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Strategies to improve quality of life in bladder cancer patients Expert Rev. Pharmacoecon. Outcomes Res. 14(4), 537–544 (2014)
Marius Roaldsen1,2, Erling Aarsaether1,2, Tore Knutsen1 and Hiten RH Patel*1,2 1 Department of Urology and Endocrine Surgery, University Hospital of North Norway, N-9038 Tromsø, Norway 2 Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway *Author for correspondence: Tel.: +47 7762 6000 Fax: +47 7762 6421 [email protected]
Bladder cancer is a heterogeneous disease that includes both tumors with low risk of dissemination as well as highly malignant tumors with a considerable potential to metastasize. The patient’s quality of life is closely related to the management of the disease. The challenge for the urologist is to acknowledge the malignant potential of the cancer and to adjust the approach to the patient accordingly. Patients with low-risk bladder cancer should avoid an exaggerated follow-up, but on the other hand high-risk patients must be sufficiently surveyed to secure that definitive surgical treatment is performed before it’s too late. When the decision to perform a cystectomy has been made, it is crucial that the patient understands the consequences of the surgery as well as the possible options for urinary reconstruction. This review focuses on aspects of bladder cancer management that we believe are vital for the quality of life of these patients. KEYWORDS: bladder cancer • ERAS • evidence-based medicine • guidelines • oncology • quality of life • shared decision-making
Bladder cancer is the fourth most common cancer among men in the UK and Norway. For men and women together, it is the seventh most common cancer. However, it is the most expensive cancer per capita in the USA [1,2] and Europe, and as such, bladder cancer represents a substantial challenge for both health professionals and budgets. Patients with curable disease may either have to go through major surgery or participate in a vigorous follow-up with frequent invasive procedures. The frequent examinations during follow-up are often experienced as a burden for the patient. It is time consuming for the urologist and represents a large expense for the healthcare system. Furthermore, frequent visits to the urologist have an impact on the quality of life of these patients, and thus we should strive to provide good care consistent with updated guidelines, but also avoid unnecessary interference with everyday life. Patients with curable disease can be divided into two subgroups with quite different challenges and outcomes: muscle-invasive bladder cancer and non-muscle-invasive bladder cancer. In this review, we will discuss important aspects of disease management that are critical for quality of life of
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both patient groups. Management of patients with metastatic bladder cancer is beyond the scope of this review. Information
Some aspects of healthcare are important for all patients. Good communication and information is important and must not be neglected. All patients receiving a cancer diagnosis should be informed about their condition in an atmosphere that leaves room for questions, whether it is in the emergency room or under more appropriate facilities in the ward. The need for information can sometimes be difficult to satisfy, but all healthcare professions involved in the treatment should aspire to fulfill the patients’ need for information. The information should preferably be given by the same doctor over time and in layman’s terms. If the demand for information is met, it often improves the level of patient satisfaction and also ultimately improves the quality of life. Studies reveal that patients would like the physician and the other health professionals involved to see them as a person; as an unique individual. Patients experiencing that they are being genuinely cared for and
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not only treated as a cancer patient with a number in line, have been shown to exhibit improved patient satisfaction [3]. This will also increase the tolerance for complications and side effects. On the other side, patients experiencing a lack of empathy from involved healthcare professionals will be much more likely to complain about issues regarding their care, which may include either valid complaints or minor issues. A sound doctor/patient relationship cannot be underestimated, but requires patience and time, which is difficult to provide in a hospital environment where the demand for efficiency and cost-effective care is increasing. However, a good doctor/patient relationship is always a valuable investment both in short and long term, as it will prevent misunderstanding and unpleasant surprises for the patient about side effects and challenges in their new life as a cancer patient. In patients with muscle-invasive bladder cancer, the need for information will change as they progress through the different stages of treatment from diagnosis to survivorship as described by Mohamed et al. [4]. All healthcare professionals who provide care for these patients should be familiar with the different traumas and the corresponding needs for information that develop during this exhaustive treatment pathway. Written information in the form of brochures, booklets or folders makes it easier to meet a patient’s need for information. They allow for easier communication and increase the likelihood that the information will be absorbed and correctly interpreted. The first time the cancer diagnosis is given, the information will often feel overwhelming with only a small part remembered afterward. Therefore, written information may be of great help as it gives the patient the opportunity to, when the worst shock has passed, read the brochure at a time of their choosing. Patients experiencing that the demand for information has been met, have been reported to exhibit better health-related quality of life and lower levels of depression and anxiety [5]. This is important to bear in mind that good information gives you healthier patients! Shared decision-making
Shared decision-making can also improve patient care [6–8]. This is a process, in which patients are encouraged by their health professional to participate in selecting the most appropriate health treatment or care management option for their individual needs and preferences. For many diseases there are several treatment options. In the instance of bladder cancer, there are several alternatives when it comes to urinary reconstruction after cystectomy. Involving the patient in shared decision-making allows him/her to participate in the important decisions about his/her life and treatment. Whereas some patients prefer the urologist to single-handedly manage their disease according to what is current institutional practice, an increasing number of patients are searching the web for information about available treatment options, although not necessarily with the competence to interpret the quality or the relevance of this information. Most patients would be happy to be more involved in the decision-making concerning their treatment; however, to be able to participate, it is important 538
