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Urothelial Cancers: Ureter, Renal Pelvis, and Bladder
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Seminars in Oncology Nursing, Vol 28, No 3 (August), 2012: pp 154-162
UROTHELIAL CANCERS: URETER, RENAL PELVIS, AND BLADDER ALLISON TYLER OBJECTIVES: To review the diagnosis, treatment, and nursing management of patients with urothelial cancers.
DATA SOURCES: PubMed, Ovid MEDLINE, Text books, and clinical experience. CONCLUSION: Progress is being made in the surgical and systemic management of urothelial cancers, and the oncology nurse is in a position to make an impact on patient education and overall quality of life. IMPLICATIONS FOR NURSING PRACTICE: Nursing care begins at pre-diagnostic testing and continues through treatment for metastatic disease. Nurses must be knowledgeable about diagnostic tests, treatment options, and the quality-of-life implications of associated surgeries and/or treatments to support and guide patients. Education should be comprehensive, addressing not only treatment side effects but also long-term implications on patients’ lives and lifestyles.
KEY WORDS: Urothelial, renal pelvis, chemotherapy, psychosocial, sexuality
U
ROTHELIAL cell carcinoma (UCC), often referred to as ‘‘transitional cell carcinoma (TCC),’’ is a cancer that occurs within the urinary system; namely the bladder, ureter, urethra, or renal pelvis. The urothelium is a form of elastic epithelial tissue that lines
Allison Tyler, BSN, RN, OCNÒ, CCRP: Prostate/Bladder Cancer Clinical Research Nurse Coordinator, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. Address correspondence to Allison Tyler, BSN, RN, OCNÒ, CCRP, Prostate/Bladder Cancer Clinical Research Nurse Coordinator, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave., Desk R33, Cleveland, OH 44915. e-mail: [email protected] Ó 2012 Elsevier Inc. All rights reserved. 0749-2081/2803-$36.00/0. doi:10.1016/j.soncn.2012.05.004
the inner surface of the urinary organs. UCC is the most common type of bladder malignancy, comprising nearly 95% of all bladder cancers.1 UCC of the upper urinary tract (renal pelvis and ureter) is uncommon, accounting for only 2% to 6% of cases.2 This article will review the incidence, diagnosis, treatment options, nursing management, and psychosocial-sexual issues of this patient population and the challenges they may face.
OVERVIEW OF UROTHELIAL CANCER Urothelial cancer is a disease of the late middle and elderly ages, primarily affecting people between the ages of 50 and 75. Unlike many other types of malignancies, the rates of new cases, as well as the number of related cancer deaths, have remained relatively stable over the past
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several decades.3 In 2012, it is estimated that there will be 73,510 new cases of UCC, with 55,600 cases in men and only 17,910 cases in women.3 Men are three times more likely to be diagnosed with UCC than women, and whites are twice as likely to be diagnosed than African Americans.4 There are currently more than 500,000 survivors of UCC in the United States alone.1 The single-most significant risk factor in the development of UCC is exposure to cigarette smoke. It is estimated that nearly 80% of all UCC can be attributed to cigarette smoking, whether it be your own or through inhalation of secondhand smoke.1 When a person inhales tobacco smoke, some of the carcinogens are absorbed through the lungs into the blood. The chemicals are then filtered by the kidneys and concentrated in the urine, where they can cause damage to the urothelium, increasing the chance of developing urothelial cancer.1 Other environmental risk factors include occupational exposure to industrial chemical substances, chemotherapy (most notably, cyclophosphamide) and radiation therapy, chronic bladder irritation and infections, and arsenic exposure. Non-environmental risk factors include age, race and ethnicity, gender, a personal history of UCC, birth defects of the bladder, and genetic factors such as mutations of the retinoblastoma (Rb1) gene, Cowden disease, and hereditary non-polyposis colorectal cancer (HNPCC) syndrome.1
DIAGNOSIS OF LOWER TRACT UCC (BLADDER) AND STAGING Given the location of this malignancy, it is not surprising that hematuria is the primary complaint leading to the initiation of diagnostic testing. Hematuria may fluctuate, being present one day and not the next, over the course of weeks to months. However, if the cause of the hematuria is indeed UCC, it will always recur. A challenge with this particular symptom is that hematuria may be caused by a myriad of other medical issues, including infections, an enlarged prostate (in men), renal calculi, and other benign renal conditions. Alone, hematuria is not diagnostic, but is a valuable tool in identifying patients for whom further workup may be necessary. If UCC is suspected, patients will undergo a cystoscopy for direct evaluation of the lower urinary tract and bladder. If abnormal
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areas are noted on the cystoscopy, biopsies of the affected area(s) are taken. Biopsies are especially useful in that they offer insight into the tumor’s invasiveness, or how deep into the bladder wall the cancer has penetrated.4 If the disease is in the inner or ‘superficial’ layer of the cells, it is considered non-invasive, while if it has grown into the deeper layers or muscles of the bladder, it is considered invasive, and is in turn more difficult to treat. Used in adjunct to cystoscopy, is urine cytology, which is more useful for patients with high-grade disease (grade 3), as those highly abnormal cells are more likely to shed.5 There are currently several urine biomarker tests approved by the US Food and Drug Administration for the assistive diagnosis and surveillance of UCC. However, none of these tests are as sensitive as the actual visual cystoscopy, and are not used alone for diagnostic purposes.5,6 Grade and stage are critical factors in determining treatment and patient outcomes for those with UCC. Grading is the basic 1-3, with grade 1 (low grade) being well differentiated; grade 2 being moderately differentiated; and grade 3 (high grade) being poorly differentiated. Low-grade tumors are usually non-invasive; however, the have a proclivity toward recurrence, while high-grade tumors tend to be invasive and are more likely to metastasize.7 UCC is staged using the American Joint Committee on Cancer Staging (AJCC) tumor-node-metastasis system. Two different types of staging, clinical or pathologic, can be performed in this patient population. The method used is dependent on the manner in which patients were diagnosed. Clinical stage is based on the physician’s judgment, incorporating the results of any cystoscopies, biopsies, and radiographic imaging that have been done. For a pathologic stage to be determined, a cystectomy and probable pelvic lymphadenectomy must be performed. Table 1 outlines the full AJCC TNM staging system.8
DIAGNOSIS OF UPPER URINARY TRACT (RENAL PELVIS, URETER) Upper urinary tract UCC is most common among patients with a median age of 65 to 67 years, and there is evidence that advancing age directly correlates with more invasive/higher-grade disease.9 As mentioned previously, cancer of the upper urinary tract is an uncommon disease, making up less than 6% of UCC cases. In regard to renal pelvis UCC, it accounts for less than 7% of renal carcinomas.10
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TABLE 1. AJCC 2002 TNM Staging System for Bladder Carcinoma Primary tumor TX Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Noninvasive papillary carcinoma Tis Carcinoma in situ T1 Tumor invades subepithelial connective tissue (lamina propria) T2 Tumor invades musclularis propria bladder wall T2a Tumor invades superficial muscle (inner half) T2b Tumor invades deep muscle (outer half) T3 Tumor invades perivesical tissue T3a Microscopically T3b Macroscopically (extravesical mass) T4 Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, and abdominal wall T4a Tumor invades prostate, uterus, or vagina T4b Tumor invades pelvic or abdominal wall Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastases in a single lymph node, 2 cm or less in greatest dimension N2 Metastases in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes, none more than 5 cm in greatest dimension N3 Metastasis in a lymph node more than 5 cm in greatest dimension Distant Metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Data from Edge et al.8
