Bladder and Kidney Cancer

From WiserWiki

[edit] Bladder and Kidney Cancer

Michael J. Droller

[edit] BLADDER CANCER

Bladder cancer generally refers to malignancy of the transitional cell epithelium, which comprises more than 90% of all forms of urothelial cancer.Squamous cell cancer is seen in approximately 5% of cases, whereas adenocarcinoma is diagnosed in 2% to 3%.Approximately 54,000 new cases of bladder cancer are diagnosed annually.Men are affected three to four times as often as women.At least 75% of new cases are categorized as superficial (see Tumor Staging) and are usually amenable to conservative treatment.Whereas 75% of these may recur, only 10% to 15% may become progressive or life-threatening.In contrast, 25% of bladder cancers when initially diagnosed are deeply invasive of the bladder wall.These are potentially life-threatening and require prompt aggressive surgical treatment for there to be any chance of success.

[edit] Epidemiology

In 1895, Rehn suggested an association between urothelial cancer and exposure to aniline dye, based on his observations that several factory workers had developed bladder cancer.Subsequent studies correlated exposure to aromatic amines and to related substances in other industries (e.g., rubber manufacturing, hairdressing) with an increased risk for urothelial cancer.This led to the institution of various guidelines and regulations designed to minimize these risks.

Probably the greatest and most clearly characterized associative risk for urothelial cancer and carcinogen exposure has been that observed with cigarette smoking.Cigarette smoking produces a threefold to fourfold increase in the risk for developing bladder cancer.Correlations have been made between the intensity of exposure (number of cigarettes smoked, degree of inhalation) and the increased risk of developing bladder cancer.Unfortunately, these have not received widespread publicity, and public awareness of this needs to be increased.

Correlations between the use of artificial sweeteners, coffee intake, and tryptophan (as a health food additive) and the risk for development of bladder cancer have also been suggested.However, these associations have been called into question and remain unproven.Urinary infections with certain organisms capable of converting urinary metabolites to carcinogens have also been proposed as risk factors.

Genetic risk factors for urothelial cancer have not yet been clearly identified.Although recent studies have associatedseveral specific genetic changes with the development of particular types of bladder cancer, they have not clarified any genetic predisposition to the development of urothelial cancer.On the other hand, a growing body of evidence suggests the existence of populations with distinct urothelial enzymatic profiles that may be associated with an increased or decreased likelihood of cancer development, depending on whether carcinogens are activated or detoxified by the urothelium.Whether this may be associated further with specific types of cancer development is unknown.

[edit] Presenting Signs and Symptoms

The most common presenting symptom in patients with bladder cancer is gross painless hematuria.Such hematuria is characteristically observed throughout the urinary stream.If hematuria in men occurs only at the beginning or end of urination, it is more likely associated with a prostatic problem.However, urothelial cancer still needs to be excluded.Often, hematuria may not be visualized grossly but may be seen only on urinalysis.Here too, the possible presence of urothelial cancer must be evaluated, since the amount of hematuria is not an indication of whether a transitional cell cancer may be present.

Occasionally, patients complain of an increasing sense of urgency or discomfort while urinating.Although these symptoms are often indistinguishable from those associated with acute bacterial cystitis, their persistence in the absence of a positive culture should prompt an evaluation for bladder cancer.

The most common presenting sign of bladder cancer is microscopic hematuria.In many instances, the patient may not have seen blood in the urine.However, there is no association between the amount of blood and the likelihood that a bladder cancer is present.Therefore the occurrence of blood in the urine, at least the first time, should always prompt an evaluation to diagnose or exclude bladder cancer.At the same time, microscopic hematuria is common in the general population in the absence of any diagnosable abnormality.There is no consensus regarding the frequency with which such hematuria should be evaluated.However, it does not seem unreasonable to consider a screening evaluation with urinary cytology and kidney and bladder ultrasound (see Diagnostic Evaluation) every 2 to 3 years for such individuals above the age of 50 years and perhaps more frequently for those with risk factors (cigarette smoking, other environmental exposures).

[edit] Diagnostic Evaluation

Standard examinations to evaluate gross or microscopic hematuria when urothelial cancer is suspected include intravenous pyelography, cystoscopy, and urinary cytology.Upper tract imaging is necessary both to exclude the possibility of upper tract disease (renal cell carcinoma, urothelial cancer, kidney stones) and to determine whether upper tract obstruction by a bladder tumor is present.Sonography may be used instead of pyelography as an initial screening tool but does not permit as full a visualization of the entire collecting system.Retrograde pyelography may be performed if a patient is allergic to intravenous contrast.This permits both direct visualization of the bladder by cystoscopy and imaging of the entire upper tract.

