Neoadjuvant Chemo Rarely Used in Upper Tract Urothelial Cancer

Therapy used in less than 5% of cases, even in those with higher clinical stage.
Therapy used in less than 5% of cases, even in those with higher clinical stage.

SAN DIEGO—Patient survival from upper urinary tract urothelial carcinoma (UTC) has not improved in the last 10 to 15 years. Five-year survival rates approach just 60% for high-grade, locally invasive disease. Yet, new U.S. trend data show that neoadjuvant chemotherapy, a promising therapy, is underused for upper tract UTC, according to researchers presenting at the American Urological Association's 2016 annual meeting.

Patients often have chronic kidney disease after radical nephroureterectomy, explained lead investigator Clinton D. Bahler, MD, MS, of Indiana University School of Medicine in Indianapolis. “Optimal adjuvant chemotherapy is often not possible due to poor renal function after surgery. Neoadjuvant chemotherapy is more feasible since patients have better renal function. Preliminary data also suggest chemotherapy before surgery improves outcomes.”

Using the National Cancer Database, Dr Bahler and colleagues identified 34,220 cases of upper tract UTC treated with renal extirpative therapy during 2006–2012. (Patients with distant metastatic disease were excluded.) Neoadjuvant chemotherapy was administered in 429 cases (1.3%) and adjuvant or salvage chemotherapy in 3,468 (10.1%). Neoadjuvant chemotherapy usage rose slightly yet significantly from 0.8% to 1.8% from 2006 to 2012. By clinical stage, neoadjuvant therapy was administered in 0.7%, 1.2%, 1.9%, 4.1%, and 11.7% for cT1, cT2, cT3, cT4, and cN1-3, respectively. 

Multivariable analysis revealed that neoadjuvant chemotherapy recipients tended to be younger, have a lower Charlson comorbidity score, have nodal involvement, receive treatment at academic centers in the Midwest or West, and to be treated after 2009. Demographic and socioeconomic factors such as gender, race, treatment location, insurance type, and income did not predict who received the therapy.

When the investigators examined clinical stage 2 or 3 cases, those receiving neoadjuvant chemotherapy had a higher rate of downstaging on final pathology to less than stage T2 disease (23% vs 2%). Similarly, patients with lymph node involvement had more downstaging to node negative disease (40% vs 12%).  The investigators encouraged caution when evaluating these results due to the small sample size.

Randomized trials and prospective data from national and international registries would help identify patients likely to benefit from neoadjuvant chemotherapy for upper tract UTC, according to the researchers.

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