Upper urinary tract urothelial cell cancer can be multi-factorial, with tumors in different locations in the urinary tract, and tumors tend to occur ipsilaterally.11 Presenting symptoms of upper tract UCC include hematuria (in 75% of patients), which is often in conjunction with flank pain (in 33% of patients).12 Intravenous urography is performed to evaluate the upper urinary tract and will identify filling defects in the majority of patients, but does not distinguish malignancy from a benign process. Additional imaging with contrast computed tomography is useful; as is additional testing with upper urinary tract endoscopy (ureteroscopy).13 As with lower tract UCC, urine cytology is unreliable in detecting low-grade tumors, and false-positive results occur in upwards of 30% of tested patients. Therefore, urine cytology should only be used as a diagnostic supplement.14 Increased specificity and sensitivity may be achieved by adding the use
of brush cytology, which is the use of a cytology brush to collect cell samples from the mucosa.15 Another diagnostic option, achieved through growing and improving technical instrumentation, is ureteropyeloscopy (the use of scope to directly visualize the ureter and renal pelvis). However, this presents an increased risk of ureter perforation and postoperative stricture; therefore, appropriate patient selection is key.16
SURGICAL MANAGEMENT: LOWER TRACT UCC Primary treatment of lower tract UCC is wholly dependent on whether or not the disease is invasive. For a patient with non-invasive UCC, complete transurethral resection of the tumor(s) is warranted; followed by close cystoscopic surveillance.17 The frequency of repeat cystoscopies will vary by physician practice; however, every 3 months is not an unusual practice. Should recurrent masses be detected on surveillance scopes, treatment options would include repeat resections or intravesical chemotherapy. For those patients that have invasive UCC, primary treatment is a radical cystectomy. Depending on the degree of muscular penetration by the cancer, this may be a more invasive surgery than one might realize. For men, this may include a local lymphadenectomy and prostatectomy. And for women, sometimes a full pelvic exenteration with the removal of local lymph nodes, the uterus, ovaries, and parts of the vagina, in addition to the bladder itself.4 Depending on the location of the disease, the urethra may also be removed. Given that the urothelial tissue lines the entire urinary tract, a patient with cancer in one area, such as the bladder, is at high risk for developing disease in the other organs lined with urothelial tissue. Removing all the potentially affected organs increases the chance that surgery may be curative. At the other end of this spectrum are patients with localized disease surrounded by healthy tissue. These select patients may be candidates for partial cystectomy; thereby preserving part of the natural, functioning bladder and its surrounding organs. An unavoidable outcome of cystectomy is an alteration in urination. The nature of the change is highly dependent on the type of surgery a patient has and the type of urinary diversion the patient chooses or is given. There are three primary types of urinary diversions: continent, incontinent, and neobladder. These are described in detail in Table 2.
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TABLE 2. Urinary Diversions
Type of Diversion Ileal Conduit [Bricker Conduit] Continent Diversion [Indiana Pouch]
Neobladder
Nephrostomy Ureterostomy
Description Ureters are diverted to drain into a short part of the ileum. The end of this ileal segment is brought out to a stoma. Urine drains out of the stoma into an external collection bag. A reservoir is constructed out of the right colon and a small segment of ileum, which is brought out to the skin as a stoma. A one-way valve mechanism is created so that urine is kept inside the reservoir and will not leak out to the skin. Patients self-catheterize through the stoma to drain the reservoir. The surgeon creates a reservoir made of small intestine and connects it to the urethra, allowing the patient to void through the urethra; similar to normal urination. The reservoir is made to mimic the normal storage function of the urinary bladder. An indwelling catheter is placed through the skin, usually in the flank area, directly into the renal pelvis, allowing for the drainage of urine into external collection bags. One or both ureters are connected directly to the abdominal wall, creating stoma(s). Urine drains from the ureter(s) into external collecting bag(s).
Data from the National Institute of Diabetes and Digestive and Kidney Diseases.47
SURGICAL MANAGEMENT: UPPER TRACT UCC Surgical options for cancer of the renal pelvis and/or ureter differs from the cystectomy used on lower-tract disease. For more extensive disease, a nephroureterectomy is performed; removing the entire kidney, ureter, and bladder cuff.18 For cases of localized, low-grade, low-stage disease, nephron-sparing surgeries may be done. Namely, a pyelotomy with tumor ablation or a partial nephrectomy.19 Selecting patients that fit the above criteria is critical to ensure that only appropriate patients are treated in this manner. Regarding disease specific to the ureters, segmental resections of the ureter are conducted, which removes the diseased part of the ureter and then reattaches the ends of the ureter. This surgery can only be completed if the lower third of the ureter, near the bladder, is affected and the cancer must be superficial.20
THERAPY FOR LOCALIZED DISEASE Currently, the most effective intravesical therapy for patients with carcinoma in situ or high-grade superficial bladder cancer is an immunotherapy, or a treatment designed to elicit or amplify an immune response, called Bacille Calmette- Gu erin (BCG).21 BCG is a live, attenuated vaccine originally developed for the treatment of tuberculosis.22 BCG is instilled into the bladder via urinary catheter and patients are instructed to
move about and to not void for several hours; allowing the agent to wash the entire bladder wall. Treatment with BCG is typically given as 120 mg instillations once a week for 6 weeks, then with maintenance doses monthly over the next 12 to 18 months. Response rates for this regimen in patients with high-risk pathology are nearly 70%.23 The expected side effects are urinary irritation, along with a potential for immunotherapeutic reactions such as fever, malaise, nausea, and an overall cumulative effect, with symptoms worsening with additional treatments.24 A weapon in the fight against recurrence for patients with non-invasive bladder cancer is the use of intravesical chemotherapy (the diffusion of chemotherapeutic agents into the layers of the bladder). For patients who have had resected disease, the use of intravesical chemotherapy serves multifactorial goals of destroying any residual disease, preventing tumor recurrence, and delaying tumor progression.6 The designated chemotherapeutic agent is instilled into the bladder, via a catheter, for a specified time frame, during which the patient is instructed to not void. Patients are then encouraged to move about, causing the chemotherapy to splash around, coating the inside of the bladder. Patients then void the agents out. The current standard agent for this type of therapy is mitomycin C, an alkylating agent that inhibits DNA synthesis.25 Also used for this purpose, individually, are doxorubicin, epirubicin, thiotepa, and gemcitabine. On average, intravesical agents reduce recurrence by 15% to 41% and are most effective
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when treatment is initiated within 24 hours of resection.26 Predictably, side effects from these therapies tend to be spot specific, with the most common noted complaint being chemical cystitis.27 All these agents may also be used for the treatment of disease in the renal pelvis or ureter, through topical exposure via either antegrade or retrograde routes. The antegrade route involves the placement of a nephrostomy tube, through which the agents are infused for direct contact with the renal pelvis.28 The retrograde route requires the placement of a ureteric catheter with direct infusion to the diseased area or, alternatively, the patient may have the agent instilled into his or her bladder and then be placed in Trendelenburg position.29 Muscle-invasive, localized disease of the bladder is generally managed by surgery. However, there are some patients that are highly motivated to preserve the bladder and therefore opt for neoadjuvant chemotherapy or chemoradiation. Neoadjuvant chemotherapy, usually with either methotrexate/ vinblastine/doxorubicin/cisplatin (MVAC) or cisplatin/ methotrexate/vinblastine (CMV), is given before cystectomy, with the goal of reducing tumor volume and preserving the bladder, by means of a partial cystectomy.30 Chemoradiotherapy is the combination of chemotherapy with radiation therapy, given in an effort to increase the chance of preserving the bladder, while exposing the tumor to radiation and, at the same time, treating any potential metastases that are not yet visible on radiographic imaging.31
METASTATIC DISEASE Once disease has spread beyond the primary site, the previously mentioned therapies are of limited utility, given that they target very specific, localized areas. Systemic chemotherapy use in UCC dates back several decades; however, researchers continue to strive for therapeutic improvements to improve response rates and patient quality of life. Historically, treatment for advanced urothelial carcinoma was with MVAC or CMV. These combinations demonstrated response rates in phase II trials as high as 75%, with approximately 30% of cases achieving complete responses.32,33 These combinations nearly quadrupled survival rates, from 3 to 4 months to 12 to 14 months.33 A clinical trial conducted in the United Kingdom in the 1990s compared methotrexate and vinblastine (MV) with CMV and demonstrated an extraordinary 1-year survival benefit for the CMV group at
29%, compared with only 16% for the MV group.34 This trial showed a significant overall survival benefit of 7 months in the CMV group compared with 4.5 months in the MV group.34 Subsequently, it became apparent that cisplatin was an essential component in chemotherapy regimens for UCC. More recently, studies with gemcitabine in combination with cisplatin have produced results similar to MVAC.35 These results led to a large randomized trial that compared MVAC with gemcitabine and cisplatin (GC). The two arms were very similar in terms of median survival, with 13.8 months for GC and 14.8 months for MVAC; as well as in overall response rates, with 46% in the GC arm 49% in the MVAC arm.36,37 Overall toxicity was less in the GC arm, which researchers have determined offset the small survival benefit of the MVAC arm, and has consequently resulted in primary usage of the doublet over MVAC.37 Table 3 provides an overview of treatment options for UCC. Currently there are no data available to support any specific second-line therapy for patients that have failed front-line systemic chemotherapy. There are some data (though limited) that supports re-treatment with the front-line regimen if the patient achieved long-term disease-free progression (more than 6 months); however more research is needed.38
NURSING MANAGEMENT Patients that are diagnosed, treated, and living with urothelial cancers face a multitude of challenges, from surgical complications to chemotherapy side effects. Each different phase of the disease presents its own unique issues and the oncology nurse is in a prime position to assist patients as they navigate these life changes. At the onset, educating patients is a task that will have a lasting impact and should continue throughout a patient’s disease course, as each day for the cancer patient presents new and often unexpected tribulations. For patients undergoing radical cystectomy, extensive conversations regarding urinary diversions and continence should begin preoperatively. Wound care, stoma teaching, neo-bladder training or self-catheterization techniques (if applicable), and symptoms of infection are all critical topics for discussion with patients. As patients progress on to treatment with chemotherapy, whether it is neo-adjuvant or front-line, risks and side effect management should
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TABLE 3. Treatment Options for UCC Surgical Options Transurethral resection of bladder tumor (TURBT) Segmental (partial) cystectomy Radical cystectomy Immunotherapy (intravesical) Bacille Calmette-Guerin (BCG) Interferon alfa Chemotherapy-intravesical Mitomycin C Doxorubicin Epirubicin Thiotepa Gemcitabine Chemotherapy-systemic Methotrexate, vinblastine, doxorubicin, plus cisplatin Gemcitabine plus cisplatin Cisplatin, methotrexate, plus vinblastine Gemcitabine plus carboplatin
Removes tumors that are confined to the inner layers of the bladder. Burns away cancer cells with an electric current (fulguration). Removal of the portion of the bladder that contains cancer cells. Removal of the entire bladder, as well as surrounding lymph nodes.
Sometimes used in combination with BCG Singleton agents Most common
Multiple agents, in combination MVAC GC CMV GemCarb
Data from the American Cancer Society,1 Raghavan and Tuthill,4 and Sternberg.31
be thoroughly addressed. Common adverse events of chemotherapy for UCC are fatigue, myelosuppression and the subsequent risk of infection, nausea and vomiting, hair loss, kidney damage, tinnitus, and dysgeusia. Patients should be instructed on the importance of reporting side effects as soon as they begin to occur, as delays in event reporting often result in dosing delays and/or dose reductions, some of which may be avoided with aggressive, early symptom management. A treatment goal for all patients should be to achieve as much appropriate therapy as possible while maintaining a satisfactory quality of life. Another element to consider when dealing with UCC is that it is a disease of the late middle-age and elderly population. This patient population is likely to have pre-existing co-morbidities as well as issues such as cardiomyopathy, general frailty, hearing loss, and altered mental, functional, and nutritional status. As one ages, the body develops decreased gut motility, decreased liver mass, decreased renal function, and becomes more prone to myelosuppression.39 Given that chemotherapy may have serious consequences in many of these areas, it is imperative to monitor the elderly patient closely. Frequent chemistry panels to assess for hydration status and to evaluate the potential for electrolyte wasting, auditory testing to monitor for changes that may be potentiated by chemotherapy, and blood
counts to evaluate degree of myelosuppression are all areas of consideration for patients with UCC being treated with chemotherapy. Research has also shown that there is a disconnect between how a provider believes they are handling a patient’s treatment-related side effects and how the patient actually feels his or her side effects are being managed.40,41 This suggests that we as providers must be more aggressive and consistent with addressing a patient’s concerns regarding any potential treatment-related effects they may be experiencing, critically listen to the patient, and consequently incorporate their feedback into their treatment plan. Thorough followup regarding the success or lack thereof of the intervention will then close the circle. Tools such as medication dosing diaries and symptom trackers can be invaluable in providing fail-safes to ensure comprehensive and exhaustive symptom management.
