(UroToday.com) 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. Upper tract urothelial carcinoma accounts for 5-10% of all urothelial cancers, with an incidence of 2 per 100,000 people in Western countries. Concurrent disease with bladder cancer occurs in 17% of patients, with recurrence in the bladder among 22-47% of individuals. Furthermore, upper tract urothelial carcinoma develops in 2-4% of patients with a history of bladder cancer, and 60% of upper tract urothelial carcinoma cases are invasive at diagnosis.
This case discussion highlighted the treatment of high-grade upper tract urothelial carcinoma in a patient with adequate renal function. The patient was a 71-year-old female with a 2 cm left upper pole tumor found incidentally for surveillance of lymphoma with a CT urogram demonstrating cN0 and no metastasis. The patient’s eGFR was 62, hemoglobin was 11.5, performance status was ECOG 1, and a subsequent biopsy of the mass demonstrated high-grade T1 upper tract urothelial carcinoma:
Dr. Matin then posed to the panel the following treatment options for this patient:
- Nephroureterectomy +/- lymph node dissection
- Neoadjuvant chemotherapy followed by nephroureterectomy +/- lymph node dissection
- Endoscopic management
Dr. Porten states that the question is whether a radical nephroureterectomy with lymph node dissection is a curative operation, or if neoadjuvant chemotherapy should be utilized prior to surgery given the limitations of our clinical staging. Furthermore, she does worry that since the function of the affected kidney looks appropriate, there would be a chance that she would not be able to get a cisplatin-based regimen after surgery. Dr. Margulis added that this is a high-grade, bulky tumor on retrograde pyelogram, and given that the biopsy already shows invasion, he worries that this patient is at high risk for occult metastatic disease and would favor neoadjuvant chemotherapy.
This patient’s post-nephroureterectomy estimated GFR is likely to be 30-40 depending on compensatory changes based on a nuclear renogram showing 50%/50% split renal function and her current eGFR, which may have an impact on her ability to receive adjuvant therapy. Dr. Matin notes that even though the biopsy showed cT1 disease, upper tract biopsies are not fully reliable given that imaging can underestimate invasion in upper tract urothelial carcinoma. Given these shortcomings, preoperative nomograms for predicting high-risk non-organ confined upper tract urothelial carcinoma (T3-4, N+) have been developed. For example, Petros et al.1 developed a nomogram that is 82% accurate for predicting non-organ confined disease. Based on this patient’s risk factors, she is at ~60% risk of having pT3/pT4 or N+ disease:
Additional nomograms have also been developed, including a nomogram from Dr. Matin and Dr. Margulis’ group, suggesting that the aforementioned patient has a 2-year relapse-free probability of ~82% and a 5-year relapse-free probability of 72%:2
Dr. Matin notes that after nephroureterectomy, this patient’s GFR is unlikely to allow cisplatin-based adjuvant chemotherapy. After a multidisciplinary discussion with the patient, the patient decided to undergo neoadjuvant chemotherapy followed by a nephroureterectomy. After receiving 4 cycles of gemcitabine/cisplatin without difficulty she underwent a robotic nephroureterectomy with bladder cuff, a lymphadenectomy (hilar plus para-aortic), and intravesicular gemcitabine. Pathology demonstrated a 1.5 cm high-grade renal pelvis urothelial cancer, ypTa ypN0/19 R0. After 18 months of follow-up, she is still without recurrence with an eGFR of 28.
Dr. Matin notes that based on unpublished work from his institution of MD Anderson Cancer (n=132), the 5 and 10-year data is as follows:
- Disease-specific survival: 87.7% and 78.9%, respectively
- Metastasis free survival: 81% and 75.4%, respectively
- Overall survival: 73.7% and 35.9%, respectively\
Metastatic recurrences occurred at a median of 15.5 months (IQR 8.9-27), with 50% of recurrences in the lymph nodes and 25% in the lungs. To summarize the role of neoadjuvant chemotherapy, Dr. Matin emphasized that:
- Clinicians should assess risk stratification using one or both (if high grade on biopsy) nomograms
- The post-nephroureterectomy GFR should be estimated, either by educated cognition or formally with a nuclear renogram
- If high-risk and estimated post-nephroureterectomy GFR is >55 there is the option for neoadjuvant chemotherapy or initial surgery (with the option of adjuvant if pathologic high risk). Clinicians should also consider a lymphadenectomy
- If high-risk and estimated post-nephroureterectomy GFR is <55 proceed with neoadjuvant chemotherapy
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.
References:
- Petros FG, Qiao W, Shingla N, et al. Preoperative multiplex nomogram for prediction of high-risk nonorgan-confined upper-tract urothelial carcinoma. Urol Oncol. 2019 Apr;37(4):292.e1-292.e9.
- Freifeld Y, Ghandour R, Singla N, et al. Preoperative predictive model and nomogram for disease recurrence following radical nephroureterectomy for high grade upper tract urothelial carcinoma. Urol Oncol. 2019 Oct;37(10):758-764.