A Phase III Surgical Trial to Evaluate the Benefit of a Standard versus an Extended Pelvic Lymphadenectomy Performed at Time of Radical Cystectomy for Muscle Invasive Urothelial Cancer

Summary

The primary purpose of this study is to compare the effects, good and/or bad, of performing a standard lymph node removal versus an extended lymph node removal in patients undergoing radical cystectomy (removal of the bladder) for bladder cancer. The extended lymph node surgery removes additional lymph nodes that are farther away from the bladder than those removed during standard lymph node surgery.

eligible participants will be randomized during surgery to one of two treatment arms:
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arm a (Standard): Standard lymph node removal at the same time the bladder is surgically removed
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arm B (experimental): extended lymph node removal at the same time the bladder is surgically removed
Following surgery, all participants will be provided standard cancer care as indicated by the stage of cancer.

Participant Eligibility

Registration -- Inclusions:

1. Patients must have histologically-proven (T2, T3, or T4a) urothelial carcinoma of the bladder (UCB) that requires primary radical cystectomy for definitive treatment. Patients must not have clinical stage consistent with a low-risk of node metastasis (CIS only, T1). Patients with a T4b (fixed lesion) are not eligible for this study.

NOTE: Patients with predominant urothelial carcinoma with elements of adenocarcinoma, squamous cell carcinoma, micropapillary or minor components of other rare phenotypes are eligible. Patients with predominantly small cell, squamous cell, or adenocarcinoma histologies are not eligible. Patients with other non-urothelial cancers are not eligible (e.g., sarcoma, lymphoepithelial, nested variant).

Clinical stage is based on all of the following: TURBT(s) that determined the need for cystectomy, bimanual exam and cross sectional imaging.

2. There must be plans for the cystectomy and lymph node dissection (LND) to be performed within 28 calendar days following registration. Laparoscopic surgery is not allowed.

3. Surgery must be planned to be performed by a pre-approved, study-specific credentialed surgeon (see Section 12.1 for credentialing process). The registering physician MUST be the pre-approved, credentialed surgeon intended to perform the assigned procedure.

4. Prior neoadjuvant chemotherapy for this cancer is permitted however patients must have completed treatment within 70 days prior to cystectomy and recovered from all associated toxicities at the time of registration.


5. Patients must have no evidence of visceral or nodal metastatic disease proximal to the common iliac bifurcation on 2 view chest x-ray or CT of the chest and abdominal-pelvic imaging with computerized tomography or MRI of the abdomen and pelvis. Chest x-ray or CT of the chest and CT or MRI of the abdomen and pelvis must be obtained within 56 days prior to registration. PET/CT may be used as an alternative to CT or MRI or to resolve possible areas of metastases seen on cross sectional imaging.

6. Patients must have bilirubin, SGOT, SGPT and alkaline phosphatase values within the institutional upper limit of normal (ULN). These laboratory values must be obtained within 28 days prior to registration. Patients with levels of one or more of these enzymes greater than IULN may still be enrolled if metastatic disease is excluded with appropriate imaging which may include dedicated liver imaging, bone scan, PET, CT, MRI, or biopsy when appropriate.

7. Patient must be offered the opportunity to participate in specimen banking for future use to include the translational medicine studies outlined in Section 15.0.

8. Patient must have a Zubrod performance status (see Section 10.5) of 0, 1, or 2 and in the registering physician[Single Quote]s opinion be medically suitable to undergo cystectomy.

9. Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

10. As part of the OPEN registration process (see Section 13.4 for OPEN access instructions), the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

Step 2 (Randomization) - Inclusions
Patients must meet all of the criteria in Step 1 above and be registered to the study in order to be eligible for Step 2 (Randomization). Randomization will occur at the time of surgery following complete intra-abdominal and pelvic exploration ruling out visceral metastatic disease and gross nodal disease in the extended template (common iliac, pre-sciatic [fossa of Marseilles], pre-sacral, para-aortic, pre-aortic, pre-caval, para-caval) nodes.