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Treatment methods include surgery, chemotherapy, radiation therapy and medication.
Surgery is the most common treatment for cancer of the urethra. One of the following types of surgery may be done: Open excision, Electro-resection with flash, Laser surgery, Cystourethrectomy, Cystoprostatectomy, Anterior body cavity, or Incomplete or basic penectomy surgery.
Chemotherapy is sometimes used to destroy urethral cancer cells. It is a systemic urethral cancer treatment (i.e., destroys urethral cancer cells throughout the body) that is administered orally or intravenously. Medications are often used in combination to destroy urethral cancer that has metastasized. Commonly used drugs include cisplatin, vincristine, and methotrexate.
Side effects include anemia (causing fatigue, weakness), nausea and vomiting, loss of appetite, hair loss, mouth sores, increased risk for infection, shortness of breath, or excessive bleeding and bruising.
Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope, which in that case is called a resectoscope. The procedure is called transurethral resection of bladder tumor—TURBT—and serves primarily for pathological staging. In case of non-muscle invasive bladder cancer the TURBT is in itself the treatment, but in case of muscle invasive cancer, the procedure is insufficient for final treatment.
Immunotherapy by intravesicular delivery of Bacillus Calmette–Guérin (BCG) is also used to treat and prevent the recurrence of superficial tumors. BCG is a vaccine against tuberculosis that is prepared from attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans. BCG immunotherapy is effective in up to 2/3 of the cases at this stage, and in randomized trials has been shown to be superior to standard chemotherapy. The mechanism by which BCG prevents recurrence is unknown, but the presence of bacteria in the bladder may trigger a localized immune reaction which clears residual cancer cells.
Patients whose tumors recurred after treatment with BCG are more difficult to treat. Many physicians recommend cystectomy for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU) and the American Urological Association (AUA) However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort. Device assisted chemotherapy is one such group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology - electromotive drug administration (EMDA) – uses an electric current to enhance drug absorption after surgical removal of the tumor. Another technology, thermotherapy, uses radio-frequency energy to directly heat the bladder wall, which together with chemotherapy shows a synergistic effect, enhancing each other's capacity to kill tumor cells. This technology was studied by different investigators.
Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy) and the urinary stream is diverted into an isolated bowel loop (called an ileal conduit or Urostomy). In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.
A combination of radiation and chemotherapy in conjunction with transurethral (endoscopic) bladder tumor resection can also be used to treat invasive disease. Review of available large data series on this so-called trimodality therapy has indicated similar long-term cancer specific survival rates, with improved overall quality of life versus patients undergoing radical cystectomy with urinary reconstruction. These patients are usually highly selected and do not have multi-focal disease or carcinoma in-situ, which is associated with a higher rate of recurrence, progression, and death from bladder cancer versus patients who undergo radical cystectomy.
Photodynamic diagnosis may improve surgical outcome on bladder cancer.
For muscle invasive urothelial urinary bladder cancer there are a number of treatment options. Gold standard is radical cystectomy as mentioned. In males this usually includes also the removal of the prostate and in females; ovaries, uterus and parts of the vagina.
First-line chemotherapy regimens for advanced or metastatic TCC consists of gemcitabine and cisplatin) (GC) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC).
Taxanes or vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy).
Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.
In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival.
Transitional cell carcinoma (TCC) can be very difficult to treat. Treatment for localized stage TCC is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) or a few weeks after the surgery as a six dose regimen.
Localized/early TCC can also be treated with infusions of BCG into the bladder. These are given weekly for either 6 weeks (induction course) or 3 weeks (maintenance/booster dose). Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to the BCG causing severe intolerance and a possible reduction in bladder volume due to scarring.
In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.
Because most bladder cancers are invasive into the bladder wall, surgical removal is usually not possible. The majority of transitional cell carcinomas are treated with either traditional chemotherapy or nonsteroidal anti-inflammatory drugs.
Surgery is the mainstay of treatment for clinically localized disease. In feasible cases, a partial cystectomy with "en-bloc" resection of the median umbilical ligament and umbilicus can achieve good results. In progressed stages, radiotherapy seems not to lead to sufficient response rates. However, chemotherapy regimes containing 5-FU (and Cisplatin) have been described to be useful in these cases. In recent years, targeted therapies have been demonstrated to be useful in reports of single cases. These agents included Sunitinib, Gefitinib, Bevacizumab and Cetuximab.