PSYCHOSOCIAL ISSUES The diagnosis and subsequent treatment of cancer may be a tremendous source of psychological stress. Given the impact on sexual function and the physical changes that often follow treatment-related surgery, a patient with advanced urothelial cancer may face a more traumatic and
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challenging road than patients with many other types of cancers. Common postoperative problems such as visible scarring, urinary leakage and associated odors, the need for self-catheterization and, depending on the type of urinary reconstruction, the potential need for an external collection reservoir, can all have a negative impact on a patient’s body image and self-esteem. A clinical trial conducted in Sweden found that patients who received one of three different types of urinary reconstruction (ileal conduits with an appliance, continent cutaneous diversions, or a neobladder) 85% of patients continued to complain of emotional problems regarding the management of urine 12 months postoperatively. At 5 years postoperatively, 65% of those patients continued to have the same complaints, with no notable difference between the various types of diversions.42 Nearly 40% of postoperative UCC patients report reduced self-esteem, which did not improve with the passage of time.43 Often after an extensive surgery, as patients with UCC are prone to having, patients will grieve the loss of their body parts.44 Patients react to their cancer diagnosis and its treatment with a wide range of emotions; from anger to urgency for treatment to sadness and feeling alone. The oncology nurse has a unique knowledge of patient care from the operating room through end-stage disease. The nurse is in the ideal position to guide these patients through the journey of adjusting to their ‘new normal.’ Rigorous education and the dissemination of simple tips, such as the use of pads to protect from incontinence, on how to balance fluid intake with a voiding schedule to allow for minimal disruption of daily life activities, and the benefit of locating bathrooms ahead of time when traveling, may ease fears and relieve anxiety, significantly improving a patient’s quality of life. Maximizing use of available resources, across departments, may impact patients. Reaching out to social work, psychology, urology, stoma care, and cancer rehabilitation specialists will add to the comprehensive team approach to patient care, which will ultimately greatly benefit the patient.
SEXUALITY Sexual function and the maintenance of intimate relationships is an important aspect of healthy quality of life for cancer patients.45 Yet, given the sensitive nature of sexuality and associated discomfort with the topic, related issues are
often left unaddressed or inadequately addressed by patients and providers alike. For the patient with UCC, the ramifications of surgery on sexual function are considerable. For women, parts of the vaginal wall and uterus have likely been removed, affecting child-bearing potential, hormonal balance, and causing vaginal dysfunction.42 About half of men suffer nerve damage that leaves them impotent; and if they are able to obtain erections postoperatively, they will not produce any ejaculate because of the loss of the prostate, which in turn has significant ramifications on the patient’s sexual function and pleasure.4,42 Additionally, patients may be fearful or embarrassed by the presence of external collection devices or stomas and the associated risk of urine leakage. Research has also shown that patients with bladder cancer are fearful of harming their partners through sexual contact; largely because of the toxic nature of intravesical therapies.46 The prevalence of sexual dysfunction is very high (54%) for patients with invasive urothelial carcinoma; however, patients’ libidos are generally intact and active.46 Accordingly, health care providers should address the patient’s sexual needs and explore alternatives to traditional intercourse, in an effort to facilitate the development of healthy, safe, satisfying sexual relationships and the retention of emotional intimacy. One available and researched technique is ‘‘Sensate Focus.’’ This is a term associated with a set of specific sexual exercises based on sensual massage techniques, for either couples or individuals, and are aimed at developing non-coital foreplay.45 This allows couples the opportunity to be physically intimate without the pressure or angst of achieving the ‘goal’ of actual intercourse, ultimately decreasing anxiety. Direction is usually at the hand of a therapist, with the objective of appreciating a new set of sensual alternatives to actual intercourse. Oncology nurses have the aptitude to be of great assistance to patients and their partners by proactively introducing the subject of sexuality and sexual function. Through the integration of sex education and open communication, a sense of hope can be fostered for patients who are eager to retain a sense of physical intimacy with their partner.
CONCLUSION UCC is one of the most common cancers in the United States. Progress continues to be made in detection, surgical and systemic treatment options,
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and the quality-of-life challenges of afflicted patients. Increasing therapeutic research, refined surgical techniques, and growing awareness of the psychosocial impact of a cancer diagnosis on patients is
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suggestive of a promising future in this specialty. Oncology nurses have the distinction of being in a position to have a significant impact on patients as they learn of, fight with, and live with cancer.
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implications for conservative management. Urology 2011;78:82-86. 17. Hall MC, Chang SS, Dalbagni G, et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta1, T1, and Tis): 2007 update. J Urol 2007;178:2314-2330. 18. Hattori R, Yoshino Y, Gotoh M, et al. Laparoscopic nephroureterectomy for transitional cell carcinoma of renal pelvis and ureter: Nagoya experience. Urology 2006;67:701-705. 19. Li WM, Shen JT, Li CC, et al. Oncologic outcomes following three different approaches to the distal ureter and bladder cuff in nephroureterectomy for primary upper urinary tract urothelial carcinoma. Eur Urol 2010;57:963-969. 20. Jeldres C, Lughezzani G, Sun M, et al. Segmental ureterectomy can safely be performed in patients with transitional cell carcinoma of the ureter. J Urol 2010;183:1324-1329. 21. Sylvester RJ, van der Meijden APM, Lamm DL. Intravesical Bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 2002;168:1964-1970. 22. Lamm DL, Thor DE, Harris SC, et al. Bacillus CalmetteGuerin immunotherapy of superficial bladder cancer. J Urol 1980;124:38-40. 23. Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance Bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol 2000;163:1124-1129. 24. Berry DL, Blumenstein BA, Magyary DL, et al. Local toxicity patterns associated with intravesical Bacillus Calmette-Guerin: a Southwest Oncology Group Study. Int J Urol 1996;3:98-100. 25. Au LJ, Badalament RA, Wientjes MG, et al. Methods to improve efficacy of intravesical Mitomycin C: results of a randomized phase III trial. J Natl Cancer Inst 2001;93: 597-604. 26. Lamm DL, Riggs DR, Traynelis CL, et al. Apparent failure of current intravesical chemotherapy prophylaxis to influence the long-term course of superficial transitional cell carcinoma of the bladder. J Urol 1995;153:1444-1450. 27. Thrasher JV, Crawford ED. Complications of intravesical chemotherapy. Urol Clin North Am 1992;19:529-536. 28. Eastham JA, Huffman JL. Technique of mitomycin C instillation in the treatment of upper urinary tract urothelial tumors. J Urol 1993;150(2 Pt 1):324-325. 29. Jabbour ME, Smith AD. Primary percutaneous approach to upper urinary tract transitional cell carcinoma. Urol Clin North Am 2000;27:739-750. 30. Sternberg CN. Current perspectives in muscle-invasive bladder cancer. Eur J Cancer 2002;38:460-467. 31. Sternberg CN. Neo-adjuvant chemotherapy in the treatment of muscle invasive bladder cancer. In: Lerner SP, Schoenberg MP, Sternberg CN, eds. Textbook of bladder cancer. United Kingdom: Taylor & Francis; 2006: pp. 657-664.
