Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma.

Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy.

We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression.

234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS).

Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.

Urologic oncology. 2020 May 16 [Epub ahead of print]

Nirmish Singla, Alana Christie, Yuval Freifeld, Rashed A Ghandour, Solomon L Woldu, Timothy N Clinton, Firas G Petros, Haley Robyak, Hsin-Chih Yeh, Dong Fang, Dmitry Enikeev, Aditya Bagrodia, Arthur I Sagalowsky, Yair Lotan, Jay D Raman, Surena F Matin, Vitaly Margulis

Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX., Division of Biostatistics, Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, TX., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX., Division of Urology, Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA., Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan., Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing, China., Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia., Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. Electronic address: .