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Bladder cancer
Table of Contents
- GENERAL INFORMATION
- CELLULAR CLASSIFICATION
- TREATMENT OPTION OVERVIEW
- STAGE 0 BLADDER CANCER
Tis or Ta, N0, M0
- STAGE I BLADDER CANCER
T1, N0, M0
- STAGE II BLADDER CANCER
T2a, N0, M0 or T2b, N0, M0
- STAGE III BLADDER CANCER
T3a, N0, M0 or T3b, N0, M0 or
T4a, N0, M0
- STAGE IV BLADDER CANCER
T4b, N0, M0, any T, N1-N3, M0,
or any T, any N, M1
- RECURRENT BLADDER CANCER
Approximately 70% to 80% of patients with newly
diagnosed bladder cancer will present with superficial bladder tumors (i.e.,
stage Ta, Tis, or T1). Those who do present with superficial, noninvasive
bladder cancer are often curable, and those with deeply invasive disease can
sometimes be cured by surgery, irradiation, or a combination of modalities
that include chemotherapy. Studies have demonstrated that some patients with
distant metastases have achieved long-term complete response following
treatment with combination chemotherapy regimens. There are clinical trials
suitable for patients with all stages of bladder cancer; whenever possible,
patients should be included in clinical trials designed to improve on standard
therapy.
The major prognostic factors in carcinoma of
the bladder are the depth of invasion into the bladder wall and the degree of
differentiation of the tumor. Most superficial tumors are well differentiated.
Patients in whom superficial tumors are less differentiated, large, multiple,
or associated with carcinoma in situ (Tis) in other areas of the bladder
mucosa are at greatest risk for recurrence and the development of invasive
cancer. Such patients may be considered to have the entire urothelial surface
at risk for the development of cancer. Tis may exist for variable durations.
Adverse prognostic features associated with a greater risk of disease
progression include the presence of multiple aneuploid cell lines, nuclear p53
overexpression, and expression of the Lewis-x blood group antigen.[1-4]
Patients with Tis who have a complete response to bacillus Calmette-Guerin
have approximately a 20% risk of disease progression at 5 years; patients with
incomplete response have approximately a 95% risk of disease progression.[1]
Several treatment methods (i.e., transurethral surgery, intravesical
medications, and cystectomy) have been used in the management of patients with
superficial tumors, and each method can be associated with 5-year survival in
55% to 80% of patients treated.[1,2,5]
Invasive tumors that are confined to the
bladder muscle on pathologic staging after radical cystectomy are associated
with approximately a 75% 5-year progression-free survival rate. Patients with
more deeply invasive tumors (which are also usually less well differentiated)
experience 5-year survival rates of 20% to 40% following radical cystectomy.
When the patient presents with locally extensive tumor that invades pelvic
viscera or with metastases to lymph nodes or distant sites, 5-year survival is
uncommon, but considerable symptomatic palliation can still be achieved.[6]
Expression of the tumor suppressor gene p53
also has been associated with an adverse prognosis for patients with invasive
bladder cancer. A retrospective study of 243 patients treated by radical
cystectomy found that the presence of nuclear p53 was an independent predictor
for recurrence among patients with stage T1, T2, or T3 tumors.[7]
Another retrospective study showed p53 expression to be of prognostic value
when considered with stage or labeling index.[8]
References:
- Hudson MA, Herr HW: Carcinoma
in situ of the bladder. Journal of Urology 153(3, Part 1): 564-572, 1995.
- Torti FM, Lum BL: The biology
and treatment of superficial bladder cancer. Journal of Clinical Oncology
2(5): 505-531, 1984.
- Lacombe L, Dalbagni G, Zhang
ZF, et al: Overexpression of p53 protein in a high-risk population of
patients with superficial bladder cancer before and after bacillus
Calmette-Guerin therapy: correlation to clinical outcome. Journal of
Clinical Oncology 14(10): 2646-2652, 1996.
- Stein JP, Grossfeld GD,
Ginsberg DA, et al.: Prognostic markers in bladder cancer: a contemporary
review of the literature. Journal of Urology 160(3 pt 1): 645-659, 1998.
- Witjes JA, Caris CT, Mungan
NA, et al.: Results of a randomized phase III trial of sequential
intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus
mitomycin C alone in patients with superficial bladder cancer. Journal of
Urology 160(5): 1668-1672, 1998.
- Thrasher JB, Crawford ED:
Current management of invasive and metastatic transitional cell carcinoma
of the bladder. Journal of Urology 149(5): 957-972, 1993.
- Esrig D, Elmajian D, Groshen
S, et al.: Accumulation of nuclear p53 and tumor progression in bladder
cancer. New England Journal of Medicine 331(19): 1259-1264, 1994.
- Lipponen PK: Over-expression
of p53 nuclear oncoprotein in transitional-cell bladder cancer and its
prognostic value. International Journal of Cancer 53: 365-370, 1993.
More than 90% of bladder carcinomas are
transitional cell carcinomas derived from the uroepithelium. About 6% to 8%
are squamous cell carcinomas, and 2% are adenocarcinomas.[1]
Adenocarcinomas may be either of urachal origin or of nonurachal origin; the
latter type is generally thought to arise from metaplasia of chronically
irritated transitional epithelium.[2] Pathologic grade,
which is based on cellular atypia, nuclear abnormalities, and the number of
mitotic figures, is of great prognostic importance.
References:
- Mostofi FK, Davis CJ,
Sesterhenn IA: Pathology of tumors of the urinary tract. In: Skinner DG,
Lieskovsky G, Eds.: Diagnosis and Management of Genitourinary Cancer.
Philadelphia, WB Saunders, 1988, pp 83-117.
- Wilson TG, Pritchett TR,
Lieskovsky G, et al.: Primary adenocarcinoma of bladder. Urology 38(3):
223-226, 1991.
TREATMENT OPTION OVERVIEW
Prolonged survival in most patients with
superficial cancers is achieved by transurethral resection (TUR) with or
without intravesical chemotherapy. However, cure is not possible for the
majority of patients with deeply invasive tumors and for most patients with
regional or distant metastases. In North America, the standard treatment of
patients with invasive bladder cancers is radical cystectomy and urinary
diversion. Other treatment approaches include TUR and segmental resection with
or without radiation therapy, combined chemotherapy-radiation therapy, or
either followed by salvage cystectomy, when needed, for local failure.
Therefore, many newly diagnosed bladder cancer patients are candidates for
participation in a clinical trial. Clinical trials include studies of
chemoprevention of superficial disease, adjuvant chemotherapy for advanced
local or regional disease, preservation of bladder function with
chemotherapy-radiation therapy, and development of more effective systemic
therapy and methods of palliation for metastatic tumors.[1-6]
Reconstructive techniques that fashion
low-pressure storage reservoirs from the reconfigured small and large bowel
eliminate the need for external drainage devices and, in some male patients,
allow voiding per urethra. These techniques are designed to improve the
quality of life for patients who require cystectomy.[7]
The designations in PDQ that treatments
are "standard" or "under clinical evaluation" are not to
be used as a basis for reimbursement determinations.
References:
- Thrasher JB, Crawford ED:
Current management of invasive and metastatic transitional cell carcinoma
of the bladder. Journal of Urology 149(5): 957-972, 1993.
- Housset M, Maulard C, Chretien
Y, et al.: Combined radiation and chemotherapy for invasive
transitional-cell carcinoma of the bladder: a prospective study. Journal
of Clinical Oncology 11(11): 2150-2157, 1993.
- Kachnic LA, Kaufman DS, Heney
NM, et al.: Bladder preservation by combined modality therapy for invasive
bladder cancer. Journal of Clinical Oncology 15(3): 1022-1029, 1997.
- Lamm DL, Riggs DR, Shriver JS,
et al.: Megadose vitamins in bladder cancer: a double-blind clinical
trial. Journal of Urology 151(1): 21-26, 1994.
- Raghavan D, Huben R:
Management of bladder cancer. Current Problems in Cancer 19(1): 1-64,
1995.
- Sauer R, Birkenhake S, Kuhn R,
et al.: Efficacy of radiochemotherapy with platin derivatives compared to
radiotherapy alone in organ-sparing treatment of bladder cancer.
International Journal of Radiation Oncology, Biology, Physics 40(1):
121-127, 1998.
- Hautmann RE, Miller K, Steiner
U, et al.: The ileal neobladder: 6 years of experience with more than 200
patients. Journal of Urology 150(1): 40-45, 1993.
Tis or Ta, N0, M0
Stage 0 bladder tumors can be cured by a
variety of forms of treatment, even though the tendency for new tumor
formation is high. In a series of patients with Ta or T1 tumors who were
followed for a minimum of 20 years or until death, the risk of bladder cancer
recurrence following initial resection was 80%.[1] Patients
at greatest risk of recurrent disease are those whose tumors are large, poorly
differentiated, multiple, or associated with nuclear p53 overexpression. In
addition, patients with carcinoma in situ (Tis) or dysplasia of grossly
uninvolved bladder epithelium are at greater risk of recurrence and
progression.[1-3]
Transurethral resection (TUR) and fulguration
are the most common and conservative forms of management. Patients who require
more aggressive forms of treatment are those with extensive multifocal
recurrent disease and/or other unfavorable prognostic features. Segmental
cystectomy is applicable to only a small minority of patients because of the
tendency of bladder carcinoma to involve multiple regions of the bladder
mucosa and to occur in areas that cannot be segmentally resected. In series of
patients who were followed for more than 10 years after management of
superficial tumors, the risk of developing a transitional cell carcinoma of
the upper urinary tract has been reported in the 2% to 13% range.[1,4]
Intravesical therapy with thiotepa, mitomycin,
doxorubicin, or bacillus Calmette-Guerin (BCG) is most often used in patients
with multiple tumors or recurrent tumors or as a prophylactic measure in
high-risk patients after TUR. Administration of intravesical BCG plus
subcutaneous BCG following TUR was compared with TUR alone in patients with Ta
and T1 lesions. Treatment with BCG delayed progression to muscle-invasive
and/or metastatic disease, improved bladder preservation, and decreased the
risk of death from bladder cancer.[4,5]
Another randomized study of patients with superficial bladder cancer also
reports a decrease in tumor recurrence in patients given intravesical and
percutaneous BCG compared with controls.[6] Two
nonconsecutive 6-week treatment courses with BCG may be necessary to obtain
optimal response.[7] Patients with a T1 tumor at the
3-month evaluation after a 6-week course of BCG and patients with Tis that
persists after a second 6-week BCG course have a high likelihood of developing
muscle-invasive disease and should be considered for cystectomy.[7-9]
A randomized study that compared intravesical and subcutaneous BCG with
intravesical doxorubicin showed better response rates and freedom from
recurrence with the BCG regimen for recurrent papillary tumors as well as for
Tis.[10] Although BCG may not prolong overall survival for
Tis disease, it appears to afford complete response rates of about 70%,
thereby decreasing the need for salvage cystectomy.[11]
Studies show that intravesical BCG delays tumor recurrence and tumor
progression.[5,12] Preliminary results
from a prospective randomized trial suggest that maintenance BCG, when given
to patients who are disease-free after a 6-week induction course, improves
survival.[13] One study that compared mitomycin with
interferon alfa-2b showed an improved outcome with mitomycin, although
interferon was better tolerated.[14]
Treatment options:
Standard:
- 1. TUR with fulguration.[15]
2. TUR with fulguration followed by
intravesical BCG. BCG is the treatment of choice for Tis.[4,6,8,11,12]
3. TUR with fulguration followed by
intravesical chemotherapy.[2,10,15]
4. Segmental cystectomy (rarely
indicated).[15]
5. Radical cystectomy in selected patients
with extensive or refractory superficial tumor.[15,16]
Under clinical evaluation:
- 1. Photodynamic therapy after intravenous
hematoporphyrin derivative appears capable of completely eradicating
tumors in one half of the treated patients who were in a small study with
minimal follow-up.[17] Further evaluation of this
technique is needed.
2. Intravesical interferon alfa-2a has
shown activity against papillary tumors and Tis both as primary treatment
and as secondary treatment after failure of other intravesical agents.[18]
3. Use of chemoprevention agents after
treatment to prevent recurrence.[19]
References:
- Holmang S, Hedelin H,
Anderstrom C, et al.: The relationship among multiple recurrences,
progression and prognosis of patients with stages TA and T1 transitional
cell cancer of the bladder followed for at least 20 years. Journal of
Urology 153(6): 1823-1827, 1995.
- Igawa M, Urakami S, Shirakawa
H, et al.: Intravesical instillation of epirubicin: effect on tumour
recurrence in patients with dysplastic epithelium after transurethral
resection of superficial bladder tumour. British Journal of Urology 77(3):
358-362, 1996.
- Lacombe L, Dalbagni G, Zhang
ZF, et al: Overexpression of p53 protein in a high-risk population of
patients with superficial bladder cancer before and after bacillus
Calmette-Guerin therapy: correlation to clinical outcome. Journal of
Clinical Oncology 14(10): 2646-2652, 1996.
- Herr HW, Schwalb DM, Zhang ZF,
et al.: Intravesical Bacillus Calmette-Guerin therapy prevents tumor
progression and death from superficial bladder cancer: ten-year follow-up
of a prospective randomized trial. Journal of Clinical Oncology 13(6):
1404-1408, 1995.
- Lamm DL, Griffith JG:
Intravesical therapy: does it affect the natural history of superficial
bladder cancer? Seminars in Urology 10(1): 39-44, 1992.
- Sarosdy MF, Lamm DL: Long-term
results of intravesical bacillus Calmette-Guerin therapy for superficial
bladder cancer. Journal of Urology 142(3): 719-722, 1989.