Endoscopic injection involves applying a gel around the ureteral opening to create a valve function and stop urine from flowing back up the ureter. The gel consists of two types of sugar-based molecules called dextranomer and hyaluronic acid. Trade names for this combination include Deflux and Zuidex. Both constituents are well-known from previous uses in medicine. They are also biocompatible, which means that they do not cause significant reactions within the body. In fact, hyaluronic acid is produced and found naturally within the body.
Medical treatment entails low dose antibiotic prophylaxis until resolution of VUR occurs. Antibiotics are administered nightly at half the normal therapeutic dose. The specific antibiotics used differ with the age of the patient and include:
- Amoxicillin or ampicillin – infants younger than 6 weeks
- Trimethoprim-sulfamethoxazole (co-trimoxazole) – 6 weeks to 2 months
After 2 months the following antibiotics are suitable:
- Nitrofurantoin {5–7 mg/kg/24hrs}
- Nalidixic acid
- Bactrim
- Trimethoprim
- Cephalosporins
Urine cultures are performed 3 monthly to exclude breakthrough infection. Annual radiological investigations are likewise indicated. Good perineal hygiene, and timed and double voiding are also important aspects of medical treatment. Bladder dysfunction is treated with the administration of anticholinergics.
Increasing fluid intake can facilitate the passage of small bladder stones. However, larger stones may require other methods of treatment. Fragmentation of bladder stones can be achieved by use of a cystoscope which is inserted into the bladder. The urologist visualizes the stone and uses ultrasonic energy or laser lithotripsy to cause fragmentation of the stones into small pieces, which are then flushed out of the bladder. This procedure requires anesthesia and may require admission to a hospital. Complications of this treatment include infection and damage to the bladder. Some stones are too large even for cystoscopic treatment and may require open cystotomy, in which an incision is made in the bladder and the stones are removed manually.
The best way to prevent bladder stones is to drink plenty of liquids. Juices containing citrates are thought to reduce the risk of stone formation. A study published in the "Clinical Journal of the American Society of Nephrology" indicate orange juice is more effective at preventing stone formation than other citrus juices. Men who have difficulty with urination due to prostatic hypertrophy should seek treatment. In those with benign prostatic hyperplasia urinating in a sitting position appears to improve bladder emptying which might decrease bladder stones in this group.
The primary treatment for urethral diverticulum is surgical. The surgery is conducted transvaginally, usually when there is no acute inflammation to better aid dissection of the delicate tissues.
PUNLMPs are treated like non-invasive low grade papillary urothelial carcinomas, excision and regular follow-up cystoscopies.
There is a rare occurrence of a pelvic recurrence of a low-grade superficial TCC after cystectomy. Delayed presentation with recurrent low-grade urothelial carcinoma is an unusual entity and potential mechanism of traumatic implantation should be considered. Characteristically low-grade tumors are resistant to systemic chemotherapy and curative-intent surgical resection of the tumor should be considered.
Prognosis is highly variable and dependent upon a multitude of factors. Reoccurrence does occur. Treatment is determined on a case-by-case basis.
Diet modification is often recommended as a first-line method of self-treatment for interstitial cystitis, though rigorous controlled studies examining the impact diet has on interstitial cystitis signs and symptoms are currently lacking. Individuals with interstitial cystitis often experience an increase in symptoms when they consume certain foods and beverages. Avoidance of these potential trigger foods and beverages such as caffeine-containing beverages including coffee, tea, and soda, alcoholic beverages, chocolate, citrus fruits, hot peppers, and artificial sweeteners may be helpful in alleviating symptoms. Diet triggers vary between individuals with IC; the best way for a person to discover his or her own triggers is to use an elimination diet. Sensitivity to trigger foods may be reduced if calcium glycerophosphate and/or sodium bicarbonate is consumed. The foundation of therapy is a modification of diet to help patients avoid those foods which can further irritate the damaged bladder wall.
The mechanism by which dietary modification benefits people with IC is unclear. Integration of neural signals from pelvic organs may mediate the effects of diet on symptoms of IC.
Bladder instillation of medication is one of the main forms of treatment of interstitial cystitis, but evidence for its effectiveness is currently limited. Advantages of this treatment approach include direct contact of the medication with the bladder and low systemic side effects due to poor absorption of the medication. Single medications or a mixture of medications are commonly used in bladder instillation preparations. DMSO is the only approved bladder instillation for IC/BPS yet it is much less frequently used in urology clinics.
