Moghaddam, Farshad Sheybaee

454 Background: Immune checkpoint inhibitor (ICI)-based combination therapy has become the standard of care for advanced renal cell carcinoma (RCC). A pathologic complete response (pCR) in the primary tumor may be observed in up to one-third of patients; however, data on the outcomes of these patients remain limited. This study aimed to evaluate the clinical outcomes of patients who achieved a pCR following ICI therapy. Methods: Patients with advanced RCC who underwent nephrectomy following ICI therapy were evaluated across five high-volume U.S. academic centers between 2015 and 2023. Clinical characteristics and outcomes were compared between those with and without a pCR in the primary tumor (ypT0N0/Nx). Multivariable logistic regression models were used to identify factors associated with pCR. Recurrence-free (RFS) and overall survival (OS) rates were estimated using the Kaplan-Meier (KM) method. Results: A total of 182 patients were included (Table 1). Among all patients, downstaging to ≤ypT1N0/Nx was observed in 45 patients (25%), of whom 21 (11%) achieved a pCR. In multivariable analysis, the presence of clinical thrombus was marginally associated with a lower likelihood of achieving pCR (odds ratio [95% CI]: 0.39 [0.15–1.00], p=0.06). During a median follow-up of 25 months, 70 patients (38%) experienced recurrence, including 4 (2%) in the pCR group. Median time to recurrence was 7.5 months. KM analysis demonstrated a higher estimated 5-year RFS in the pCR group compared to those with residual disease; however, the difference was not statistically significant (68% vs. 54%, p=0.2). In addition, OS rates were comparable between the two groups. Conclusions: In our cohort, 11% of patients who underwent nephrectomy following ICI therapy for advanced RCC showed pCR, which correlated with improved oncologic outcomes. Despite the lower recurrence rates observed in the pCR group, sustained long-term surveillance remains necessary due to the continued, albeit reduced, risk of disease recurrence. Clinical characteristics of patients who underwent post-ICI nephrectomy, stratified by their pathologic complete response (pCR). Variable pCR (n=21) No pCR (n=161) p-value Median (IQR) age, year 61 (56 – 70) 64 (56 – 71) 0.46 Gender (male), n (%) 15 (71) 118 (73) 0.8 Tumor advancement, n (%) Locally advanced Metastatic 2 (10)19 (90) 36 (22)125 (78) 0.26 Risk group (for metastatic), n (%) Favorable Intermediate Poor 3 (25)6 (50)3 (25) 38 (34)59 (54)13 (12) 0.42 ICI regimen, n (%) ICI monotherapy ICI+ICI ICI+TKI 4 (19)9 (43)8 (38) 46 (28)64 (40)51 (32) 0.64 Immunotherapy cycles (>4), n (%) 8 (50) 49 (37) 0.42 Median (IQR) clinical tumor size, cm 9.3 (6.7 – 11.9) 8.4 (6.6 – 12) 0.68 Clinical nodal involvement, n (%) 8 (38) 53 (33) 0.63 Clinical thrombus, n (%) 12 (57) 60 (37) 0.1 ICI: immune checkpoint inhibitor; TKI: tyrosine kinase inhibitor.

Objectives To develop an internationally validated, structured robot‐assisted radical nephroureterectomy (RARNU) training programme through expert consensus. Materials and Methods A RARNU‐specific questionnaire was developed/adapted from previously published, validated questionnaires for robot‐assisted urological procedures. This included five key domains and 11 surgical steps. In all, 30 upper tract urothelial carcinoma experts were invited to participate. A two‐stage modified Delphi approach was employed. Consensus was defined as ≥80% agreement. Modifications and additional statements were proposed during the second round following qualitative/quantitative feedback from the initial round. Results Response rates for the first and second Delphi rounds were 80% (24/30) and 92% (22/24), respectively. All agreed that adoption of a standardised training curriculum can improve clinical outcomes during the RARNU learning curve. There was ≥92% agreement on all proposed RARNU steps. Five RARNU clinical modules of increasing complexity were defined using individual step difficulty and number of prior RARNU cases required, with ≥96% agreement among respondents. Respondents unanimously agreed that the final assessment should be based on a procedure‐specific scale focusing on the hilar dissection, ureteric dissection, and bladder cuff excision steps. No consensus was reached for the annual minimum RARNU volume required for eligibility as a RARNU curriculum host centre. Conclusion This is the first structured training curriculum for RARNU using international expert consensus. This will help guide surgical educators and trainees toward independent completion of a full RARNU.

Objectives: To report the outcomes of minimally invasive (MIS) nephrectomy following immune checkpoint inhibitor (ICI) therapy. Materials and Methods: This multicenter retrospective cohort study included consecutive patients who underwent nephrectomy following ICI therapy at five high-volume US academic centers between 2015 and 2023. Baseline clinical features and perioperative findings were recorded. After propensity-score matching (PSM), outcomes were compared between MIS and open nephrectomies. The primary outcome was 90-day complications, and secondary outcomes included length of hospital stay (LOS) and 90-day readmission. Results: A total of 158 patients were included, of whom 76 and 82 underwent MIS and open nephrectomies, respectively. The MIS procedures included robotic ( n = 56) and laparoscopic ( n = 20). A total of six (8%) patients converted to open. On multivariable analysis, patients with nonmetastatic vs metastatic renal-cell carcinoma (RCC) (hazard ratio [HR] 3.1, p = 0.01), those with smaller tumor size (HR 1.2 for each cm, p = 0.001), and no clinical evidence of inferior vena cava thrombus (HR 29, p = 0.002) were more likely to undergo the MIS approach compared with open approach. After PSM, including 56 MIS and 36 open nephrectomies, the MIS group compared with the open group had lower estimated blood loss (100 vs 460 mL, p < 0.001) and shorter LOS (2 vs 4 days, p < 0.001). Nevertheless, 90-day complications and readmissions were similar between the two groups. There were no 90-day mortality rates in either group. Conclusion: The MIS approach appears safe and offers more favorable perioperative outcomes compared with open surgery in properly selected patients with advanced RCC who are candidates for nephrectomy following ICI therapy.