and TaGIG2 (or low-grade uroepithelial carcinoma) with a diameter >3cm Low-risk patients have a 1-year recurrence rate of 15% and a 5-year rate of 30%; patients in the intermediate-risk group have a 1-year recurrence rate of 38% and a 5-year rate of 62%; patients in the high-risk group have a 1-year recurrence rate of 61% and a 5-year rate of 78%. It seems that the recurrence rate of bladder tumor after cystectomy is still very high, but don’t worry, this data is the average value, in some professional diagnostic and treatment centers, through the superb surgery and active follow-up treatment, the recurrence rate is much lower than this average value, and if you follow the physician’s requirement of timely review, the vast majority of recurrence of the patient can be treated by minimally invasive surgery. 10.Treatment of non-muscle invasive bladder cancer lTUR-BT is the main treatment for non-muscle invasive bladder uroepithelial cancer. lFor low-risk non-muscle invasive bladder uroepithelial cancer, only single-agent immediate bladder perfusion chemotherapy can be performed after surgery. l For intermediate- and high-risk non-muscle invasive uroepithelial carcinoma of the bladder, postoperative single-agent immediate bladder perfusion chemotherapy should be followed by follow-up chemotherapeutic agents or BCG maintenance perfusion therapy. l For high-risk non-muscle invasive uroepithelial carcinoma of the bladder, BCG bladder perfusion therapy is preferred (maintained for at least 1 year). l For non-muscle invasive bladder uroepithelial cancer that is ineffective in bladder perfusion treatment (e.g. tumor progression, multiple tumor recurrences, Tis and T1G3 tumors that are ineffective in TUR-BT and bladder perfusion treatment, etc.), then radical cystectomy is recommended. 11. Why do some bladder cancer patients need to undergo secondary cystectomy? Transurethral resection of bladder tumors (TURBT) has two purposes: one is to remove all the tumors visible to the naked eye, and the other is to remove tissues for pathological grading and staging. In the past 10 years, the concept of secondary cystectomy has been gradually proposed both at home and abroad: i.e., to perform cystectomy again within 2-6 weeks after the initial cystectomy. The main reasons are: ① The residual positive rate of bladder tumor after the first electrosurgery is very high, even in the United States, Europe and other large cancer centers this data is as high as 30-52%, so it is necessary to carry out the second TUR in order to remove the residual tumor tissue. (ii) Comparative analysis of pathological specimens after secondary TUR with those after the first operation revealed that the pathological staging after secondary TUR was higher than that of the initial operation in 10%-20% of patients, especially those patients in whom the initial TUR did not cut into the myxoid layer or in whom no myxoid layer could be seen in the specimen. Inaccurate staging also affects the choice of subsequent treatment options and prognostic assessment of the patient. Why is there such a high rate of tumor positivity found on re-electrocution within a short period of time (4-6 weeks) after electrocision? It may be related to these factors: 1) the biologic characteristics of bladder cancer with multicentricity and multiplicity: latent early tumors in easily missed; high-grade tumors with high malignancy, tumors easy to implant and intravascular metastasis, etc.; 2) of course, the quality of the initial electrodesiccation procedure is also crucial: if the initial electrodesiccation did not cut the muscularis propria or the muscularis propria could not be seen in the specimen, the rate of finding positive tumors on reelectrodesis was significantly increased. Therefore, for 1) inadequate initial TURBT; 2) no muscle layer tissue in the initial electrodesiccation specimen, except for TaGl (low-grade) tumors and simple carcinoma in situ; 3) T1 stage tumors; 4) G3 (high-grade) tumors, except for simple carcinoma in situ. It is recommended to do secondary electrocision within 2-6 weeks after surgery in order to accurately stage, reduce postoperative tumor recurrence, and better control bladder tumors. At present, secondary electrosurgical resection is unanimously recommended in domestic and international bladder cancer diagnosis and treatment guidelines, and it has become the standard treatment method nowadays. 12.How to reflect the malignant degree of bladder cancer? It mainly depends on the degree of differentiation. In 1973, the World Health Organization (WHO) classified bladder tumors into papillary tumors according to the degree of differentiation of bladder tumor cells; uroepithelial carcinoma grade 1, well-differentiated, with low malignancy; uroepithelial carcinoma grade 11, moderately-differentiated, with medium degree of malignancy; and uroepithelial carcinoma grade 111, poorly-differentiated, with high degree of malignancy. In order to better reflect the risk tendency of the tumor, in 2004, WHO classified uroepithelial tumors of the bladder and other uroepithelial tumors into papillary tumors, papillary uroepithelial tumors with low malignant tendency, low-grade papillary uroepithelial carcinomas (with low malignancy) and high-grade papillary uroepithelial carcinomas (with high malignancy). 13. How to know whether bladder cancer is early or advanced? It mainly depends on the infiltration depth and metastasis of the tumor, and the infiltration depth is the basis for clinical (T) and pathological (P) staging of the tumor. According to the depth of infiltration of cancer into bladder muscle wall (except papilloma), it is mostly classified into: Tis carcinoma in situ; Ta papillary carcinoma without infiltration; T1 infiltration of mucous membrane lamina propria; T2: infiltration of muscular layer, which is further classified into T2a infiltration of superficial muscular layer (1/2 inside the muscular layer), T2b infiltration of deep muscular layer (1/2 outside the muscular layer); T3 infiltration of bladder peripheral adipose tissues, which is further classified into T3a microscopic Clinically, it is customary to refer to Tis, Ta, and T1, stage tumors as superficial bladder cancer generally belonging to early stage tumors. The spread of tumor mainly infiltrates into the bladder wall until it involves extraves bladder tissues and adjacent organs. Lymphatic metastasis is the most important metastatic pathway, mainly to the pelvic lymph nodes, such as the closed hole, endoskeletal, exoskeletal and common skeletal lymph node groups. About 50% of the lymphatic vessels of those infiltrating the superficial muscular layer have cancer cells, and almost all of the lymphatic vessels of those infiltrating the deep muscular layer have cancer cells, and most of those infiltrating to the periphery of the bladder have already metastasized to distant lymph nodes. Hematogenous metastasis mostly occurs in the late stage, mainly to liver, lung, bone and skin. Those with poorly differentiated tumor cells are prone to infiltration and metastasis. Postoperative adjuvant treatment Non-muscle invasive bladder cancer has a high postoperative recurrence rate after TURBT, and a small portion of patients may even progress to muscle invasive bladder cancer. TURBT surgery alone for carcinoma in situ does not solve the problem of high postoperative recurrence rate and disease progression. Therefore, postoperative adjuvant bladder perfusion therapy, including bladder perfusion chemotherapy and bladder perfusion immunotherapy, is recommended for all patients with nonmuscle invasive bladder cancer. l Commonly used drugs for bladder perfusion: piroxicam, epirubicin, doxorubicin, hydroxycamptothecin, mitomycin, gemcitabine can also be used for bladder perfusion chemotherapy. l Immunotherapy commonly used drugs: Bacillus Calmette-Guérin (BCG), others also include interferon, Keyhole Worm Chi hemocyanin, and so on. In the follow-up of non-muscle invasive bladder cancer, cystoscopy is still the gold standard, and biopsy and pathology should be performed once abnormalities are found during the examination. Ultrasonography, urine exfoliative cytology, IVU and other tests also have some value, but they cannot completely replace the status and role of cystoscopy. It is recommended that all patients with non-muscle invasive bladder cancer undergo the first cystoscopy at 3 months after surgery, but it can be advanced appropriately in the presence of incomplete surgical resection and rapid tumor progression, and the subsequent follow-up is decided according to the level of risk of recurrence and progression of bladder cancer. High-risk patients are recommended to undergo cystoscopy every 3 months in the first 2 years, every 6 months from the third year, and once a year from the fifth year until lifetime; low-risk patients with negative first cystoscopy are recommended to undergo a second cystoscopy at 1 year after surgery, and once a year thereafter until the fifth year; and intermediate-risk patients have a follow-up program between the two, which is based on the patient’s individual prognostic factors and general condition. In case of recurrence during the follow-up, the follow-up program after treatment will be restarted according to the above program. 16.9 Points of Attention for Bladder Cancer Patients in Daily Life ①. Quit smoking; ②. Avoid contact with aromatic amines and do not dye hair; ③. Actively treat chronic urinary tract infection Chronic bacterial infection and schistosomal infection lead to long-term inflammation of bladder, and repeated repair of inflammation may cause tumor development, so bladder cancer patients should actively treat chronic cystitis; ④. Drink less coffee; ⑤. Actively treat urinary stones; ⑥. Actively deal with non-specific inflammation of the bladder; ⑦. Do not take analgesics for a long time; ⑧. Do not consume large amounts of saccharin; ⑨. Drink more water, do not hold urine: “Drink more water, do not hold urine” is the classic urology medical advice, yes, “drink more water, do not hold urine” applies to the prevention of almost all urological diseases. “Drinking more water” can increase the volume of urine, the harmful substances in the urine can be diluted, “do not hold urine” in time to empty the bladder, reduce the toxic effect of harmful substances in the urine on the bladder mucosa, reduce the risk of bladder tumors.