Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Importance of wide re-resection in adult spermatic cord sarcomas: Report on oncologic outcomes at a single institution.

BACKGROUND AND OBJECTIVES: We evaluated the effect of re-resection with wide margins (undertaken because initial resection performed elsewhere was incomplete) on survival in patients with spermatic cord sarcoma (SCS). METHODS: After excluding those with metastatic disease and those not undergoing surgical intervention, the records of 72 consecutive patients treated for SCS between 1981 and 2011 at Memorial Sloan Kettering Cancer Center were reviewed. Recurrence-free survival (RFS) and cancer-specific survival were calculated using the Kaplan-Meier method for comparing between the 48 patients who underwent wide re-resection (WRR) within 5 months of diagnosis and the 24 who did not. The relationship of age, tumor size, tumor histology, adjuvant radiation, and wide re-resection with recurrence and death was assessed by univariate Cox regression. RESULTS: WRR significantly improved RFS (hazard ratio [HR] 0.16, 95%CI 0.07-0.37; P < 0.0001), despite the fact that patients receiving WRR had higher-grade disease. Tumor-positive margins upon WRR were strongly associated with both disease recurrence (HR 5.56; 95%CI 1.14-27.11, P = 0.034) and death from cancer (HR 6.16, 95%CI 1.25-30.29; P = 0.025). CONCLUSIONS: A WRR with negative margins is effective in the management of patients with SCS and leads to improved RFS.

Pilot Study to Assess Safety and Clinical Outcomes of Irreversible Electroporation for Partial Gland Ablation in Men with Prostate Cancer.

PURPOSE: Partial prostate gland ablation is a strategy to manage localized prostate cancer. Irreversible electroporation can ablate localized soft tissues. We describe 30 and 90-day complications and intermediate term functional outcomes in men undergoing prostate gland ablation using irreversible electroporation. MATERIALS AND METHODS: We reviewed the charts of 25 patients with prostate cancer who underwent prostate gland ablation using irreversible electroporation as a primary procedure and who were followed for at least 6 months. RESULTS: Median followup was 10.9 months. Grade 3 complications occurred in 2 patients including epididymitis (1) and urinary tract infection (1). Fourteen patients experienced grade 2 or lower complications, mainly transient urinary symptoms, hematuria and urinary tract infections. Of 25 patients 4 (16%) had cancer in the zone of ablation on routine followup biopsy at 6 months. Of those with normal urinary function at baseline 88% and 94% reported normal urinary function at 6 and 12 months after prostate gland ablation, respectively. By 12 months only 1 patient with normal erectile function at baseline reported new difficulty with potency and only 2 patients (8%) required a pad for urinary incontinence. CONCLUSIONS: Prostate gland ablation with irreversible electroporation is feasible and safe in selected men with localized prostate cancer. Intermediate term urinary and erectile function outcomes appear reasonable. Irreversible electroporation is effective in the ablation of tumor bearing prostate tissue as a majority of men had no evidence of residual cancer on biopsy 6 months after prostate gland ablation.

Pathological Stage T3a Significantly Increases Disease Recurrence across All Tumor Sizes in Renal Cell Carcinoma.

PURPOSE: Tumor size and stage are important prognostic parameters in renal cell carcinoma. While pathological stage T1 and T2 are defined by size alone, the presence of certain intrinsic features can up stage a tumor to pathological stage T3a regardless of size. We investigate the effect of pathological tumor stage on the relationship between tumor size and risk of disease recurrence. MATERIALS AND METHODS: Data were reviewed on patients who underwent nephrectomy at our institution between 2006 and 2013 to identify all those with pathological stage T1, T2 and T3a tumors. A proportional hazards Cox model was built with time to recurrence as outcome, and pathological stage and tumor size as covariates. An interaction term for stage and tumor size was included. RESULTS: The final cohort included 1,809 patients. On multivariable analysis, when adjusted for tumor size, patients with pT3a tumors had a greater risk of tumor recurrence compared to those with pT1/T2 tumors (HR 3.70; 95% CI 2.31, 5.92; p <0.0001). The risk of disease recurrence increased more rapidly as tumor size increased only with the presence of perinephric fat invasion (p=0.006). CONCLUSIONS: Using the AJCC 2010 staging criteria we validated pathological stage T3a as a poor prognostic factor in renal cell carcinoma regardless of tumor size. Our results also demonstrated an increased rate of risk of recurrence with perinephric fat invasion. Given this increased risk of recurrence, even in tumors less than 4 cm, closer surveillance is warranted in such cases and the role of perinephric involvement necessitates further investigation.

Biodynamic prediction of neoadjuvant chemotherapy response: Results from a prospective multicenter study of predictive accuracy among muscle-invasive bladder cancer patients.