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32. Harker WG, Meyers FJ, Freiha FS, et al. Cisplatin, methotrexate, and vinblastine: an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study. J Clin Oncol 1985;3:1463-1470. 33. Yagoda A. The role of cisplatin-based chemotherapy in advanced urothelial tract cancer. Semin Oncol 1989;16 (suppl 6):98-104. 34. Mead GM, Russell M, Clark P, et al. A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party. Br J Cancer 1998;78:1067-1075. 35. Moore MJ, Tannock IF, Ernst DS, et al. Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer. J Clin Oncol 1997;15:3441-3445. 36. Kaufman D, Raghavan D, Carducci M, et al. Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer. J Clin Oncol 2000;18:1921-1927. 37. von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;18:3068-3077. 38. Kattan J, Culine S, Theodore C, et al. Second-line MVAC therapy in patients previously treated with the MVAC regimen for metastatic urothelial cancer. Ann Oncol 1993;4:793-794.
39. Lichtman SM, Skirvin JA, Venulapalli S. Pharmacology of antineoplastic agents in older cancer patients. Crit Rev Oncol Haematol 2003;46:101-114. 40. Osoba D, Hsu MA, Copley-Merriman C, et al. Stated preferences of patients with cancer for health-related quality-of-life (HRQOL) domains during treatment. Qual Life Res 2006;15:273-283. 41. de Boer-Dennert M, de Wit R, Schmitz PIM, et al. Patient perceptions of the side-effects of chemotherapy: the influence of 5-HT3 antagonists. Br J Cancer 1997;76:1055-1061. 42. Mansson A, Mansson W. When the bladder is gone: quality of life following different types of urinary diversion. World J Urol 1999;17:211-218. 43. Mansoon A, Christensson P, Johnson G, et al. Can preoperative psychological defensive strategies and mood in bladder cancer patients and type of lower urinary tract reconstruction predict postcystectiomy psychological adjustment? Br J Urol 1998;82:348-356. 44. Beitz JM, Zuzelo PR. The lived experience of having a neobladder. Western J Nurs Res 2003;25:294-316. 45. Silver L. The sexual rehabilitation of persons with cancer. Cancer Pract 2000;8:10-15. 46. van der Aa MN, Bekker MD, van der Kwast TH, et al. Sexual function of patients under surveillance for bladder cancer. BJU Int 2009;104:35-40. 47. Urostomy and Continent Urinary Diversion. National Institute of Diabetes and Digestive and Kidney Diseases. Available at: http://kidney.niddk.nih.gov/kudiseases/pubs/urostomy/# urostomy. (accessed December 17, 2011).
Seminars in Oncology Nursing, Vol 28, No 3 (August), 2012: pp 154-162
UROTHELIAL CANCERS: URETER, RENAL PELVIS, AND BLADDER ALLISON TYLER OBJECTIVES: To review the diagnosis, treatment, and nursing management of patients with urothelial cancers.
DATA SOURCES: PubMed, Ovid MEDLINE, Text books, and clinical experience. CONCLUSION: Progress is being made in the surgical and systemic management of urothelial cancers, and the oncology nurse is in a position to make an impact on patient education and overall quality of life. IMPLICATIONS FOR NURSING PRACTICE: Nursing care begins at pre-diagnostic testing and continues through treatment for metastatic disease. Nurses must be knowledgeable about diagnostic tests, treatment options, and the quality-of-life implications of associated surgeries and/or treatments to support and guide patients. Education should be comprehensive, addressing not only treatment side effects but also long-term implications on patients’ lives and lifestyles.
KEY WORDS: Urothelial, renal pelvis, chemotherapy, psychosocial, sexuality
U
ROTHELIAL cell carcinoma (UCC), often referred to as ‘‘transitional cell carcinoma (TCC),’’ is a cancer that occurs within the urinary system; namely the bladder, ureter, urethra, or renal pelvis. The urothelium is a form of elastic epithelial tissue that lines
Allison Tyler, BSN, RN, OCNÒ, CCRP: Prostate/Bladder Cancer Clinical Research Nurse Coordinator, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. Address correspondence to Allison Tyler, BSN, RN, OCNÒ, CCRP, Prostate/Bladder Cancer Clinical Research Nurse Coordinator, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave., Desk R33, Cleveland, OH 44915. e-mail: [email protected] Ó 2012 Elsevier Inc. All rights reserved. 0749-2081/2803-$36.00/0. doi:10.1016/j.soncn.2012.05.004
the inner surface of the urinary organs. UCC is the most common type of bladder malignancy, comprising nearly 95% of all bladder cancers.1 UCC of the upper urinary tract (renal pelvis and ureter) is uncommon, accounting for only 2% to 6% of cases.2 This article will review the incidence, diagnosis, treatment options, nursing management, and psychosocial-sexual issues of this patient population and the challenges they may face.
OVERVIEW OF UROTHELIAL CANCER Urothelial cancer is a disease of the late middle and elderly ages, primarily affecting people between the ages of 50 and 75. Unlike many other types of malignancies, the rates of new cases, as well as the number of related cancer deaths, have remained relatively stable over the past
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several decades.3 In 2012, it is estimated that there will be 73,510 new cases of UCC, with 55,600 cases in men and only 17,910 cases in women.3 Men are three times more likely to be diagnosed with UCC than women, and whites are twice as likely to be diagnosed than African Americans.4 There are currently more than 500,000 survivors of UCC in the United States alone.1 The single-most significant risk factor in the development of UCC is exposure to cigarette smoke. It is estimated that nearly 80% of all UCC can be attributed to cigarette smoking, whether it be your own or through inhalation of secondhand smoke.1 When a person inhales tobacco smoke, some of the carcinogens are absorbed through the lungs into the blood. The chemicals are then filtered by the kidneys and concentrated in the urine, where they can cause damage to the urothelium, increasing the chance of developing urothelial cancer.1 Other environmental risk factors include occupational exposure to industrial chemical substances, chemotherapy (most notably, cyclophosphamide) and radiation therapy, chronic bladder irritation and infections, and arsenic exposure. Non-environmental risk factors include age, race and ethnicity, gender, a personal history of UCC, birth defects of the bladder, and genetic factors such as mutations of the retinoblastoma (Rb1) gene, Cowden disease, and hereditary non-polyposis colorectal cancer (HNPCC) syndrome.1
DIAGNOSIS OF LOWER TRACT UCC (BLADDER) AND STAGING Given the location of this malignancy, it is not surprising that hematuria is the primary complaint leading to the initiation of diagnostic testing. Hematuria may fluctuate, being present one day and not the next, over the course of weeks to months. However, if the cause of the hematuria is indeed UCC, it will always recur. A challenge with this particular symptom is that hematuria may be caused by a myriad of other medical issues, including infections, an enlarged prostate (in men), renal calculi, and other benign renal conditions. Alone, hematuria is not diagnostic, but is a valuable tool in identifying patients for whom further workup may be necessary. If UCC is suspected, patients will undergo a cystoscopy for direct evaluation of the lower urinary tract and bladder. If abnormal
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areas are noted on the cystoscopy, biopsies of the affected area(s) are taken. Biopsies are especially useful in that they offer insight into the tumor’s invasiveness, or how deep into the bladder wall the cancer has penetrated.4 If the disease is in the inner or ‘superficial’ layer of the cells, it is considered non-invasive, while if it has grown into the deeper layers or muscles of the bladder, it is considered invasive, and is in turn more difficult to treat. Used in adjunct to cystoscopy, is urine cytology, which is more useful for patients with high-grade disease (grade 3), as those highly abnormal cells are more likely to shed.5 There are currently several urine biomarker tests approved by the US Food and Drug Administration for the assistive diagnosis and surveillance of UCC. However, none of these tests are as sensitive as the actual visual cystoscopy, and are not used alone for diagnostic purposes.5,6 Grade and stage are critical factors in determining treatment and patient outcomes for those with UCC. Grading is the basic 1-3, with grade 1 (low grade) being well differentiated; grade 2 being moderately differentiated; and grade 3 (high grade) being poorly differentiated. Low-grade tumors are usually non-invasive; however, the have a proclivity toward recurrence, while high-grade tumors tend to be invasive and are more likely to metastasize.7 UCC is staged using the American Joint Committee on Cancer Staging (AJCC) tumor-node-metastasis system. Two different types of staging, clinical or pathologic, can be performed in this patient population. The method used is dependent on the manner in which patients were diagnosed. Clinical stage is based on the physician’s judgment, incorporating the results of any cystoscopies, biopsies, and radiographic imaging that have been done. For a pathologic stage to be determined, a cystectomy and probable pelvic lymphadenectomy must be performed. Table 1 outlines the full AJCC TNM staging system.8
DIAGNOSIS OF UPPER URINARY TRACT (RENAL PELVIS, URETER) Upper urinary tract UCC is most common among patients with a median age of 65 to 67 years, and there is evidence that advancing age directly correlates with more invasive/higher-grade disease.9 As mentioned previously, cancer of the upper urinary tract is an uncommon disease, making up less than 6% of UCC cases. In regard to renal pelvis UCC, it accounts for less than 7% of renal carcinomas.10
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TABLE 1. AJCC 2002 TNM Staging System for Bladder Carcinoma Primary tumor TX Primary tumor cannot be assessed T0 No evidence of primary tumor Ta Noninvasive papillary carcinoma Tis Carcinoma in situ T1 Tumor invades subepithelial connective tissue (lamina propria) T2 Tumor invades musclularis propria bladder wall T2a Tumor invades superficial muscle (inner half) T2b Tumor invades deep muscle (outer half) T3 Tumor invades perivesical tissue T3a Microscopically T3b Macroscopically (extravesical mass) T4 Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, and abdominal wall T4a Tumor invades prostate, uterus, or vagina T4b Tumor invades pelvic or abdominal wall Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastases in a single lymph node, 2 cm or less in greatest dimension N2 Metastases in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes, none more than 5 cm in greatest dimension N3 Metastasis in a lymph node more than 5 cm in greatest dimension Distant Metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis Data from Edge et al.8
Upper urinary tract urothelial cell cancer can be multi-factorial, with tumors in different locations in the urinary tract, and tumors tend to occur ipsilaterally.11 Presenting symptoms of upper tract UCC include hematuria (in 75% of patients), which is often in conjunction with flank pain (in 33% of patients).12 Intravenous urography is performed to evaluate the upper urinary tract and will identify filling defects in the majority of patients, but does not distinguish malignancy from a benign process. Additional imaging with contrast computed tomography is useful; as is additional testing with upper urinary tract endoscopy (ureteroscopy).13 As with lower tract UCC, urine cytology is unreliable in detecting low-grade tumors, and false-positive results occur in upwards of 30% of tested patients. Therefore, urine cytology should only be used as a diagnostic supplement.14 Increased specificity and sensitivity may be achieved by adding the use
of brush cytology, which is the use of a cytology brush to collect cell samples from the mucosa.15 Another diagnostic option, achieved through growing and improving technical instrumentation, is ureteropyeloscopy (the use of scope to directly visualize the ureter and renal pelvis). However, this presents an increased risk of ureter perforation and postoperative stricture; therefore, appropriate patient selection is key.16
SURGICAL MANAGEMENT: LOWER TRACT UCC Primary treatment of lower tract UCC is wholly dependent on whether or not the disease is invasive. For a patient with non-invasive UCC, complete transurethral resection of the tumor(s) is warranted; followed by close cystoscopic surveillance.17 The frequency of repeat cystoscopies will vary by physician practice; however, every 3 months is not an unusual practice. Should recurrent masses be detected on surveillance scopes, treatment options would include repeat resections or intravesical chemotherapy. For those patients that have invasive UCC, primary treatment is a radical cystectomy. Depending on the degree of muscular penetration by the cancer, this may be a more invasive surgery than one might realize. For men, this may include a local lymphadenectomy and prostatectomy. And for women, sometimes a full pelvic exenteration with the removal of local lymph nodes, the uterus, ovaries, and parts of the vagina, in addition to the bladder itself.4 Depending on the location of the disease, the urethra may also be removed. Given that the urothelial tissue lines the entire urinary tract, a patient with cancer in one area, such as the bladder, is at high risk for developing disease in the other organs lined with urothelial tissue. Removing all the potentially affected organs increases the chance that surgery may be curative. At the other end of this spectrum are patients with localized disease surrounded by healthy tissue. These select patients may be candidates for partial cystectomy; thereby preserving part of the natural, functioning bladder and its surrounding organs. An unavoidable outcome of cystectomy is an alteration in urination. The nature of the change is highly dependent on the type of surgery a patient has and the type of urinary diversion the patient chooses or is given. There are three primary types of urinary diversions: continent, incontinent, and neobladder. These are described in detail in Table 2.
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TABLE 2. Urinary Diversions
Type of Diversion Ileal Conduit [Bricker Conduit] Continent Diversion [Indiana Pouch]
Neobladder
Nephrostomy Ureterostomy
Description Ureters are diverted to drain into a short part of the ileum. The end of this ileal segment is brought out to a stoma. Urine drains out of the stoma into an external collection bag. A reservoir is constructed out of the right colon and a small segment of ileum, which is brought out to the skin as a stoma. A one-way valve mechanism is created so that urine is kept inside the reservoir and will not leak out to the skin. Patients self-catheterize through the stoma to drain the reservoir. The surgeon creates a reservoir made of small intestine and connects it to the urethra, allowing the patient to void through the urethra; similar to normal urination. The reservoir is made to mimic the normal storage function of the urinary bladder. An indwelling catheter is placed through the skin, usually in the flank area, directly into the renal pelvis, allowing for the drainage of urine into external collection bags. One or both ureters are connected directly to the abdominal wall, creating stoma(s). Urine drains from the ureter(s) into external collecting bag(s).
Data from the National Institute of Diabetes and Digestive and Kidney Diseases.47
SURGICAL MANAGEMENT: UPPER TRACT UCC Surgical options for cancer of the renal pelvis and/or ureter differs from the cystectomy used on lower-tract disease. For more extensive disease, a nephroureterectomy is performed; removing the entire kidney, ureter, and bladder cuff.18 For cases of localized, low-grade, low-stage disease, nephron-sparing surgeries may be done. Namely, a pyelotomy with tumor ablation or a partial nephrectomy.19 Selecting patients that fit the above criteria is critical to ensure that only appropriate patients are treated in this manner. Regarding disease specific to the ureters, segmental resections of the ureter are conducted, which removes the diseased part of the ureter and then reattaches the ends of the ureter. This surgery can only be completed if the lower third of the ureter, near the bladder, is affected and the cancer must be superficial.20
THERAPY FOR LOCALIZED DISEASE Currently, the most effective intravesical therapy for patients with carcinoma in situ or high-grade superficial bladder cancer is an immunotherapy, or a treatment designed to elicit or amplify an immune response, called Bacille Calmette- Gu erin (BCG).21 BCG is a live, attenuated vaccine originally developed for the treatment of tuberculosis.22 BCG is instilled into the bladder via urinary catheter and patients are instructed to
move about and to not void for several hours; allowing the agent to wash the entire bladder wall. Treatment with BCG is typically given as 120 mg instillations once a week for 6 weeks, then with maintenance doses monthly over the next 12 to 18 months. Response rates for this regimen in patients with high-risk pathology are nearly 70%.23 The expected side effects are urinary irritation, along with a potential for immunotherapeutic reactions such as fever, malaise, nausea, and an overall cumulative effect, with symptoms worsening with additional treatments.24 A weapon in the fight against recurrence for patients with non-invasive bladder cancer is the use of intravesical chemotherapy (the diffusion of chemotherapeutic agents into the layers of the bladder). For patients who have had resected disease, the use of intravesical chemotherapy serves multifactorial goals of destroying any residual disease, preventing tumor recurrence, and delaying tumor progression.6 The designated chemotherapeutic agent is instilled into the bladder, via a catheter, for a specified time frame, during which the patient is instructed to not void. Patients are then encouraged to move about, causing the chemotherapy to splash around, coating the inside of the bladder. Patients then void the agents out. The current standard agent for this type of therapy is mitomycin C, an alkylating agent that inhibits DNA synthesis.25 Also used for this purpose, individually, are doxorubicin, epirubicin, thiotepa, and gemcitabine. On average, intravesical agents reduce recurrence by 15% to 41% and are most effective
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when treatment is initiated within 24 hours of resection.26 Predictably, side effects from these therapies tend to be spot specific, with the most common noted complaint being chemical cystitis.27 All these agents may also be used for the treatment of disease in the renal pelvis or ureter, through topical exposure via either antegrade or retrograde routes. The antegrade route involves the placement of a nephrostomy tube, through which the agents are infused for direct contact with the renal pelvis.28 The retrograde route requires the placement of a ureteric catheter with direct infusion to the diseased area or, alternatively, the patient may have the agent instilled into his or her bladder and then be placed in Trendelenburg position.29 Muscle-invasive, localized disease of the bladder is generally managed by surgery. However, there are some patients that are highly motivated to preserve the bladder and therefore opt for neoadjuvant chemotherapy or chemoradiation. Neoadjuvant chemotherapy, usually with either methotrexate/ vinblastine/doxorubicin/cisplatin (MVAC) or cisplatin/ methotrexate/vinblastine (CMV), is given before cystectomy, with the goal of reducing tumor volume and preserving the bladder, by means of a partial cystectomy.30 Chemoradiotherapy is the combination of chemotherapy with radiation therapy, given in an effort to increase the chance of preserving the bladder, while exposing the tumor to radiation and, at the same time, treating any potential metastases that are not yet visible on radiographic imaging.31
METASTATIC DISEASE Once disease has spread beyond the primary site, the previously mentioned therapies are of limited utility, given that they target very specific, localized areas. Systemic chemotherapy use in UCC dates back several decades; however, researchers continue to strive for therapeutic improvements to improve response rates and patient quality of life. Historically, treatment for advanced urothelial carcinoma was with MVAC or CMV. These combinations demonstrated response rates in phase II trials as high as 75%, with approximately 30% of cases achieving complete responses.32,33 These combinations nearly quadrupled survival rates, from 3 to 4 months to 12 to 14 months.33 A clinical trial conducted in the United Kingdom in the 1990s compared methotrexate and vinblastine (MV) with CMV and demonstrated an extraordinary 1-year survival benefit for the CMV group at
29%, compared with only 16% for the MV group.34 This trial showed a significant overall survival benefit of 7 months in the CMV group compared with 4.5 months in the MV group.34 Subsequently, it became apparent that cisplatin was an essential component in chemotherapy regimens for UCC. More recently, studies with gemcitabine in combination with cisplatin have produced results similar to MVAC.35 These results led to a large randomized trial that compared MVAC with gemcitabine and cisplatin (GC). The two arms were very similar in terms of median survival, with 13.8 months for GC and 14.8 months for MVAC; as well as in overall response rates, with 46% in the GC arm 49% in the MVAC arm.36,37 Overall toxicity was less in the GC arm, which researchers have determined offset the small survival benefit of the MVAC arm, and has consequently resulted in primary usage of the doublet over MVAC.37 Table 3 provides an overview of treatment options for UCC. Currently there are no data available to support any specific second-line therapy for patients that have failed front-line systemic chemotherapy. There are some data (though limited) that supports re-treatment with the front-line regimen if the patient achieved long-term disease-free progression (more than 6 months); however more research is needed.38
NURSING MANAGEMENT Patients that are diagnosed, treated, and living with urothelial cancers face a multitude of challenges, from surgical complications to chemotherapy side effects. Each different phase of the disease presents its own unique issues and the oncology nurse is in a prime position to assist patients as they navigate these life changes. At the onset, educating patients is a task that will have a lasting impact and should continue throughout a patient’s disease course, as each day for the cancer patient presents new and often unexpected tribulations. For patients undergoing radical cystectomy, extensive conversations regarding urinary diversions and continence should begin preoperatively. Wound care, stoma teaching, neo-bladder training or self-catheterization techniques (if applicable), and symptoms of infection are all critical topics for discussion with patients. As patients progress on to treatment with chemotherapy, whether it is neo-adjuvant or front-line, risks and side effect management should
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TABLE 3. Treatment Options for UCC Surgical Options Transurethral resection of bladder tumor (TURBT) Segmental (partial) cystectomy Radical cystectomy Immunotherapy (intravesical) Bacille Calmette-Guerin (BCG) Interferon alfa Chemotherapy-intravesical Mitomycin C Doxorubicin Epirubicin Thiotepa Gemcitabine Chemotherapy-systemic Methotrexate, vinblastine, doxorubicin, plus cisplatin Gemcitabine plus cisplatin Cisplatin, methotrexate, plus vinblastine Gemcitabine plus carboplatin
Removes tumors that are confined to the inner layers of the bladder. Burns away cancer cells with an electric current (fulguration). Removal of the portion of the bladder that contains cancer cells. Removal of the entire bladder, as well as surrounding lymph nodes.