Cystoscopy is used to examine the urothelium that lines both the urethra and the bladder.Abnormal areas can be characterized, and the type of tumor that may be present can be defined.Although the cystogram phase of the intravenous pyelogram can be occasionally used to visualize a bladder tumor, it is generally of insufficient sensitivity to definitively exclude the presence of either a small or a flattened bladder cancer (i.e., carcinoma in situ).

A voided urine sample should be sent for cytologic assessment.Catheterized specimens should be avoided at first, since instrumentation may produce false-positive readings.On the other hand, barbotage (bladder wash) specimens can be obtained to provide a more cellular sample that can facilitate analysis using cytologic testing or flow cytometry.More recently, urine nuclear matrix protein-22 (NMP-22) (see Superficial Disease) has been used at initial diagnosis and in follow-up for patients with bladder cancer.

The sine qua non of bladder cancer diagnosis is histologic examination of tissue removed by transurethral biopsy of the bladder epithelium and resection of the bladder tumor.Biopsies should be obtained of any areas in the bladder that appear abnormal to assess the urothelium for the presence of epithelial dysplasia or carcinoma in situ (see Tumor Staging).Bladder tumors should be fully resected so that the tumor configuration can be characterized, the grade of cells that make up the tumor can be determined, and the depth of tumor penetration into the bladder wall can be measured.

[edit] Tumor Staging

A staging system has evolved based on correlations between the depth to which a particular bladder cancer has penetrated the bladder wall and its potential behavior.Bladder cancers have traditionally been classified as either “superficial” or “deeply invasive.” Superficial tumors are either confined to the mucosal layer or have penetrated through the epithelial basement membrane into the underlying connective tissue (lamina propria).Deeply invasive tumors have extended into the superficial or deep muscle layer or extended even more deeply into the perivesical fat.An increased depth of penetration has been correlated with a greater likelihood of metastatic disease.

The most common form of bladder cancer is a papillary, mucosally confined tumor that generally appears as a solitary lesion resembling a clustering of raspberry-shaped fronds on a fibrovascular stalk.Even when multiple tumors are seen, they tend to be of low or moderate grade.These tumors may recur in 75% of instances after the initial lesion has been resected.However, less than 3% of such tumor diatheses are associated with the later development of progressive disease.Though occasionally multiple, these lesions are rarely associated with either atypia or frank carcinoma in situ either at their margin or at other sites in the bladder.Such tumors rarely present a life-threatening risk.

In contrast, superficial tumors that have infiltrated the epithelial basement membrane and underlying lamina propria have been associated with subsequent progression in as many as 30% of instances.These tumors are often of a higher grade than their mucosally confined counterparts and are often seen in association with atypia or flat carcinoma in situ at their margin or at other sites in the bladder.Although they may appear endoscopically to have a papillary configuration (as do the mucosally confined lesions), they may also have a moresolid or nodular appearance, especially when part of a more diffuse malignant diathesis.

There are two types of muscle-infiltrative bladder cancers: those that are invasive of only the superficial muscle and those that penetrate more deeply either into the deep muscle or perivesical fat.The former have been characterized as invading in a broad front and involve the bladder wall vasculature and lymphatics in approximately one third of instances.They may have a less progressive course than their more deeply infiltrative counterparts, which present with a more nodular configuration, appear to penetrate the bladder wall in a more tentacular pattern, and may involve the bladder wall vasculature and lymphatics in two thirds of cases.

The more superficial muscle-infiltrative cancers have been associated with a 40% to 65% 5-year survival rate, and a variety of bladder-conserving approaches have been applied with some success in treating these types of tumors (see Treatment).The more deeply muscle-infiltrative cancers have generally been associated with a 10% to 15% 5-year survival rate despite aggressive surgical therapies; 50% of these patients have metastatic disease within 2 years of diagnosis despite their having undergone prompt cystectomy.These forms of disease may therefore already be systemic at the time of the initial clinical diagnosis.Although deeply invasive tumors have undoubtedly proceeded through progressive phases of infiltration into the bladder wall, only 10% to 15% clinically arise from earlier superficial cancers.The majority have already reached an advanced stage at their earliest clinical presentation.