BACKGROUND: Biodynamic signatures (temporal patterns of microscopic motion within a 3-dimensional tumor explant) offer phenomic biomarkers that are highly predictive for therapeutic response. OBJECTIVE: By utilizing motility contrast tomography, which provides a simple, fast assessment of motion patterns in living tissue, we evaluated the predictive accuracy of a biodynamic drug response classifier in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). DESIGN, SETTING, AND PARTICIPANTS: One hundred five consecutive bladder cancer patients suspected of having MIBC were screened in a multi-institutional prospective observational study (NCT03739177) from July 2018 to June 2020, of whom, 30 completed NAC and radical cystectomy. INTERVENTION(S): Biodynamic signatures from treatment-naïve fresh bladder tumor specimens obtained after transurethral resection were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin per institutional guidelines and were followed through radical cystectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: A 4-level classifier was developed to predict pathologic complete response (pCR) vs. incomplete response utilizing a one-left-out cross-validation protocol to minimize over-fitting. Area under the curve evaluated predictive utility. RESULTS: Thirty percent (9 of 30) achieved pCR. Utilizing the 4-level classifier, biodynamically "favored" (scoring ≥ 3) and "strongly favored" (scoring 4) regimens accurately predicted pCR at rates of 66.7% (4 of 6 patients) and 100% (4 of 4 patients), respectively. Biodynamically "favored" scores predicted pCR with 88% sensitivity and 95% negative predictive value, P < 0.0001. Only 5.0% (1 of 20 patients) achieved pCR from regimens scoring 1 or 2, indicating poor to no response from NAC. Area under the receiver operating curve was 96% (95% Confidence Interval: 79%-99%, P < 0.0001). Future direction involves validating this model prospectively. PRINCIPAL CONCLUSIONS: Biodynamic scoring accurately predicts response in MIBC patients receiving NAC and holds promise to substantially improve the scope of appropriate management intervention.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Comparison of ablation defect on MR imaging with computer simulation estimated treatment zone following irreversible electroporation of patient prostate.

To determine whether patient specific numerical simulations of irreversible electroporation (IRE) of the prostate correlates with the treatment effect seen on follow-up MR imaging. Computer models were created using intra-operative US images, post-treatment follow-up MR images and clinical data from six patients receiving IRE. Isoelectric contours drawn using simulation results were compared with MR imaging to estimate the energy threshold separating treated and untreated tissue. Simulation estimates of injury to the neurovascular bundle and rectum were compared with clinical follow-up and patient reported outcomes. At the electric field strength of 700 V/cm, simulation estimated electric field distribution was not different from the ablation defect seen on follow-up MR imaging (p = 0.43). Simulation predicted cross sectional area of treatment (mean 532.33 ± 142.32 mm(2)) corresponded well with the treatment zone seen on MR imaging (mean 540.16 ± 237.13 mm(2)). Simulation results did not suggest injury to the rectum or neurovascular bundle, matching clinical follow-up at 3 months. Computer simulation estimated zone of irreversible electroporation in the prostate at 700 V/cm was comparable to measurements made on follow-up MR imaging. Numerical simulation may aid treatment planning for irreversible electroporation of the prostate in patients.

Factors Associated with Recovery of Renal Function following Radical Nephrectomy for Kidney Neoplasms.

BACKGROUND AND OBJECTIVES: Partial nephrectomy or radical nephrectomy is the standard of care for patients with kidney neoplasms, but surgery may result in loss of renal function. We sought to identify patient characteristics associated with renal functional recovery following radical nephrectomy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective study among 572 patients with kidney neoplasms who underwent RN between 2006 and 2013. The primary endpoint was recovery of postoperative eGFR to the preoperative level. We plotted the trajectory of each patient's eGFR from their first postoperative visit up to 3 years after surgery. Cumulative incidence and competing risks regression estimated associations between patient and clinical characteristics and eGFR recovery, stratified by preoperative eGFR. RESULTS: Median age was 61.5 years; 68% of patients were male, and 89% were white. Overall, eGFR increased over time following an initial postoperative decrease. Median postoperative follow-up among survivors was 10.8 (minimum, 0.03; maximum, 36.0) months; during follow-up, 263 patients achieved eGFR recovery. Median time to eGFR recovery was 25.3 months. Two-year cumulative incidence of eGFR recovery was 49% overall and 44% and 58% among those with preoperative eGFR≥60 and <60 ml/min per 1.73 m(2), respectively (P<0.001). On multivariable analysis, younger age at surgery and female sex were significantly associated with a higher chance of eGFR recovery among patients with preoperative eGFR<60 ml/min per 1.73 m(2). Among patients with preoperative eGFR≥60 ml/min per 1.73 m(2), hypertension was significantly associated with a lower chance of eGFR recovery, whereas increased tumor size was significantly associated with a higher chance of eGFR recovery. CONCLUSIONS: Overall, almost half of the patients in this study recovered to their preoperative eGFR by 2 years following surgery. Distributions of preoperative risk factors differed by preoperative eGFR, leading to distinct factors that were significantly associated with chance of eGFR recovery.

