ASCO Endorses European Association Guideline on Management of Muscle-Invasive and Metastatic Bladder Cancer

ASCO Endorses European Association Guideline on Management of Muscle-Invasive and Metastatic Bladder Cancer

Bladder cancer is among the 10 most common malignancies worldwide. In the United States, nearly 30% of all newly diagnosed patients present with muscle-invasive disease, and half of those patients go on to develop distant metastases; another 5% present with metastatic disease.1 To confront this challenging disease, ASCO recently released an endorsement of a clinical practice guideline issued in 2014 and updated in March 2015 by the European Association of Urology (EAU).

Dr. Matthew Milowsky
“Bladder cancer is a complex disease that occurs in older individuals with many coexisting medical issues, leading to particularly difficult management decisions,” said Matthew I. Milowsky, MD, who led a panel that reviewed the EAU’s guideline along with Cheryl T. Lee, MD. “The ASCO endorsement of the EAU guideline presents the provider with a roadmap that, if followed, will undoubtedly improve quality of care for patients with muscle-invasive and metastatic bladder cancer.”

Dr. Lee noted that comparable comprehensive guidelines for this stage disease were previously lacking in the United States. ASCO’s endorsement was published with several qualifying statements. Among the most important primary messages of both the guideline and the endorsement is the need for a multidisciplinary approach to management of this malignancy.

“Multidisciplinary input via tumor board discussions and/or directed consultations is critical to the optimal treatment of patients with muscle-invasive and metastatic bladder cancer,” Dr. Milowsky told the ASCO Daily News. For example, a referral to a medical oncologist should be made for discussion of neoadjuvant chemotherapy, while a referral to a radiation oncologist is important for discussion of bladder preservation in patients with muscle-invasive disease. “Implementation of these guidelines requires the integration of urology, medical, and radiation oncology expertise in order to provide the highest level of care to patients,” Dr. Milowsky said.

Specific recommendations are included for management of varying types of bladder cancer. For patients with T2-T4a, cN0M0 disease, neoadjuvant chemotherapy is recommended and should always be a cisplatin-based combination regimen. For patients who did not receive neoadjuvant chemotherapy, adjuvant chemotherapy may be offered, although ASCO added a qualifying statement that this applies specifically to patients with high-risk disease.

For those same patients with T2-T4a, cN0M0 tumors, as well as in patients with high-risk, non–muscle-invasive bladder cancer, radical cystectomy is recommended. Chemoradiation-based organ preservation treatment can also be offered to certain patients with muscle invasive bladder cancer.

ASCO noted that any decision regarding bladder-sparing or radical cystectomy specifically in elderly/geriatric patients with invasive bladder cancer should be based on tumor stage, bladder function, and the ability to tolerate major surgery, radiotherapy, and/or chemotherapy.

Patients who present with metastatic disease and are fit for treatment should receive cisplatin-containing combination therapy, with gemcitabine-cisplatin; methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC); or MVAC plus granulocyte colony-stimulating factor.

The ASCO endorsement included a qualifying statement regarding patients with metastatic disease whose disease progressed following treatment with platinum-based combination therapy. For these patients, entry into a clinical trial is preferred. If clinical trial participation is not an option, single-agent therapy can be offered, using paclitaxel, docetaxel, or vinflunine. Also, ASCO qualified a recommendation for the use of zoledronic acid in patients with bone metastases, noting it “may be offered” because the evidence for its use specifically in bladder cancer is limited.

There was one EAU recommendation that ASCO did not endorse. This was a statement that preoperative radiotherapy for patients with operable muscle-invasive bladder cancer can result in tumor downstaging after 4 to 6 weeks, which the ASCO authors wrote could not be endorsed based on the evidence reviewed by EAU.

EAU and ASCO agree that at the present time, no biomarkers can be recommended in daily clinical practice. Based on current research, no biomarker has an impact on predicting outcomes, treatment decisions, or monitoring of therapy.

The guideline also contains recommendations regarding health-related quality of life in these patients, including the use of validated questionnaires to assess this measure in patients with muscle-invasive bladder cancer. ASCO added a qualifying statement regarding the offer of a continent urinary diversion: this should be offered specifically to patients undergoing cystectomy.

The guideline also notes that preoperative patient selection and careful postoperative follow-up are “cornerstones for achieving good long-term results,” and that patients should be encouraged to participate actively in the decision-making process. There are also specific recommendations for follow-up regarding local recurrence, distant recurrence, and secondary urothelial tumors.

“Overall, the panel commends the EAU on the development of its guideline on muscle invasive and metastatic bladder cancer and intends to disseminate it broadly to specialists and generalists in the United States who provide care for these patients,” the authors concluded.

– David Levitan