Quality Indicators in the Management of Bladder Cancer

Accreditation Statement

This activity has been designated to meet the educational needs of physicians and nurses involved in the management of patients with cancer. There is no fee for this article. No commercial support was received for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians.

NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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This activity is approved for 1.0 contact hour. Approval as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.

All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 70% minimum passing score and complete the evaluation at http://education.nccn.org/node/17316; and 4) view/print certificate.

Release date: April 11, 2013; Expiration date: April 11, 2014.

Learning Objectives

Upon completion of this activity, participants will be able to:

• Identify proposed quality indicators for non–muscle-invasive and muscle-invasive bladder cancer.

• Discuss treatment recommendations and guidelines for non–muscle-invasive and muscle-invasive bladder cancer.

Driven by third-party payers, patients, and health care providers, increasing interest has been shown in improving treatment outcomes and providing cost-conscience care. These efforts include the development of quality indicators for many disease processes and clinical care scenarios. The National Quality Forum, Agency for Healthcare Research and Quality (AHRQ), Leapfrog Group, and RAND Corporation represent only a few of the public and private entities involved in these endeavors. For a quality measure to be useful in improving patient outcomes, it must be based on high-level clinical evidence and/or expert opinion and be measurable (http://www.qualityforum.org/Home.aspx). An indicator that is difficult to measure lacks impact; a major avenue to improve care is to track and report quality measures to health care providers and patients. The goal of providing this feedback is to effect change that will improve patient outcomes and safety, and to identify barriers to high-quality care.

Despite an incidence of bladder cancer in the United States of more than 73,000 patients per year and a prevalence of more than 500,000 people,¹ a paucity of widely accepted quality indicators exists for this disease. However, guidelines based on level 1 evidence and expert opinion do exist for the treatment of patients with both non–muscle-invasive and muscle-invasive bladder cancer (NMIBC and MIBC, respectively).^2–4 With these guidelines as the accepted urologic standard, an initial set of quality indicators for bladder cancer care can be proposed.

Appropriate Imaging for Bladder Cancer Staging

Quality care for NMIBC starts with appropriate staging of the disease. Transurethral resection of bladder tumor (TURBT) is a crucial component of staging, because it defines tumor grade, stage, and underlying histology. Imaging should be performed before TURBT. The presence of perivesical stranding and bladder wall thickening suggests invasive (clinical stage T2–T3) disease, whereas hydronephrosis indicates possible clinical T3 disease. TURBT can cause perivesical stranding and bladder wall thickening, lowering the imaging sensitivity for these findings. Cross-sectional imaging with either a CT scan or an MRI evaluates the local disease burden and assesses for nodal and distant metastases. The accuracy of CT and an MRI for staging the local extent of disease varies from 73% to 96% and 55% to 92%, respectively.⁸ CT and MRI have similar sensitivity for identifying nodal enlargement suggestive of metastatic disease.⁹ In addition, delayed CT or MR urogram phases are essential to assess for upper tract disease. In situations in which patients cannot undergo contrast-enhanced imaging because of allergy or poor renal function, retrograde pyelograms combined with renal ultrasound or noncontrast CT or MRI can rule out concurrent upper tract neoplasm. Chest CT can be performed at the time of abdominal and pelvic components to rule out lung metastases; alternatively, a chest radiograph should be obtained. Bone scan and brain imaging are not routinely indicated unless the patient exhibits specific signs or symptoms, making metastasis to these sites a concern.

Restaging TURBT

Detrusor muscle in the pathologic specimen indicates completeness of resection and decreases the likelihood of understaging.¹⁰ In the presence of bulky, high-grade Ta disease, any T1 bladder cancer (even with muscle in the specimen), or an incomplete initial resection, current guidelines recommend a restaging transurethral resection 2 to 6 weeks after the initial resection.⁴ Approximately 30% of patients with T1 bladder cancer are understaged in the absence of a restaging TURBT, resulting in potential undertreatment.^11,12 Accordingly, restaging TURBT should be considered an important quality indicator. Unfortunately, as few as 4.9% of eligible patients undergo this procedure within 60 days of initial resection.¹³

Table 1

Proposed Quality Indicators for Non–Muscle-Invasive Bladder Cancer

View Table

Examination Under Anesthesia

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer recommend bimanual palpation of the bladder with the patient under anesthesia for a more thorough staging,¹⁴ and this should be performed at TURBT (to view the most recent version of these guidelines, visit NCCN.org). Presence of a palpable mass suggests T2–T3 disease, whereas the presence of a fixed bladder or invasion into the vagina or rectum indicates T4 disease. Again, the importance of accurate clinical staging cannot be overstated, because level 1 evidence exists for the use of platinum-based neoadjuvant chemotherapy for patients with T2–T4 localized bladder cancer followed by radical cystectomy to optimize disease outcomes.¹⁵