- Coplen DE, Marcus MD, Myers
JA, et al.: Long-term follow-up of patients treated with 1 or 2, 6-week
courses of intravesical bacillus Calmette-Guerin: analysis of possible
predictors of response free of tumor. Journal of Urology 144(3): 652-657,
1990.
- Catalona WJ, Hudson MA, Gillen
DP, et al.: Risks and benefits of repeated courses of intravesical
bacillus Calmette-Guerin therapy for superficial bladder cancer. Journal
of Urology 137(2): 220-224, 1987.
- Herr HW: Progression of stage
T1 bladder tumors after intravesical bacillus Calmette-Guerin. Journal of
Urology 145(1): 40-44, 1991.
- Lamm DL, Blumenstein BA,
Crawford ED, et al.: A randomized trial of intravesical doxorubicin and
immunotherapy with bacille Calmette-Guerin for transitional-cell carcinoma
of the bladder. New England Journal of Medicine 325(17): 1205-1209, 1991.
- De Jager R, Guinan P, Lamm D,
et al.: Long-term complete remission in bladder carcinoma in situ with
intravesical TICE bacillus Calmette Guerin: overview analysis of six phase
II clinical trials. Urology 38(6): 507-513, 1991.
- Herr HW, Wartinger DD, Fair
WR, et al.: Bacillus Calmette-Guerin therapy for superficial bladder
cancer: a 10-year followup. Journal of Urology 147(4): 1020-1023, 1992.
- Lamm DL, Crawford ED,
Blumenstein B, et al.: Maintenance BCG immunotherapy of superficial
bladder cancer: a randomized prospective Southwest Oncology Group study.
Proceedings of the American Society of Clinical Oncology 11: A-627, 203,
1992.
- Boccardo F, Cannata D,
Rubagotti A, et al.: Prophylaxis of superficial bladder cancer with
mitomycin or interferon alfa-2b: results of a multicentric Italian study.
Journal of Clinical Oncology 12(1): 7-13, 1994.
- Soloway MS: The management of
superficial bladder cancer. In: Javadpour N, Ed.: Principles and
Management of Urologic Cancer. Baltimore: Williams and Wilkins, 2nd ed.,
1983, pp 446-466.
- Amling CL, Thrasher JB,
Frazier HA, et al.: Radical cystectomy for stages TA, TIS, and T1
transitional cell carcinoma of the bladder. Journal of Urology 151(1):
31-36, 1994.
- Prout GR, Lin CW, Benson RC,
et al.: Photodynamic therapy with hematoporphyrin derivative in the
treatment of superficial transitional-cell carcinoma of the bladder. New
England Journal of Medicine 317(20): 1251-1255, 1987.
- Torti FM, Shortliffe LD,
Williams RD, et al.: Alpha-interferon in superficial bladder cancer: a
Northern California Oncology Group study. Journal of Clinical Oncology
6(3): 476-483, 1988.
- Lamm DL, Riggs DR, Shriver
JS, et al.: Megadose vitamins in bladder cancer: a double-blind clinical
trial. Journal of Urology 151(1): 21-26, 1994.
Some citations in the text of this section are
followed by a level of evidence. The PDQ editorial boards use a formal ranking
system to help the reader judge the strength of evidence linked to the
reported results of a therapeutic strategy. Refer to the PDQ levels of
evidence summary for more information.
T1, N0, M0
Stage I bladder tumors can be cured by a
variety of forms of treatment, even though the tendency for new tumor
formation is high. In a series of patients with Ta or T1 tumors who were
followed for a minimum of 20 years or until death, the risk of bladder
recurrence following initial resection was 80%.[1] Patients
at greatest risk of recurrent disease are those whose tumors are large, poorly
differentiated, multiple, or associated with nuclear p53 overexpression. In
addition, patients with carcinoma in situ (Tis) or dysplasia of grossly
uninvolved bladder epithelium are at greater risk of recurrence and
progression.[1-3]
Transurethral resection (TUR) and fulguration
are the most common and conservative forms of management. Patients who require
more aggressive forms of treatment are those with extensive multifocal
recurrent disease and/or other unfavorable prognostic features. Segmental
cystectomy is applicable to only a small minority of patients because of the
tendency of bladder carcinoma to involve multiple regions of the bladder
mucosa and to occur in areas that cannot be segmentally resected. In series of
patients who were followed for more than 10 years after management of
superficial tumors, the risk of developing a transitional cell carcinoma of
the upper urinary tract has been reported in the 2% to 13% range.[1,4]
Intravesical therapy with thiotepa, mitomycin,
doxorubicin, or BCG (bacillus Calmette-Guerin) is most often used in patients
with multiple tumors or recurrent tumors or as a prophylactic measure in
high-risk patients after TUR. Administration of intravesical BCG combined with
subcutaneous BCG following TUR was compared with TUR alone in patients with Ta
and T1 lesions. Treatment with BCG delayed progression to muscle-invasive
and/or metastatic disease, improved bladder preservation, and decreased the
risk of death from bladder cancer.[4] Another randomized
study in patients with superficial bladder cancer also reports a decrease in
tumor recurrence in patients given intravesical and percutaneous BCG compared
with controls.[5] Two nonconsecutive 6-week courses with
BCG may be necessary to obtain optimal response.[6]
Patients with a T1 tumor at the 3-month evaluation after a 6-week course of
BCG and patients with Tis that persists after a second 6-week BCG course have
a high likelihood of developing muscle-invasive disease and should be
considered for cystectomy.[6-8] A
randomized study that compared intravesical and subcutaneous BCG to
intravesical doxorubicin showed better response rates and freedom from
recurrence with the BCG regimen for recurrent papillary tumors as well as for
Tis.[9] Preliminary results of one study have shown a
possible survival benefit with maintenance BCG after a 6-week induction
course.[10] Another study that compared alternating
mitomycin and BCG with BCG alone, both given for 24 months, found that the
efficacy was equal, but that the side effects of the combined regimen were
slightly less.[11][Level of evidence: 1iiDii] A similar
trial comparing sequential mitomycin and BCG to mitomycin alone also found no
major differences in toxic effects or efficacy.[12][Level
of evidence: 1iiDii]
Treatment options:
Standard:
- 1. TUR with fulguration.[13,14]
2. TUR with fulguration followed by
intravesical BCG.[4,5,7,8,11]
3. TUR with fulguration followed by
intravesical chemotherapy.[2,11]
4. Segmental cystectomy (rarely
indicated).[13]
5. Radical cystectomy in selected patients
with extensive or refractory superficial tumor.[15]
6. Interstitial implantation of
radioisotopes with or without external-beam irradiation.[16,17]
Under clinical evaluation:
- 1. Use of chemoprevention agents after
treatment to prevent recurrence.[18]
2. Intravesical therapies.
References:
- Holmang S, Hedelin H,
Anderstrom C, et al.: The relationship among multiple recurrences,
progression and prognosis of patients with stages TA and T1 transitional
cell cancer of the bladder followed for at least 20 years. Journal of
Urology 153(6): 1823-1827, 1995.
