Neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) may benefit select older patients and those with locally advanced disease, according to study findings presented at the AUA2021 Virtual Experience.
Previous studies have demonstrated that NAC prior to radical nephroureterectomy (RNU) for UTUC improves oncologic outcomes. These outcomes, however, have not previously been explored in an elderly population even though the highest incidence of UTUC is among individuals aged 70 to 90 years, Nico C. Grossmann, MD, of the Medical University of Vienna in Austria, and colleagues noted.
In a multicenter study that included 170 patients, Dr Grossmann’s team found that patients older than a median 68 years who were eligible for treatment with cisplatin-based NAC prior to radical nephroureterectomy (RNU) may experience pathologic improvements from this multimodal therapy similar to those of their younger counterparts.
All study patients had clinically nonmetastatic, high-risk UTUC treated with NAC and RNU. Of the 170 patients, 77 (45%) were older than 68 years. The median follow-up was 29 months. The younger and older groups had similar rates of pathologic objective response and pathologic complete response (51% vs 48% and 9.7% vs 9.1%, respectively). Although overall survival was lower in the older group, both groups had similar recurrence-free and cancer-specific survival, according to the investigators.
NAC included a combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in 41% of patients, gemcitabine-cisplatin (GC) in 40%, and non-cisplatin chemotherapy in 19%. The pathologic complete response rate was 14% among MVAC recipients compared with 5% and 3.1% among patients who received GC or non-cisplatin chemotherapy, respectively. On multivariable analysis, MVAC was independently associated with 4.4-fold increased odds of pathologic complete response compared with GC.
“Despite the reluctance to provide systemic therapy in elderly patients, these patients seem to benefit similarly from cisplatin-based NAC as their younger counterparts,” the authors concluded in their study abstract. “Elderly patients who are ineligible for cisplatin treatment had the lowest response rates and are most likely to benefit from immediate RNU. Further studies are needed focusing on potential predictors to identify elderly patients most likely to benefit from perioperative cisplatin-based combination chemotherapy.”
In a separate study of 289 patients with locally advanced UTUC — 144 of whom had NAC followed by RNU and 145 who underwent RNU alone (control group) —pathologic downstaging occurred significantly more frequently in the NAC group than the control group:69% vs 24%, Yuka Kubota, MD, of Hirosaki University Graduate School of Medicine in Hirosaki, Japan, and colleagues reported. The rate of downstaging to pT1 or less disease was significantly higher in the NAC than control group (42% vs 9%). The NAC group, which received 2 to 4 courses of either cisplatin- or carboplatin-based regimens, had a significantly lower rate of lymph node invasion (25% vs 49%). In adjusted analyses, the NAC group had a significant 41% decreased risk for death compared with the control group.
The study patients had undergone RNU at 7 hospitals from 2000 to 2020. NAC use increased during the study period from 19% in 2006-2010 to 58% in 2011-2015 and 79% in 2016-2020.
Grossmann NC, Pradere B, D’Andrea D, et al. Neoadjuvant chemotherapy in elderly patients with upper tract urothelial cancer: Oncologic outcomes from a multicenter study. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Abstract MP48-05.
Kubota Y, Hatakeyama S, Kkamoto T, et al. Oncological outcomes of neoadjuvant chemotherapy in patients with locally advanced upper tract urothelial carcinoma: A multicenter retrospective study. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. Abstract MP48-06.