Bladder cancer is a malignant overgrowth of cells in the bladder. The most common overgrowth is located within the bladder lumen, which is the mucosal epithelium of the bladder. In the body, the surface of the cavernous organs is usually made up of epithelial cells. For example, the inside of your cheek, stomach, intestines, gallbladder, and also the bladder are all made up of a layer of epithelial cells. Each organ has its own class of epithelial cells. The mucosal epithelial cells of the bladder are called uroepithelial cells, and the cancer that arises from them is called uroepithelial cancer, which accounts for 90-95% of all bladder cancers and is the most common type of bladder cancer.
Disease Introduction
Bladder cancer is a malignant overgrowth of cells in the bladder. The most common overgrowth is located within the bladder lumen, which is the mucosal epithelium of the bladder. In the body, the surface of the cavernous organs is usually made up of epithelial cells. For example, the inside of your cheek, stomach, intestines, gallbladder, and also the bladder are all made up of a layer of epithelial cells. Each organ has its own class of epithelial cells. The mucosal epithelial cells of the bladder are called uroepithelial cells and the cancer that arises from them is called uroepithelial cancer, which accounts for 90-95% of all bladder cancers and is the most common type of bladder cancer. Other less common types of bladder cancer are squamous cell carcinoma and adenocarcinoma. Cancer that spreads to the bladder from elsewhere in the body, called metastatic bladder cancer, is generally rare and occasionally grows into the bladder from an adjacent organ, such as the prostate, colon, rectum or cervix. Worldwide, bladder cancer ranks as the fourth most common solid tumor in men and the seventh most common in women, with more than 350,000 new bladder cancer diagnoses each year. The American Cancer Society counted 61,420 new cases of bladder cancer and 13,060 deaths in the United States in 2006. In China, bladder cancer is still the most common malignant tumor of the urinary system, with a standardized incidence rate of 4.0/100,000 for men and 1.5/100,000 for women in 2005. In recent years, the incidence rate of bladder cancer in some cities in China has shown a trend of steady increase. In major cities in China, such as Beijing, Shanghai and Tianjin, the incidence of bladder cancer has ranked sixth among common malignant tumors in men, and the mortality rate has ranked seventh. In Shanghai, for example, the incidence rate of bladder cancer in 2005 was 15.26/100,000 for men and 4.37/100,000 for women. Compared with other countries in the world, such as North America and Western Europe, China is still one of the countries with a low incidence rate of bladder cancer. Bladder cancer occurs at the age of 51 to 70 years old, with the peak incidence at 65 years old, but rarely before 30 years old. About 80%-85% of patients have tumor confined to the bladder, and 15%-20% have regional lymph node metastasis or distant metastasis. Among the inpatients of the Department of Urology of Cancer Hospital of Fudan University, bladder tumor accounts for 35%, and the age of onset ranges from 24 to 90 years old, with a median age of 61 years old.
Disease classification
Broadly speaking, bladder cancer mainly includes two types: primary cancer and metastatic cancer. Primary bladder cancer originates from the bladder itself, while metastatic cancer originates from other organs, except that the cancer cells spread to the bladder, usually through the bloodstream, lymphatic system or directly invade the bladder from neighboring organs, such as the prostate, rectum, and cervix.
Primary bladder cancer is much more common than metastatic bladder cancer. The most common of these is uroepithelial cancer, which accounts for more than 90% of cases. Bladder cancer can take many forms.