A 50% solution of DMSO had the potential to create irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long-term use of DMSO is questionable, as its mechanism of action is not fully understood though DMSO is thought to inhibit mast cells and may have anti-inflammatory, muscle-relaxing, and analgesic effects. Other agents used for bladder instillations to treat interstitial cystitis include: heparin, lidocaine, chondroitin sulfate, hyaluronic acid, pentosan polysulfate, oxybutynin, and botulinum toxin A. Preliminary evidence suggests these agents are efficacious in reducing symptoms of interstitial cystitis, but further study with larger, randomized, controlled clinical trials is needed.
The treatment for tonsil carcinoma includes the following methods:
Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.
Left untreated, urethral diverticulum can cause significant morbidity (sickness).
During surgery, there is a risk for complications due to the highly vascular nature of the tissue. The urethral sphincters and its smooth muscle, as well as the neck of the bladder, can be injured regardless of the surgical approach. Other complications from surgery can include urinary incontinence, stress incontinence, a urethrovaginal fistula, or recurrent diverticula. Horseshoe-shaped diverticula and diverticula that completely surround the urethra are both associated with worse outcomes, as are those located close to the bladder, and large (over 3–4 cm) diverticula.
Treatment options range from no treatment for a mild cystocele to surgery for a more extensive cystocele. If a cystocele is not bothersome, the clinician may only recommend avoiding heavy lifting or straining that could cause the cystocele to worsen. If symptoms are moderately bothersome, the doctor may recommend a pessary, a device placed in the vagina to hold the bladder in place. Treatment can consist of a combination of non-surgical and surgical management. Treatment choice is also related to age, desire to have children, severity of impairment, desire to continue sexual intercourse and other diseases that a woman may have.
Cervical cancers can recur with symptoms of vaginal bleeding and/or discharge, pelvic pain, pain in the back and legs, leg swelling (edema), chronic cough and weight loss. It can recur in the vagina, pelvis, lymph nodes, lung, or liver. “If radiation was not given previously, recurrences that are confined to the pelvis may be treated with external beam radiation with chemotherapy and intracavitary or interstitial radiation therapy. If radiation therapy was already given, the only option is the removal of the vagina, uterus, and the bladder and/or rectum with the creation of an artificial bladder-a pelvic exenteration. The five-year survival rate after a pelvic exenteration is about 50 percent.” (womenscancercenter.com) Chemotherapy is useful in women with recurrent tumors which cannot be removed surgically or in women with metastatic diseases. Chances of survival of chemotherapy, if diagnosed in early stage, is grater than 50%.
The most important criterion for improving long-term prognosis is success of the initial closure. If a patient requires more than one closure their chance of continence drops off precipitously with each additional closure - at just two closures the chance of voiding continence is just 17%.
Even with successful surgery, people may have long-term complications. Some of the most common include:
- Vesicoureteral reflux
- Bladder spasm
- Bladder calculus
- Urinary tract infections
A number of antimuscarinic drugs (e.g., darifenacin, hyoscyamine, oxybutynin, tolterodine, solifenacin, trospium, fesoterodine) are frequently used to treat overactive bladder. β3 adrenergic receptor agonists (e.g., mirabegron), may be used, as well. They are, however, a second line treatment due to the risk of side effects.
Few people get complete relief with medications and all medications are no more than moderately effective.
A typical person with overactive bladder may urinate 12 times per day. Medication may reduce this number by 2-3 and reduce urinary incontinence events by 1-2 per day.
Various devices (Urgent PC Neuromodulation System) may also be used. Botulinum toxin A (Botox) is approved by the Food and Drug Administration in adults with neurological conditions, including multiple sclerosis and spinal cord injury. Botulinum Toxin A injections into the bladder wall can suppress involuntary bladder contractions by blocking nerve signals and may be effective for up to 9 months. The growing knowledge of pathophysiology of overactive bladder fuelled a huge amount of basic and clinical research in this field of pharmacotherapy. A surgical intervention involves the enlargement of the bladder using bowel tissues, although generally used as a last resort. This procedure can greatly enlarge urine volume in the bladder.
OAB may be treated with electrical stimulation, which aims to reduce the contractions of the muscle that tenses around the bladder and causes urine to pass out of it. There are invasive and non-invasive electrical stimulation options. Non-invasive options include the introduction of a probe into the vagina or anus, or the insertion of an electrical probe into a nerve near the ankle with a fine needle. These non-invasive options appear to reduce symptoms while they are in use, and are better than no treatment, or treatment with drugs, or pelvic floor muscle treatment, but the quality of evidence is low. It is unknown which electrical stimulation option works best. Also, it is unknown whether the benefits last after treatment stops.