Pagliaro, Lance C

Aim: Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/– ICI may be a feasible choice. Methods: We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/– ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1–14) of TC over median 12 weeks (range 3–53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist’s discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7–10.4), median PFS of 4.6 months (IQR 3.3–10.2), and median OS of 9.4 months (IQR 6.3–15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/– ICI was overall well tolerated with expected type and severity of adverse events. Conclusions: Strategies to overcome ICI resistance are needed, and TC +/– ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.

Abstract Background The Surgery in Early Metastatic Seminoma (SEMS) trial examined retroperitoneal lymph node dissection as first-line treatment for patients with isolated 1-3 cm retroperitoneal lymphadenopathy. To date, the standard of care for these patients has been either chemotherapy or radiotherapy. Herein, we evaluated the relative cost-effectiveness of these management strategies. Methods A microsimulation model assessed the cost-effectiveness of retroperitoneal lymph node dissection, chemotherapy, and radiotherapy for stage IIA seminoma. Sensitivity analyses were performed to evaluate model robustness. Retroperitoneal lymph node dissection recurrence probabilities were obtained from the SEMS trial. All other probability and utility values were obtained from published literature. Primary outcomes included costs from a commercial insurer’s perspective, effectiveness (quality adjusted life-years [QALYs]), and incremental cost-effectiveness ratios using a willingness-to-pay threshold of $100 000/QALY. Results At a lifetime horizon, the mean costs per patient for retroperitoneal lymph node dissection, radiotherapy, and chemotherapy were $58 469, $98 783, and $104 096, and the mean QALYs were 40.61, 40.70, and 39.15, respectively. Retroperitoneal lymph node dissection was found to be the most cost-effective approach because of high costs and accrued disutility of chronic toxicities associated with radiotherapy (cost-effectiveness ratios = $433 845/QALY) and chemotherapy (dominated). On 1-way sensitivity analyses, retroperitoneal lymph node dissection was no longer cost-effective if the probabilities of infertility and cardiovascular toxicity after radiotherapy were less than 13% and 16%, respectively, or if the 2-year probability of progression after retroperitoneal lymph node dissection was more than 26%. Conclusions Retroperitoneal lymph node dissection was the most cost-effective treatment approach for stage IIA seminoma. These findings support clinical guideline consideration of including retroperitoneal lymph node dissection as a treatment option for well-selected patients with stage IIA seminoma.