Carcinoma in situ is an entity that consists of neoplastic cells that are confined to and may undermine the urothelial layer, are high grade, and generally do not produce papillary lesions.In as many as 30% of instances, cancer cells in these lesions infiltrate microscopically into the lamina propria.These cancer diatheses may ultimately demonstrate aggressive infiltration of the bladder wall at varying intervals after initial diagnosis, especially when carcinoma in situ is found in the context of papillary tumors that have penetrated the lamina propria.Nodular or solid tumors may arise directly in areas of carcinoma in situ and infiltrate the bladder wall before any evidence of cancer is clinically evident.Whether aggressive treatments need to be applied in all of these situations or whether some of the tumors can be controlled with conservative measures requires further study.

Endoscopically, areas of carcinoma in situ may appear reddened, velvety, and “inflamed,” and therefore this condition is sometimes misdiagnosed as cystitis.While carcinoma in situ is often accompanied by irritative symptoms, superficial or deeply infiltrative cancers are generally asymptomatic.The presence of carcinoma in situ generally indicates a more diffuse tumor diathesis with an often more aggressive potential behavior.Urinary cytologic testing may be particularly useful in suggesting its existence.

In addition to stage, the grade of a bladder cancer is also useful in determining the prognosis of a particular tumor diathesis.Grade is determined by the degree of differentiation of cells that make up the tumor.Cells in well-differentiated (grade 1) tumors maintain a normal appearance with regularly shaped nuclei and a normal nuclear/cytoplasmic ratio.Although the number of cell layers in such tumors is often greater than in the normal epithelium, the normal polarity of these cell layers is generally maintained.Cells in higher-grade tumors (grades 2 and 3) have a more irregular nuclear shape, clumped chromatin, prominent nuclei, and a very high nuclear/cytoplasmic ratio.Cell polarity is generally lost.The higher the grade, the more deeply invasive a particular bladder cancer is likely to be.The exception is carcinoma in situ, which is generally composed of high-grade cells that have remained confined to the epithelium without grossly penetrating the bladder wall.Nonetheless their biologic potential for aggressive behavior is high, and the cells in carcinoma in situ may progress to deep muscle invasion over variable intervals.

[edit] Treatment

[edit] Superficial Disease.

Transurethral resection, which is used to obtain tissue for pathologic diagnosis, is generally successful in fully excising a tumor when it is the type that is mucosally confined and low grade.Although recurrence is frequently seen (50% to 75% of instances), repeat transurethral resection will again restore a normal epithelium.Transurethral resection has little morbidity, and in this setting, there is minimal risk for progressive disease to occur.When rapid recurrence is seen or a multiplicity of tumors does not permit effective resection, instillation of chemotherapeutic agents may facilitate elimination of disease.

Transurethral resection is also an effective treatment for the superficial papillary tumors that may have infiltrated the lamina propria.However, if extensive infiltration has occurred, transurethral resection may not remove all of the cancer.It is therefore common to instill adjunctive intravesical agents to eradicate any tumor cells remaining after resection.This may be especially appropriate in situations when lamina propria–infiltrative tumors are high grade and are associated with carcinoma in situ elsewhere in the urothelium.

The most common intravesical agents used as adjuncts to transurethral resection for the treatment of superficial disease are thiotepa, mitomycin-C, and doxorubicin, all chemotherapeutic agents, and bacillus Calmette-Guérin, an immunotherapeutic agent.The former have been most effective in preventing the recurrence of mucosally confined papillary transitional cell tumors.The latter has been most effective in preventing the recurrence of carcinoma in situ and in the adjunctive treatment of high-grade lamina propria–invasive tumors.Morbidities associated with these treatments have generally been rare.Continued surveillance with cystoscopy and urinary cytologic testing is necessary for detecting treatment failure early so that intervention can be more aggressive.

The greatest risk associated with high-grade lamina propria–infiltrative cancers, especially when accompanied by carcinoma in situ, is the possibility of rapid progression.Radical cystectomy may be important to consider in these instances, since many of these cancers, once they have progressed to the bladder wall musculature, are found to be metastatic and beyond the realm of regional cure.

Interest has grown in the identification of substances that might serve as markers to detect tumor recurrence or indicate the possibility of tumor progression.Despite the promise of initial reports on a variety of substances for which the urine has been assayed (bladder tumor antigen [BTA] [BTA Stat or BTA Trak test]; NMP-22; telomerase; fibrin degradation products [Acudiff]; ImmunoCyt; hyaluronidase) validation of their clinical usefulness and reliability remains to be determined.

[edit] Muscle-infiltrative Cancer.

