FOIU 2018: Should the Primary Be Treated in Patients with Metastatic Disease? - Upper Tract Urothelial Cancer

Tel-Aviv, Israel ( Seth Lerner, MD discussed the topic of treating the primary tumor in patients with metastatic upper tract urothelial carcinoma (MUTUC). The outline of his talk included the unique biology of UTUC disease, the incidence and patterns of metastasis of UTUC, the efficacy of systematic chemotherapy, the outcomes of post systemic treatment, and locoregional surgical consolidation.

Lerner began his discussion on the low utilization of lymph node dissection (LND) in UTUC, which is approximately 27% as reported in a recent Canadian study. In a recent retrospective review of 9 studies1, it was shown that 13.3-40% of patients with at least a T2 and clinically node-negative disease, the nodes are pathologically positive. LND improves cancer specific survival (CSS) in patients with renal pelvis but not ureteral tumors. The pathological tumor stage and grade are the most important prognostic factors in UTUC, after radical nephroureterectomy.

Another important point that is currently being explored is the genomic profiling of this disease. Although UTUC is treated in a very similar manner to bladder cancer, genomic profiling suggests that they are very much distinct entities.2 The key findings of this genomic profiling in UTUC show the following prevalent genetic mutations: FGFR3 (74%), APOBEC predominant signature, NPHS1 in 11%, RHOB (11%), and FGFR3-TACC3 fusion.

Lerner discussed some important feature of UTUC disease. When assessing the incidence of metastasis, 40-50% of patients have pTa-T1 disease, and 50-60% of patients have Pt2 disease or above. Approximately 25% of these patients already have regional metastases. The incidence of regional disease increased by 2.6% over time, whereas the incidence of distant disease (8-9%) did not change over time. The frequency of renal pelvic tumors is about 1.5-2 times that of ureteral tumors. Multifocal renal pelvis and ureteral tumors are present in 7-24% of cases and there is no significant difference in laterality. When tumors arise in the ureter, they are most commonly found in the distal ureter. 

Lerner moved on to discuss the prognosis of these tumors. The association of ureter location with worse outcomes may be stage-specific. T3 disease may have a more favorable outcome in the renal pelvis. The risk of bladder cancer may be higher in ureteral tumors. Lastly, multifocality and carcinoma in situ (CIS) are associated with worse outcomes and higher bladder cancer risk, and that is why it must be mentioned in the pathology reports.

The next topic discussed was trends in the stage of this disease, based on different population-based studies from the SEER and NCDB databases. Over the last 40 years there has been an increase in Ta, Tis, and a decrease in T1, and T2 disease. The rate of T3 and metastases is stable at around 8-9%. More than 50% have muscle-invasive disease, and there has been an increase in high-grade disease in general. Metastasis sites following surgical therapy include nodes, lung, liver, and bone. Stage-specific outcomes are similar between bladder and UTUC, but UTUC probably has a more aggressive disease. 

Systemic therapy recommended is cisplatin-based chemotherapy including MVAC, dose-dense MVAC, or gemcitabine/cisplatin. However, many are unfit for cisplatin, including patients with performance status > =2, grade 2 hearing loss or peripheral neuropathy, and NYHA class > -3 heart failure. Treating the primary tumor before systemic therapy results in EGFR reduction, which may be problematic if chemotherapy is planned later.

Percutaneous surgery options are usually reserved for low-grade disease in a solitary kidney, and has a known risk factor of seeding.

Lerner concluded his exceptional talk with some important points. Postchemotherapy surgical consolidation for patients with nodal and/or visceral metastatic disease may be beneficial in selected cases. Nephron-sparing surgery may make sense with ureter only tumors, especially in solitary kidneys. LND may provide long-term cancer control.  The decision to perform a nephroureterectomy may be based on palliation or residual high-grade cancer with objective response in locoregional disease. There is no high-level evidence to support any particular approach.

1. Dominguez-Escrig JL et al. Eur Urology Focus 2017
2. Moss et al. Eur Urology 72:61, 2017

Presented by: Seth Lerner, MD, Baylor College of Medicine, Houston, TX, US

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan  at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel