Table 1.

Summary of Workshop Discussion on the Conduct of Adjuvant Bladder Cancer Trials

Section	Workshop Discussion Points
Patient and Disease Characteristics
Histologic subtypes	• Patients with predominant UC who have a component of variant histologic characteristics should be included in adjuvant trials. However, patients with pure, non-UC histologic characteristics, especiallymixed neuroendocrine/small cell tumors, if included, should be analyzed separately.
Prior neoadjuvant therapy	•At least 3 cycles of neoadjuvant cisplatin-based chemotherapy with a planned cisplatin dose of 70 mg/m2/cycle is a reasonable eligibility criterion. • Patients who have received non-cisplatin-based or less than 3 cycles of cisplatin-based neoadjuvant treatment should be managed/stratified as having received no neoadjuvant chemotherapy, and their eligibilityshould be based on postcystectomystage.
Site of disease	• Patients with muscle-invasive upper-tract UC should be included in adjuvant trials.
Surgical considerations	•Patients with microscopic positive margins (R1) should be eligible, although statistical stratification may be considered. • It is not clear if gross positive margins (R2) should be included in studies. • Bilateral (standard) lymph node dissection is both favored and sufficient for accurate staging information.
Timing of adjuvant therapy	• Adjuvant therapy can be initiated as soon as the patient recovers from surgery, with a goalof 1to4 months postsurgery.
Duration ofadjuvanttherapy	• The length of checkpoint inhibitor therapy in adjuvant clinicaltrials of bladder cancer is not known owing to lack of data. Future trials could further examine duration of treatment.
Radiologic Considerations
Radiologic imaging post-surgery	• Cross-sectional imaging of the chest, abdomen, and pelvis with IV contrast should be done within 4 wk prior to entering an adjuvant trial.
Principles of serial imaging	•Patients' prior imaging examinations should be archived and should include as many examinations as possible, including reports anda clinicalhistory documenting any prior acute and chronic diseases and prior surgeries and interventions. • CT imaging with contrast is the imaging modality of choice, when feasible. • Trials should aim to adhere to imaging acquisition, display, and radiologic interpretation technique as advised by the Quantitative Imaging BiomarkersAlliance.1
Defining radiographic eligibility for adjuvant bladder cancer trials and radiographic recurrence	•Biopsy should be done, when feasible, to determine if anymalignant disease is present. • Common thresholds to the radiologic assessment of patients for trial eligibilityand progression of disease should be implemented (Box).
Defining date of recurrence	• Backdating scans to when a new lesion was initiallynoted on imaging is considered as the most temporally accurate manner to assess the date of recurrence but introduces inconsistency. Using the date when prespecified size criteria are met (Box) is considered more consistent but lacks temporalaccuracy. Whichever method is used should be applied consistently and accurately throughout the trial.
Managing New Urothelial Cancers Within the Urothelial Tract
Second primary cancers	•All new high-grade upper-tract primarytumors and all new muscle-invasive bladder cancer tumors are considered as events for the disease-free survival end point. • It is not clear whether new bladder second primary tumors that are ≤T1 category should be counted as an event for the disease-free survival end point. • Patients with tumors that are both low-grade and non-muscle-invasive could remain on trial if they can be managed endoscopically.
Urethralsecond primary tumors	• Patients with non-muscle invasive tumors manageable either endoscopically or with urethrectomy may remain on study. Patients with muscle-invasive recurrences should be removed from the trial and counted as disease recurrence.
Urine test utilization	• Trials should specify if urine tests should be used for post-operative surveillance and, if so, the specific test and testing interval required.
Augmented endoscopy	• Standard-of-care guidelines for endoscopic surveillance should be followed and defined at the start of the trial.
Random bladder biopsies	• Trials should specify whether random bladder biopsies should be obtained or not obtained to rule out occult carcinoma in situ. Further evidence is needed to inform whether this should be done for all patients with intact bladders.
Systemic agents and BCG vaccine	• Further evidence is needed to inform whether it would be appropriate to continue a systemic agent in conjunction with BCG or other intravesical therapy.
Considerations for the Patient
Rare cancers	• There is concern about the consistency of histologic subtype classification/diagnosis and its potential effect on enrollment.
Biopsy	• Taking biopsies solely for the purposes of research should be carefully balanced with the best interests of the patient.
Placebo	• Trial designs that eliminate the use of placebo, more heavily weight the arm with an active agent, or allow crossover (where justified by trial data) are favored by patients.
Blinding	• Patients agree to blinding; however, they should be unblinded under certain circumstances.

Abbreviations: CT, computed tomographic; UC, urothelial carcinoma.