1. papillary, which looks like cauliflower or watercress with a thin tip attached to the bladder wall; 2. flattened, which looks like flakes or strips, velvety, with a reddish surface and no tip attached to the bladder wall; 3. solid, which looks like warts, lumpy, with a wide base and a wide tip attached to the bladder wall. About 70% of uroepithelial carcinomas are papillary, and it has a better prognosis than broad-based and non-tipped tumors. Less common bladder cancers include squamous cell carcinoma, adenocarcinoma, and carcinoma of the umbilical canal. Squamous cell carcinoma accounts for approximately 3-7% of bladder cancers; in Egypt, it accounts for 75% of all bladder cancers. A parasitic infection called schistosomiasis is common in Egypt, and infection with this parasite creates a chronic irritation in the bladder that predisposes the patient to squamous cell carcinoma after several years. Other conditions that can cause chronic irritation in the bladder, such as prolonged catheterization, can also predispose patients to squamous cell carcinoma. Squamous cell carcinoma does not metastasize to lymph nodes as much as uroepithelial carcinoma, but it can spread directly and penetrate the bladder to reach adjacent organs. Squamous cell carcinoma is more locally invasive and insensitive to radiotherapy, so it has a worse prognosis than urothelial carcinoma. Adenocarcinoma of the bladder is very rare, accounting for approximately 2% of all bladder cancers. This tumor is also associated with chronic irritation, is highly invasive, and has an even worse prognosis. Umbilical ureteral carcinoma is a specific type of bladder adenocarcinoma that originates in the outer layer of the bladder and invades the inner layer of the bladder due to a different origin than the bladder uroepithelium. It can metastasize to organs such as lymph nodes, liver, lungs and bones.
Causes of morbidity
The pathogenesis of bladder cancer is a multifactorial mixture, multi-gene involvement and multi-step formation process. The accumulation of abnormal genotypes coupled with the external environment eventually leads to the malignant phenotype. More than 80% of bladder cancer cases are associated with carcinogenic risk factors.
Smoking and occupational exposure to aromatic amines are clear risk factors for bladder cancer. The risk of bladder cancer in smokers is two to four times higher than that in nonsmokers, and the risk is related to the number of cigarettes smoked, the duration and the degree of inhalation. About half of all bladder cancers in Western countries are associated with smoking. The specific carcinogens in tobacco that cause bladder cancer have not been identified, and studies have shown that the presence of nitrosamines, 2-naphthylamines, and p-aminobiphenyl in smoke increases the urinary tryptophan metabolites in smokers. Certain occupations such as workers involved in the production of aromatic amines, dyes, rubber, aluminum, and leather, painters, and frequent users of dyes can increase the risk of bladder cancer, one of the main reasons being exposure to aromatic amines such as 2-naphthylamine and benzidine.
In addition to the two major factors mentioned above, other risk factors associated with the development of bladder cancer include.
1, carcinogens in drinking water, drinking tap water disinfected by chlorine and containing chlorinated by-products can increase the risk of bladder cancer; arsenic contamination in drinking water in Taiwan and Argentina, South America is also associated with increased risk of bladder cancer.
2, coffee, coffee drinkers have a higher risk of bladder cancer than non-drinkers, but there is no dose and time trend between the two, the results of epidemiological studies have ruled out a strong correlation between coffee and bladder cancer, but do not rule out the correlation between the two.
3.Urinary tract diseases, chronic stimulation of urethral epithelium or human metabolites increase the level of carcinogens in urine for a long time, which can make the urethral epithelium proliferate and then become cancerous, for example, squamous bladder cancer is related to Schistosoma egypti infection or bladder stones.
4.Drugs, large amounts of painkillers containing finasteride can increase the risk of bladder cancer, and the drug is currently off the market. The risk of bladder cancer can be increased several times in patients with lymphoma treated with cyclophosphamide, and the tumor is often infiltrative.
Artificial sweeteners, studies in the late 1970s reported that sweeteners could increase the risk of bladder cancer in men by 60%, but subsequent studies have failed to confirm the correlation, so currently the International Agency for Research on Cancer no longer includes sweeteners as carcinogens of human bladder cancer.
Family history, the risk of bladder cancer in the immediate family of bladder cancer patients is about twice that of those without a family history, and the risk is higher in the immediate family of young bladder cancer patients. In addition, some studies have shown that a high intake of fluids, vegetables and fruits can reduce the risk of bladder cancer. The main risk factors for bladder cancer in our population are smoking, occupational exposure to aromatic amines, family history of bladder cancer, alcohol and coffee consumption, and gender.
Types of pathology
Based on histogenesis, bladder tumors can be divided into epithelial and non-epithelial tumors. Epithelial tumors account for more than 95% of bladder tumors, with uroepithelial carcinoma predominating, accounting for 90%, followed by squamous carcinoma and adenocarcinoma, accounting for 3% to 7% and 2%, respectively. Other rare types include small cell carcinoma, carcinoid tumor, malignant melanoma, etc. Nearly 20% to 30% of uroepithelial carcinomas have regional squamous or adenoid metaplasia, which is an indicator of poor prognosis. There are three types of tumor growth according to the tumor growth pattern. One type of tumor is that the tumor and mesenchyme together form into papillary tumor or papillary carcinoma toward the bladder lumen, accounting for 70%; the other type is that the tumor grows infiltratively within the epithelium, forming invasive papillary tumor or invasive carcinoma, accounting for 25%; the non-papillary and non-invasive ones (carcinoma in situ) account for 5%. Tumor invasion of the bladder wall proceeds in three ways: tumor infiltration in the form of an encapsulated infiltrate in a dense mass, accounting for 70%; isolated projecting infiltrate, accounting for 27%; and infiltrative spread along lymphatic vessels within the muscle parallel or perpendicular to the mucosal surface, accounting for 3%. Since the actual invasion of the bladder wall is much more extensive than what is seen clinically, the tumor cannot be adequately resected and is prone to recurrence. Bladder tumors can occur in any part of the bladder, but the triangle and the vicinity of the ureteral orifice are the most frequent, accounting for more than half of the cases, followed by the lateral, posterior, apical, and anterior bladder walls. Malignant tumors of non-epithelial origin are mainly from mesenchymal tissue, accounting for less than 2% of all bladder tumors, such as rhabdomyosarcoma, smooth muscle sarcoma, lymphoma, and angiosarcoma.
The metastatic pathways of bladder cancer include hematologic, lymphatic, direct diffusion and implantation metastasis. Lymphatic metastasis occurs earliest and is the most common metastatic route, most often to closed-hole lymph nodes, followed by external iliac lymph nodes, presacral, internal iliac, common iliac and peri-cyst lymph nodes. Bloodstream metastasis often occurs in advanced stage patients, and the common metastatic organs are lung, liver, bone and adrenal gland. Bladder cancer can invade the bladder wall and directly invade the prostate, urethra, uterus, vagina, etc., and even directly invade the pelvic and abdominal walls. Implantation metastasis often occurs intraoperatively and is one of the reasons for the recurrence of incision and urethral stump after surgery.
Disease staging
Non-muscle invasive bladder cancer includes bladder cancer at Ta, T1 and Tis stages, also known as superficial bladder cancer. Muscle-invasive bladder cancer is bladder cancer at stage T2 or higher. Non-muscle invasive bladder cancer confined to the mucosa (Ta-Tis) and submucosa (T1) accounts for 75% to 85%, and muscle invasive bladder cancer accounts for 15% to 25%, with approximately 70% of the former being Ta stage lesions, 20% being T1 stage lesions, and 10% being Tis. carcinoma in situ (Tis), although it also belongs to non-muscle invasive bladder cancer, is It is generally poorly differentiated and is a highly malignant tumor with a higher chance of infiltrating into the muscular layer. Therefore, Tis should be distinguished from Ta and T1 stage bladder cancer.
Clinical manifestations
Disease symptoms
1. Hematuria: Painless carnal hematuria is the most common symptom, which can appear in more than 80% of patients, among which 17% have severe hematuria, but 15% may start with only microscopic hematuria. The hematuria is mostly complete, with intermittent episodes, but may also present as initial or final hematuria, and some patients may discharge blood clots or putrid tissue. The duration of hematuria and the amount of bleeding are related to the malignancy, stage, size, number, scope and morphology of the tumor, but not necessarily proportional. Carcinoma in situ often presents as microscopic hematuria, and hematuria in bladder umbilical ureter carcinoma can be insignificant. Bladder tumors of non-uroepithelial origin can have no hematuria if the lesion does not penetrate the bladder mucosa.
2.Bladder irritation symptoms: urinary frequency, urinary urgency and painful urination, accounting for about 10%, are related to widely distributed carcinoma in situ and invasive bladder cancer, especially when the lesion is located in the bladder triangle. Therefore, “cystitis” that cannot be cured for a long time should be alerted to the possibility of bladder cancer, especially in situ cancer.
3.Urinary flow obstruction symptoms: Large tumor, tumor in the bladder neck and blood clot blockage can cause poor urination or even urinary retention. Tumor infiltrating ureteral orifice can cause upper urinary tract obstruction, back pain, hydronephrosis and renal function damage.
4.Expression of advanced tumor: When advanced tumor invades tissues and organs around bladder or has pelvic lymph node metastasis, it will lead to pain in bladder area, urethrovaginal fistula, lower limb edema and other corresponding symptoms.
5.When the tumor is large, the mass can be found by vaginal or rectal double palpation, but this method is not accurate enough, plus double palpation may not be able to examine all parts of the bladder, and it is difficult to examine the poorly relaxed abdominal wall clearly.
Diagnostic differentiation
Most patients are examined because they suspect bladder cancer by visual or microscopic hematuria; others may have symptoms of urinary irritation, such as frequent, urgent, or painful urination; and some are found to have a mass inside the bladder due to positive urine exfoliation cytology or during CT examination because of low back pain.
Disease examination
Some doctors will do a rectal exam (and for female patients a pelvic exam) during the visit to determine if the bladder tumor is palpable and if it has invaded out of the bladder. Other common tests include.
1. urinary exfoliative cytology or other urine screening tests.
2, abdominal plain film and intravenous urography.
3. cystoscopy, which examines the inside of the bladder under direct vision, and the doctor may also do a biopsy, which is a grabbing of a few pieces of tissue suspected of being a tumor. The biopsy specimen will be sent to a pathologist who will diagnose the exact type of tumor and the depth of infiltration under the microscope, and further tests and treatment will be based on the biopsy results.
Regardless of the biopsy results, each patient must undergo an x-ray of the upper urinary tract, i.e. abdominal plain film and intravenous urography, to confirm that the kidneys and ureters are free of tumors, as these two parts are not visible under cystoscopy. You may also need to have your heart checked again, such as an electrocardiogram or echocardiogram, especially if your doctor decides to perform a biopsy under anesthesia or to do a tumor removal in the operating room. If there are abnormalities in these tests, you will need to be further evaluated by a cardiologist. In addition, there are some patients, especially those over 50 years of age or who smoke, who need a chest x-ray before receiving anesthesia. Finally, patients with suspected more advanced bladder cancer will require CT of the abdomen and pelvis to assess whether the tumor has invaded the bladder and to determine the presence of enlarged lymph nodes.
Differential diagnosis
The main symptom of bladder tumor is hematuria, so it should be differentiated from diseases that present with hematuria.
1.Upper urinary tract tumor: The hematuria of renal pelvis and ureteral uroepithelial tumor is similar to that of bladder tumor, both of which are painless throughout the whole process. The hematuria of bladder tumor may be accompanied by bladder irritation symptoms, sometimes affecting urination, and may be accompanied by blood clots or “rotting flesh”. However, kidney or ureteral tumors usually do not have bladder irritation symptoms, and the urinary clots are in the form of streaks and do not contain “rotting flesh”. The source of the blood in the urine can be distinguished by imaging and cystoscopy. It should be noted that some bladder tumors can be combined with upper urinary tract tumors.
2.Non-specific cystitis: Mostly female, hematuria occurs suddenly and is often accompanied by bladder irritation symptoms. Routine urine examination can see white blood cells and pus cells, and the diagnosis can be confirmed by bacterial growth found in the middle urine culture.
3.Urolithiasis: Generally, hematuria is light, and microscopic hematuria is common, which can be aggravated after labor, often accompanied by painful symptoms of urinary tract stones.