- Igawa M, Urakami S, Shirakawa
H, et al.: Intravesical instillation of epirubicin: effect on tumour
recurrence in patients with dysplastic epithelium after transurethral
resection of superficial bladder tumour. British Journal of Urology 77(3):
358-362, 1996.
- Lacombe L, Dalbagni G, Zhang
ZF, et al: Overexpression of p53 protein in a high-risk population of
patients with superficial bladder cancer before and after bacillus
Calmette-Guerin therapy: correlation to clinical outcome. Journal of
Clinical Oncology 14(10): 2646-2652, 1996.
- Herr HW, Schwalb DM, Zhang ZF,
et al.: Intravesical Bacillus Calmette-Guerin therapy prevents tumor
progression and death from superficial bladder cancer: ten-year follow-up
of a prospective randomized trial. Journal of Clinical Oncology 13(6):
1404-1408, 1995.
- Sarosdy MF, Lamm DL: Long-term
results of intravesical bacillus Calmette-Guerin therapy for superficial
bladder cancer. Journal of Urology 142(3): 719-722, 1989.
- Coplen DE, Marcus MD, Myers
JA, et al.: Long-term follow-up of patients treated with 1 or 2, 6-week
courses of intravesical bacillus Calmette-Guerin: analysis of possible
predictors of response free of tumor. Journal of Urology 144(3): 652-657,
1990.
- Catalona WJ, Hudson MA, Gillen
DP, et al.: Risks and benefits of repeated courses of intravesical
bacillus Calmette-Guerin therapy for superficial bladder cancer. Journal
of Urology 137(2): 220-224, 1987.
- Herr HW: Progression of stage
T1 bladder tumors after intravesical bacillus Calmette-Guerin. Journal of
Urology 145(1): 40-44, 1991.
- Lamm DL, Blumenstein BA,
Crawford ED, et al.: A randomized trial of intravesical doxorubicin and
immunotherapy with bacille Calmette-Guerin for transitional-cell carcinoma
of the bladder. New England Journal of Medicine 325(17): 1205-1209, 1991.
- Lamm DL, Crawford ED,
Blumenstein B, et al.: Maintenance BCG immunotherapy of superficial
bladder cancer: a randomized prospective Southwest Oncology Group study.
Proceedings of the American Society of Clinical Oncology 11: A-627, 203,
1992.
- Rintala E, Jauhiainen K,
Kaasinen E, et al.: Alternating mitomycin C and bacillus Calmette-Guerin
instillation prophylaxis for recurrent papillary (stages Ta to T1)
superficial bladder cancer. Journal of Urology 156(1): 56-60, 1996.
- Witjes JA, Caris CT, Mungan
NA, et al.: Results of a randomized phase III trial of sequential
intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus
mitomycin C alone in patients with superficial bladder cancer. Journal of
Urology 160(5): 1668-1672, 1998.
- Soloway MS: The management of
superficial bladder cancer. In: Javadpour N, Ed.: Principles and
Management of Urologic Cancer. Baltimore: Williams and Wilkins, 2nd ed.,
1983, pp 446-466.
- Herr HW, Reuter VE:
Evaluation of new resectoscope loop for transurethral resection of bladder
tumors. Journal of Urology 159(6): 2067-2068, 1998.
- Amling CL, Thrasher JB,
Frazier HA, et al.: Radical cystectomy for stages TA, TIS, and T1
transitional cell carcinoma of the bladder. Journal of Urology 151(1):
31-36, 1994.
- Goffinet DR, Schneider MJ,
Glatstein EJ, et al.: Bladder cancer: results of radiation therapy in 384
patients. Radiology 117(1): 149-153, 1975.
- Vanderwerf-Messing B, Hop WC:
Carcinoma of the urinary bladder, category T1 NX M0 treated either by
radium implant or by transurethral resection only. International Journal
of Radiation Oncology, Biology, Physics 7(3): 299-303, 1981.
- Lamm DL, Riggs DR, Shriver
JS, et al.: Megadose vitamins in bladder cancer: a double-blind clinical
trial. Journal of Urology 151(1): 21-26, 1994.
Some citations in the text of this section are
followed by a level of evidence. The PDQ editorial boards use a formal ranking
system to help the reader judge the strength of evidence linked to the
reported results of a therapeutic strategy. Refer to the PDQ levels of
evidence summary for more information.
T2a, N0, M0 or T2b, N0, M0
Stage II bladder cancer may be controlled in
some cases by transurethral resection (TUR), but often more aggressive forms
of treatment are dictated by recurrent tumor or by the large size, multiple
foci, or undifferentiated grade of the neoplasm. Segmental cystectomy is
appropriate only in very selected patients. Radical cystectomy is considered
standard treatment. In some reports, bladder-sparing radiation therapy with
salvage cystectomy when indicated yields similar therapeutic results to those
of radical cystectomy and can be delivered to patients who are not candidates
for surgery. In some studies, one half or more of patients who had
bladder-preserving therapy (initial TUR of as much tumor as possible with
chemotherapy and concomitant radiation therapy) were disease-free 3 to 4 years
after treatment;[1-3] radical cystectomy
was reserved for patients who did not achieve a complete response. Some
investigators think that the prognosis is worse for patients with
hydronephrosis on the initial intravenous pyelogram, and therefore, they are
not candidates for this approach.[1,3]
Choice of treatment is affected by a patient's overall medical condition and
consideration of the adverse effects of therapy. Radical cystectomy includes
removal of the bladder, perivesical tissues, prostate, and seminal vesicles in
men and the uterus, tubes, ovaries, anterior vaginal wall, and urethra in
women and may or may not be accompanied by pelvic lymph node dissection.[4]
Studies suggest that radical cystectomy with preservation of sexual function
can be performed in some men and that new forms of urinary diversion can
obviate the need for an external urinary appliance.[5-8]
In a retrospective analysis from a single institution, elderly patients (70
years of age or older) in good general health were found to have similar
clinical and functional results following radical cystectomy when compared to
younger patients.[9] The only prospective, randomized trial
reported to date did not show any survival advantage for preoperative
radiation therapy and radical cystectomy compared with radical cystectomy
alone.[10] Treatment with concurrent chemotherapy and
radiation therapy has been associated with improved rates of local control
compared with historical series of patients treated with radiation therapy
alone. The only prospective, randomized comparison of radiation therapy and
chemoradiotherapy reported an improved rate of local control when cisplatin
was given in conjunction with radiation therapy.[11]
Treatment options:
Standard:
- 1. Radical cystectomy with or without pelvic
lymph node dissection.[12]
2. External-beam irradiation (nonsurgical
candidates and selected cases).[13-15]
3. Interstitial implantation of
radioisotopes before or after external-beam irradiation.[16]
4. TUR with fulguration (in selected
patients).
5. Segmental cystectomy (in selected
patients).[12]
Under clinical evaluation:
- Multiple clinical trials are evaluating the
potential of chemotherapy
administered prior to cystectomy, following cystectomy, or in conjunction
with external-beam radiation therapy to improve local tumor control,
prevent distant metastases, or allow preservation of the bladder.[1-3,17-21]
The combination regimen methotrexate, vinblastine, doxorubicin, and
cisplatin produced a pathologic complete response in approximately 20% of
patients treated prior to definitive surgery.[19]
However, there is no evidence to date that the use of neoadjuvant
cisplatin or cisplatin-based regimens will improve the survival of
patients with locally advanced bladdercancer.[22]
[Level of evidence: 1iiA] In a bladder-sparing clinical trial ofexternal
radiation therapy with chemotherapy, initial results from the Radiation
Therapy Oncology Group have shown that 2 cycles of neoadjuvant
methotrexate, cisplatin, and vinblastine do not improve down staging toa
complete response, patient survival, or freedom from metastatic
diseaseover radiation and concurrent cisplatin alone.[3]
[Level of evidence: 1iiA]
References:
- Kachnic LA, Kaufman DS, Heney
NM, et al.: Bladder preservation by combined modality therapy for invasive
bladder cancer. Journal of Clinical Oncology 15(3): 1022-1029, 1997.
- Housset M, Maulard C, Chretien
Y, et al.: Combined radiation and chemotherapy for invasive
transitional-cell carcinoma of the bladder: a prospective study. Journal
of Clinical Oncology 11(11): 2150-2157, 1993.
- Shipley WU, Winter KA, Kaufman
DS, et al.: Phase III trial of neoadjuvant chemotherapy in patients with
invasive bladder cancer treated with selective bladder preservation by
combined radiation therapy and chemotherapy: inital results of Radiation
Therapy Oncology Group 89-03. Journal of Clinical Oncology 16(11):
3576-3583, 1998.
- Olsson CA: Management of
invasive carcinoma of the bladder. In: deKernion JB, Paulson DF, Eds.:
Genitourinary Cancer Management. Philadelphia: Lea and Febiger, 1987, pp
59-94.
- Brendler CB, Steinberg GD,
Marshall FF, et al.: Local recurrence and survival following nerve-sparing
radical cystoprostatectomy. Journal of Urology 144(5): 1137-1141, 1990.
- Skinner DG, Boyd SD,
Lieskovsky G: Clinical experience with the Kock continent ileal reservoir
for urinary diversion. Journal of Urology 132(6): 1101-1107, 1984.
- Fowler JE: Continent urinary
reservoirs and bladder substitutes in the adult: part I. Monographs in
Urology 8(2): 1987.
- Fowler JE: Continent urinary
reservoirs and bladder substitutes in the adult: part II. Monographs in
Urology 8(3): 1987.
- Figueroa AJ, Stein JP,
Dickinson M, et al.: Radical cystectomy for elderly patients with bladder
carcinoma: an updated experience with 404 patients. Cancer 83(1): 141-147,
1998.
- Smith JA, Crawford ED,
Blumenstein B, et al.: A randomized prospective trial of pre-operative
irradiation plus radical cystectomy versus surgery alone for transitional
cell carcinoma of the bladder: a Southwest Oncology Group study. Journal
of Urology 139(4, Part 2): 266A, 1988.
- Coppin CM, Gospodarowicz MK,
James K, et al.: Improved local control of invasive bladder cancer by
concurrent cisplatin and preoperative or definitive radiation. Journal of
Clinical Oncology 14(11): 2901-2907, 1996.
- Richie JP: Surgery for
invasive bladder cancer. Hematology/Oncology Clinics of North America
6(1): 129-145, 1992.
- Gospodarowicz MK, Hawkins NV,
Rawlings GA, et al.: Radical radiotherapy for muscle invasive transitional
cell carcinoma of the bladder: failure analysis. Journal of Urology
142(6): 1448-1454, 1989.
- Yu WS, Sagerman RH, Chung CT,
et al.: Bladder carcinoma: experience with radical and preoperative
radiotherapy in 421 patients. Cancer 56(6): 1293-1299, 1985.
- Jahnson S, Pedersen J,
Westman G: Bladder carcinoma - a 20-year review of radical irradiation
therapy. Radiotherapy and Oncology 22(2): 111-117, 1991.
- van der Werf-Messing BH, van
Putten WL: Carcinoma of the urinary bladder category T2,3 NX M0 treated by
40 Gy external irradiation followed by cesium-137 implant at reduced dose
(50%). International Journal of Radiation Oncology, Biology, Physics
16(2): 369-371, 1989.
- Tester W, Porter A, Asbell S,
et al.: Combined modality program with possible organ preservation for
invasive bladder carcinoma: results of RTOG protocol 85-12. International
Journal of Radiation Oncology, Biology, Physics 25(5): 783-790, 1993.
- Natale RB, Southwest Oncology
Group: NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized
Comparison of Cystectomy Alone vs Neoadjuvant MVAC (MTX/VBL/DOX/CDDP) plus
Cystectomy in Patients with Locally Advanced Transitional Cell Carcinoma
of the Bladder (Summary Last Modified 09/98), SWOG-8710, clinical trial,
closed, 07/01/1998.
- Scher H, Herr H, Sternberg C,
et al.: Neo-adjuvant chemotherapy for invasive bladder cancer: experience
with the M-VAC regimen. British Journal of Urology 64(3): 250-256, 1989.
- Skinner DG, Daniels JR,
Russell CA, et al.: The role of adjuvant chemotherapy following cystectomy
for invasive bladder cancer: a prospective comparative trial. Journal of
Urology 145(3): 459-467, 1991.
- Tester W, Caplan R, Heaney J,
et al.: Neoadjuvant combined modality program with selective organ
preservation for invasive bladder cancer: results of Radiation Therapy
Oncology Group phase II trial 8802. Journal of Clinical Oncology 14(1):
119-126, 1996.
- Advanced Bladder Cancer
Overview Collaboration: Does neoadjuvant cisplatin-based chemotherapy
improve the survival of patients with locally advanced bladder cancer: a
meta-analysis of individual patient data from randomized clinical trials.
British Journal of Urology 75(2): 206-213, 1995.
Some citations in the text of this section are
followed by a level of evidence. The PDQ editorial boards use a formal ranking
system to help the reader judge the strength of evidence linked to the
reported results of a therapeutic strategy. Refer to the PDQ levels of
evidence summary for more information.
