UNJ Oct 2005-323.ps 9/15/05 10:59 AM Page 323 C Bladder Cancer: Current Optimal O N Intravesical Treatment T I Donald L. Lamm N William R. McGee U Kaye Hale I N G ladder cancer is more Superficial bladder cancer can be treated surgically, but patients are common than generally at high risk for recurrence. Tumors are categorized as low, intermedi- appreciated; 62,240 new ate, and high-risk based on grade, stage, and pattern of recurrence. E cases and 12,710 deaths Low-risk tumors are best treated with a single instillation of D Bwere expected in the United chemotherapy (thiotepa, doxorubicin, or mitomycin) (Lamm, 2002). U States in 2004 (Jemal et al., Though effective, the toxicity of bacillus Calmette-Guerin 2004). Patients typically present immunotherapy (BCG) restricts its use to treat higher-grade tumors. C with either microscopic or gross Intermediate risk tumors can be treated with chemotherapy as well, A hematuria. Bleeding from a blad- but will often require immunotherapy. High-risk tumors are best treat- T der tumor is generally intermit- ed with intravesical BCG using a 3-week maintenance schedule. Side tent. Therefore resolution, either I effects of BCG immunotherapy can be decreased by logarithmic spontaneously or after antibiotic O reductions in dose. Patients who fail BCG may be rescued with BCG treatment for presumed bladder N infection, does not reduce the plus interferon alfa or radical cystectomy. need for urologic evaluation. Diagnostic studies most com- monly used are intravenous even with aggressive surgery with recurrent tumors or multi- urography, urine cytology, and (cystectomy) (Dalbagni et al., ple tumors had recurrence rates cystoscopy. Fortunately, about 2001). Prognosis, as noted later, of 91% (Heney, 1992). As few as 80% of patients present with is also highly dependent on 20% of patients who are disease- superficial disease that can be grade. free at 3 months will have tumor successfully treated surgically Historically, two-thirds of recurrence within 5 years. (Lamm, Griffith, Pettit, & Nseyo, patients have tumor recurrence Invasion of the stroma (lamina 1992). Effective treatment plans within 5 years, and nearly 90% propria) increases the risk of can lead to high survival rates. have recurrence by 15 years invasion into the bladder muscle The goals of treatment are (a) (Lamm & Griffith, 1992). Two fac- from 4% to 30% (Vicente, reduce tumor recurrence, (b) tors best predict recurrence: (a) Laguna, Duarte, Algaba, & lower the risk of disease progres- history of previous recurrence, Chechile, 1991). High-grade sion, and (c) improve survival. particularly if within 3 months, tumors have a significantly Preventing progression to mus- and (b) the presence of multiple worse prognosis. In the National cle-invasive disease is key, tumors. Solitary tumors recurred Bladder Cancer Group study, because only 50% of these in 51% of patients, while those only 2% of patients with low- patients will survive 5 years Publisher’s Note: Publication of this article was supported by a grant provided by Nurse Competence in Aging, a 5-year initiative funded by The Atlantic Philanthropies Donald L. Lamm, MD, FACS, is (USA) Inc., awarded to the American Nurses Association (ANA) through the President, BCG Oncology, P.C., American Nurses Foundation (ANF), and representing a strategic alliance between Phoenix, AZ. ANA, the American Nurses Credentialing Center (ANCC), and the John A. Hartford Foundation Institute for Geriatric Nursing, New York University, The Steinhardt School William R. McGee is a Medical of Education, Division of Nursing. Student, Arizona College of For more information, contact the John A. Hartford Foundation Institute for Geriatric Osteopathic Medicine, Glendale, AZ Nursing, New York University, The Steinhardt School of Education, Division of Nursing, 246 Greene Street, 5th Floor, New York, NY 10003, or call (212) 998-9018, Kaye Hale, CMA, is a Medical or email [email protected] or access the Web site at www.hartfordign.org Assistant, BCG Oncology, Phoenix, AZ. Note: CE Objectives and Evaluation Form appear on page 333. UROLOGIC NURSING / October 2005 / Volume 25 Number 5 323 UNJ Oct 2005-324.ps 9/15/05 10:59 AM Page 324 C grade (grade I Stage Ta) tumors higher progression-free survival der cancer. Soy proteins appear O had progression to muscle inva- (p<0.01) (Fleshner et al., 1999). to inhibit bladder carcinogenesis, sion, compared with 48% of Therefore, early smoking cessa- and garlic extract has been con- N patients with high-grade (grade tion is not only effective at pre- firmed, in the murine bladder T III Stage T1) tumors. The pres- venting recurrence of superficial cancer model, to inhibit the I ence of carcinoma in situ (CIS) bladder cancer, it is also the least growth of transplanted bladder significantly worsens the progno- toxic and most cost effective cancer. N sis of high-grade disease, increas- option (Chen, Su, Guo, Additional agents associated U ing progression risk from 10% to Houseman, & Christiani, 2005). with reduced risk of bladder can- I 65% in one study (Bostwick, Genetic predisposition is cer or anti-tumor effect in ani- 1992). The best predictor of clearly a factor in the develop- mals include selenium, green tea, N death from superficial bladder ment of bladder cancer, but and nonsteroidal anti-inflamma- G cancer is the presence of high- familial occurrence is rare. tory drugs including ketoprofen, grade disease. Mortality for low- Environmental factors impact sulindac, and piroxicam. Clinical ® E grade tumors was 6% compared DNA to modify tumor suppressor studies are evaluating Celebrex with 21% for high-grade tumors genes (p53), genes controlling and the anti-schistosomal agent, D (Heney, 1992). cell proliferation (Rb), growth Oltipraz®, which inhibits nitro- U The European Organization factor genes (erbB-2), and others samine carcinogenesis (Lamm et C for Research and Treatment of (p15, p16). Chemical carcinogens al., 1994). Cancer (EORTC) divided superfi- are thought to account for 20% of A cial bladder cancer patients into bladder cancers in the United PHARMACOLOGIC T low, intermediate, and high-risk States. TREATMENT I groups based on their experience Dietary factors are also with thousands of patients potentially important in bladder Intravesical Chemotherapy O enrolled in prospective studies. cancer. Diets low in vitamin A Four intravesical drugs are N The authors’ experience corrobo- and low serum carotene levels available and commonly used as rates that – low-risk patients are are associated with increased chemotherapy in the United those with solitary grade I Stage risk of bladder cancer. Multiple States with one more that has Ta tumors; intermediate-risk animal studies and two clinical been studied and used, but is cur- patients are those with multiple trials demonstrated that vitamin rently not available. Randomized or recurrent grade I Stage Ta A derivatives reduce the devel- trials have failed to demonstrate tumors, or grade II Ta tumor(s) opment and recurrence of blad- that any of the chemotherapies — (single or multiple); high-risk der cancer. Pyridoxine (vitamin thiotepa, doxorubicin, mitomycin patients are those with one or B6) is reported to enhance tumor C, epirubicin, or the previously more of the following: grade III immunity in animals. B6 was as available valrubicin — is superior disease (high-grade, in the new effective as thiotepa (discussed to the others. Randomized trials terminology), lamina propria later) in reducing bladder cancer also failed to show that (T1) invasive disease, CIS, or recurrence after 1 year, but subse- chemotherapy reduces progres- recurrence at 3 months. quent studies failed to confirm sion or reduces mortality. The its benefit (Byar & Blackard, EORTC/MRC meta analysis DIET, LIFESTYLE, GENETIC, 1977). Vitamins C and E may showed a long-term reduction in AND ENVIRONMENTAL reduce patient’s risk of develop- tumor recurrence of 6%, but no RISK FACTORS ing bladder cancer but studies reduction in disease progression Smoking has long been rec- are inconsistent. Evidence for or mortality (Pawinski et al., ognized as an important risk fac- anti-tumor activity also exists for 1996). tor for bladder cancer, but only folic acid and vitamin D (Kamat Since the side effects of recently has the importance of & Lamm, 1999). Finally, a vita- chemotherapy are generally less smoking cessation been demon- min preparation containing high than bacillus Calmette-Guerin strated. One study reviewed 286 doses of vitamins A, B6, C, and E (BCG) immunotherapy, chemo- patients, including ex-smokers, demonstrated in a randomized therapy is the treatment of choice patients who quit smoking at the clinical trial to reduce tumor for low-risk patients (see Table 1). time of diagnosis, and patients recurrence significantly, and is Patients who fail to respond to who continued to smoke. Ex- commercially available as alkylating agents (thiotepa or mit- smokers presented at a later age, Oncovite® from Mission omycin C) may be best treated had an improved recurrence-free Pharmacal (Lamm et al., 1994). with an intercalating agent (dox- survival compared to quitters Increased intake of dietary orubicin, epirubicin, or valru- and current smokers (p<0.03), fat, particularly cholesterol, is bicin) and vice versa. and most importantly, had a linked to increased risk of blad- Data now clearly show that 324 UROLOGIC NURSING / October 2005 / Volume 25 Number 5 UNJ Oct 2005-325.ps 9/15/05 10:59 AM Page 325 Table 1. given in conjunction with tumor C Efficacy and Toxicity Comparisons of Intravesical resection, doses of 30 mg to 60 O Therapy in Bladder Cancer mg are used in 15 cc to 30 cc of sterile water and held for 2 N Recurrence hours. Treatment is given weekly T Drug CR CIS * Reduction Toxicity and Side Effects for 4 to 8 weeks, depending on I volume of residual disease. BCG 72%-84% 40% Cystitis: 90% When repeated treatments are N Fever/chills: 4% used, blood counts should be U BCG infection: 1% obtained, since thiotepa has a I molecular weight of 188 and Mitomycin C 52% 14% Myelosuppression: 0-10% drugs with molecular weight less N Cystitis: 10% G Rash: 6% than 300 are more readily absorbed from the bladder.