4, benign prostatic hyperplasia: painless carnal hematuria can also occur, often caused by ruptured bleeding from angry veins on the surface of the gland. As there are often symptoms of urinary obstruction, sometimes combined with infection and stones, the symptoms of hematuria are similar to those of bladder tumors, and the two can also coexist. However, in BPH, the hematuria is often transient and intermittent for months or years. Urine cytology, urinary tumor markers, and cystoscopy can help identify the difference.
5.Adenocystitis: clinical manifestations are very similar to bladder tumor, hematuria is usually not serious, and can be identified by cystoscopy and biopsy.
6, urinary tract tuberculosis: there are often general systemic manifestations of tuberculosis infection, with hypothermia, night sweats, wasting, hematuria end aggravation, often combined with bladder irritation symptoms, mainly urinary frequency. Mycobacterium tuberculosis appears in the urine, and the culture of Mycobacterium tuberculosis may be positive. Cystoscopy and biopsy can clarify the diagnosis.
7.Prostate cancer: Prostate cancer invading the urethra and bladder can appear hematuria, but often accompanied by difficult urination symptoms. The serum prostate-specific antigen (PSA) measurement, rectal ultrasound plus prostate biopsy can help diagnose prostate cancer, and sometimes cystoscopy is needed.
8. Radiation cystitis: Radiation cystitis can occur after radiation therapy for pelvic organ tumors, and the acute stage occurs a few days after radiation therapy, mainly manifesting as hematuria and bladder irritation symptoms. Cystoscopy and biopsy are usually needed to confirm the diagnosis.
9.Cervical cancer: When advanced cervical cancer invades the bladder, hematuria may appear, but usually there is vaginal bleeding first, and invasive cancer lesions can be seen on cystoscopy.
First aid measures
Conservative treatment includes indwelling catheter, continuous bladder irrigation and use of hemostatic drugs. If conservative treatment is ineffective and the patient develops increased heart rate, accelerated pulse rate, decreased blood pressure, dizziness, and false sweating, then immediate surgical hemostasis is required to flush out the clot through cystoscopy and stop the bleeding area in the bladder under cystoscopy. Patients sometimes need dialysis treatment as well as nephrostomy to release the obstruction depending on the situation when the upper urinary tract is obstructed due to clot filling in the bladder and post-renal anuria causing acute renal failure.
Surgical treatment
Surgery is the mainstay of treatment for limited-stage bladder cancer. Transurethral resection of bladder tumor (TURBT) is preferred for superficial (non-muscle-invasive) bladder cancer, and depending on the specific tumor stage and pathological classification, different bladder intravesical infusion chemotherapy or immunotherapy regimens are used postoperatively. . Radical cystectomy is preferred for muscle-infiltrating bladder cancer, and systemic chemotherapy can be selectively used preoperatively and postoperatively to improve the efficacy. For some patients with invasive bladder cancer who are unable to undergo radical surgery or have the desire to preserve the bladder, a bladder-preserving combination of endoluminal surgery, radiotherapy and systemic chemotherapy can be used. For metastatic bladder cancer (including lymph node metastasis), systemic chemotherapy is the only way to prolong patient’s survival. Surgery, radiotherapy or arterial interventions only provide palliative effects such as hemostasis and pain relief to improve patient’s quality of life.
TURBT is Transurethral Resection of Bladder Tumor (TURBT). It is a minimally invasive procedure with no incision on the body surface and patients recover quickly after surgery. It requires a special type of cystoscope capable of removing bladder tumors, called an electrosurgery. It is inserted through the same route as the cystoscope, through the external urethral opening. The mirror has an electrosurgical ring that is able to retract back and forth, so that when an electric current is passed through it, the ring cuts the tissue and also cauterizes the tissue to stop the bleeding. After the electrodes are removed, the excised pieces of tissue can be flushed out from inside the bladder. This tissue is then sent to a pathologist to determine under a microscope if it is cancerous. It usually takes several days for the pathologist to examine these tissues.
