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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.
Treatment methods include surgery, chemotherapy, radiation therapy and medication.
Selective α-blockers are the most common choice for initial therapy. They include alfuzosin, doxazosin, silodosin, tamsulosin, and terazosin. They have a small to moderate benefit. All five are equally effective but have slightly different side effect profiles. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction, headaches, nasal congestion, and weakness.
Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH. Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong.
The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in patients were more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets.
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.
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.
When in acute urinary retention, treatment of the urethral stricture or diversion is an emergency. Options include:
- Urethral dilatation and catheter placement. This can be performed in the Emergency Department, a practitioner's office or an operating room. The advantage of this approach is that the urethra may remain patent for a period of time after the dilation, though long-term success rates are low.
- Insertion of a suprapubic catheter with catheter drainage system. This procedure is performed in an Operating Room, Emergency Department or practitioner's office. The advantage of this approach is that it does not disrupt the scar and interfere with future definitive surgery.
The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery, and the emergence of fertility-sparing therapy in developed nations. Because cervical cancers are radiosensitive, radiation may be used in all stages where surgical options do not exist. Surgical intervention may have better outcomes than radiological approaches. In addition, chemotherapy can be used to treat cervical cancer, and has been found to be more effective than radiation alone.
Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). For stage IA2, the lymph nodes are removed, as well. Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy.
If a cone biopsy does not produce clear margins (findings on biopsy showing that the tumor is surrounded by cancer free tissue, suggesting all of the tumor is removed), one more possible treatment option for women who want to preserve their fertility is a trachelectomy. This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care, as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the woman is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the woman has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1b cancers and some stage 1a cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation.
A radical trachelectomy can be performed abdominally or vaginally and opinions are conflicting as to which is better. A radical abdominal trachelectomy with lymphadenectomy usually only requires a two- to three-day hospital stay, and most women recover very quickly (about six weeks). Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage. A wait of at least one year is generally recommended before attempting to become pregnant after surgery. Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. Yet, women are recommended to practice vigilant prevention and follow-up care including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive.
Early stages (IB1 and IIA less than 4 cm) can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Women treated with surgery who have high-risk features found on pathologic examination are given radiation therapy with or without chemotherapy to reduce the risk of relapse.
Larger early-stage tumors (IB2 and IIA more than 4 cm) may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy (which then usually requires adjuvant radiation therapy), or cisplatin chemotherapy followed by hysterectomy. When cisplatin is present, it is thought to be the most active single agent in periodic diseases. Such addition of platinum-based chemotherapy to chemoradiation seems not only to improve survival but also reduces risk of recurrence in women with early stage cervical cancer (IA2-IIA).
Advanced-stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin, for women with late-stage (IVB) cervical cancer treatment. Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects.
For surgery to be curative, the entire cancer must be removed with no cancer found at the margins of the removed tissue on examination under a microscope. This procedure is known as exenteration.
Most hormone dependent cancers become resistant to treatment after one to three years and resume growth despite hormone therapy. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term castration-resistant has replaced "hormone refractory" because while they are no longer responsive to castration treatment (reduction of available androgen/testosterone/DHT by chemical or surgical means), these cancers still show reliance upon hormones for androgen receptor activation.
The cancer chemotherapic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. A second-line chemotherapy treatment is cabazitaxel. A combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC.
The immunotherapy treatment with sipuleucel-T in CRPC increases survival by 4 months. The second line hormonal therapy abiraterone increases survival by 4.6 months when compared to placebo. Enzalutamide is another second line hormonal agent with a 5-month survival advantage over placebo. Both abiraterone and enzalutamide are currently being tested in clinical trials in those with CRPC who have not previously received chemotherapy.
Only a subset of people respond to androgen signaling blocking drugs and certain cells with characteristics resembling stem cells remain unaffected. Therefore, the desire to improve outcome of people with CRPC has resulted in the claims of increasing doses further or combination therapy with synergistic androgen signaling blocking agents. But even these combination will not affect stem-like cells that do not exhibit androgen signaling. It is possible that for further advances, a combination of androgen signaling blocking agent with stem-like cell directed differentiation therapy drug would prove ideal.
