Case 1: 74yo male; healthy. Presented with gross hematuria. TURBT revealed focal high grade T1 UCC
Dr. Lerner: Re-resection is required; All guidelines recommend it. Persistent disease is found in 33-55% of repeat resections. The incidence of T2 disease is as high as 45% after a first resection if no muscle was present! Also, repeat resection is a good way to go back and look for CIS.
Fluorescence cystoscopy detects additional CIS in 15-20% of patients. This is important because CIS + HGT1 in combination poses the highest risk of progression.
Outcome 1: Re-review of pathology reveals 20% micropapillary component to the tumor
Dr. Lotan: Variant histologies are present in up to 25% of TUR samples. Finding it depends on how hard you look and the experience of the pathologist. Any variant histology is considered high risk given the high likelihood of progression. BCG is an option for these patients with some evidence to suggest benefit; but patients should be notified of the higher risk of progression and metastases with variant histology. AUA guidelines currently recommend considering upfront cystectomy in these cases.
Outcome 2: BCG induction given – but tumor remains unresponsive
Dr. Lerner: It is important for Urologists to familiarize themselves with the definitions for unresponsive bladder cancer. He highlighted many single-arm trials currently underway for patients with unresponsive disease, which will hopefully give his better treatment options for variant histologies in the future.
Dr. Vapiwala: Chemoradiation is a feasible alternative; evidence, however, shows better PFS for those who are complete responders to aggressive TURBT and systemic therapy.
As of right now, most patients with residual/persistent disease should undergo cystectomy, but nonsurgical patients can undergo chemoradiation. Patients highly motivated to keep their bladder can enter clinical trials
Case 2: 62F with muscle-invasive bladder cancer, cN+
Dr. Lotan: The role of PET imaging is undefined. Pre-cystectomy CT vs. FDG-PET/CT shows similar accuracy and statistical metrics, so it is likely an unnecessary test at this point.
Dr. Friedlander: Patients should receive cisplatin-based therapy (Category 1 evidence) if they can tolerate it. Carboplatin does not have the same effect in the neoadjuvant setting.
Checkpoint immunotherapy (IO therapy) use in the neoadjuvant setting may be possible and is quite promising. There are multiple ongoing studies testing the various approved checkpoint inhibitors in the neoadjuvant setting.
For cN+ patients, we have limited knowledge about most appropriate treatment. Important to keep in mind, true pelvic nodes are now considered Stage IIIB (2017 AJCC TNM). They were previously considered Stage IV and were excluded from trials.
Dr. Lerner: cN+ disease patients should get 5-6 cycles of chemotherapy. Evidence shows a 30% 5-year survival with neoadjuvant therapy and surgery, so some patients are curable with cN+ disease! Strongly consider the use of IO therapy if a patient is cisplatin ineligible. Lastly, extended PLND is warranted in these patients because Dr. Lerner feels that this procedure may be curative in some.
Dr. Vapiwala: Definitive radiotherapy in combination with chemotherapy is associated with improved OS compared to chemotherapy alone, so an argument to be made for treating cN+ patients with chemoradiation if they don’t want or can’t undergo surgery. However, it is critical to not back off on the radiation doses given. Luckily, better technology is allowing us to deliver necessary doses while limiting bowel toxicity (50Gy minimum to bladder/nodes) using 3D-conformal techniques.
The treatment algorithms for localized bladder cancer are rapidly changing with the introduction of newer agents and techniques. However, maintaining core principles of management will remain important as we continue to try to improve outcomes for these patients.
Presenter(s): Eila Skinner (Stanford), Yair Lotan, Seth Lerner (Baylor), Neha Vapiwala (UPenn), Terence Friedlander (UCSF)
Written by: Shreyas Joshi, MD, Fox Chase Cancer Center, Twitter: @ssjoshimd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA