Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma

Abstract

Purpose There is limited evidence to support the use of adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Against this backdrop, we hypothesized that such treatment is associated with overall survival (OS) benefit in patients with locally advanced and/or positive regional lymph node disease. Patients and Methods Within the National Cancer Database (2004 to 2012), we identified 3,253 individuals who received AC or observation after RNU for pT3/T4 and/or pN+ UTUC. Inverse probability of treatment weighting (IPTW) -adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare OS of patients in the two treatment groups. In addition, we performed exploratory analyses of treatment effect according to age, gender, Charlson comorbidity index, pathologic stage (pT3/T4N0, pT3/T4Nx and pTanyN+), and surgical margin status. Results Overall, 762 (23.42%) and 2,491 (76.58%) patients with pT3/T4 and/or pN+ UTUC received AC and observation, respectively, after RNU. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer for AC versus observation (47.41 [interquartile range,19.88 to 112.39] v 35.78 [interquartile range, 14.09 to 99.22] months; P < .001). The 5-year IPTW-adjusted rates of OS for AC versus observation were 43.90% and 35.85%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, AC was associated with a significant OS benefit (hazard ratio, 0.77 [95% CI, 0.68 to 0.88]; P < .001). This benefit was consistent across all subgroups examined (all P < .05), and no significant heterogeneity of treatment effect was observed (all P > .05). Conclusion We report an OS benefit in patients who received AC versus observation after RNU for pT3/T4 and/or pN+ UTUC. Although our results are limited by the usual biases related to the observational study design, we believe that the present findings should be considered when advising post-RNU management of advanced UTUC, pending level I evidence.

Perioperative Chemotherapy on Survival in Patients With Upper Urinary Tract Urothelial Carcinoma Undergoing Nephroureterectomy: A Population-Based Study

“…In addition, a significant CSS benefit was observed in LNM. In addition, this finding is consistent with the previous study (11,14). To further investigate the stage-specific impact of perioperative chemotherapy on survival in UTUC patients, we performed Cox regression analyses to mitigate potential selection bias.…”

“…On the one hand, individuals undergoing perioperative chemotherapy were likely to be those with the good general condition and renal function. On the other hand, the patients receiving chemotherapy may be those with more aggressive pathologic characteristics (11).…”

“…A meta-analysis performed by Leow et al showed that cisplatinbased AC might bring an OS and disease-free survival (DFS) for UTUC patients (10). Seisen et al reported an evident OS benefit in patients undergoing AC for pT3/T4 and/or LNM UTUC compared to observation following NU (11). A recent cohort demonstrated that AC could significantly improve recurrence-free survival (RFS) not OS or CSS in patients with pT3NanyM0 (12).…”

Prognostic effect of cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: a comparative study using inverse probability of treatment weighting

“…This could randomly favour the CN arm, as these patients may be those in a better general condition or those of a more favourable prognostic group. However, there are novel statistical methods such as inverse probability of treatment weighting (IPTW) and sensitivity analyses without assumptions that improve adjustment for measured and unmeasured confounders and thus control for selection bias [11]. As such, we sought to compare OS between patients undergoing CN and no CN (NCN) for synchronous mRCC at our tertiary care centre using these modern statistical approaches.…”

<p>Optimal Management of Upper Tract Urothelial Carcinoma: Current Perspectives</p>

“…Leow et al performed meta-analysis of retrospective studies in 2014 which found an overall survival (HR 0.43, 95% CI 0.21-0.89, p=0.023) and disease-free survival benefit (HR 0.49, 95% CI 0.24-0.99, p=0.048) among patients who received adjuvant cisplatin-based chemotherapy compared to those who underwent RNU alone. 78 Seisen et al followed on with a large observational study (n=3253) using the National Cancer Data Base in the United States, confirming an overall survival benefit for patients with pT3/T4 and/or pN+ UTUC in the real-world setting, 88 with an HR 0.77 (95% CI 0.68-0.88, p<0.001).…”