Transurethral laser treatment is similar to TURBT in that the laser vaporizes the tissue, has some penetration depth and coagulation, bleeds minimally, sometimes eliminates the need for a postoperative catheter, has a low incidence of intraoperative bladder perforation and has no closed nerve reflex. Commonly used lasers are Nd:YAG (neodymium-yttrium aluminum garnet) laser, Ho:YAG (holmium-yttrium aluminum garnet) laser. Photodynamic therapy (PDT) is to inject photosensitive substance through intravenous, which can selectively reach the lagging tumor, and to irradiate the bladder mucosa with special wavelength of light through cystoscope into optical fiber, which can produce direct destructive effect on the tumor, as well as destroy blood vessels and produce immune effect, especially for in situ cancer and recurrent tumor. However, the above treatment modalities still do not surpass TURBT in terms of overall effectiveness.
Radical cystectomy for bladder cancer is radical cystectomy, which is an operation to remove the entire bladder, and it is divided into 3 steps: 1) removing the diseased bladder; 2) clearing the lymph nodes; 3) creating a new urinary storage sac. For male patients, radical bladder cancer surgery usually requires the removal of the prostate gland, the seminal vesicle gland and part of the vas deferens; for female patients, the uterus, cervix and part of the vagina are removed, and the ovaries can be selectively preserved. In women, the uterus, cervix and part of the vagina are removed.
The body will still produce urine after cystectomy. Therefore, the best approach is to replace the original bladder with an artificial one. However, so far, all artificial materials soaked in urine for a long time form stones and cannot really be used in patients. The only way is to use the patient’s own organ. Currently urologists have successfully used the small intestine, large intestine and stomach to replace the bladder. For most patients who have not received radiation therapy, a small section of the ileum is the best replacement organ for the bladder. Because the large intestine is relatively unaffected by radiation therapy, patients who have received prior radiation therapy can choose a segment of the large intestine as a replacement.
Currently, most urologists will allow patients undergoing radical bladder cancer surgery to choose one of the following three methods of urinary diversion
1. Ileal cystectomy: The simplest method of urinary diversion. It uses a section of ileum as the output tract to drain urine through the skin to the outside of the body and then collects the urine through a stoma bag. The ureter is anastomosed at the proximal end of the ileal output tract, while the distal end of the ileal output tract is sutured to the skin of the abdominal wall to form a papilla. The nipple is covered with a stoma bag to collect the outflow of urine and the patient only needs to empty the bag every 4-6 hours at regular intervals. Patients wearing an ostomy bag are not affected in any way by wearing clothes and no one can tell you are wearing an ostomy bag. After a short period of adaptation, almost all patients can live a normal life as before.
2. Controlled urinary diversion: It also uses a section of ileum instead of the bladder, the difference is that with this method, the patient does not have to wear an ostomy bag, and the urine formed in the body is first diverted into a storage sac made of ileum, which is connected to the skin of the abdominal wall through a long, thin tube. The output tract made of intestinal tubing has an opening in the skin surface of the abdominal wall the size of an eraser. Patients undergoing this procedure only need to have a catheter inserted through the papillae of the skin of the output tract several times a day to drain urine from the urinary bladder. This procedure is a bit more complicated than the first method, and patients need to carry a catheter with them. However, it also has the obvious advantage that the patient does not have to wear an ostomy bag. It is important to note that if the storage bladder does not drain the urine in time, then too much urine may accumulate and even trigger the rupture of the storage bladder.
3.Neobladder surgery: It is the most complicated one, and this surgery can basically return the patient to the normal urinary function before surgery. Like the above two procedures, it replaces the bladder with a section of ileum, but the length of the intestinal tube is longer, almost 50 cm – 60 cm. As with controlled urinary diversion, the surgeon first uses the intestinal tube to make a urinary bladder capable of storing urine, and then implants the ureters on either side of the bladder. Next, the capsule is not attached to the skin of the abdominal wall through the output tract, but is anastomosed directly to the urethral stump, which allows the patient to urinate through the original urethra as before the bladder was removed. The advantages of this procedure are clear, but not all patients are suitable for this approach. The new bladder, unlike the original normal bladder, does not have a forcing muscle and the patient must learn to contract the abdominal wall muscles to increase the pressure in the new bladder and urinate. The muscles controlling urination in the new bladder are weak, so some patients may experience urinary incontinence after surgery, although they can mostly return to normal after 2-3 months through pelvic floor muscle lifting exercises.