The current standard of treatment for muscle-infiltrative bladder cancer is radical cystectomy.The 5-year survival rates, or “cures,” have been reported to be as high as 70% to 80% when the muscle-infiltrative cancers are more superficial.The 5-year survival rates for deeply infiltrative cancers have been only 10% to 15%.Although occasional long-term survival rates have been described in patients with cancers that have involved one or two pelvic lymph nodes microscopically, gross involvement of the pelvic lymph nodes or extension of disease beyond the pelvic lymphatics have in most instances not been associated with cure by radical surgery.

Occasionally, bladder cancers that have invaded only the superficial musculature have been amenable to treatment by transurethral resection or by partial cystectomy.Such patients, however, need to be selected carefully, and these approaches are generally reserved for patients who are not candidates for cystectomy and who may require palliation rather than cure.Those with deep muscle invasion who are not candidates for cystectomy may undergo deep transurethral resection and adjunctive radiation therapy and chemotherapy.Although 5-year estimated survival rates with these approaches have been suggested to approximate those seen with cystectomy and control of regional disease has been satisfactory, such patients seem best served by cystectomy for long-term disease-free survival.

Additional treatments have been applied to enhance response rates.These have included preoperative radiation therapy, preoperative chemotherapy, and adjunctive chemotherapy.Although occasional long-term responders have been seen, these have largely comprised anecdotal events, and predictably effective regimens remain to be defined.In essence, deeply infiltrative bladder cancer in most instances is likely to represent a systemic disease.No predictably effective systemic chemotherapeutic regimen has yet been discovered.

Recent studies have suggested that certain molecular markers (p53, Rb) may be associated in muscle-invasive tumors (and some lamina propria–invasive tumors) with the likelihood of progression.Further studies are needed to validate these relationships before they can be applied routinely in clinical management.

Because removal of the bladder remains the standard therapy for deeply infiltrative bladder cancer, urinary diversion is an important component of treatment of patients with this condition.Major advances have been made in using segments of bowel to create continent reservoirs and even to attach these reservoirs to the urethra.Generally, the ileum, or segments of colon, has been used in creating these reservoirs.Although no reservoir is perfect in replacing the normally functioning bladder, this imaginative use has led to dramatic improvement in the quality of life in both men and women undergoing cystectomy.

[edit] Summary

Much remains to be learned about the biology and natural history of bladder cancer.Increased use of molecular analysis is providing information about the different pathways of bladder cancer development and may ultimately offer the opportunity to apply distinct treatments for specific types of bladder cancer based on molecular profile.In the future it may be possible to reverse the carcinogenic progress by applying knowledge of the molecular events that underlie the development of various types of bladder tumor to change their course through the restoration of the normal genetic complement.In addition, more effective systemic therapies may be identified that will not only treat regional bladder cancer but also deal effectively with sites of metastasis.

[edit] KIDNEY CANCER

Kidney cancer, or renal cell carcinoma, is a malignancy thought to arise from the proximal tubule cells of the kidney.It is most commonly seen in men and women between 40 and 60 years of age, affecting men more commonly than women (1.5:2).It is estimated that 28,500 new cases of renal cell cancer will be diagnosed in the United States in 2000 (17,000 males; 10,500 females), and that 11,000 will die of their disease (6500 males; 4500 females).

Little is known about the carcinogenic process or epidemiologic factors that account for the development of renal cell carcinoma.Associations have been suggested between exposures to heavy metals such as mercury and cadmium and the development of kidney malignancies.Similar associations between cigarette smoking or environmental pollutants and renal cancer have not been described.Patients on chronic dialysis who develop multicystic disease are at risk for the development of renal cell cancers.The mechanism underlying this phenomenon is not understood.Some forms of renal cancer have a genetic basis.A hereditary basis in the predisposition to develop renal cell cancer in the majority of cases, however, remains to be determined.

[edit] Presenting Signs and Symptoms

The triad of hematuria, flank pain, and palpable abdominal mass that has traditionally been associated with the presence of renal cell cancer is now rarely seen.A patient may have only gross or microscopic hematuria without other symptoms.Patients with sudden-onset gross hematuria should always be evaluated for renal cell cancer.

Renal colic may occur if a blood clot obstructs the ureter.Rarely is an abdominal mass palpated unless the cancer has grown very large.Renal cell cancer is most often diagnosed when imaging studies are performed in the evaluation of asymptomatic microscopic hematuria.In addition, it is becoming more common for a renal mass to be diagnosed coincidentally when imaging studies are performed for unrelated symptoms (see Diagnostic Studies).

