Guidelines update: Bladder, kidney, prostate cancer

In a 2012 paper, researchers from RAND Corp. called clinical practice guidelines “one of the foundations of efforts to improve health care” (Implement Sci 2012; 7:62). The pace of modern medical advances underscores the importance of published clinical guidance, and has in fact led to an increase in the speed of guideline development and updates. The field of genitourinary cancer is no stranger to this trend.

This article highlights the key points of two urologic cancer guidelines (which provide evidence-based guidance) and two consensus statements (which provide consensus recommendations by a multidisciplinary panel of experts) that have been published in the past year. The guidelines discuss nonmuscle-invasive bladder cancer and small renal masses, while the consensus statements examine immunotherapy for renal cell carcinoma and prostate cancer.

Nonmuscle-invasive bladder cancer (AUA/SUO)

The 2016 American Urological Association/Society of Urologic Oncology guideline on the diagnosis and treatment of nonmuscle-invasive bladder cancer (NMIBC) provides clinicians with a risk-stratification approach to treating this condition. The full guideline was published in The Journal of Urology (2016; 196:1021–9).

Dr. ChangDepending on the patient’s unique experience with NMIBC, sometimes more follow-up and surveillance are warranted, whereas with other patients, their clinical teams should be mindful about when it’s more appropriate to “back off,” says Sam S. Chang, MD, professor of urologic surgery and urologic surgeon/oncologist at Vanderbilt University, Nashville, TN, who helped develop the guideline.

Leveraging a risk-stratified approach, the guideline puts patients into one of three categories: low, intermediate, and high risk. The guideline’s treatment algorithm incorporates the tumor’s characteristics while factoring in the individual patient’s response to therapy. Attempting to help clinicians evaluate and treat individual patients, the guideline includes 38 statements, which rely on a variety of evidence.

During diagnosis, specifically, the guideline recommends that clinicians perform a thorough cystoscopic examination of the patient’s entire urethra and bladder, in addition to evaluating and documenting the size, location, configuration, number, and mucosal abnormalities of the tumor. Experts also recommend that during the initial diagnosis, a complete visual resection of the bladder tumor(s) should be performed, in addition to imaging of the patient’s upper urinary tract.

For a patient who has been treated for NMIBC in the past and has normal cystoscopy and positive cytology, prostatic urethral biopsies and upper tract imaging, in addition to enhanced cystoscopic techniques, such as blue light cystoscopy, should be considered.

Also, in a patient with suspected or known low- or intermediate-risk bladder cancer, a single postoperative instillation of intravesical chemotherapy, such as mitomycin C or epirubicin, should be considered within 24 hours of transuretheral resection of a bladder tumor. For patients at intermediate risk-those who completely respond to induction bacillus Calmette-Guerin (BCG)-their clinical team should consider maintenance BCG for 1 year, as tolerated by the patient. In addition to recommendations on BCG relapse, salvage regimens, and other aspects of management, the document also provides risk-adjusted surveillance and follow-up strategies.

Next: Small renal masses (ASCO)

Small renal masses (ASCO)

Dr. RussoIt wasn’t until the 1990s that kidney preservation in patients with small renal masses started to take hold, largely at Memorial Sloan Kettering Cancer Center, Mayo Clinic, and Cleveland Clinic in the United States and by health care providers in Europe. At Memorial Sloan Kettering in New York, urologic surgeon Paul Russo, MD, contrasts the number of kidney-sparing operations his team did each year when he was a fellow in the late 1980s-three total-with the three he performed on a recent day.

That’s when a consensus started to develop around the positive outcomes patients could experience if only the tumor was removed and the kidney was spared, a decision that’s predicated by the size of the tumor and its location in the kidney, Dr. Russo says. He notes that 70% of cancerous masses found in the kidney are considered small-4 cm or less-and the vast majority of these are amenable to partial nephrectomy.

Even a stage T1b tumor-at 7 cm or less-is still relatively small, adds Dr. Russo, who helped develop the American Society of Clinical Oncology’s clinical practice guideline on management of small renal masses, which was published earlier this year (J Clin Oncol 2017; 35:668–80). (Approximately 30% of cancerous masses found in the kidney are considered large and/or metastatic.)

Partial nephrectomy is the recommended treatment in patients whose tumor measures 4 cm or less. The guideline recommends radical nephrectomy only in instances where the tumor is significantly complex and not technically amenable to a kidney-sparing approach. Further, patients who develop progressive chronic kidney disease-in particular, proteinuria and/or a glomerular filtration rate of less than 60 mL/min/1.73 m2-should receive a referral to a nephrologist.

Biopsy is best utilized in patients with a small renal mass when the results could alter management. In contrast, patients with significant comorbidities and limited life expectancy with a small renal mass are better candidates for active surveillance, and biopsy in that setting can be omitted.

The guideline authors note that for patients with significant comorbidities and limited life expectancy, active surveillance is the appropriate response for initial treatment. The reasoning behind this recommendation is many of the asymptomatic masses found in patients over 70 years of age are often relatively indolent with limited metastatic potential and unlikely to threaten the patient during their remaining lifetime. In addition, the competing comorbidities, taken alone or together, are far more life threatening in the near term.