T3a, N0, M0 or T3b, N0, M0 or T4a,
N0, M0
A few highly selected patients with stage III
bladder cancer may be suitable for segmental cystectomy or interstitial
irradiation. The relatively high frequency of extensive intramural tumor
spread and lymph node involvement make radical cystectomy and external-beam
irradiation more logical forms of treatment in most patients. Because of the
relatively poor results of either of these modalities when used alone,
preoperative irradiation followed by radical cystectomy has been widely used
during the past decade. This combined modality treatment appears to reduce the
rate of local recurrence and is associated with especially good results in
patients whose resected bladders contain no pathologic evidence of cancer.
However, similar results achieved with radical cystectomy alone in some series
have brought this issue under scrutiny. The only prospective, randomized trial
reported to date did not show any survival advantage for preoperative
radiation therapy and radical cystectomy compared with radical cystectomy
alone.[1] Studies suggest that radical cystectomy with
preservation of sexual function can be performed in some men and that new
forms of urinary diversion can obviate the need for an external urinary
appliance.[2-5]
In the United States, external-beam irradiation
has been generally reserved for patients who are poor medical candidates for
radical cystectomy. However, selected patients have been treated with
transurethral resection (TUR) and definitive radiation therapy, with salvage
cystectomy reserved for those whose treatment fails.[6,7]
One series suggests that patients treated with preoperative radiation therapy
and immediate cystectomy had an outcome similar to those treated with radical
irradiation alone, with salvage cystectomy reserved for local recurrence.[6]
In combined modality studies, one half or more of patients who had
bladder-preserving therapy were disease-free 3 to 4 years after treatment,[8-11]
with salvage cystectomy reserved for patients who did not achieve a complete
response. Some investigators think that the prognosis is worse for patients
with hydronephrosis on the initial intravenous pyelogram, and therefore, they
are not candidates for this approach.[8,11]
Because the frequency of distant metastases is
becoming apparent with improved local control of advanced bladder cancer,
systemic preoperative or postoperative adjuvant chemotherapy is now under
evaluation in clinical trials. Treatment with concurrent chemotherapy and
radiation therapy has been associated with improved rates of local control
compared with radiation therapy alone. The only prospective, randomized trial
reported to date resulted in an improved rate of local control when cisplatin
was given in conjunction with radiation therapy.[12]
All patients with this stage should be
considered candidates for clinical trials.
Treatment options:
Standard:
- 1. Radical cystectomy.[1]
2. External-beam irradiation.[13-15]
3. External-beam irradiation with
interstitial implantation of radioisotopes.[16]
4. Segmental cystectomy (in highly selected
cases).[17]
5. Combined external-beam irradiation and
cisplatin.[8-12]
Under clinical evaluation:
- Multiple trials are evaluating the potential
of chemotherapy administered
prior to cystectomy, following cystectomy, or in conjunction with
external-beam radiation therapy to improve local tumor control, prevent
distant metastases, or allow preservation of the
bladder.[8-11,18-21]
The combination regimen methotrexate,
vinblastine, doxorubicin, and cisplatin produced a pathologic complete
response in approximately 20% of patients treated prior to definitive
surgery.[22] Results from two clinical studies suggest
that a combined
modality treatment with neoadjuvant methotrexate, cisplatin, and
vinblastine
(MCV) followed by radiation therapy and concurrent cisplatin can result in
high rates of tumor clearance and can allow bladder preservation in some
patients.[8,11,21]
However, there is no evidence to date that the use of
neoadjuvant cisplatin or cisplatin-based regimens will improve the
survival
of patients with locally advanced bladder cancer.[23][Level
of evidence:
1iiA] In a bladder-sparing clinical trial of external radiation therapy
with chemotherapy, initial results from the Radiation Therapy Oncology
Group
have shown that 2 cycles of neoadjuvant MCV do not improve down staging to
a
complete response, patient survival, or freedom from metastatic disease
over
radiation and concurrent cisplatin alone.[11][Level of
evidence: 1iiA]
References:
- Smith JA, Crawford ED,
Blumenstein B, et al.: A randomized prospective trial of pre-operative
irradiation plus radical cystectomy versus surgery alone for transitional
cell carcinoma of the bladder: a Southwest Oncology Group study. Journal
of Urology 139(4, Part 2): 266A, 1988.
- Brendler CB, Steinberg GD,
Marshall FF, et al.: Local recurrence and survival following nerve-sparing
radical cystoprostatectomy. Journal of Urology 144(5): 1137-1141, 1990.
- Skinner DG, Boyd SD,
Lieskovsky G: Clinical experience with the Kock continent ileal reservoir
for urinary diversion. Journal of Urology 132(6): 1101-1107, 1984.
- Fowler JE: Continent urinary
reservoirs and bladder substitutes in the adult: part I. Monographs in
Urology 8(2): 1987.
- Fowler JE: Continent urinary
reservoirs and bladder substitutes in the adult: part II. Monographs in
Urology 8(3): 1987.
- Sell A, Jakobsen A, Nerstrom
B, et al.: Treatment of advanced bladder cancer category T2 T3 and T4a: a
randomized multicenter study of preoperative irradiation and cystectomy
versus radical irradiation and early salvage cystectomy for residual
tumor: DAVECA protocol 8201. Scandinavian Journal of Urology and
Nephrology 138(Suppl): 193-201, 1991
- Jenkins BJ, Caulfield MJ,
Fowler CG, et al.: Reappraisal of the role of radical radiotherapy and
salvage cystectomy in the treatment of invasive (T2/T3) bladder cancer.
Journal of Urology 62(4): 343-346, 1988.
- Kachnic LA, Kaufman DS, Heney
NM, et al.: Bladder preservation by combined modality therapy for invasive
bladder cancer. Journal of Clinical Oncology 15(3): 1022-1029, 1997.
- Housset M, Maulard C, Chretien
Y, et al.: Combined radiation and chemotherapy for invasive
transitional-cell carcinoma of the bladder: a prospective study. Journal
of Clinical Oncology 11(11): 2150-2157, 1993.
- Tester W, Porter A, Asbell S,
et al.: Combined modality program with possible organ preservation for
invasive bladder carcinoma: results of RTOG protocol 85-12. International
Journal of Radiation Oncology, Biology, Physics 25(5): 783-790, 1993.
- Shipley WU, Winter KA,
Kaufman DS, et al.: Phase III trial of neoadjuvant chemotherapy in
patients with invasive bladder cancer treated with selective bladder
preservation by combined radiation therapy and chemotherapy: inital
results of Radiation Therapy Oncology Group 89-03. Journal of Clinical
Oncology 16(11): 3576-3583, 1998.
- Coppin CM, Gospodarowicz MK,
James K, et al.: Improved local control of invasive bladder cancer by
concurrent cisplatin and preoperative or definitive radiation. Journal of
Clinical Oncology 14(11): 2901-2907, 1996.
- Gospodarowicz MK, Hawkins NV,
Rawlings GA, et al.: Radical radiotherapy for muscle invasive transitional
cell carcinoma of the bladder: failure analysis. Journal of Urology
142(6): 1448-1454, 1989.