that the patient receives good validated information that is adapted to non-healthcare professions. This is being implemented at the University Hospital of North Norway, where work on an interactive information and decision-making tool has been initiated [9]. The process is based on software where the patient has access to information about their disease and treatment options, as well as informative videos and videos with patients talking about their experience with their treatment options. It also includes questionnaires where the patient can answer questions that are relevant for the choices they have to make. When they have gone through this, they sit down with their doctor to discuss the alternatives. This web portal, which so far has been targeted toward patients with chronic renal failure, serves both to educate the patient and as a decision-making tool, and will be developed for patients with bladder cancer in the near future. A Cochrane review [7] has looked at the impact of decision aids and found that it improved the patients’ knowledge of their options, which resulted in more accurate expectations about benefits and disadvantages of their treatment. The review also demonstrated that patients utilizing decision aids participated more in the decision-making and took choices more consistent with their way of living and thus improved their quality of life. This may be a great asset for both the patient and the doctor and we are currently investing time and resources to develop this interactive decision-making portal. Surveillance of patients with non-muscle-invasive bladder cancer
Non-muscle-invasive bladder cancer is a disease with excellent long-term survival, but with a high level of recurrence. As a consequence, patients with non-muscle-invasive bladder cancer will undergo a meticulous follow-up that is carried out over many years or even the rest of the patients’ life [10]. This is also the reason for the high burden and cost of the disease. Many patients have to continue the follow-up with numerous cystoscopies, computer tomography scans, trans-urethral resections and intravesical instillation of Bacillus Calmette–Gue´rin until they die or until they receive definitive surgical treatment with radical cystectomy. After the primary diagnosis, a patient may easily have to pay 15 visits to the urologist within 12 months [2]. As this severely impacts quality of life [11,12], a critical evaluation of how the follow-up is conducted is necessary. This may prevent patients with low-risk disease to avoid redundant examinations, but should also secure that patients with intermediate and high-risk disease receive the recommended number of controls. Our department utilizes the guidelines from the European Association of Urology [10,13]. Following transurethral resection, the patient’s risk of recurrence and progression is calculated based on tumor size, number of tumors, histopathology scoring, recurrence, tumor category and the presence of carcinoma in situ. The scores provide a probability for recurrence and progression of the disease that have been solidly documented in a summary of seven randomized Phase III trials [14]. However, the follow-up guidelines are heavily based on expert Expert Rev. Pharmacoecon. Outcomes Res. 14(4), (2014)
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Strategies to improve quality of life in bladder cancer patients
opinion and do not comply with the highest standards of evidence-based medicine. In fact, the only study to our knowledge comparing bladder cancer surveillance programs in a randomized prospective design included only 97 patients [15]. The lack of evidence for the surveillance guidelines represents a challenge for the urologist in the management of these patients. It may also explain the surprisingly low clinical consensus and compliance with guidelines among urologists when it comes to follow-up of these patients. Chamie and colleagues examined the Medicare data from 4790 patients with a diagnosis of highgrade, non-muscle-invasive bladder cancer between 1992 and 2002, and found that only one patient received all the recommended measures [16]. This illustrates a problem, in which patients with bladder cancer are likely to receive different care at different institutions. Another interesting finding in the study from Chamie et al. was that a statistically significant survival advantage was found among those who received at least half of the recommended care, when compared with those who received less than this level of care. This suggests that compliance to current guidelines may improve not only quality of life, but also survival and should motivate urologists to utilize them. We know from our own experience at our institution that many patients with low-risk bladder cancer previously went through the same follow-up as patients with high-risk bladder cancer. This means that many patients have had an excessive follow-up with invasive procedures that have not improved their outcome in addition to increased hospital costs, and a misuse of patients’ time that could have been utilized for better purposes. We now perform a risk stratification of all patients at every appointment, to make sure they get the follow-up according to current guidelines. In the absence of surveillance programs based on high-level evidence, we still believe this is the most appropriate way to deal with our patients. Reducing risk of recurrence following transurethral resection
Transurethral resection of the bladder should always be performed by minimizing the probability for recurrence as much as possible. We advocate the use of photodynamic diagnosis with 5-aminolevulinic acid or hexyl aminolevulinate in addition to white-light cystoscopy during transurethral surgery, since it has been shown to improve cancer detection and reduce recurrence. A recent review in European urology [17] has looked at the benefit of photodynamic diagnosis and found that it improved tumor detection and reduced the number of residual cancers after transurethral resection compared with white-light cystoscopy only. Although it has not been shown to alter progression to more advanced disease, utilization of photodynamic diagnosis is likely to reduce the number of hospital admissions for transurethral resections and consequently improve quality of life. Since photodynamic diagnosis increases the chance of a complete transurethral resection, we believe it should be offered on a routine basis, especially when the presence of carcinoma in situ may be expected [18]. The use of intravesical chemotherapy immediately after transurethral resection represents another informahealthcare.com
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strategy to minimize the risk of recurrence. A meta-analysis of seven randomized trials demonstrated that immediate instillation of chemotherapy after transurethral resection of bladder cancer was associated with a risk reduction of almost 40% for bladder cancer recurrence [2,19]. A study has also calculated a loss of 0.02 quality-adjusted life-years per patient not receiving immediate intravesical chemotherapy [20]. In spite of high-level evidence for the use of intravesical chemotherapy following transurethral resection, reports have documented a surprisingly low utilization of this strategy to reduce the risk of bladder cancer recurrence [2,21,22]. The reason for this is not known, but in contrast to guidelines for follow-up, the existing level of evidence for the administration of intravesical chemotherapy is so solid that it should encourage a change in practice. Laser ablation of bladder tumors can be a good alternative for selected patient with low-risk non-muscle-invasive bladder cancer. Wong et al. have shown that it can be done safely in an outpatient clinic and that it is cost-effective [23]. Laser ablation represents an interesting treatment option, especially for elderly patient with comorbidity. The obvious disadvantage is the loss of histopathologic specimens for examination of the tumor. Selection of patients for urinary diversion
