Feasibility and tissue concordance of genomic sequencing of urinary cytology in upper tract urothelial carcinoma.

BACKGROUND: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. METHODS: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). RESULTS: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. CONCLUSIONS: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.

Impact of systemic Immune-inflammation Index on oncologic outcomes in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer.

PURPOSE: To evaluate the predictive and prognostic value of the Systemic Immune-inflammation Index (SII) in a large cohort of patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa). METHODS: We retrospectively analyzed our multicenter database comprising 6,039 consecutive patients. The optimal preoperative SII cut-off value was assessed with the Youden index calculated on a time-dependent receiver operating characteristic (ROC) curve. Logistic regression and Cox regression analyses were used to investigate the association of SII with pathologic features and biochemical recurrence (BCR), respectively. The discriminatory ability of the models was evaluated by calculating the concordance-indices (C-Index). The clinical benefit of the implementation of SII in clinical decision making was assessed using decision curve analysis (DCA). RESULTS: Patients with high preoperative SII (≥ 620) were more likely to have adverse clinicopathologic features. On multivariable logistic regression analysis, high preoperative SII was independently associated with extracapsular extension (odds ratio [OR] 1.16, P = 0.041), non-organ confined disease (OR 1.18, P = 0.022), and upgrading at RP (OR 1.23, P < 0.001). We built two Cox regression models including preoperative and postoperative variables. In the preoperative multivariable model, high preoperative SII was associated with BCR (hazard ratio [HR] 1.34, 95% CI 1.15-1.55, P < 0.001). In the postoperative multivariable model, SII was not associated with BCR (P = 0.078). The addition of SII to established models did not improve their discriminatory ability nor did it increase the clinical net benefit on DCA. CONCLUSION: In men treated with RP for clinically nonmetastatic PCa, high preoperative SII was statistically associated with an increased risk of adverse pathologic features at RP as well as BCR. However, it did not improve the predictive accuracy and clinical value beyond that obtained by current predictive and prognostic models. SII together with a panel of complementary biomarkers is praised to help guide decision-making in clinically nonmetastatic PCa.

Role of systemic immune-inflammation index in patients treated with salvage radical prostatectomy.

PURPOSE: To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP). MATERIALS AND METHODS: This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker. RESULTS: A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45-7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33-4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12-103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70-27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23-398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67-21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1). CONCLUSIONS: In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance.