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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.

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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

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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. Liver Doxorubicin 48% 16% Cystitis: 26% function studies are not required, E since the primary toxicity of Epirubicin 73% 20% Decreased capacity: 9% thiotepa is due to myelosuppres- D Anaphylaxis: Rare sion. The intravenous dose of U Cystitis: 10%-37% thiotepa is 0.5 mg/kg, so a single C treatment is safe even if, as is Thiotepa 28% 17% Myelosuppression: 9% common with large tumors and A Cystitis: 19% recent resection, 100% absorp- Azoospermia: Rare T tion occurs. I *Carcinoma in situ Thiotepa has been used in many body cavities, including O the greatest benefit of intravesical creased urine output reduces the peritoneum. Unlike most N chemotherapy occurs when treat- drug concentration, overnight other chemotherapies, which are ment is given to prevent seeding dehydration is recommended caustic, thiotepa can be instilled and initiated within 6 hours of prior to drug instillation. Patients safely in the bladder even if per- tumor resection. Continued treat- are generally asked to retain the foration has occurred. Thiotepa ment for 4 to 8 weeks is appro- instilled drug for 2 hours. Care can also be instilled in the blad- priate for patients with residual must be taken to completely der in patients who are undergo- disease until complete response empty the bladder prior to instill- ing cystectomy or partial cystec- is obtained, but “maintenance” ing chemotherapy. An ultra- tomy to reduce the risk of wound chemotherapy or “prophylactic” sound of the bladder after inser- seeding. Thiotepa generally caus- chemotherapy has not been tion of a catheter is useful in con- es little or no symptoms of cysti- demonstrated to be effective. The firming complete emptying, tis. For these reasons, this is the use of chemotherapy in the since, surprisingly, catheteriza- chemotherapy of choice at the absence of existing malignancy tion does not reliably empty. authors’ facility. Studies suggest should be avoided. Animal stud- This was objectively determined that a single instillation reduces ies have demonstrated that by Au et al. (2001). It resulted in the risk of tumor recurrence by repeated instillation of thiotepa, a protocol that required confir- about 20%. doxorubicin, or mitomycin C can mation of bladder emptying with Doxorubicin. The standard induce hyperplasia, dysplasia, a bladder scan prior to intravesi- dosage of doxorubicin is 50 mg in carcinoma in situ, and even, in cal mitomycin instillation into 25 cc of sterile water. As with the case of mitomycin C, invasive the bladder for all patients. We other chemotherapies, optimal transitional cell carcinoma recommend that patients lie response occurs when given as a (Friedman, Mooppan, Rosen, & prone for 15 minutes to displace single instillation at the time of Kim, 1991). the air bubble introduced with tumor resection. An exposure of In contrast to systemic the catheter, thereby ensuring 30 minutes is used when given at chemotherapy, where the admin- contact at the bladder dome. the time of surgery. When given istered dose is of primary impor- Available intravesical chemo- to treat existing disease rather tance, with topical intravesical therapies: Thiotepa. The standard than prevent recurrence, treat- chemotherapy, response is pro- dosage of thiotepa is 30 mg in 15 cc ment is held for 2 hours, and portional to drug concentration sterile water. When given as a sin- given weekly for 4 to 8 weeks, and duration of exposure. Since gle instillation at the time of depending on volume of residual duration of exposure is limited tumor resection, an exposure of disease. Side effects include irri- by bladder capacity, and in- 30 minutes is used. When not tative bladder symptoms and,

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C very infrequently, decreased perforation or any risk for low-grade urothelial carcinoma is O bladder capacity. extravasation is present, since relatively more responsive to Mitomycin C. The standard this would put the patient at risk chemotherapy than high-grade N dosage of mitomycin C is 40 mg for peritonitis. carcinoma. In contrast, with BCG T in 20 cc sterile water. Contra- Valrubicin. Valrubicin was immunotherapy, low-grade tumors I indications include hypersensi- specifically approved for BCG- appear to be relatively less respon- tivity, bladder perforation, refractory carcinoma in situ of sive. Therefore, chemotherapy is N myelosuppression, and thrombo- the bladder, where it is effective used initially in low-grade dis- U cytopenia. The main side effects in about 20% of patients. The ease, where the risk of progres- I are skin rash, irritative bladder standard dose is 800 mg in 75 mL sion is very low and the side symptoms, bladder calcifica- normal saline weekly for 6 effects and cost of a single post- N tions, and myelosuppression. weeks. However, valrubicin is operative treatment are also G