Treatment for kidney cancer depends on the type and stage of the disease. Surgery is the most common treatment as kidney cancer does not often respond to chemotherapy and radiotherapy. Surgical complexity can be estimated by the RENAL Nephrometry Scoring System. If the cancer has not spread it will usually be removed by surgery. In some cases this involves removing the whole kidney however most tumors are amenable to partial removal to eradicate the tumor and preserve the remaining normal portion of the kidney. Surgery is not always possible – for example the patient may have other medical conditions that prevent it, or the cancer may have spread around the body and doctors may not be able to remove it. There is currently no evidence that body-wide medical therapy after surgery where there is no known residual disease, that is, adjuvant therapy, helps to improve survival in kidney cancer. If the cancer cannot be treated with surgery other techniques such as freezing the tumour or treating it with high temperatures may be used. However these are not yet used as standard treatments for kidney cancer.
Other treatment options include biological therapies such as everolimus, torisel, nexavar, sutent, and axitinib, the use of immunotherapy including interferon and interleukin-2. Immunotherapy is successful in 10 to 15% of people. Sunitinib is the current standard of care in the adjuvant setting along with pazopanib; these treatments are often followed by everolimus, axitinib, and sorafenib. Immune checkpoint inhibitors are also in trials for kidney cancer, and some have gained approval for medical use.
In the second line setting, nivolumab demonstrated an overall survival advantage in advanced clear renal cell carcinoma over everolimus in 2015 and was approved by the FDA. Cabozantinib also demonstrated an overall survival benefit over everolimus and was approved by the FDA as a second-line treatment in 2016. Lenvatinib in combination with everolimus was approved in 2016 for patients who have had exactly one prior line of angiogenic therapy.
In Wilms' tumor, chemotherapy, radiotherapy and surgery are the accepted treatments, depending on the stage of the disease when it is diagnosed.
Adjuvant chemotherapy is a recent innovation, consisting of some combination of paclitaxel (or other taxanes like docetaxel), doxorubicin (and other anthracyclines), and platins (particularly cisplatin and carboplatin). Adjuvant chemotherapy has been found to increase survival in stage III and IV cancer more than added radiotherapy. Mutations in mismatch repair genes, like those found in Lynch syndrome, can lead to resistance against platins, meaning that chemotherapy with platins is ineffective in people with these mutations. Side effects of chemotherapy are common. These include hair loss, low neutrophil levels in the blood, and gastrointestinal problems.
In cases where surgery is not indicated, palliative chemotherapy is an option; higher-dose chemotherapy is associated with longer survival. Palliative chemotherapy, particularly using capecitabine and gemcitabine, is also often used to treat recurrent endometrial cancer.
There are a number of possible additional therapies. Surgery can be followed by radiation therapy and/or chemotherapy in cases of high-risk or high-grade cancers. This is called adjuvant therapy.
Permanent stents are often metal coils, which are inserted into the male urethra. The braided mesh is designed to expand radially, applying constant gentle pressure to hold open the sections of the urethra that obstruct the flow of urine. The open, diamond-shape cell design of the stent allows the stent to eventually become embedded in the urethra, thus minimizing the risk for encrustation and migration. Permanent stents are used to relieve urinary obstructions secondary to benign prostatic hyperplasia (BPH), recurrent bulbar urethral stricture (RBUS), or detrusor external sphincter dyssynergia (DESD). The main motive for removal of permanent stents is worsening of symptoms even with device fitted. Other reasons have been migration, clot retention, hematuria, and urinary retention. The only FDA approved permanent stent is the Urolume. Usually, permanent stents are used only for men who are unwilling or unable to take medications or who are reluctant or unable to have surgery. Most doctors do not consider permanent stents a viable long-term treatment for most men.
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.
Drugs used after and in addition to surgery are called adjuvant therapy. Chemotherapy or other types of therapy prior to surgery are called neoadjuvant therapy. Aspirin may reduce mortality from breast cancer.
There are currently three main groups of medications used for adjuvant breast cancer treatment: hormone-blocking agents, chemotherapy, and monoclonal antibodies.
Hormone blocking therapy
Chemotherapy
Monoclonal antibodies
Palliative care is medical care which focuses on treatment of symptoms of serious illness, like cancer, and improving quality of life. One of the goals of treatment in palliative care is symptom control rather than a cure of the underlying cancer. Pain is common in metastatic prostate cancer, and cancer pain related to bone metastases can be treated with bisphosphonates, medications such as opioids, and palliative radiation therapy to known metastases. Spinal cord compression can occur with metastases to the spine and can be treated with steroids, surgery, or radiation therapy. Other symptoms that can be addressed through palliative care include fatigue, delirium, lymphedema in the scrotum or penis, nausea, vomiting, and weight loss.
In breast cancer survivors, it is recommended to first consider non-hormonal options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators (SERMs) for osteoporosis, and vaginal estrogen for local symptoms. Observational studies of systemic hormone replacement therapy after breast cancer are generally reassuring. If hormone replacement is necessary after breast cancer, estrogen-only therapy or estrogen therapy with an intrauterine device with progestogen may be safer options than combined systemic therapy.
A permanent urethral stent was approved for use in men with bulbar urethral strictures in 1996, but was recently removed from the market.
A temporary thermoexpandable urethral stent (Memotherm) is available in Europe, but is not currently approved for use in the United States.
If suspected antenatally, a consultation with a paediatric surgeon/ paediatric urologist maybe indicated to evaluate the risk and consider treatment options.
Treatment is by endoscopic valve ablation. Fetal surgery is a high risk procedure reserved for cases with severe oligohydramnios, to try to limit the associated lung underdevelopment, or pulmonary hypoplasia, that is seen at birth in these patients. The risks of fetal surgery are significant and include limb entrapment, abdominal injury, and fetal or maternal death. Specific procedures for "in utero" intervention include infusions of amniotic fluid, serial bladder aspiration, and creating a connection between the amniotic sac and the fetal bladder, or vesicoamniotic shunt.
There are three specific endoscopic treatments of posterior urethral valves:
- Vesicostomy followed by valve ablation - a stoma, or hole, is made in the urinary bladder, also known as "low diversion", after which the valve is ablated and the stoma is closed.
- Pyelostomy followed by valve ablation - stoma is made in the pelvis of the kidney as a slightly "high diversion", after which the valve is ablated and the stoma is closed
- Primary (transurethral) valve ablation - the valve is removed through the urethra without creation of a stoma
The standard treatment is primary (transurethral) ablation of the valves. Urinary diversion is used in selected cases, and its benefit is disputed.
Following surgery, the follow-up in patients with posterior urethral valve syndrome is long term, and often requires a multidisciplinary effort between paediatric surgeons/ paediatric urologists, pulmonologists, neonatologists, radiologists and the family of the patient. Care must be taken to promote proper bladder compliance and renal function, as well as to monitor and treat the significant lung underdevelopment that can accompany the disorder. Definitive treatment may also be indicated for the vesico-ureteral reflux.
Vitamin A is associated with a lower risk as are vitamin B12, vitamin C, vitamin E, and beta-Carotene.
Laser therapy uses high-intensity light to treat cancer by shrinking or destroying tumors or precancerous growths. Lasers are most commonly used to treat superficial cancers that are on the surface of the body or the lining of internal organs. It is used to treat basal cell skin cancer and the very early stages of others like cervical, penile, vaginal, vulvar, and non-small cell lung cancer. It is often combined with other treatments, such as surgery, chemotherapy, or radiation therapy. Laser-induced interstitial thermotherapy (LITT), or interstitial laser photocoagulation, uses lasers to treat some cancers using hyperthermia, which uses heat to shrink tumors by damaging or killing cancer cells. Laser are more precise than surgery and cause less damage, pain, bleeding, swelling, and scarring. A disadvantage is surgeons must have specialized training. It may be more expensive than other treatments.
Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patient's health and preferences. The treatment intent may or may not be curative.
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.
Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patient's quality of life and might possibly lead to renal failure with risk of death.
Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days.
The first step in the treatment of HC should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.. Hyperbaric oxygen (HBO2) therapy has been proven to be effective in treating radiation-induced hemorrhagic cystitis.
In a small minority of cases of urethral syndrome, treatment with antibiotics is effective, which indicates that in some cases it may be caused by bacterial infection which does not show up in either urinalysis or urine culture. For chronic urethral syndrome, a long term, low-dose antibiotic treatment is given on a continuous basis or after intercourse each time if intercourse appears to trigger symptoms.
As low oestrogen may also be considered a source for urethral syndrome, hormone replacement therapy, and oral contraceptive pill (birth-control pills) containing oestrogen are also used to treat the symptoms of this condition in women.