Muscle-invasive bladder cancer is associated with quite different challenges, when compared with non-muscle-invasive disease. To be cured, these patients must undergo extensive surgery of the pelvis with accompanying high rate of complications and side effects such as impotence, incontinence and pain. The goldstandard treatment is radical cystectomy. In men, it involves a complete extirpation of the bladder along with the prostate and seminal vesicles and in some cases also the urethra. The extensive pelvic surgery will cause some nerve damage and often leads to impotence. In women, the surgery entails the removal of the uterus, cervix, ovaries and anterior vagina en bloc with the bladder. Following removal of the bladder, reconstruction of the lower urinary tract is of paramount importance [24,25]. In principle, the three alternatives are incontinent cutaneous diversion (ileal conduit/bricker conduit), continent cutaneous diversion and finally the orthotropic neobladder. Ileal conduit is considered the easiest and least complicated reconstruction to perform these surgical procedures and utilizes only 10–15 cm of small bowel for the diversion. It is considered to be the procedure of choice for patients with short life expectancy and comorbidity. It is also the procedure of choice when the patient has renal or liver failure, as complications associated with metabolic acidosis, as a consequence of reabsorption from the bowel used for reconstruction, is avoided [26]. Because it involves the construction of a stoma, this is the procedure that alters the body image of the patient the most. These patients will have to wear a urinary collecting bag all the time and for most patients this represents a dramatic change. It can alter social interaction, body image and affect sexual function. The patients are frequently concerned about odor, urinary leakage and stoma care. Taken together, this can result in social isolation of the patient and hinder them from participating in hobbies and travel activities [24,27–29]. 539
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Continent cutaneous reconstruction is a procedure that utilizes a larger part of the bowel, usually 45 cm of small bowel or a part of the colon to make an artificial bladder and represents a legitimate option when the urethra is unavailable because of cancer involvement or because of incontinence. The patient is still dependent on a stoma, but the advantage is that he/she does not have to use a collecting bag, resulting in an increased preservation of body image when compared with ileal conduit. The reservoir has to be emptied with a catheter approximately every 4 h. Failure to comply with catheterization may lead to major complications with renal failure and rupture of the reservoir [30]. If the patients can’t follow this regime, they are not candidates for this kind of reconstruction. Studies evaluating quality of life have shown improved body image and sexual function in these patients as compared with those with an ileal conduit [31]. However, the patients must be informed of the need for night time catheterization, since it may lead to sleep disturbance and as such may have an negative impact on quality of life [29]. Orthotopic neobladder is the procedure that alters the body image the least. The reservoir is attached to the urethral stump and voiding is initiated with relaxing of the pelvic floor and increasing the abdominal pressure with valsalva maneuver or crede` pressure. Patients unable to empty the bladder voluntarily must empty it with a catheter. The advantages are the lack of stoma, the ability to void through the urethra and subsequently the preservation of body image when compared with ileal conduit [32] and continent cutaneous reconstruction. The disadvantages represent the use of a larger part of the bowel, longer operation time and more postoperative complications. The patients also have to be able to perform catheterization if they are unable to empty the bladder. Incontinence is one of the major concerns for this patient group and for many patients this is what has the greatest impact on their life. There have been many studies comparing different reconstruction procedures after cystectomy [24–26,29–35]; however, the findings have been somewhat varied making it difficult to draw a conclusion on what kind of reconstruction is the best. As there are advantages and disadvantages for each procedure, it must be a joint decision between patient and surgeon. It is of utmost importance that the patients have been provided adequate and accurate information on the different solutions available, so that they are able to participate in choosing the kind of reconstruction that is most appropriate. By utilizing the premise of shared decision-making, a good patient/doctor relationship and access to written information, it is more likely that the patients will get the reconstruction that works best for them and ensures that they are better prepared for life after surgery. Strategies for bladder preservation in muscle-invasive bladder cancer
A conservative approach for muscle-invasive bladder cancer was originally introduced as an alternative to cystectomy in patients who were not candidates for radical surgery because of comorbidity. Before the chemotherapy era, radiation therapy alone 540
was utilized in patients who were considered inoperable. Radiotherapy as the only treatment modality for muscle-invasive bladder cancer is currently reserved for patients with considerable comorbidity and a poor performance status that disqualifies them for chemotherapy. Partial cystectomy represents another bladder preservation strategy. This is a procedure that involves removal of only the part of the bladder where the cancer is localized, and is likely to preserve sexual function, since the nerves surrounding the prostate are spared. The published survival rates have been encouraging [36–39], but only a small number of patients, that is, 5–10% of those with clinically T1 or T2 disease will be candidates for such a procedure [40]. Neoadjuvant chemotherapy followed by partial cystectomy or transurethral resection of bladder tumor (TURBT) is also an option that may be considered in patients with muscle-invasive bladder cancer, but only a few studies have investigated the outcome of such a strategy. In the study by Herr et al., which included a highly selected group of patients, the 10-year survival rate of neoadjuvant chemotherapy followed by partial cystectomy or transurethral resection was 74%, and a 58% bladder intact survival was reported [41]. However, for this strategy to be effective, a re-staging TURBT following chemotherapy documenting the absence of muscle-invasive cancer is a prerequisite. The reliability of this re-staging TURBT has been questioned in the SWOG SO219 Trial after 6 of 10 patients undergoing cystectomy were found to have muscle-invasive cancer, despite the fact that the re-staging TURBT was negative [42]. Although the combination of chemotherapy and TURBT as well as chemotherapy and radiotherapy has been shown to improve outcomes in patients with a bladderpreserving strategy compared with either of these alone, the most effective means is to combine all of them [43,44]. The combination of TURBT, chemotherapy and radiation therapy is commonly referred to as trimodality treatment, and has been fronted by the Massachusetts General Hospital and the Radiation Oncology Group for the last 30 years [44,45]. Trimodality treatment has been shown to confer long-term survival rates comparable to contemporary cystectomy series [45,46], and between 62 and 85% of the patients successfully achieving the preservation of their native bladder after 5 years [43]. However, the results of trimodality treatment are not directly comparable to retrospective cystectomy data, since the results from the surgical series are based on pathological staging, while the tumors from the trimodality treatment trials are clinically staged. This observation is likely to favor the surgical series, since many cancers are upstaged at the time of surgery [40]. As for the other bladder-preserving strategies mentioned above, the purpose of trimodality treatment is to improve quality of life, yet only a few studies have compared this treatment strategy with the gold standard of cancer-free survival, that is, radical cystectomy. Of the two studies to our knowledge that may be used to answer this question, only one of them included chemotherapy in addition to radiotherapy [47], while the other compared radiation therapy alone with radical cystectomy. Both these studies documented an improved quality of Expert Rev. Pharmacoecon. Outcomes Res. 14(4), (2014)