While mitomycin C is highly currently not available in the appropriately low. effective, like doxorubicin it United States. Available intravesical immuno- E should never be given if bladder therapies: BCG immunotherapy. perforation is suspected. In a ran- Intravesical Immunotherapy BCG, or bacillus Calmette-Guerin, is D domized study, recurrence was Like chemotherapy, immuno- an attenuated form of the bacteri- U nearly cut in half by using an therapy for superficial bladder um Mycobacterium tuberculo- C optimized schedule: 40 mg/20 cc cancer is instilled in the bladder sis, used to prevent tuberculo- (compared with 20 mg/20 cc), with the goal of eradicating exist- sis. It is a potent immune stim- A overnight dehydration, ultra- ing disease, reducing disease ulant. The standard dose of T sound-confirmed complete blad- recurrence and progression, and BCG is 81 mg for TheraCys® and I der emptying, alkalinization improving patient survival. 50 mg for TICE®, both in 50 cc using 1.3 g of sodium bicarbonate Immunotherapy has very little physiologic saline. Treatment O the night before, morning of, and else in common with chemothera- should be postponed for at least N 30 minutes prior to treatment. py. It is important, therefore, to 1 to 2 weeks following tumor Mitomycin C is inactivated by keep the anticipated treatment resection or bladder biopsy. A acid urine (Au et al. 2001). schedules, side effects, and results purified protein derivative Recent studies also suggest separate (see Table 1). Cytotoxic (PPD) test may be performed as that local hyperthermia, which chemotherapy directly kills can- the response and side effects can be obtained with a cer cells, while immunotherapy vary according to PPD status. microwave applicator inserted generally stimulates the patient’s Those with a positive PPD will into the bladder with a special immune response. Increasing the have a more vigorous and accel- catheter (not available in the dose of chemotherapy results in erated response, with more United States), can also enhance increased cancer cell killing. hypersensitivity. Treatments are the efficacy of mitomycin C, However, increasing immuno- repeated weekly for 6 weeks, albeit with a significant increase therapy beyond the effective with dose reductions to 1/3, in systemic absorption. Myelo- dose will begin to suppress the 1/10, 1/30, or 1/100 as needed suppression is the primary sys- patient’s immune response. to prevent increasing or severe temic toxicity of mitomycin. Chemotherapy penetrates the symptoms of bladder irritation. Epirubicin. Epirubicin is a bladder by diffusion down a con- Three additional instillations, very popular intravesical drug in centration gradient, while BCG given at 3 months (6 weeks after Europe. Standard dosage is 80 immunotherapy attaches by completion of the initial 6-week mg in 40 cc sterile water. The means of specific receptors. Such course) increase the complete main side effects are irritative differences have important clini- response in CIS from 56% to bladder symptoms. Systemic cal consequences. While chemo- 84%. Maintenance BCG, using absorption is minimal, but sys- therapy is best given immediate- up to 3 weekly instillations in temic administration is associat- ly at the time of tumor resection, disease-free patients given at 3, ed with myelosuppression, car- immediate immunotherapy does 6, 12, 18, 24, 30, and 36 months, diomyopathy, congestive heart not reduce tumor recurrence, and decreased 7-year recurrence in failure, and arrythmias. Like dox- in the case of BCG, can result in high-risk patients from 52% to orubicin, mitomycin C, and val- life-threatening toxicity. Main- 25% and significantly reduced rubicin, epirubicin is a vesicant tenance chemotherapy has not disease worsening. However, and will result in necrosis with improved results, but mainte- since only 16% of patients extravasation. Best results occur nance BCG immunotherapy not received treatment at each with immediate postoperative only reduces recurrence, but also scheduled interval, it is clear instillation, but instillation appears to be required to reduce that a reduced treatment regi- should not be done if bladder disease progression. Surprisingly, men may be appropriate, and in

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our hands, the 30-month main- of developing malignancy with- Combination Intravesical C tenance dose is now omitted in in the prostatic urethra and Therapy O many patients. It is also clear upper urinary tracts. These BCG immunotherapy has that the risk for recurrence and patients require long-term fol- been combined with chemother- N progression lasts for decades. lowup with prostatic urethral apy, primarily mitomycin C. T Therefore, based on what is biopsies and upper-tract ureter- These studies demonstrate no I known of the long-term risk of al washes, imaging studies, or improvement in efficacy com- disease progression with CIS or ureteroscopy to prevent silent pared with BCG alone. Com- N high-grade disease, we continue progression from disease in bination chemotherapy is now U 3-week maintenance at years those sites. standard for patients with I (counting from the start of treat- Interferon Alfa 2b. Though metastatic transitional cell carci- N ment) 4, 5, 6, 8, 10, and 12 for not specifically approved for noma but has not been adequate- patients with CIS or high-grade superficial bladder cancer, ly studied in patients with super- G disease. interferon alfa 2b has a response ficial disease. Combination The primary side effects of rate of 47% in CIS and 25% in immunotherapy, specifically the E BCG are increased urinary fre- papillary tumors. These results use of BCG plus interferon alfa quency, dysuria, hematuria, and compare favorably with those of 2b, is highly effective. About D flu-like symptoms. Systemic intravesical chemotherapy. The 60% of patients who fail to U symptoms can include arthral- results in prophylaxis have respond to BCG can be rescued C gia/arthritis, rash, fatigue, fever, been less favorable, but a recent with BCG plus interferon and systemic BCG infection, study reported a reduction in (O’Donnell, Krohn, & DeWolf, A which can present as pneu- recurrence from 68% to 28% 2001). The standard dose is 50 T monitis, hepatitis, epididymitis, (Papatsoris, Deliveliotis, Gian- mg to 81 mg of BCG plus 50 mil- I prostatitis, renal abscess, or sep- nopoulos, & Dimopoulos, 2004). lion units of interferon alfa 2b. sis. BCG is sensitive to cipro- The primary advantage of interfer- Treatments are given weekly for 6 O floxacin and other fluoro- on treatment is the absence of sig- weeks, with maintenance using N quinolones as well as most anti- nificant side effects. Doses as high up to 3 weekly instillations at 3 tubercular antibiotics, such as as 1 billion units have been or 6 months, and then every 6 to isoniazid, ethambutol, etc. Sep- given intravesically without 12 months. The dose of BCG is tic reactions should be treated dose-limiting side effects (Turti reduced to 1/3, 1/10, 1/100 as with combination antibiotics et al., 1988). The standard dose needed to prevent increased side including isoniazid and rifam- is 50 to 100 million units week- effects. While we try to avoid giv- picin as well as steroids. Ster- ly for 6 weeks. Additional main- ing a second 6-week course of oids should be tapered gradual- tenance treatments may be ben- BCG to patients who have previ- ly to prevent relapse. eficial, but the ideal regimen is ously received BCG because they BCG induces an anti-tumor unknown. Based on the favor- are at risk of immunosuppres- response in bladder cancer by able experience with 3-week sion, the addition of interferon drawing lymphocytes and maintenance BCG, we have appears to reduce this risk. macrophages to the bladder and used this regimen for patients stimulating a cellular (TH1) treated with interferon as well. NURSING IMPLICATIONS immune response. Cytokines Interferon is remarkably Nurses are key to vital associate with this response non-toxic. Many patients who patient communication for opti- result in symptoms of bladder have major BCG reactions have mal intravesical therapy. This is inflammation and even flu-like long-term persistence of the particularly critical with BCG symptoms. Patients who have a organism within their systems. where increasing symptoms need fever associated with BCG have Interferon in combination with to be noted so that dosage can be a lower risk of tumor recur- BCG appears to potentiate the reduced before major side effects rence, but fever and increasing effect of BCG. Therefore later use occur. Patients need to know that local symptoms can also herald of interferon as a single agent BCG requires special antibiotic a severe BCG reaction. There- may be very useful in potentia- treatment, and symptoms such as fore, we have adopted the poli- tion of these residual levels in night sweats, fever, and chills cy of reducing the dose of BCG BCG-intolerant patients. TB can present months and even in patients with increasing side transmission is only a risk for years after BCG administration. effects. immunosuppressed patients or This information should be com- The primary effect of BCG is those with open wounds. No municated directly to the urolo- local, at the site of administra- other special precautions are gist, since physicians in other tion. Patients with high-grade required. specialties, even infectious dis- bladder cancer or CIS are at risk ease, may not be aware of this

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C consideration. A nurse should be series. Journal of Urology, 165(4), cal trial. Journal of Urology, 151(1), 1111-1116. 21-26. O able to explain the procedure selected by the physician, under- Fleshner, N., Garland, J., Moadel, A., Herr, O’Donnell, M.A., Krohn, J., & DeWolf, W.C. N H., Ostroff, J., Trambert, R., et al. (2001). Salvage intravesical therapy stand, discuss, and interview for (1999). Influence of smoking status with interferon-alpha 2b plus low T possible complications, and be on the disease-related outcomes of dose bacillus Calmette-Guerin is I able to assist as directed in the patients with tobacco-associated effective in patients with superficial administration of intravesical superficial transitional cell carcino- bladder cancer in whom bacillus N ma of the bladder. Cancer, 86(11), Calmette-Guerin alone previously treatment. 