Progression to distant metastasis within 3 years after radical nephroureterectomy (RNU) for high-grade upper tract urothelial carcinoma (UTUC) represents a potential surrogate for overall survival, according to a recent study.

The finding could help in patient counseling and expedite results from ongoing randomized controlled clinical trials and lead to more rapid approval of new therapies, Alberto Martini, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues reported in Clinical Genitourinary Cancer.

Dr Martini and colleagues studied 823 patients with high-grade UTUC treated with RNU at 8 tertiary referral centers. During a median 5.6 years of follow-up for survivors, 391 patients experienced any recurrence and 212 progressed to distant metastasis (DM).

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Progression to DM within 3 years of RNU was the most important intermediate clinical endpoint for predicting overall survival (OS). It was associated with a 4.4-fold increased risk for death and had a c index of 0.81 compared with 0.74, 0.76, and 0.78 for progression to DM within 1, 2, or 4 years, respectively, according to the investigators.

The study also demonstrated that any disease recurrence within 3 years of RNU was significantly associated with a 3.2-fold increased risk for death, and with a c index of 0.79 was the most informative intermediate clinical endpoint relative to recurrence within 1, 2, and 4 years, which had c indexes of 0.73, 0.75, and 0.77, respectively. The OS rate was 34% among patients who had any disease recurrence within 3 years from RNU compared with 81% for those who had recurrence beyond 3 years from surgery.

“From our analyses,” Dr Martini’s team wrote, “it emerged that DM represents the best candidate as a surrogate endpoint and its role deserves to be investigated more. This is in line with other neoplasms, where distant progression has been demonstrated to be a surrogate for OS.”


Martini A, Lonati C, Necchi A, et al. Metastasis within three years from radical nephroureterectomy as a potential surrogate for overall survival. Clin Genitourin Cancer. Published online March 10, 2022. doi:10.1016/j.clgc.2022.03.007