Testing the external validity of the pout III trial (adjuvant platnium-based chemotherapy in upper tract urothelial carcinoma) in a North American cohort

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Conference Proceeding

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Eur Urol


Introduction & Objectives: The management of patients with locally advanced upper tract urothelial carcinoma (UTUC) is challenging given the lack of level-one evidence, due to the disease’ overall rarity. The European POUT III randomized controlled trial provided convincing evidence that adjuvant platinum based chemotherapy is the new standard of care following nephroureterectomy for locally-invasive or node-positive UTUC. We assessed this European randomized controlled trial's generalizability (external validity) to a North American cohort, using a nationwide database.

Materials & Methods: To compare the trial patients with those seen in practice, we simulated the trial inclusion criteria using data from the National Cancer Database (NCDB). We identified adult patients with histologically confirmed, transitional cell carcinoma who underwent radical nephroureterectomy and met the trial inclusion criteria. The available demographic characteristics of the NCDB cohort were then compared with the POUT III trial cohort using Chi-squared test.

Results: The NCDB cohort included 3,380 patients. The NCDB cohort had a significantly higher proportion of older patients (age≥ 80 23.5% vs 5%), and more males (68% vs. 56.2%) than the POUT cohort (Table 1, both p<0.001). Additionally, the rate of advanced nodal disease was higher in the NCDB (N1 9.6%, N2 9.3%) than in the POUT (N1 6%, N2 3%) cohort (p<0.001). Finally, a more extensive lymph node dissection was performed in NCDB vs POUT patients (node≥10 10.9% vs 3%, p<0.001). Sensitivity analysis removing all subjects with a Charlson Comorbidity Index > 0, as a proxy of health fitness, did not change the significance of any results.

Conclusions: While the primary disease stage was similar between the NCDB and POUT, the rate of advanced disease was higher in NCDB (might be explained partially by the more extensive lymph node dissection performed). Moreover, NCDB patients were older and more frequently male, compared to the European trial patients. With these differences, the applicability of the POUT III findings in North American patients may warrant further investigation.



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