Sometimes used in combination with BCG Singleton agents Most common
Multiple agents, in combination MVAC GC CMV GemCarb
Data from the American Cancer Society,1 Raghavan and Tuthill,4 and Sternberg.31
be thoroughly addressed. Common adverse events of chemotherapy for UCC are fatigue, myelosuppression and the subsequent risk of infection, nausea and vomiting, hair loss, kidney damage, tinnitus, and dysgeusia. Patients should be instructed on the importance of reporting side effects as soon as they begin to occur, as delays in event reporting often result in dosing delays and/or dose reductions, some of which may be avoided with aggressive, early symptom management. A treatment goal for all patients should be to achieve as much appropriate therapy as possible while maintaining a satisfactory quality of life. Another element to consider when dealing with UCC is that it is a disease of the late middle-age and elderly population. This patient population is likely to have pre-existing co-morbidities as well as issues such as cardiomyopathy, general frailty, hearing loss, and altered mental, functional, and nutritional status. As one ages, the body develops decreased gut motility, decreased liver mass, decreased renal function, and becomes more prone to myelosuppression.39 Given that chemotherapy may have serious consequences in many of these areas, it is imperative to monitor the elderly patient closely. Frequent chemistry panels to assess for hydration status and to evaluate the potential for electrolyte wasting, auditory testing to monitor for changes that may be potentiated by chemotherapy, and blood
counts to evaluate degree of myelosuppression are all areas of consideration for patients with UCC being treated with chemotherapy. Research has also shown that there is a disconnect between how a provider believes they are handling a patient’s treatment-related side effects and how the patient actually feels his or her side effects are being managed.40,41 This suggests that we as providers must be more aggressive and consistent with addressing a patient’s concerns regarding any potential treatment-related effects they may be experiencing, critically listen to the patient, and consequently incorporate their feedback into their treatment plan. Thorough followup regarding the success or lack thereof of the intervention will then close the circle. Tools such as medication dosing diaries and symptom trackers can be invaluable in providing fail-safes to ensure comprehensive and exhaustive symptom management.
PSYCHOSOCIAL ISSUES The diagnosis and subsequent treatment of cancer may be a tremendous source of psychological stress. Given the impact on sexual function and the physical changes that often follow treatment-related surgery, a patient with advanced urothelial cancer may face a more traumatic and
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challenging road than patients with many other types of cancers. Common postoperative problems such as visible scarring, urinary leakage and associated odors, the need for self-catheterization and, depending on the type of urinary reconstruction, the potential need for an external collection reservoir, can all have a negative impact on a patient’s body image and self-esteem. A clinical trial conducted in Sweden found that patients who received one of three different types of urinary reconstruction (ileal conduits with an appliance, continent cutaneous diversions, or a neobladder) 85% of patients continued to complain of emotional problems regarding the management of urine 12 months postoperatively. At 5 years postoperatively, 65% of those patients continued to have the same complaints, with no notable difference between the various types of diversions.42 Nearly 40% of postoperative UCC patients report reduced self-esteem, which did not improve with the passage of time.43 Often after an extensive surgery, as patients with UCC are prone to having, patients will grieve the loss of their body parts.44 Patients react to their cancer diagnosis and its treatment with a wide range of emotions; from anger to urgency for treatment to sadness and feeling alone. The oncology nurse has a unique knowledge of patient care from the operating room through end-stage disease. The nurse is in the ideal position to guide these patients through the journey of adjusting to their ‘new normal.’ Rigorous education and the dissemination of simple tips, such as the use of pads to protect from incontinence, on how to balance fluid intake with a voiding schedule to allow for minimal disruption of daily life activities, and the benefit of locating bathrooms ahead of time when traveling, may ease fears and relieve anxiety, significantly improving a patient’s quality of life. Maximizing use of available resources, across departments, may impact patients. Reaching out to social work, psychology, urology, stoma care, and cancer rehabilitation specialists will add to the comprehensive team approach to patient care, which will ultimately greatly benefit the patient.
SEXUALITY Sexual function and the maintenance of intimate relationships is an important aspect of healthy quality of life for cancer patients.45 Yet, given the sensitive nature of sexuality and associated discomfort with the topic, related issues are
often left unaddressed or inadequately addressed by patients and providers alike. For the patient with UCC, the ramifications of surgery on sexual function are considerable. For women, parts of the vaginal wall and uterus have likely been removed, affecting child-bearing potential, hormonal balance, and causing vaginal dysfunction.42 About half of men suffer nerve damage that leaves them impotent; and if they are able to obtain erections postoperatively, they will not produce any ejaculate because of the loss of the prostate, which in turn has significant ramifications on the patient’s sexual function and pleasure.4,42 Additionally, patients may be fearful or embarrassed by the presence of external collection devices or stomas and the associated risk of urine leakage. Research has also shown that patients with bladder cancer are fearful of harming their partners through sexual contact; largely because of the toxic nature of intravesical therapies.46 The prevalence of sexual dysfunction is very high (54%) for patients with invasive urothelial carcinoma; however, patients’ libidos are generally intact and active.46 Accordingly, health care providers should address the patient’s sexual needs and explore alternatives to traditional intercourse, in an effort to facilitate the development of healthy, safe, satisfying sexual relationships and the retention of emotional intimacy. One available and researched technique is ‘‘Sensate Focus.’’ This is a term associated with a set of specific sexual exercises based on sensual massage techniques, for either couples or individuals, and are aimed at developing non-coital foreplay.45 This allows couples the opportunity to be physically intimate without the pressure or angst of achieving the ‘goal’ of actual intercourse, ultimately decreasing anxiety. Direction is usually at the hand of a therapist, with the objective of appreciating a new set of sensual alternatives to actual intercourse. Oncology nurses have the aptitude to be of great assistance to patients and their partners by proactively introducing the subject of sexuality and sexual function. Through the integration of sex education and open communication, a sense of hope can be fostered for patients who are eager to retain a sense of physical intimacy with their partner.
CONCLUSION UCC is one of the most common cancers in the United States. Progress continues to be made in detection, surgical and systemic treatment options,
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and the quality-of-life challenges of afflicted patients. Increasing therapeutic research, refined surgical techniques, and growing awareness of the psychosocial impact of a cancer diagnosis on patients is
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suggestive of a promising future in this specialty. Oncology nurses have the distinction of being in a position to have a significant impact on patients as they learn of, fight with, and live with cancer.
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