- Yu WS, Sagerman RH, Chung CT,
et al.: Bladder carcinoma: experience with radical and preoperative
radiotherapy in 421 patients. Cancer 56(6): 1293-1299, 1985.
- Jahnson S, Pedersen J,
Westman G: Bladder carcinoma - a 20-year review of radical irradiation
therapy. Radiotherapy and Oncology 22(2): 111-117, 1991.
- van der Werf-Messing BH, van
Putten WL: Carcinoma of the urinary bladder category T2,3 NX M0 treated by
40 Gy external irradiation followed by cesium-137 implant at reduced dose
(50%). International Journal of Radiation Oncology, Biology, Physics
16(2): 369-371, 1989.
- Skinner DG: Current
perspectives in the management of high-grade invasive bladder cancer.
Cancer 45(7): 1866-1874, 1980
- Logothetis CJ, Johnson DE,
Chong C, et al.: Adjuvant chemotherapy of bladder cancer: a preliminary
report. Journal of Urology 139(6): 1207-1211, 1988.
- Natale RB, Southwest Oncology
Group: NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized
Comparison of Cystectomy Alone vs Neoadjuvant MVAC (MTX/VBL/DOX/CDDP) plus
Cystectomy in Patients with Locally Advanced Transitional Cell Carcinoma
of the Bladder (Summary Last Modified 09/98), SWOG-8710, clinical trial,
closed, 07/01/1998.
- Skinner DG, Daniels JR,
Russell CA, et al.: The role of adjuvant chemotherapy following cystectomy
for invasive bladder cancer: a prospective comparative trial. Journal of
Urology 145(3): 459-467, 1991.
- Tester W, Caplan R, Heaney J,
et al.: Neoadjuvant combined modality program with selective organ
preservation for invasive bladder cancer: results of Radiation Therapy
Oncology Group phase II trial 8802. Journal of Clinical Oncology 14(1):
119-126, 1996.
- Scher H, Herr H, Sternberg C,
et al.: Neo-adjuvant chemotherapy for invasive bladder cancer: experience
with the M-VAC regimen. British Journal of Urology 64(3): 250-256, 1989.
- Advanced Bladder Cancer
Overview Collaboration: Does neoadjuvant cisplatin-based chemotherapy
improve the survival of patients with locally advanced bladder cancer: a
meta-analysis of individual patient data from randomized clinical trials.
British Journal of Urology 75(2): 206-213, 1995.
Some citations in the text of this section are
followed by a level of evidence. The PDQ editorial boards use a formal ranking
system to help the reader judge the strength of evidence linked to the
reported results of a therapeutic strategy. Refer to the PDQ levels of
evidence summary for more information.
T4b, N0, M0, any T, N1-N3, M0, or
any T, any N, M1
Currently, only a small fraction of patients
with stage IV bladder carcinoma can be cured. The potential for cure is
restricted to patients with stage IV disease with involvement of pelvic organs
by direct extension or small volume metastases to regional lymph nodes. These
patients can receive radical cystectomy with or without preoperative
irradiation. Studies suggest that radical cystectomy with preservation of
sexual function can be performed in some men and that new forms of urinary
diversion can obviate the need for an external urinary appliance.[1-3]
The prognosis of patients with T4 tumors is generally poor with either radical
cystectomy or radiation therapy.
Prognosis is so poor in patients with stage IV
disease that consideration of entry into a clinical trial is appropriate. The
focus of care for many stage IV patients is on palliation of symptoms from
bladder tumor that is often massive. Urinary diversion may be indicated, not
only for palliation of urinary symptoms, but also for preservation of renal
function in candidates for chemotherapy. Combination chemotherapy regimens
that include methotrexate, cisplatin, and vinblastine, with or without
doxorubicin are encouraging and have induced some pathological complete
responses.[4,5] A prospective,
randomized trial of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC)
compared with cisplatin, cyclophosphamide, and doxorubicin demonstrated
improved response and median survival rates with the former regimen.[6]
Results from a randomized trial that compared M-VAC to single-agent cisplatin
in advanced bladder cancer show a significant advantage with M-VAC in both
response rate and median survival.[7] The (outpatient)
regimen of paclitaxel and carboplatin has been shown to be active and well
tolerated. Partial responses in the range of 50% have been reported in phase
II trials.[8,9][Level of evidence:
3iiiDiii] Phase III trials further evaluating the role of this regimen are in
progress.[10] Patients should be encouraged whenever
possible to participate in these trials.
Treatment options:
For T4b, N0, M0 or any T, N1-N3, M0 patients:
Standard:
- 1. Radical cystectomy alone (in
node-negative patients).[11]
2. External-beam irradiation.[12]
3. Urinary diversion or cystectomy for
palliation.
4. Chemotherapy as an adjunct to local
treatment.[13-17]
Under clinical evaluation:
- Multiple trials are evaluating the potential
of chemotherapy administered
prior to cystectomy, following cystectomy, or in conjunction with
external-beam radiation therapy to improve local tumor control, prevent
distant metastases, or allow preservation of the bladder.[11,13-16,18,19]
For any T, any N, M1 patients:
Standard:
- 1. Chemotherapy alone or as an adjunct to
local treatment.[4,5]
2. External-beam irradiation (palliative).
3. Urinary diversion or cystectomy for
palliation.
Under clinical evaluation:
- Other chemotherapy regimens appear active in
the treatment of metastatic
disease. Chemotherapy agents that have shown activity in metastatic
bladder
cancer include paclitaxel, ifosfamide, gallium nitrate, and gemcitabine.[20]
Refer to PDQ or to CancerNet (http://cancernet.nci.nih.gov)
for a listing of
clinical trials.
References:
- Brendler CB, Steinberg GD,
Marshall FF, et al.: Local recurrence and survival following nerve-sparing
radical cystoprostatectomy. Journal of Urology 144(5): 1137-1141, 1990.
- Skinner DG, Boyd SD,
Lieskovsky G: Clinical experience with the Kock continent ileal reservoir
for urinary diversion. Journal of Urology 132(6): 1101-1107, 1984.
- Richie JP: Surgery for
invasive bladder cancer. Hematology/Oncology Clinics of North America
6(1): 129-145, 1992.
- Sternberg CN, Yagoda A, Scher
HI, et al.: Methotrexate, vinblastine, doxorubicin, and cisplatin for
advanced transitional cell carcinoma of the urothelium. Cancer 64(12):
2448-2458, 1989.
- Harker WG, Meyers FJ, Freiha
FS, et al.: Cisplatin, methotrexate, and vinblastine (CMV): an effective
chemotherapy regimen for metastatic transitional cell carcinoma of the
urinary tract, a Northern California Oncology Group study. Journal of
Clinical Oncology 3(11): 1463-1470, 1985.
- Logothetis CJ, Dexeus FH, Finn
L, et al.: A prospective randomized trial comparing MVAC and CISCA
chemotherapy for patients with metastatic urothelial tumors. Journal of
Clinical Oncology 8(6): 1050-1055, 1990.
