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Adjuvant chemotherapy improves OS in upper tract urothelial carcinoma
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Adjuvant chemotherapy following radical nephroureterectomy prolonged survival by 1 year compared with observation in patients with upper tract urothelial carcinoma, according to a study published in Journal of Clinical Oncology.
Radical nephroureterectomy with bladder cuff removal remains the standard of care for most upper tract urothelial carcinomas.
However, limited evidence supports the role of adjuvant chemotherapy after radical nephroureterectomy.
“Specifically, methodologic concerns, such as relatively small sample size and selection bias, have been advocated to explain inconsistent results observed after adjuvant chemotherapy,” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology and the Kidney Cancer Center at Dana-Farber Cancer Institute, and colleagues wrote.
Despite these previous study limitations, the researchers hypothesized this treatment regimen may be associated with survival benefit in patients with locally advanced or positive regional lymph node upper tract urothelial carcinoma.
Researchers compared the effect of adjuvant chemotherapy with observation following radical nephroureterectomy in 3,253 patients registered in the National Cancer Data Base.
Of the patients with locally advanced or positive regional lymph node upper tract urothelial carcinomas, 23.42% (n = 762) received adjuvant chemotherapy and 76.58% (n = 2,491) were observed after radical nephroureterectomy.
Median follow-up in the weighted population was 49.54 months.
Inverse probability of treatment weighting (IPTW)–adjusted Kaplan-Meier curves showed that median OS was superior for those who received adjuvant chemotherapy compared with observation (47.41 vs. 35.78; P < .001). Five-year IPTW–adjusted rates were 43.9% vs. 35.85%.
IPTW–adjusted Cox proportional hazards regression analysis demonstrated a significant OS benefit with adjuvant chemotherapy (HR = 0.77; 95% CI, 0.68-0.88), which was maintained after bootstrapping (HR = 0.78; 95% CI, 0.65-0.93) and propensity score adjustment (HR = 0.82; 95% CI, 0.73-0.93).
This benefit appeared consistent across all subgroups examined, and researchers observed no significant heterogeneity of treatment effect (P < .05).
“We found that individuals who received adjuvant chemotherapy were nearly 25% less likely to die than their counterparts who received observation,” Choueiri and colleagues wrote. “This translated into a 12-month OS benefit in favor of adjuvant chemotherapy.”
Researchers might be able to extrapolate from the more extensive and commonly available data on the treatment of urothelial tumors of the bladder, rather than focusing on separate upper tract studies, Arlene O. Siefker-Radtke, MD, and Matthew T. Campbell, MD, MS, from The University of Texas MD Anderson Cancer Center, wrote in an accompanying editorial.
“Gene expression profiling suggests that urothelial tumors are no longer one disease, and that subtype may predict for sensitivity to chemotherapy and or immunotherapy,” they added. “As upper tract urothelial carcinomas are rarer than their lower tract counterpart, it is important that we use the knowledge gained from both to enhance our understanding and impact of therapies in the treatment of urothelial cancers.”
In particular, additional evidence could support the use of perioperative chemotherapy in this patient population as precision medicine advances.
“Applying the knowledge gained from both upper and lower tract tumors will become even more important as we move into the field of personalized medicine, categorizing urothelial cancers into their biologic counterparts to develop the most efficacious therapeutic strategies to treat them,” they wrote. – by Kristie L. Kahl
Disclosure: Please see the full study and editorial for a list of all other researchers’ and editorial authors’ relevant financial disclosures.
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