Physical examination rarely elicits any abnormality associated with renal cell cancer.The ability to palpate a renal mass is limited by both the size of the mass and the location of each kidney under the rib cage.Flank tenderness is rarely demonstrated.Occasionally, the development or enlargement of a scrotal varicocele is observed.However, this may be seen only if the cancer has involved the renal vein on the left or has extended into the vena cava on the right.

Paraneoplastic syndromes occasionally accompany the development of renal cell cancer.Fevers of unknown origin, anemia, and polycythemia have been reported in approximately 1% to 3% of renal cell cancers.

[edit] Diagnostic Studies

Imaging studies are critical in documenting the presence of a renal mass.Previously, the most commonly used diagnostic imaging study was intravenous pyelography.This has now been largely replaced by sonography.Sonography avoids the use of intravenous contrast materials to which patients maybe allergic and permits distinctions to be made between masses that are solid and those that are cystic.In general, renal cell cancers are solid masses.It is rare to see a renal cell cancer involving a simple renal cyst.This may not be the case, however, if a cyst is multiseptated, is thick-walled and irregular, or contains irregular calcifications in its wall.

The presence of a solid mass or complex cyst on ultrasound generally indicates the need for a computed tomography (CT) scan.This should be performed both with and without intravenous contrast to determine both the character of the lesion and the presence of enhancement with contrast.Enhancement generally indicates a malignancy, and this appearance on CT scan is virtually pathognomonic of a renal cell cancer.Some mass lesions such as oncocytoma may be indistinguishable radiographically from a renal cell cancer.Others such as angiomyolipoma can be distinguished easily because of the characteristic low density of fat.

CT and ultrasound studies are also useful in determining whether the renal vein and vena cava have tumor thrombi.Lymph nodes at the renal hilum and around the great vessels may also be assessed for increased size and the possible presence of metastatic disease.Magnetic resonance imaging (MRI), nuclear scanning, and arteriography rarely aid in the evaluation of renal cell cancer, although the latter may occasionally be useful in planning the surgical approach when a partial nephrectomy is being considered.

It has become more common to diagnose kidney cancer as an incidental finding on sonograms or CT scans that have been performed for symptoms (back or abdominal pain) that are entirely unrelated to the presence of the cancer.Tumors that are diagnosed under these circumstances are often far smaller than those that have been seen previously when imaging studies were performed for signs or symptoms associated directly with these mass lesions.

Once a diagnosis of renal cell cancer has been made, a nuclear bone scan and a pulmonary CT scan are generally performed to exclude metastases to these sites.

[edit] Staging of Kidney Cancer

A staging system for kidney cancer has evolved on the basis of correlations that have been observed between extent of the malignancy, likelihood of metastatic disease, and amenability to cure by surgical excision.Smaller lesions (those smaller than 3 cm in diameter) have generally been called adenomas to distinguish them from renal cell cancers on the assumption that the likelihood of these lesions metastasizing is small.Recent studies have disputed the validity of these suggestions.

Given the increased frequency with which small solid masses are now diagnosed, such observations must be considered in the management of these cancers.Smaller cancers are more likely to be confined within the renal capsule and appear to have the best prognosis.Once a cancer has extended beyond the renal capsule, survival for 5 years is far less likely.Kidneys that have extended beyond Gerota's fascia have an even poorer likelihood of cure.Such tumors often involve adjacent structures or have metastasized to adjacent lymph nodes and distant sites.Renal cell cancers occasionally extend tumor thrombi into the renal vein and vena cava.The prognosis for these patients is generally far better than it is for those who have involvement of the regional lymph nodes.

[edit] Treatment

Surgical excision is the only treatment that is predictably effective for kidney cancers.“Radical” nephrectomy involves removal of the kidney and the surrounding fat contained within Gerota's fascia.The adrenal gland, often contained in its own compartment within Gerota's fascia, may be removed with the kidney.Hilar lymph nodes are often also removed, but this serves largely a diagnostic purpose rather than one that enhances therapy.Many urologists now favor leaving the ipsilateral adrenal gland if CT scan or MRI demonstrates it to be normal.

Some have suggested that simple enucleation or segmental nephrectomy may be the appropriate approach for smaller renal masses.Earlier studies in which such procedures were performed in the setting of a solitary kidney, bilaterally poorly functioning kidneys, or multiple cancers in both kidneys (such that preservation of renal tissue was an important objective in managing the patient) documented that renal-sparing approaches were as successful in achieving equivalent 5-year survival rates for low-stage, low-grade disease as was radical nephrectomy.

