To examine the oncologic outcomes in patients treated for UTUC by radical nephroureterectomy (RNU) relative to their smoking history in a contemporary cohort that includes use of neoadjuvant and intravesical chemotherapy (IVC).

We analyzed a multi-institutional cohort of patients treated with RNU for UTUC between 2000 and 2020. Patients were classified as never smokers, those with a <20 pack-year smoking history, and those with a ≥20 pack-years of smoking history. Overall survival (OS), cancer-specific survival, intravesical recurrence, contralateral upper tract recurrence, and metastasis were compared.

One thousand seven hundred ninety-six patients were included. No significant differences in the risks of intravesical recurrence, contralateral upper tract recurrence, metastasis, or cancer-specific survival were identified based on smoking status. OS was significantly higher in the never smoking group, with hazard ratio for death of 1.38 (95% CI 1.09-1.73) for <20 pack years smoking history and 1.34 (95% CI 1.12-1.61) for ≥20 pack years smoking history (P = .002). Rates of intravesical recurrence and OS were improved among smokers who received IVC compared to those who did not.

Patients with a history of RNU for UTUC with any smoking history had worse OS compared to those with no smoking history, but no differences were seen in intravesical, contralateral upper tract, and extraurothelial recurrence or in cancer-specific survival. Counseling on smoking cessation remains an important element of ongoing care to optimize health outcomes in these patients.