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life in favor of a bladder-preserving strategy [47,48]. The patients selected for bladder preservation therapy were found to exhibit improved sexual function and most of them also reported a preservation of bladder function [47,48]. Retrospective quality-oflife studies have since confirmed that the vast majority of patients subjected to trimodality treatment retain a wellfunctioning bladder [49–51], and this has recently been documented in a prospective analysis [52]. However, the successful improvement in quality of life as well as the reported acceptable rates of cancer-free survival must be balanced against the substantial number of follow-ups that are mandatory to make sure that the disease does not recur. Nevertheless, bladderpreserving therapy is a reasonable option in selected patients and represents an alternative for improved quality of life through preserved bladder function as well as sexual function. New irradiation techniques and new-generation drugs are being evaluated and we believe trimodality treatment will be an option for a larger patient population in the future. Enhanced recovery after surgery
In the perioperative period, we advocate the use of Enhanced Recovery After Surgery (ERAS) principles [53]. The ERAS society has focused on evidence-based practice in the perioperative period instead of treating according to tradition. As a result, they have reduced complication rates and the length of hospital stay. The main work from this group has been on colonic and rectal surgery, but many of the principles can be transferred to other disciplines of surgery. In regard to cystectomy, the evidence of perioperative treatment is limited [54,55], although we still believe many of these principles can be transferred to this setting. Cerantola et al. [54] have assessed the literature on ERAS on cystectomy and have recommended its implementation. The ERAS principles can be summarized as follows: optimization of patient education and information, increased focus on preoperative nutrition and minimization of fasting. The ERAS society also recommends that bowel preparation should be omitted and advocates the use of pre-anesthetic medication without long active sedatives. Prolonged antithrombotic treatment for 4 weeks with low–molecular-weight heparin is recommended. In addition, epidural analgesia for 72 h and early removal of nasogastric tubes should be performed. Postoperative nausea and vomiting prophylaxis is recommended, while early oral nutrition and mobilization are encouraged. Multimodal approach for stimulation of gut functions with chewing gum and magnesium is recommended. Karl et al. [56] have randomized patients for radical cystectomy for ERAS and a conservative surgical regime. They found that the ERAS group had shorter time in the intensive care unit, lower morbidity, less demand for analgesia and higher quality of life. Daneshmand et al. [57] reported shorter time to bowel movement and shorter hospital stay on the ERAS regime. Minimal-invasive surgery has great impact on recovery and the ERAS society [54] and the authors strongly advocate the use of this. Robotic surgery has made this possible even with cystectomy and the literature on this is evolving. Patients subjected to minimally invasive surgery informahealthcare.com
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experience less blood loss, less analgesic requirements and shorter time to bowel movements [58,59]. Robotic-assisted cystectomy with intracorporal ileal conduit is safe and reproducible and is likely to be offered to a substantial number of patients in the future [58–61]. Some recent publications have also highlighted the use of the mm-opioid receptor antagonist almivopan in order to enhance recovery after cystectomy. Oral administration of almivopan was shown to reduce the time to bowel recovery from 6.8 to 5.5 days [62]. Kauf et al. reported that almivopan decreased medical care costs associated with postoperative ileus and reduced length of hospital stay for cystectomy patients with 2.6 days [63]. These findings make almivopan an attractive drug in the setting of radical cystectomy and suggest that mm-opioid receptor antagonists may have a role in future ERAS protocols. Expert commentary
To improve the quality of life in bladder cancer patients, many aspects must be taken into consideration. Key points are to provide good, accurate and a sufficient amount of information and involve the patient in the decision-making of his/her disease. Development of new and minimally invasive procedures in the treatment of bladder cancer will benefit more patients in the future and bladder preservation strategies should be considered in selected patients. Evidence-based medicine is the cornerstone of our practice, and in the areas where evidence is scarce we have to try to provide this by asking the right questions and contribute to the existing research. Five-year view
In the near future, we anticipate that the increased focus on quality of care for bladder cancer patients will lead to a stronger adherence to guidelines among urologists. For patients with nonmuscle-invasive disease, this may reduce the number of hospital admissions and as such increase the quality of life. Tomorrow’s patients are likely to exhibit higher demands for information and to be more actively involved in the decision-making on their way through the disease trajectory. We believe shared decisionmaking aids will become more available and that more cancer centers will offer more individually tailored treatment options. The increased quality of life associated with bladder preservation therapy may lead to more patients enquiring about this kind of treatment option. Beyond the 5-year perspective, more efficient chemotherapy drugs are in the pipeline and are likely to further expand the number of patients that will be candidates for bladder preservation therapy. The strong attention toward evidence-based perioperative handling of the surgical patient will reduce hospital stay as well as the morbidity and mortality associated with radical cystectomy, and patients scheduled for cystectomy will increasingly be offered minimal invasive surgery. Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This 541
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includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues • Good and validated information is crucial to satisfy patient’s needs.
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• Shared decision-making will improve patient’s satisfaction and may prove a valuable tool for patient education. • Current adherence to guidelines is inadequate. • Immediate instillation of intravesical chemotherapy following transurethral resection of bladder tumor reduces the number of transurethral procedures for patients with non-muscle-invasive bladder cancer. • Urinary reconstruction following cystectomy must be carefully adjusted to the patient’s preference and functional level. • Enhanced recovery after surgery and the increased focus on evidence-based perioperative treatment will reduce morbidity and mortality in radical cystectomy patients. • Minimally invasive surgery is likely to be offered to a substantial number of patients in the future. • Bladder preservation therapy for muscle-invasive bladder cancer is a valid option in selected patients.
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Caffo O, Veccia A, Fellin G, et al. Trimodality treatment in the conservative management of infiltrating bladder cancer: a critical review of the literature. Crit Rev Oncol Hematol 2013;86(2):176-90
Cerantola Y, Valerio M, Persson B, et al. Guidelines for perioperative care after radical cystectomy for bladder cancer: Enhanced Recovery After Surgery (ERAS ((R))) society recommendations. Clin Nutr 2013;32(6):879-87
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Efstathiou JA, Spiegel DY, Shipley WU, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol 2012;61(4): 705-11
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Review
Strategies to improve quality of life in bladder cancer patients Expert Rev. Pharmacoecon. Outcomes Res. 14(4), 537–544 (2014)
Marius Roaldsen1,2, Erling Aarsaether1,2, Tore Knutsen1 and Hiten RH Patel*1,2 1 Department of Urology and Endocrine Surgery, University Hospital of North Norway, N-9038 Tromsø, Norway 2 Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway *Author for correspondence: Tel.: +47 7762 6000 Fax: +47 7762 6421 [email protected]
Bladder cancer is a heterogeneous disease that includes both tumors with low risk of dissemination as well as highly malignant tumors with a considerable potential to metastasize. The patient’s quality of life is closely related to the management of the disease. The challenge for the urologist is to acknowledge the malignant potential of the cancer and to adjust the approach to the patient accordingly. Patients with low-risk bladder cancer should avoid an exaggerated follow-up, but on the other hand high-risk patients must be sufficiently surveyed to secure that definitive surgical treatment is performed before it’s too late. When the decision to perform a cystectomy has been made, it is crucial that the patient understands the consequences of the surgery as well as the possible options for urinary reconstruction. This review focuses on aspects of bladder cancer management that we believe are vital for the quality of life of these patients. KEYWORDS: bladder cancer • ERAS • evidence-based medicine • guidelines • oncology • quality of life • shared decision-making
Bladder cancer is the fourth most common cancer among men in the UK and Norway. For men and women together, it is the seventh most common cancer. However, it is the most expensive cancer per capita in the USA [1,2] and Europe, and as such, bladder cancer represents a substantial challenge for both health professionals and budgets. Patients with curable disease may either have to go through major surgery or participate in a vigorous follow-up with frequent invasive procedures. The frequent examinations during follow-up are often experienced as a burden for the patient. It is time consuming for the urologist and represents a large expense for the healthcare system. Furthermore, frequent visits to the urologist have an impact on the quality of life of these patients, and thus we should strive to provide good care consistent with updated guidelines, but also avoid unnecessary interference with everyday life. Patients with curable disease can be divided into two subgroups with quite different challenges and outcomes: muscle-invasive bladder cancer and non-muscle-invasive bladder cancer. In this review, we will discuss important aspects of disease management that are critical for quality of life of
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both patient groups. Management of patients with metastatic bladder cancer is beyond the scope of this review. Information
Some aspects of healthcare are important for all patients. Good communication and information is important and must not be neglected. All patients receiving a cancer diagnosis should be informed about their condition in an atmosphere that leaves room for questions, whether it is in the emergency room or under more appropriate facilities in the ward. The need for information can sometimes be difficult to satisfy, but all healthcare professions involved in the treatment should aspire to fulfill the patients’ need for information. The information should preferably be given by the same doctor over time and in layman’s terms. If the demand for information is met, it often improves the level of patient satisfaction and also ultimately improves the quality of life. Studies reveal that patients would like the physician and the other health professionals involved to see them as a person; as an unique individual. Patients experiencing that they are being genuinely cared for and
2014 Informa UK Ltd
ISSN 1473-7167
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not only treated as a cancer patient with a number in line, have been shown to exhibit improved patient satisfaction [3]. This will also increase the tolerance for complications and side effects. On the other side, patients experiencing a lack of empathy from involved healthcare professionals will be much more likely to complain about issues regarding their care, which may include either valid complaints or minor issues. A sound doctor/patient relationship cannot be underestimated, but requires patience and time, which is difficult to provide in a hospital environment where the demand for efficiency and cost-effective care is increasing. However, a good doctor/patient relationship is always a valuable investment both in short and long term, as it will prevent misunderstanding and unpleasant surprises for the patient about side effects and challenges in their new life as a cancer patient. In patients with muscle-invasive bladder cancer, the need for information will change as they progress through the different stages of treatment from diagnosis to survivorship as described by Mohamed et al. [4]. All healthcare professionals who provide care for these patients should be familiar with the different traumas and the corresponding needs for information that develop during this exhaustive treatment pathway. Written information in the form of brochures, booklets or folders makes it easier to meet a patient’s need for information. They allow for easier communication and increase the likelihood that the information will be absorbed and correctly interpreted. The first time the cancer diagnosis is given, the information will often feel overwhelming with only a small part remembered afterward. Therefore, written information may be of great help as it gives the patient the opportunity to, when the worst shock has passed, read the brochure at a time of their choosing. Patients experiencing that the demand for information has been met, have been reported to exhibit better health-related quality of life and lower levels of depression and anxiety [5]. This is important to bear in mind that good information gives you healthier patients! Shared decision-making
Shared decision-making can also improve patient care [6–8]. This is a process, in which patients are encouraged by their health professional to participate in selecting the most appropriate health treatment or care management option for their individual needs and preferences. For many diseases there are several treatment options. In the instance of bladder cancer, there are several alternatives when it comes to urinary reconstruction after cystectomy. Involving the patient in shared decision-making allows him/her to participate in the important decisions about his/her life and treatment. Whereas some patients prefer the urologist to single-handedly manage their disease according to what is current institutional practice, an increasing number of patients are searching the web for information about available treatment options, although not necessarily with the competence to interpret the quality or the relevance of this information. Most patients would be happy to be more involved in the decision-making concerning their treatment; however, to be able to participate, it is important 538
that the patient receives good validated information that is adapted to non-healthcare professions. This is being implemented at the University Hospital of North Norway, where work on an interactive information and decision-making tool has been initiated [9]. The process is based on software where the patient has access to information about their disease and treatment options, as well as informative videos and videos with patients talking about their experience with their treatment options. It also includes questionnaires where the patient can answer questions that are relevant for the choices they have to make. When they have gone through this, they sit down with their doctor to discuss the alternatives. This web portal, which so far has been targeted toward patients with chronic renal failure, serves both to educate the patient and as a decision-making tool, and will be developed for patients with bladder cancer in the near future. A Cochrane review [7] has looked at the impact of decision aids and found that it improved the patients’ knowledge of their options, which resulted in more accurate expectations about benefits and disadvantages of their treatment. The review also demonstrated that patients utilizing decision aids participated more in the decision-making and took choices more consistent with their way of living and thus improved their quality of life. This may be a great asset for both the patient and the doctor and we are currently investing time and resources to develop this interactive decision-making portal. Surveillance of patients with non-muscle-invasive bladder cancer
Non-muscle-invasive bladder cancer is a disease with excellent long-term survival, but with a high level of recurrence. As a consequence, patients with non-muscle-invasive bladder cancer will undergo a meticulous follow-up that is carried out over many years or even the rest of the patients’ life [10]. This is also the reason for the high burden and cost of the disease. Many patients have to continue the follow-up with numerous cystoscopies, computer tomography scans, trans-urethral resections and intravesical instillation of Bacillus Calmette–Gue´rin until they die or until they receive definitive surgical treatment with radical cystectomy. After the primary diagnosis, a patient may easily have to pay 15 visits to the urologist within 12 months [2]. As this severely impacts quality of life [11,12], a critical evaluation of how the follow-up is conducted is necessary. This may prevent patients with low-risk disease to avoid redundant examinations, but should also secure that patients with intermediate and high-risk disease receive the recommended number of controls. Our department utilizes the guidelines from the European Association of Urology [10,13]. Following transurethral resection, the patient’s risk of recurrence and progression is calculated based on tumor size, number of tumors, histopathology scoring, recurrence, tumor category and the presence of carcinoma in situ. The scores provide a probability for recurrence and progression of the disease that have been solidly documented in a summary of seven randomized Phase III trials [14]. However, the follow-up guidelines are heavily based on expert Expert Rev. Pharmacoecon. Outcomes Res. 14(4), (2014)
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opinion and do not comply with the highest standards of evidence-based medicine. In fact, the only study to our knowledge comparing bladder cancer surveillance programs in a randomized prospective design included only 97 patients [15]. The lack of evidence for the surveillance guidelines represents a challenge for the urologist in the management of these patients. It may also explain the surprisingly low clinical consensus and compliance with guidelines among urologists when it comes to follow-up of these patients. Chamie and colleagues examined the Medicare data from 4790 patients with a diagnosis of highgrade, non-muscle-invasive bladder cancer between 1992 and 2002, and found that only one patient received all the recommended measures [16]. This illustrates a problem, in which patients with bladder cancer are likely to receive different care at different institutions. Another interesting finding in the study from Chamie et al. was that a statistically significant survival advantage was found among those who received at least half of the recommended care, when compared with those who received less than this level of care. This suggests that compliance to current guidelines may improve not only quality of life, but also survival and should motivate urologists to utilize them. We know from our own experience at our institution that many patients with low-risk bladder cancer previously went through the same follow-up as patients with high-risk bladder cancer. This means that many patients have had an excessive follow-up with invasive procedures that have not improved their outcome in addition to increased hospital costs, and a misuse of patients’ time that could have been utilized for better purposes. We now perform a risk stratification of all patients at every appointment, to make sure they get the follow-up according to current guidelines. In the absence of surveillance programs based on high-level evidence, we still believe this is the most appropriate way to deal with our patients. Reducing risk of recurrence following transurethral resection
Transurethral resection of the bladder should always be performed by minimizing the probability for recurrence as much as possible. We advocate the use of photodynamic diagnosis with 5-aminolevulinic acid or hexyl aminolevulinate in addition to white-light cystoscopy during transurethral surgery, since it has been shown to improve cancer detection and reduce recurrence. A recent review in European urology [17] has looked at the benefit of photodynamic diagnosis and found that it improved tumor detection and reduced the number of residual cancers after transurethral resection compared with white-light cystoscopy only. Although it has not been shown to alter progression to more advanced disease, utilization of photodynamic diagnosis is likely to reduce the number of hospital admissions for transurethral resections and consequently improve quality of life. Since photodynamic diagnosis increases the chance of a complete transurethral resection, we believe it should be offered on a routine basis, especially when the presence of carcinoma in situ may be expected [18]. The use of intravesical chemotherapy immediately after transurethral resection represents another informahealthcare.com
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strategy to minimize the risk of recurrence. A meta-analysis of seven randomized trials demonstrated that immediate instillation of chemotherapy after transurethral resection of bladder cancer was associated with a risk reduction of almost 40% for bladder cancer recurrence [2,19]. A study has also calculated a loss of 0.02 quality-adjusted life-years per patient not receiving immediate intravesical chemotherapy [20]. In spite of high-level evidence for the use of intravesical chemotherapy following transurethral resection, reports have documented a surprisingly low utilization of this strategy to reduce the risk of bladder cancer recurrence [2,21,22]. The reason for this is not known, but in contrast to guidelines for follow-up, the existing level of evidence for the administration of intravesical chemotherapy is so solid that it should encourage a change in practice. Laser ablation of bladder tumors can be a good alternative for selected patient with low-risk non-muscle-invasive bladder cancer. Wong et al. have shown that it can be done safely in an outpatient clinic and that it is cost-effective [23]. Laser ablation represents an interesting treatment option, especially for elderly patient with comorbidity. The obvious disadvantage is the loss of histopathologic specimens for examination of the tumor. Selection of patients for urinary diversion
Muscle-invasive bladder cancer is associated with quite different challenges, when compared with non-muscle-invasive disease. To be cured, these patients must undergo extensive surgery of the pelvis with accompanying high rate of complications and side effects such as impotence, incontinence and pain. The goldstandard treatment is radical cystectomy. In men, it involves a complete extirpation of the bladder along with the prostate and seminal vesicles and in some cases also the urethra. The extensive pelvic surgery will cause some nerve damage and often leads to impotence. In women, the surgery entails the removal of the uterus, cervix, ovaries and anterior vagina en bloc with the bladder. Following removal of the bladder, reconstruction of the lower urinary tract is of paramount importance [24,25]. In principle, the three alternatives are incontinent cutaneous diversion (ileal conduit/bricker conduit), continent cutaneous diversion and finally the orthotropic neobladder. Ileal conduit is considered the easiest and least complicated reconstruction to perform these surgical procedures and utilizes only 10–15 cm of small bowel for the diversion. It is considered to be the procedure of choice for patients with short life expectancy and comorbidity. It is also the procedure of choice when the patient has renal or liver failure, as complications associated with metabolic acidosis, as a consequence of reabsorption from the bowel used for reconstruction, is avoided [26]. Because it involves the construction of a stoma, this is the procedure that alters the body image of the patient the most. These patients will have to wear a urinary collecting bag all the time and for most patients this represents a dramatic change. It can alter social interaction, body image and affect sexual function. The patients are frequently concerned about odor, urinary leakage and stoma care. Taken together, this can result in social isolation of the patient and hinder them from participating in hobbies and travel activities [24,27–29]. 539
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Continent cutaneous reconstruction is a procedure that utilizes a larger part of the bowel, usually 45 cm of small bowel or a part of the colon to make an artificial bladder and represents a legitimate option when the urethra is unavailable because of cancer involvement or because of incontinence. The patient is still dependent on a stoma, but the advantage is that he/she does not have to use a collecting bag, resulting in an increased preservation of body image when compared with ileal conduit. The reservoir has to be emptied with a catheter approximately every 4 h. Failure to comply with catheterization may lead to major complications with renal failure and rupture of the reservoir [30]. If the patients can’t follow this regime, they are not candidates for this kind of reconstruction. Studies evaluating quality of life have shown improved body image and sexual function in these patients as compared with those with an ileal conduit [31]. However, the patients must be informed of the need for night time catheterization, since it may lead to sleep disturbance and as such may have an negative impact on quality of life [29]. Orthotopic neobladder is the procedure that alters the body image the least. The reservoir is attached to the urethral stump and voiding is initiated with relaxing of the pelvic floor and increasing the abdominal pressure with valsalva maneuver or crede` pressure. Patients unable to empty the bladder voluntarily must empty it with a catheter. The advantages are the lack of stoma, the ability to void through the urethra and subsequently the preservation of body image when compared with ileal conduit [32] and continent cutaneous reconstruction. The disadvantages represent the use of a larger part of the bowel, longer operation time and more postoperative complications. The patients also have to be able to perform catheterization if they are unable to empty the bladder. Incontinence is one of the major concerns for this patient group and for many patients this is what has the greatest impact on their life. There have been many studies comparing different reconstruction procedures after cystectomy [24–26,29–35]; however, the findings have been somewhat varied making it difficult to draw a conclusion on what kind of reconstruction is the best. As there are advantages and disadvantages for each procedure, it must be a joint decision between patient and surgeon. It is of utmost importance that the patients have been provided adequate and accurate information on the different solutions available, so that they are able to participate in choosing the kind of reconstruction that is most appropriate. By utilizing the premise of shared decision-making, a good patient/doctor relationship and access to written information, it is more likely that the patients will get the reconstruction that works best for them and ensures that they are better prepared for life after surgery. Strategies for bladder preservation in muscle-invasive bladder cancer
A conservative approach for muscle-invasive bladder cancer was originally introduced as an alternative to cystectomy in patients who were not candidates for radical surgery because of comorbidity. Before the chemotherapy era, radiation therapy alone 540
was utilized in patients who were considered inoperable. Radiotherapy as the only treatment modality for muscle-invasive bladder cancer is currently reserved for patients with considerable comorbidity and a poor performance status that disqualifies them for chemotherapy. Partial cystectomy represents another bladder preservation strategy. This is a procedure that involves removal of only the part of the bladder where the cancer is localized, and is likely to preserve sexual function, since the nerves surrounding the prostate are spared. The published survival rates have been encouraging [36–39], but only a small number of patients, that is, 5–10% of those with clinically T1 or T2 disease will be candidates for such a procedure [40]. Neoadjuvant chemotherapy followed by partial cystectomy or transurethral resection of bladder tumor (TURBT) is also an option that may be considered in patients with muscle-invasive bladder cancer, but only a few studies have investigated the outcome of such a strategy. In the study by Herr et al., which included a highly selected group of patients, the 10-year survival rate of neoadjuvant chemotherapy followed by partial cystectomy or transurethral resection was 74%, and a 58% bladder intact survival was reported [41]. However, for this strategy to be effective, a re-staging TURBT following chemotherapy documenting the absence of muscle-invasive cancer is a prerequisite. The reliability of this re-staging TURBT has been questioned in the SWOG SO219 Trial after 6 of 10 patients undergoing cystectomy were found to have muscle-invasive cancer, despite the fact that the re-staging TURBT was negative [42]. Although the combination of chemotherapy and TURBT as well as chemotherapy and radiotherapy has been shown to improve outcomes in patients with a bladderpreserving strategy compared with either of these alone, the most effective means is to combine all of them [43,44]. The combination of TURBT, chemotherapy and radiation therapy is commonly referred to as trimodality treatment, and has been fronted by the Massachusetts General Hospital and the Radiation Oncology Group for the last 30 years [44,45]. Trimodality treatment has been shown to confer long-term survival rates comparable to contemporary cystectomy series [45,46], and between 62 and 85% of the patients successfully achieving the preservation of their native bladder after 5 years [43]. However, the results of trimodality treatment are not directly comparable to retrospective cystectomy data, since the results from the surgical series are based on pathological staging, while the tumors from the trimodality treatment trials are clinically staged. This observation is likely to favor the surgical series, since many cancers are upstaged at the time of surgery [40]. As for the other bladder-preserving strategies mentioned above, the purpose of trimodality treatment is to improve quality of life, yet only a few studies have compared this treatment strategy with the gold standard of cancer-free survival, that is, radical cystectomy. Of the two studies to our knowledge that may be used to answer this question, only one of them included chemotherapy in addition to radiotherapy [47], while the other compared radiation therapy alone with radical cystectomy. Both these studies documented an improved quality of Expert Rev. Pharmacoecon. Outcomes Res. 14(4), (2014)
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life in favor of a bladder-preserving strategy [47,48]. The patients selected for bladder preservation therapy were found to exhibit improved sexual function and most of them also reported a preservation of bladder function [47,48]. Retrospective quality-oflife studies have since confirmed that the vast majority of patients subjected to trimodality treatment retain a wellfunctioning bladder [49–51], and this has recently been documented in a prospective analysis [52]. However, the successful improvement in quality of life as well as the reported acceptable rates of cancer-free survival must be balanced against the substantial number of follow-ups that are mandatory to make sure that the disease does not recur. Nevertheless, bladderpreserving therapy is a reasonable option in selected patients and represents an alternative for improved quality of life through preserved bladder function as well as sexual function. New irradiation techniques and new-generation drugs are being evaluated and we believe trimodality treatment will be an option for a larger patient population in the future. Enhanced recovery after surgery
In the perioperative period, we advocate the use of Enhanced Recovery After Surgery (ERAS) principles [53]. The ERAS society has focused on evidence-based practice in the perioperative period instead of treating according to tradition. As a result, they have reduced complication rates and the length of hospital stay. The main work from this group has been on colonic and rectal surgery, but many of the principles can be transferred to other disciplines of surgery. In regard to cystectomy, the evidence of perioperative treatment is limited [54,55], although we still believe many of these principles can be transferred to this setting. Cerantola et al. [54] have assessed the literature on ERAS on cystectomy and have recommended its implementation. The ERAS principles can be summarized as follows: optimization of patient education and information, increased focus on preoperative nutrition and minimization of fasting. The ERAS society also recommends that bowel preparation should be omitted and advocates the use of pre-anesthetic medication without long active sedatives. Prolonged antithrombotic treatment for 4 weeks with low–molecular-weight heparin is recommended. In addition, epidural analgesia for 72 h and early removal of nasogastric tubes should be performed. Postoperative nausea and vomiting prophylaxis is recommended, while early oral nutrition and mobilization are encouraged. Multimodal approach for stimulation of gut functions with chewing gum and magnesium is recommended. Karl et al. [56] have randomized patients for radical cystectomy for ERAS and a conservative surgical regime. They found that the ERAS group had shorter time in the intensive care unit, lower morbidity, less demand for analgesia and higher quality of life. Daneshmand et al. [57] reported shorter time to bowel movement and shorter hospital stay on the ERAS regime. Minimal-invasive surgery has great impact on recovery and the ERAS society [54] and the authors strongly advocate the use of this. Robotic surgery has made this possible even with cystectomy and the literature on this is evolving. Patients subjected to minimally invasive surgery informahealthcare.com
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experience less blood loss, less analgesic requirements and shorter time to bowel movements [58,59]. Robotic-assisted cystectomy with intracorporal ileal conduit is safe and reproducible and is likely to be offered to a substantial number of patients in the future [58–61]. Some recent publications have also highlighted the use of the mm-opioid receptor antagonist almivopan in order to enhance recovery after cystectomy. Oral administration of almivopan was shown to reduce the time to bowel recovery from 6.8 to 5.5 days [62]. Kauf et al. reported that almivopan decreased medical care costs associated with postoperative ileus and reduced length of hospital stay for cystectomy patients with 2.6 days [63]. These findings make almivopan an attractive drug in the setting of radical cystectomy and suggest that mm-opioid receptor antagonists may have a role in future ERAS protocols. Expert commentary
To improve the quality of life in bladder cancer patients, many aspects must be taken into consideration. Key points are to provide good, accurate and a sufficient amount of information and involve the patient in the decision-making of his/her disease. Development of new and minimally invasive procedures in the treatment of bladder cancer will benefit more patients in the future and bladder preservation strategies should be considered in selected patients. Evidence-based medicine is the cornerstone of our practice, and in the areas where evidence is scarce we have to try to provide this by asking the right questions and contribute to the existing research. Five-year view
In the near future, we anticipate that the increased focus on quality of care for bladder cancer patients will lead to a stronger adherence to guidelines among urologists. For patients with nonmuscle-invasive disease, this may reduce the number of hospital admissions and as such increase the quality of life. Tomorrow’s patients are likely to exhibit higher demands for information and to be more actively involved in the decision-making on their way through the disease trajectory. We believe shared decisionmaking aids will become more available and that more cancer centers will offer more individually tailored treatment options. The increased quality of life associated with bladder preservation therapy may lead to more patients enquiring about this kind of treatment option. Beyond the 5-year perspective, more efficient chemotherapy drugs are in the pipeline and are likely to further expand the number of patients that will be candidates for bladder preservation therapy. The strong attention toward evidence-based perioperative handling of the surgical patient will reduce hospital stay as well as the morbidity and mortality associated with radical cystectomy, and patients scheduled for cystectomy will increasingly be offered minimal invasive surgery. Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This 541
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includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues • Good and validated information is crucial to satisfy patient’s needs.
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• Shared decision-making will improve patient’s satisfaction and may prove a valuable tool for patient education. • Current adherence to guidelines is inadequate. • Immediate instillation of intravesical chemotherapy following transurethral resection of bladder tumor reduces the number of transurethral procedures for patients with non-muscle-invasive bladder cancer. • Urinary reconstruction following cystectomy must be carefully adjusted to the patient’s preference and functional level. • Enhanced recovery after surgery and the increased focus on evidence-based perioperative treatment will reduce morbidity and mortality in radical cystectomy patients. • Minimally invasive surgery is likely to be offered to a substantial number of patients in the future. • Bladder preservation therapy for muscle-invasive bladder cancer is a valid option in selected patients.
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