The likelihood that microscopic disease is present at multiple sites in the affected kidney is only 10% to 15%.The risk for developing recurrent tumor in the original cancer bed may be only as great as 10%, depending on the size and conformation of the original cancer.Although each of these considerations has prompted the conclusion that radical nephrectomy should remain the standard approach in most patients with renal cell cancer (especially since the likelihood of cancer development in the contralateral kidney is small), the smaller size at which kidney cancers are diagnosed, in association with the increasing rate of their coincidental discovery, has prompted the suggestion that partial nephrectomy should be considered more often, especially when clinical conditions justify attempts to preserve normal renal tissues, even in the setting of bilaterally normal functioning kidneys.Because there may be increased risks associated with partial nephrectomy and because most patients experience little consequence from removal of the entire kidney, radical nephrectomy remains the standard approach to treatment.However, the use of partial nephrectomy as more acceptable standard therapy is growing, especially when the tumor is smaller than 4 cm in diameter.

Surgery is not an effective therapeutic modality in the setting of metastatic disease.Although nephrectomy has been associated anecdotally with the resolution of metastatic lesions in 1% to 2% of cases, documentation has for the most part been inadequate, and the outcome has been poor.Angioinfarction before surgery, presumably to stimulate an immune response that might lead to resolution of metastatic deposits, has also not been found to be an effective approach.

In the setting of a concurrent solitary metastasis, removal of both the primary kidney cancer and the metastatic lesion has generally been followed by the appearance of multiple additional metastases within a year of surgery.On the other hand, when a solitary metastasis has appeared after nephrectomy has been performed, its removal has occasionally been associated with long-term survival.This may reflect the occasionally unpredictable biology of the primary disease rather than an expression of surgical efficacy.

Radical nephrectomy in the setting of metastatic disease has largely been reserved for palliation.Flank pain seen inassociation with a large renal mass, uncontrollable hemorrhage (despite attempts at angioinfarction), and unremitting fever or hypercalcemia have been used as indications for radical nephrectomy even though metastatic disease may be present.Such patients ultimately die from their disease, often with limited survival times.

Radiation therapy has not been effective in the treatment of renal cell cancer.Currently, no single chemotherapeutic agent or combination of agents has been found to be effective in producing durable responses in renal cell cancer.The use of progestational agents (e.g., Megase) has produced only anecdotal responses.

Isolated reports of “spontaneous” remissions of metastatic lesions have led to suggestions that the immune response may play a role in the control of renal cell cancer.A variety of attempts have therefore been made to recruit immune response mechanisms in the design of novel approaches in the treatment of this problem.

Vaccines, cytokines, lymphokines, and immune effector cells have been used to treat patients with metastatic renal cell cancer.These approaches have at best produced mixed results with response rates ranging between 15% and 20%.These results have generally been of very limited durability.

Most recently, the efficacy of interferons, interleukin-2 (IL-2), lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TIL cells), and various combinations of these, either alone or together with cytotoxic chemotherapeutic agents, has been investigated.Although some have been reported to produce variable remissions of metastatic diseases at several sites, these responses have generally not been durable, and survival rates have remained largely unimproved.High-dose IL-2 remains the only FDA-approved treatment for metastatic renal cancer.It has a 5% complete response rate.

The unpredictable natural history of renal cell cancer, even when metastatic, has made interpretation of these results difficult and controversial.Because of this and because of the morbidity associated with many of these treatments, these approaches cannot be depended on to predictably palliate the disease or prolong survival rates in patients with metastatic renal cell cancer, and therefore they remain in the realm of investigation.

[edit] ADDITIONAL READINGS

• RM Bubowski: Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer 1997; 80:1198.
• MA Ghoneim,et al.: Radical cystectomy for carcinoma of the bladder: critical evaluation of the results in 1,026 cases. J Urol 1997; 158:393.
• V Krishnamurthi, AC Novick,et al.: Nephron sparing surgery in patients with metastatic renal cell carcinoma. J Urol 1996; 156:36.
• C Lundholm,et al.: A randomized prospective study comparing long-term intravesical instillations of mitomycin C and BCG in patients with superficial bladder carcinoma. J Urol 1996; 156:372.
• AC Novick,et al.: Conservative surgery for renal cell carcinoma: a single center experience with 100 patients. J Urol 1989; 141:835.
• SA Rosenberg,et al.: Experience with the use of high dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg 1989; 210:474.
• WU Shipley, AL Zietman,et al.: Invasive bladder cancer: treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation. J Radiat Oncol Biol Phys 1997; 39:937.