Perioperative Intravesical Chemotherapy

Studies dating back to the early 1990s evaluated the use of immediate-dose (within 24 hours) intravesical chemotherapy after TURBT with the goal of preventing disease recurrence. The 2 most commonly studied of these medications are epirubicin and mitomycin. In 2004, Sylvester et al¹⁶ published a meta-analysis of 1400 patients who received a single dose of intravesical therapy, confirming a resultant reduced risk of recurrence. Patients with single or multiple tumors benefited, with reduced odds of recurrence of 0.66 for single tumors and 0.44 for multiple tumors. However, tumors of higher grade and stage were more likely to recur, suggesting that this approach is indicated for a select group of patients with low-volume, low-grade Ta bladder cancer. These data serve as the driving force behind both the European Association of Urology (EAU) and American Urological Association (AUA) guidelines recommending a single perioperative dose of intravesical therapy after TURBT for low-grade Ta bladder cancer.

Despite the data and guidelines, some evidence suggests that this approach is infrequently implemented, with only 0.3% of Medicare patients receiving immediate intravesical therapy.¹⁷ However, this may not represent current practice. Recent data from the Urological Surgery Quality Collaborative suggest that the percentage of appropriate patients receiving a single dose of intravesical therapy after TURBT is higher, ranging from 20% to 50% of patients treated in large academic or community urology practices.¹⁸ The primary contraindication to giving this therapy, is deep resection. Allergic cystitis has been reported in up to 10% of patients undergoing immediate intravesical therapy, with the most severe cases ultimately requiring cystectomy.¹⁹ Other barriers to the use of mitomycin include a drug shortage, a belief that this therapy is not effective, or that giving the medication presents too great a risk. Continued provider education efforts and improved systems for delivering the medication are needed to expand the use of this therapy.

Use of Bacillus Calmette-Guérin in NMIBC

Bacillus Calmette-Guérin (BCG) is the most effective intravesical agent for the management of high-risk NMIBC, and its use is advocated by both AUA and EAU guidelines. BCG has been shown to reduce the risk of recurrence, and increasing data show that it may also reduce the risk of disease progression.²⁰ A complete resection is essential to optimize the response to BCG, especially for T1 disease, because BCG does not penetrate beyond the bladder mucosa basement membrane. An estimated 50% to 55% of patients with high-risk NMIBC experience a complete response to intravesical BCG. Response rates are as high as 70% in patients with carcinoma in situ alone.²¹ Shelley et al²² performed a meta-analysis of 6 randomized controlled studies including 585 patients with Ta and T1 disease undergoing TURBT with or without subsequent BCG. This study showed a 70% lower likelihood of recurrence at 1 year in patients receiving BCG. However, BCG complications are not inconsequential, with up to 71% of patients experiencing urinary frequency, 67% cystitis, 25% fever, and 23% hematuria. Serious local and systemic infections from BCG occur and may require antituberculosis therapy and even hospitalization. Although the use of BCG should be considered a quality indicator for this patient population, there are reasons why BCG may not be given or may not be effective.^23–26

Maintenance BCG

Level 1 evidence shows improved recurrence- and progression-free survivals in patients undergoing maintenance BCG therapy after a complete response to an induction course. Lamm et al²⁰ reported on a cohort of 384 patients who received induction BCG and then were randomized to surveillance versus maintenance BCG given each week for 3 weeks at 3, 6, 12, 18, 24, 30, and 36 months after the initial induction course. The median recurrence-free survival was 80 months for patients receiving maintenance therapy versus 36 months for those undergoing surveillance alone. In addition, patients on maintenance were found to have improved progression-free survival. One notable limitation of this study is that only 17% of patients completed the full maintenance course.²⁰ Although current EAU guidelines recommend at least 1 year of maintenance BCG therapy, and AUA guidelines “suggest that maintenance BCG be administered,” NCCN Guidelines list maintenance BCG as “optional,” and uncertainty exists regarding optimal dosing and length of duration of therapy.¹⁴

Multidisciplinary Care

Once MIBC is diagnosed, patients must be educated regarding treatment options so that they may make an informed treatment decision. Given the complexity of this disease and patient characteristics, a multidisciplinary approach is preferred, involving medical and radiation oncologists when appropriate. This may be in the form of a multidisciplinary bladder cancer clinic, coordinated consultations, or the presentation of individual cases to an institutional tumor board. With this, patients receive a more thorough evaluation, including input from multiple providers with unique treatment perspectives. As seen in studies examining the use of neoadjuvant chemotherapy²⁷ and the combination of tumor resection, chemotherapy, and radiation therapy,²⁸ multidisciplinary therapy for MIBC is often associated with optimal disease outcomes for individual patients.

