Management of Node Positive Upper Tract Urothelial Carcinoma with Poor Renal Function

( The 2021 American Urological Association (AUA) Summer School session on Upper Tract Urothelial Carcinoma included a case-based discussion led by moderator Dr. Surena Matin who was joined by panelists Dr. Sima Porten and Dr. Vitaly Margulis. This case highlighted the management of upper tract urothelial carcinoma with node positive disease and a low eGFR. The patient was a 55-year-old male with gross hematuria and a right distal ureteral sessile tumor that was biopsied showing high-grade urothelial carcinoma. The patient received a ureteral stent and was referred to urologic oncology with an eGFR of 42. The right kidney was noted to be atrophic (4% function) with multiple (4-5) enlarged regional lymph nodes (hilar, retrocaval, interaortocaval), with a negative chest CT and no evidence of distant metastasis:



Based on this patient with a right atrophic kidney, cTxN2+M0 with a high grade distal ureteral tumor and CKD stage 3, Dr. Matin offered the following treatment options to the panel:

  • Biopsy the lymph node followed by chemotherapy
  • Nephroureterectomy
  • Nephroureterectomy with a retroperitoneal lymph node dissection
  • Distal ureterectomy with a ureteral reimplant

Dr. Porten stated that with the high volume nodal disease it is highly unlikely that the disease course will be altered with surgery. Not fully understanding the status of the lymph nodes may also be problematic if there are two concurrent malignancies, such as lymphoma. Thus, Dr. Porten favors biopsying the lymph node followed by systemic chemotherapy. Dr. Margulis added that this patient is more than likely suffering from systemic disease and may be considered for consolidative surgery if the patient has an adequate response to chemotherapy.

The reason for chemotherapy first is that lymph node metastatic upper tract urothelial carcinoma has very poor survival, and surgery is not curative and may prevent timely postoperative chemotherapy. Additionally, if all of the disease is resected and there is no measurable disease, evaluating for efficacy with the possibility of changing systemic therapy regimens is not possible. There are several potential systemic therapy regimens available including (i) gemcitabine plus carboplatin, (ii) gemcitabine plus cisplatin, (iii) gemcitabine plus paclitaxel plus doxorubicin, or (iv) no chemotherapy but rather given the patient a checkpoint inhibitor. Dr. Matin notes that ultimately institutions/medical oncologists will have their preferences given the lack of high-level data delineating the best regimen.

This patient underwent a lymph node biopsy that showed metastatic urothelial carcinoma and received two cycles of gemcitabine plus paclitaxel plus doxorubicin (kidney sparing protocol), with an improvement in renal function to GFR >45. He was then switched to five cycles of MVAC and near complete radiographic response. Following his response to chemotherapy, he underwent an open right nephroureterectomy with a retroperitoneal lymph node dissection (hilar, retrocaval, paracaval, interaortocaval, right common iliac) with perioperative intravesicle chemotherapy. Pathology demonstrated a 2 cm tumor ypTa+Tis ypN0/16 M0R0 high-grade urothelial carcinoma of the distal ureter that was negative for lymphovascular invasion.

Dr. Matin highlighted that multidisciplinary management is mandatory for the management of loco-regional nodal disease and that chemotherapy is the primary treatment and should not be considered neoadjuvant. Generally, patients should be treated with two cycles beyond a maximal response, which typically correlates to six cycles or more of chemotherapy. Ultimately, surgery provides consolidation after a good response to chemotherapy for medically fit patients.

Moderator: Surena F. Matin, MD, MD Anderson Cancer Center, Houston, TX

Panelists: Sima Porten, MD, MPH, University of California – San Francisco, San Francisco, CA & Vitaly Margulis, MD, UT Southwestern, Dallas, TX

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the AUA2021 May Kick-off Weekend May 21-23.