Patients with high-grade upper tract urothelial carcinoma (UTUC) who prior to radical nephroureterectomy (RNU) achieved pathologically non-muscle-invasive disease following neoadjuvant chemotherapy have favorable oncologic outcomes comparable to those of patients with inherently low-stage disease who do not receive chemotherapy, according to investigators.

Vitaly Margulisa, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues identified 243 patients with non-muscle-invasive (pT0-1), high-grade UTUC according to final RNU specimens. Of these patients, 191 received no chemotherapy and 43 received neoadjuvant chemotherapy (NAC). Significantly more NAC patients had lymphovascular invasion (15.4% vs 4.3%) and T1 cancer (61% vs 40%). Two patients had pathologic complete responses after NAC. The rate of pathologic downstaging after NAC was not formally assessed, however.

No significant differences in overall survival, cancer-specific survival, and recurrence-free survival were observed between NAC and chemotherapy-naïve high-grade UTUC patients with low-stage disease at pathology, Dr Margulisa’s team reported in Urologic Oncology. Predictors of worse oncological outcomes included African-American race, Charlson comorbidity index score, and systemic recurrence.

“Our study supports a valuable role for pathologic stage as an early surrogate for oncologic endpoints in clinical trials,” Dr Margulisa’s team wrote.


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Whether the recurrence and survival benefits of NAC are attributable to directly downstaging the primary tumor, eradicating micrometastatic disease, or both remains unclear. Prospective studies, such as ECOG-ACRIN 8141 trial, may provide further insight into the timing and indications for NAC, according to the authors.

As indications for NAC in treating high-grade UTUC continue to evolve, “improvements in accurately staging UTUC clinically will play an important role in better defining candidacy for NAC while minimizing overtreatment.”

Reference

Singla N, Christie A, Freifeld Y, et al. Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma [published online May 16, 2020]. Urologic Oncol. doi: 10.1016/j.urolonc.2020.04.025

This article originally appeared on Renal and Urology News