- Loehrer PJ, Einhorn LH, Elson
PJ, et al.: A randomized comparison of cisplatin alone or in combination
with methotrexate, vinblastine, and doxorubicin in patients with
metastatic urothelial carcinoma: a cooperative group study. Journal of
Clinical Oncology 10(7): 1066-1073, 1992.
- Vaughn DJ, Malkowicz SB,
Zoltick B, et al.: Paclitaxel plus carboplatin in advanced carcinoma of
the urothelium: an active and tolerable outpatient regimen. Journal of
Clinical Oncology 16(1): 255-260, 1998.
- Redman BG, Smith DC, Flaherty
L, et al.: Phase II trial of paclitaxel and carboplatin in the treatment
of advanced urothelial carcinoma. Journal of Clinical Oncology 16(5):
1844-1848, 1998.
- Dreicer R, Eastern
Cooperative Oncology Group: Phase III Randomized Study of Methotrexate,
Vinblastine, Doxorubicin, and Cisplatin (M-VAC) Versus Carboplatin and
Paclitaxel for the Treatment of Advanced Carcinoma of the Urothelium
(Summary Last Modified 01/1999), E-4897, clinical trial, active,
09/03/1998.
- Thrasher JB, Crawford ED:
Current management of invasive and metastatic transitional cell carcinoma
of the bladder. Journal of Urology 149(5): 957-972, 1993.
- Jahnson S, Pedersen J,
Westman G: Bladder carcinoma - a 20-year review of radical irradiation
therapy. Radiotherapy and Oncology 22(2): 111-117, 1991.
- Kachnic LA, Kaufman DS, Heney
NM, et al.: Bladder preservation by combined modality therapy for invasive
bladder cancer. Journal of Clinical Oncology 15(3): 1022-1029, 1997.
- Tester W, Porter A, Asbell S,
et al.: Combined modality program with possible organ preservation for
invasive bladder carcinoma: results of RTOG protocol 85-12. International
Journal of Radiation Oncology, Biology, Physics 25(5): 783-790, 1993.
- Logothetis CJ, Johnson DE,
Chong C, et al.: Adjuvant chemotherapy of bladder cancer: a preliminary
report. Journal of Urology 139(6): 1207-1211, 1988.
- Skinner DG, Daniels JR,
Russell CA, et al.: The role of adjuvant chemotherapy following cystectomy
for invasive bladder cancer: a prospective comparative trial. Journal of
Urology 145(3): 459-467, 1991.
- Scher HI: Chemotherapy for
invasive bladder cancer: neoadjuvant versus adjuvant. Seminars in Oncology
17(5): 555-565, 1990.
- Housset M, Maulard C,
Chretien Y, et al.: Combined radiation and chemotherapy for invasive
transitional-cell carcinoma of the bladder: a prospective study. Journal
of Clinical Oncology 11(11): 2150-2157, 1993.
- Shipley WU, Winter KA,
Kaufman DS, et al.: Phase III trial of neoadjuvant chemotherapy in
patients with invasive bladder cancer treated with selective bladder
preservation by combined radiation therapy and chemotherapy: inital
results of Radiation Therapy Oncology Group 89-03. Journal of Clinical
Oncology 16(11): 3576-3583, 1998.
- Raghavan D, Huben R:
Management of bladder cancer. Current Problems in Cancer 19(1): 1-64,
1995.
The prognosis for any patient with progressive
or recurrent invasive bladder cancer is generally poor. Management of
recurrence depends on prior therapy, sites of recurrence, and individual
patient considerations. Treatment of new superficial or locally invasive
tumors that develop in the setting of previous conservative therapy for
superficial bladder neoplasia has been discussed earlier in this summary.
Recurrent or progressive disease in distant sites or after definitive local
therapy has an extremely poor prognosis, and clinical trials should be
considered whenever possible.
In patients with recurrent transitional cell
carcinoma, combination chemotherapy has produced high response rates with
occasional complete responses seen.[1,2]
Results from a randomized trial that compared M-VAC (methotrexate, vinblastine,
doxorubicin, and cisplatin) to single-agent cisplatin in advanced bladder
cancer show a significant advantage with M-VAC in both response rate and
median survival.[3] The overall response rate with M- VAC
in this cooperative group trial was 39%.[3] Other
chemotherapy agents that have shown activity in metastatic bladder cancer
include: paclitaxel, ifosfamide, gallium nitrate, and gemcitabine. Ifosfamide
and gallium have shown limited activity in patients previously treated with
cisplatin.[4-9] Refer to PDQ or to
CancerNet (http://cancernet.nci.nih.gov)
for a listing of clinical trials.
References:
- Sternberg CN, Yagoda A, Scher
HI, et al.: Methotrexate, vinblastine, doxorubicin, and cisplatin for
advanced transitional cell carcinoma of the urothelium. Cancer 64(12):
2448-2458, 1989.
- Harker WG, Meyers FJ, Freiha
FS, et al.: Cisplatin, methotrexate, and vinblastine (CMV): an effective
chemotherapy regimen for metastatic transitional cell carcinoma of the
urinary tract, a Northern California Oncology Group study. Journal of
Clinical Oncology 3(11): 1463-1470, 1985.
- Loehrer PJ, Einhorn LH, Elson
PJ, et al.: A randomized comparison of cisplatin alone or in combination
with methotrexate, vinblastine, and doxorubicin in patients with
metastatic urothelial carcinoma: a cooperative group study. Journal of
Clinical Oncology 10(7): 1066-1073, 1992.
- Roth BJ: Preliminary
experience with paclitaxel in advanced bladder cancer. Seminars in
Oncology 22(3, Suppl 6): 1-5, 1995.
- Witte RS, Elson P, Bono B, et
al.: Eastern Cooperative Oncology Group phase II trial of ifosfamide in
the treatment of previously treated advanced urothelial carcinoma. Journal
of Clinical Oncology 15(2): 589-593, 1997.
- Einhorn LH, Roth BJ, Ansari
R, et al.: Phase II trial of vinblastine, ifosfamide, and gallium
combination chemotherapy in metastatic urothelial carcinoma. Journal of
Clinical Oncology 12(11): 2271-2276, 1994.
- Pollera CF, Ceribelli A,
Crecco M, et al.: Weekly gemcitabine in advanced bladder cancer: a
preliminary report from a phase I study. Annals of Oncology 5(2): 182-184,
1994.
- Seidman AD, Scher HI,
Heinemann MH, et al.: Continuous infusion gallium nitrate for patients
with advanced refractory urothelial tract tumors. Cancer 68(12):
2561-2565, 1991.
- Roth BJ: Ifosfamide in the
treatment of bladder cancer. Seminars in Oncology 23(3, Suppl 6): 50-55,
1996.
Date Last Modified: 07/1999
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