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Introduction and Objective: The folate receptor (FR) protein is upregulated in numerous epithelial malignancies while having limited expression on normal tissues. This overexpression of FR in renal-cell carcinoma (RCC) can be exploited by attaching nearly any therapeutic or imaging agent for delivery to cancer cells. In one of its first applications, platinum-resistant ovarian cancer, folate was used to deliver pegylated liposomal doxorubicin (a folate-linked vinca alkaloid) and improved progression-free survival versus standard treatment. RCCs are thought to be the second highest FR-expressing cancer. OTL-38 is a folate analogue conjugated with a fluorescent dye that emits light in the near infrared spectrum. This longer wavelength allows for deeper penetration of the fluorescent light through tissues with the potential to better image tumors beneath adipose tissue or deeper into organ parenchyma. We are currently conducting a pilot, phase 2, nonrandomized study in patients with RCC, scheduled to undergo primary, partial, or radical nephrectomy. The aim is to explore the use of OTL-38 and fluorescence imaging to observe RCC at the margins of resection in partial nephrectomy and in lymph node(s) or other metastases for radical nephrectomy. Methods: Currently two patients have participated in the trial to date with an accrual target of 20 patients. The first was a 67-year-old male with an incidental 2.2 cm right-sided renal mass, and the second was a 70-year-old male with an enlarging 2 cm renal mass. Per protocol, both patients were administered OTL-38 in the preoperative area 1 hour before the procedure. Subsequently, both procedures were performed with robotic assistance as per normal routine with the use of Firefly fluorescence to aid in observation of OTL-38 uptake. Results: Intraoperative guidance through OTL-38 demonstrated minimal to no uptake of the OTL-38 as seen by Firefly fluorescence (green color). Surprisingly, the normal renal parenchyma showed strong uptake of OTL-38 as seen by Firefly fluorescence. Both pathology reports revealed conventional clear cell RCC. Immunohistochemistry slides of the tumor revealed only mild staining for folate. In contrast, immunohistochemistry slides of the normal renal parenchyma in the surgical margin revealed a strongly positive stain for folate. Conclusions: In conclusion, our first two patients' renal tumors did not stain strongly for folate; however, the normal renal parenchyma did, which served as an intraoperative guide to confirm a negative margin. Further study of patients will reveal whether folate receptors are, in fact, predominant or not in renal cell cancer.No competing financial interests exist.

INTRODUCTION AND OBJECTIVE: Radical nephrectomy (RN), with or without resection of the ureter, is the treatment of choice for patients with advanced malignancy of the kidney and/or upper urinary tract. We have previously developed and validated a mortality risk score to stratify postoperative outcomes in patients undergoing radical cystectomy. We hypothesized that this 30-day mortality risk score could be applied to patients undergoing RN for malignancy.METHODS: The National Surgical Quality Improvement Program (NSQIP) identified 16,617 patients that underwent RN for upper urinary tract or renal malignancy from 2013-2017. Patients with complete data were included in the analysis. Risk factors for 30-day mortality were identified on multivariable analysis using backward stepwise binary logistic regression. A previously developed and validated mortality risk score (Figure 1A) was calculated for each RN patient. A receiver operating characteristic (ROC) curve quantified the discriminatory ability of the risk calculator. Statistical significance was defined as p values <0.05.RESULTS: Of 9,345 patients included, laparoscopic/robotic technique was applied in 6,112 (65%) patients. The mean age was 64AE12 years and most patients were male (n[5950, 64%). Postoperative 30-day mortality was 1.2% (n[116). Older age, elevated creatinine, lower albumin and hematocrit, congestive heart failure, exertional dyspnea, >10% weight loss, disseminated cancer, and open surgery as mortality risk factors. After RN, 30-day mortality increased nearly exponentially with escalating risk category (Figure 1B), p<0.00001. The ROC curve for the risk score is shown in Figure 1C; the area under the curve (AUC) was 0.794 (95% CI, 0.755-0.832; p<0.00001). Relative risk of 30-day mortality increased with escalating risk category: moderate risk [4.8 (2.5-9.1, p<0.00001), high risk[16.8 (9.0-31.5, p<0.00001), and extremely high risk [36.8 (13.4-101.2, p<0.00001). The risk score applied to minimally invasive (AUC, 0.785; 95% CI, 0.722-0.849; p<0.00001) and open RN (0.781; 0.730-0.832; p<0.00001).CONCLUSIONS: A previously established mortality risk score can be employed preoperatively in patients undergoing RN for malignancy to stratify 30-day mortality risk. This 30-day mortality risk score is reliable, accurate, and applicable to both minimally invasive and open RN.