Partial cystectomy is suitable for limited muscle invasive bladder cancer, and the tumor location is favorable for a certain range of resection, and the possibility of in situ cancer should be excluded before surgery. Some non-muscle invasive bladder cancers that are not suitable for TURBT in terms of size and location, tumors within the bladder diverticulum, and tumors located around the ureteral opening are also amenable to partial cystectomy. However, this procedure is not a radical surgery, does not achieve optimal tumor control, and may lead to postoperative tumor incisional implantation, and is now less commonly used, with less than 5% of patients suitable for this procedure. For patients with invasive bladder cancer, radical cystectomy should be chosen as long as it is tolerated.
Combination therapy
Bladder-preserving combination therapy is any treatment that attempts to preserve the bladder of patients with muscle-invasive bladder cancer and spare them from total cystectomy. Bladder preservation is treated in a variety of ways, the vast majority of which are based on a combination of chemotherapy and radiation combined with transurethral resection of the bladder tumor. In the past, researchers have attempted radiation or chemotherapy alone, but the results have been unsatisfactory. Combining radiotherapy, chemotherapy and surgery can save patients from having their entire bladder removed. Despite the success of current research, the standard treatment for muscle-invasive bladder cancer is still radical cystectomy, or radical cystectomy. If the lesion cannot be completely removed, chemoradiotherapy may be considered postoperatively. Only about 40% of patients who opt for bladder-preserving treatment ultimately succeed in preserving their bladders.
Drug treatment
Urothelial carcinoma of the bladder is more sensitive to chemotherapy. Early stage non-muscle invasive bladder cancer can be treated with intrathecal chemotherapy or immunotherapy after transurethral surgery to reduce the recurrence rate after surgery and to slow tumor progression. For muscle-invasive bladder cancer in the limited stage, chemotherapy is used before and after radical surgery to achieve downstaging, improve surgical resection rate and prolong survival. In addition, systemic chemotherapy in the comprehensive treatment of preserved bladder can not only kill micro metastases, but also increase the sensitivity of radiotherapy. In advanced metastatic bladder cancer, systemic chemotherapy is the only treatment that can prolong patient’s survival. Therefore, chemotherapy has an indispensable place in the treatment of patients with bladder cancer of different stages and grades.
Intravesical bladder chemotherapy and immunotherapy
After TURBT for non-muscle invasive bladder cancer, about 50% to 70% of patients recur, and 10% to 15% of them have tumor progression to the muscular layer. Intracavitary bladder chemotherapy or immunotherapy through urethral catheter insertion can eliminate residual tumors after TURBT, prevent recurrence and delay tumor progression, and also have therapeutic effects on tumors that cannot be completely resected due to extensive lesions, such as carcinoma in situ.
Currently, there are two main types of drugs for intracavitary bladder infusion: immunomodulators and chemotherapeutic drugs. The main immunomodulators are BCG (BCG), in addition to interleukin-2 (IL-2), interferon (IFN), tumor necrosis factor (TNF), LAK cells, and tumor infiltrating lymphocytes (TIL). The main chemotherapeutic drugs are mitomycin, piribicin, epi-amycin, mitoxantrone, etc. The treatment course is routinely set to start bladder perfusion 1 week after surgery, once a week for 8-12 times, while BCG needs to be started at least 2 weeks after surgery because of the side effects. 3 months later, if the cystoscopy is normal, it will be changed to once every 2 weeks for 6 times, and then to once a month for 1-2 years after the cystoscopy is normal.
Systemic chemotherapy
Chemotherapy is most commonly used for metastatic bladder cancer or locally advanced bladder cancer that cannot be removed by surgery. About 20% of bladder cancers dis