Neoadjuvant Chemotherapy

The 5-year survival rate after cystectomy for MIBC is only approximately 50%.⁸ To improve these poor outcomes, platinum-based neoadjuvant chemotherapy should be considered for all patients with T2 or greater disease. Some advantages of platinum-based neoadjuvant chemotherapy is that drug is delivered early in the treatment course when the volume of micrometastatic disease is at its lowest, the delivery of systemic therapy is not delayed because of patient recovery after cystectomy, and negative node and margin status may be more attainable at cystectomy after chemotherapy. Platinum-based neoadjuvant chemotherapy followed by cystectomy has been shown to improve patient median survival from 46 to 77 months compared with surgery alone.^27,29 Multiple meta-analyses of randomized neoadjuvant chemotherapy trials show survival advantages of approximately 5% at 5 years after treatment.⁸ These superior disease outcomes are achieved without significant differences in perioperative complications between patients who undergo neoadjuvant chemotherapy and those who do not. Unfortunately, the use of neoadjuvant chemotherapy in patients undergoing cystectomy is limited, with as few as 17% of patients with T2 or greater disease receiving treatment, even at academic centers.^30,31 These low rates of use can be partially explained by patient comorbidity, especially renal insufficiency, and poor performance status. Some experts advocate for early cystectomy in patients who are unable to tolerate platinum-based chemotherapy regimens, although this remains an area of controversy. Despite this, missed opportunities occur to provide patients with MIBC with best possible care supported by randomized prospective data.

Urinary Diversion Teaching

Managing urinary diversion after cystectomy has a significant effect on a patient's lifestyle. Patients must be thoroughly educated regarding their preferred urinary diversion before surgery. For patients opting for an ileal conduit, meeting with an enterostomal therapist trained to educate stoma patients is important.³² The enterostomal therapist should

Table 2

Proposed Quality Indicators for Muscle-Invasive Bladder Cancer

View Table

Perioperative Antibiotics

One well-established quality indicator applied to open abdominal surgery is the appropriate use of perioperative prophylactic antibiotics to prevent surgical site infections. Despite the strength of evidence supporting this practice, studies indicate that timely antibiotic administration does not occur in upwards of 54% of cases.³³ General recommendations include administering perioperative antibiotics in an adequate dose based on patient weight within 60 minutes of the surgical incision, and discontinuing them 24 hours after surgery.³⁴ In addition, intraoperative redosing should occur after 2 antibiotic half-lives to ensure sufficient antimicrobial serum levels until the incision is closed. With entry into the urinary tract and creation of the urinary diversion from intestine, using a second- or third-generation cephalosporin as first-line antibiotic prophylaxis is recommended for cystectomy.³⁵

Thrombosis Prophylaxis

Given the presence of neoplasm, extent of comorbidities, and older patient age, patients who undergo cystectomy are at high risk for the development of deep vein thrombosis and subsequent pulmonary embolism, collectively representing up to 8% of all cystectomy perioperative complications.³⁶ This rate is an underestimate because of missed diagnosis of subclinical events. Because this represents an opportunity to prevent significant morbidity and mortality, deep vein thrombosis prophylaxis is a marker of high-quality patient care.³⁷ Prophylaxis can include mechanical (eg, early ambulation, compression stockings, intermittent pneumatic compression devices) and pharmacologic (eg, low-dose unfractionated heparin, low-molecular-weight heparin) measures.³⁷ For patients undergoing cystectomy, it is recommended that at least intermittent lower-extremity pneumatic compression devices are placed at the time of anesthesia induction and continued in the postoperative period until the patient is freely ambulating. A more aggressive regimen, including subcutaneous heparin given at the time of surgery, should be considered.³⁷ Both of these measures, combined with early ambulation, should then be continued during the postoperative admission as long as the patient has no contraindications to this treatment.

Lymphadenectomy

The extent of lymph node dissection needed during radical cystectomy for MIBC is controversial.⁸ Data show that a more extensive lymph node dissection may lead to a survival benefit.³⁸ A more limited node dissection is associated with suboptimal staging, and also worse disease outcomes for patients with node-positive and node-negative disease.⁸ Accurate pathologic staging is essential to determine the need for adjuvant therapy and to anticipate disease recurrence. For this reason, at least a standard node dissection, including the common iliac nodes lateral to the ureters, external iliac, obturator, and internal iliac lymph nodes, should be performed if possible during cystectomy.⁸

Monitoring Complications

To improve outcomes and evaluate the quality of care provided to patients undergoing cystectomy, it is important to have a standard and reproducible system for defining and tracking complications.³⁹ The Clavien-Dindo system of evaluating postoperative complications has gained favor in the urologic community. This method classifies events from I to V, with a higher number indicating a more severe complication requiring more significant intervention.⁴⁰ With this system, complications of the same grade can be grouped for ease of communication, whether in a publication or a quality-of-care report. In addition, a standard means of categorizing postcystectomy mortality is important. Several publications report 90-day mortality, because these mortalities are likely attributable to the procedure.