2337-2345. failed. Journal of Urology, 166(4), U Friedman, D., Mooppan, U.M., Rosen, Y., 1300-1304 I Conclusions & Kim, H. (1991). The effect of intrav- Papatsoris, A.G., Deliveliotis, C., Superficial bladder cancer is esical instillations of thiotepa, mito- Giannopoulos, A., & Dimopoulos, C. N mycin C, and adriamycin on normal (2004). Adjuvant intravesical mitox- a heterogeneous disease that urothelium: An experimental study antrone versus recombinant interfer- G requires a variety of treatments. in rats. Journal of Urology, 145(5), on-alpha after transurethral resection Low-risk patients typically have 1060-1063. of superficial bladder cancer: A ran- Heney, N.M. (1992). Natural history of domized prospective study. Urology E a benign course and can be effec- tively treated with transurethral superficial bladder cancer – International, 72(4), 284-291. D Prognostic features and long-term Pawinski, A., Sylvester, R., Kurth, K.H., resection followed by a single disease course. Urologic Clinics of Bouffioux, C., van der Meijden, A., U instillation of cytotoxic chemo- North America, 19(3), 429-433. Parmar, M.K., et al. (1996). A com- C therapy. Intermediate and high- Jemal, A., Tiwari, R.C., Murray, T., bined analysis of European risk patients require, in general, Ghafoor, A., Samuels, A., Ward, E., et Organization for Research and A al. (2004). Cancer statistics, 2004. CA: Treatment of Cancer, and Medical the addition of BCG immuno- Cancer Journal for Clinicians, 54(1), Research Council randomized clini- T therapy due to the risk of disease 8-29. cal trials for the prophylactic treat- I progression. BCG, and presum- Kamat, A.M., & Lamm, D.L. (1999), ment of stage TaT1 bladder cancer. ably BCG plus interferon-alfa, Chemoprevention of urological can- European Organization for Research O can significantly reduce the risk cer. Journal of Urology, 161(6), 1748- and Treatment of Cancer Geni- 1760. tourinary Tract Cancer Cooperative N of progression when used in a Lamm, DL. (2002) Superficial bladder can- Group and the Medical Research maintenance schedule. Nurses cer. Current Treatment Options in Council Working Party on Superficial provide a vital role in patient Oncology, 3(5), 403-411. Bladder Cancer. Journal of Urology, communication, and can help Lamm, D.L., & Griffith, J.G. (1992). 156(6), 1934- 1940. Intravesical therapy: Does it affect the Turti, F.M., Shortliffe, L.D., Williams, R.D., reduce potential complications. natural history of superficial bladder Pitts, W.C., Kempson, R.L., Russ, J.L., Cystectomy is used when topical cancer? Seminars in Urology, 10(1), et al. (1988). Alpha-interferon in therapies fail, and is associated 39-44. superficial bladder cancer: A with an excellent survival rate Lamm, D.L., Griffith, J.G., Pettit, L.L., & Northern California Oncology Group with local disease. Nseyo, U.O. (1992). Current prospec- Study. Journal of Clinical Oncology, • tives on the diagnosis and treatment 6, 476-478. of superficial bladder cancer. Vicente, J., Laguna, M.P., Duarte, D., Algaba, References Urology, 39(4), 301. F., & Chechile, G. (1991). Carcinoma in Au, J.L., Badalament, R.A., Wientjes, M.G., Lamm, D.L., Riggs, D.R., Shriver, J.S., situ as a prognostic factor for G3pT1 Young, D.C., Warner, J.A., Venema, vanGilder, P.F., Rach, J.F., & DeHaven, bladder tumours. British Journal of P.L., et al. (2001). Methods to improve J.L. (1994). Megadose vitamins in Urology, 68(4), 380-382. efficacy of intravesical mitomycin C: bladder cancer: A double blind clini- Results of a randomized phase III trial. Journal of the National Cancer Institute, 93(8), 597-604. Bostwick, D.G. (1992). Natural history of early bladder cancer. Journal of Call for Research Proposals Cellular Biochemistry, 16I(Suppl.), 31-38. The Society of Urologic Nurses and Associates (SUNA) is Byar, D., & Blackard, D. (1977). pleased to announce the ongoing availability of clinical proposals Comparisons of placebo, pyridoxine, with applicability to urologic nursing practice. Two types of non- and topical thiotepa in preventing dissertation awards are available. recurrence of stage I bladder cancer. Urology, 10, 556-561. 1. The Young Investigator Research Program is directed at new Chen, Y.C., Su, H.J., Guo, Y.L., Houseman, researchers. Awards for 2005 are up to $40,000. Details are E.A., & Christiani, D.C. (2005). available on SUNA’s Web site www.suna.org or by contacting Interaction between environmental [email protected]. tobacco smoke and arsenic methyla- tion ability on the risk of bladder can- 2. The Established Investigator Research Program (EIRP) is direct- cer. Cancer Causes Control, 16(2), 75- ed at experienced researchers with the same focus on clinical 81. urologic nursing. Contact [email protected] for further details. Dalbagni, G., Genega, E., Hashibe, M., Successful applicants will be honored at future SUNA national Zhang, Z.F., Russo, P., Herr, H., & conventions where they will present their study findings. Reuter, V. (2001). Cystectomy for bladder cancer: A contemporary

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