Next: Immunotherapy for treatment of RCC (Society for Immunotherapy of Cancer)

Immunotherapy for treatment of RCC (Society for Immunotherapy of Cancer)

Dr. RiniA subset of patients with metastatic kidney cancer may not need immediate treatment, says Brian Rini, MD, medical oncologist at the Cleveland Clinic Taussig Cancer Institute and professor of medicine at the Cleveland Clinic Lerner College of Medicine. That point, along with recommendations on the use of newer immunotherapy agents and older drugs, is outlined in the Society for Immunotherapy of Cancer’s consensus statement on immunotherapy for the treatment of renal cell carcinoma (RCC), which was published last year in the Journal for ImmunoTherapy of Cancer (2016; 4:81).

Since clinicians are trying to provide patients with the most benefit with the least amount of risk, that sometimes means not treating RCC patients-or certainly not treating them immediately, says Dr. Rini, the consensus statement’s first author. This is the appropriate treatment approach for patients who have very indolent disease that’s not bothering them. An additional benefit of this approach is that sometimes simply watching patients for a period of time can delay side effects while not compromising the benefit of ultimate treatment, he adds.

While interferon-alpha and interleukin-2 have been used for decades with positive results, new immunotherapy agents for the treatment of renal cell carcinoma have been approved, according to the consensus statement. These new agents prevent tumor growth by preventing vascular endothelial growth factors in addition to tumor metabolism. Immune checkpoint inhibitors, the newest class of immunotherapy agents, should also have an impact on patients with RCC.

According to the consensus statement, observation or enrollment in a clinical trial based on Level A evidence for cytokines and Level A evidence from the ASSURE clinical trial are the most appropriate treatment paths for patients with resected stage II and III renal cell cancer. Members of the task force that developed the statement agreed that nephrectomy is an important component of managing patients with renal cell carcinoma; further, the resection of oligometastases is supported, but it’s unclear how novel immunotherapy could impact these surgical approaches.

There was division among task force members on the role of high-dose interleukin-2 in treating metastatic RCC. The overall opinion was that appropriate patients who have undergone a nephrectomy should discuss interleukin-2 with their clinicians and then receive a referral to a center of excellence for further discussion of treatment options. Sixty-seven percent of the experts agreed that a discussion about interleukin-2 was appropriate, while the remaining members said it was more appropriate for clinicians to select patients for these types of conversations.

In addition to outlining new therapeutic agents and different approaches to patients, and incorporating immunotherapy into the routine management of kidney cancer, which is only just starting, Dr. Rini says this guideline “is really setting the stage for what’s to come as much as it is about taking care of patients now.”

Next: Immunotherapy for treatment of prostate carcinoma (Society for Immunotherapy of Cancer)

Immunotherapy for treatment of prostate carcinoma (Society for Immunotherapy of Cancer)

Dr. GulleyThe Society for Immunotherapy of Cancer’s consensus 2016 statement on immunotherapy for the treatment of prostate carcinoma provides a framework to inform clinicians about which patients are most appropriate for immunotherapy and which patients are not appropriate for such a treatment path, says James L. Gulley, MD, PhD, director of the Medical Oncology Service with the National Institutes for Health’s Center for Cancer Research, who contributed to the consensus statement. The consensus statement was published in the Journal for ImmunoTherapy of Cancer (2016; 4:92).

Still, Dr. Gulley points out that the consensus statement doesn’t say specifically which immunotherapy will work for individual patients. Rather, it provides guidance for the type of patients that he and other prostate cancer experts believe are most likely to benefit. Thus, not every patient is going to be an appropriate candidate for immunotherapy, he says.

According to the consensus statement, immunotherapy is indicated for metastatic castration-prone cancer in patients with minimal or no symptoms. After reviewing the available studies, the experts found that the quartile of patients who received sipuleucel-T (Provenge) versus placebo earliest in the disease process lived an average of 13 months longer and experienced a 50% decrease in the chance of death. Patients in more advanced stages of the disease who received sipuleucel-T versus placebo gained an increase of 2 months and experienced a 20% reduction in the chance of death.

As a group, the consensus panel experts state a reluctance to treat patients with rapidly progressing disease or significant visceral disease, such as liver metastasis. That’s because there was no dramatic decrease in the volume of the tumor or a decrease in prostatic ductal adenocarcinoma with sipuleucel-T treatment. Dr. Gulley says that’s likely because of the long-term effect of developing an adequate immune response during earlier stages of the disease. If clinicians believe they will run into problems earlier clinically, then they should pursue other treatments; a plurality of the experts said they would use agents like enzalutamide (XTANDI) in addition to sipuleucel-T, according to Dr. Gulley.

Disclosures: Full disclosure of the guideline and consensus panel members’ conflicts of interest is provided in the published versions of the statements: bit.ly/NMIBCstatement, bit.ly/Renalmassesstatement, bit.ly/RCCimmunotherapy, and bit.ly/PCaimmunotherapy.

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