New Chronic Kidney Disease and Overall Survival After Nephrectomy for Small Renal Cortical Tumors.

OBJECTIVE: To evaluate kidney functional and overall survival (OS) outcomes in a cohort of patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) for tumors ≤4 cm. MATERIALS AND METHODS: We performed a retrospective study on 2110 patients who underwent PN or RN with normal contralateral kidneys and normal serum creatinine from 1989 through 2012. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Primary end points were baseline incidence of CKD, OS, and new onset of eGFR ≤60 and ≤45 mL/min/1.73 m(2). RESULTS: Preoperatively, 30% and 8% of the cohort had eGFR ≤60 and ≤45 mL/min/1.73 m(2), respectively. Five-year freedom from eGFR ≤60 mL/min/1.73 m(2) was 24% (95% confidence interval [CI], 19%-30%) and 76% (95% CI, 72%-78%) for RN and PN, respectively, and 5-year freedom from eGFR ≤45 mL/min/1.73 m(2) was 51% (95% CI, 45%-56%) and 91% (95% CI, 89%-93%) for RN and PN, respectively. On multivariable analysis, hazard ratio for RN vs PN was 4.98 (95% CI, 4.11-6.04, P <.0001) for new onset of eGFR ≤60 mL/min/1.73 m(2) and 9.28 (95% CI, 7.26-11.86, P <.0001) for new onset of eGFR ≤45 mL/min/1.73 m(2). The RN group had a higher rate of death per year than the partial group (hazard ratio = 1.61, 95% CI, 1.24-2.08, P = .0003). CONCLUSION: The present study confirms published works demonstrating that a significant proportion of patients have pre-existing CKD. In patients with normal kidney function, RN is associated with a significantly higher risk for developing CKD and worse OS than PN.

Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function.

OBJECTIVE: To explore the association of non-neoplastic parenchymal changes (nNPC) with patients' health and renal function recovery after partial nephrectomy (PN). MATERIALS AND METHODS: This retrospective review identified 800 pT1a patients who underwent PN at Memorial Sloan Kettering Cancer Center from 2007 to 2012. Pathology reports were reviewed for nNPC graded as mild or severe: vascular sclerosis (VS), glomerulosclerosis (GS), and fibrosis/scarring. Correlations between nNPC and known preoperative predictors of renal function [age, sex, African-American race, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, body mass index, coronary artery disease, and hypertension (HTN)] were assessed using Spearman's rank correlation (ρ). Multivariable linear regression, adjusted for the described known preoperative risk predictors, was performed to evaluate whether the parenchymal features were able to predict 6-month postoperative eGFR. RESULTS: In this study, 46 % of tumors had benign surrounding parenchyma. We noted statistically significant yet weak associations of VS with age (ρ = 0.19; p < 0.001), ASA (ρ = 0.09; p < 0.001), preoperative eGFR (ρ = -0.14; p < 0.001), and HTN (ρ = 0.14; p < 0.001). GS also significantly correlated with HTN, but the correlation was again small (ρ = 0.12; p < 0.001). After adjusting for known risk predictors, only GS was a significant predictor of 6-month postoperative eGFR. When compared with no GS, mild and severe GS were negatively associated with a decrease of 4.9 and 10.8 mL/min/1.73 m(2) in 6-month postoperative eGFR, respectively. CONCLUSIONS: Presence of VS and GS correlated with patients' baseline health, and presence of GS predicted postoperative renal function recovery.

Adult prostate sarcoma: the Memorial Sloan Kettering experience.

OBJECTIVE: To present our institutional experience with adult prostate sarcoma over 30 years. MATERIALS AND METHODS: We reviewed 38 cases of adult prostate sarcoma diagnosed and treated at our institution between 1982 and 2012. Univariate Cox proportional hazards regression was used to determine if there was an association between specific disease characteristics (tumor size, histology, American Joint Committee on Cancer stage, and metastasis at diagnosis) and cancer-specific survival (CSS). RESULTS: A total of 38 patients were included, with a median age of 50 years (range, 17-73 years). Most men presented with lower urinary tract symptoms (45%), hematuria (24%), or acute urinary retention (21%). Diagnosis was established with prostate needle biopsy (68%) or transurethral resection of the prostate (18%). The predominant histologic subtypes were leiomyosarcoma (13 cases, 34%) and rhabdomyosarcoma (12 cases, 32%). Rhabdomyosarcoma was associated with poorer CSS (hazard ratio, 3.00; 95% confidence interval [CI], 1.13-7.92; P = .027) compared with leiomyosarcoma. We did not observe a significant relationship between tumor size and CSS. Overall, median CSS was 2.9 years (95% CI, 1.5-5.4), with 7.7 years for clinically localized disease (95% CI 2.5; upper bound not reached) and 1.5 years for metastatic disease (95% CI 1.1, 2.7). CONCLUSION: Adult prostate sarcoma has a poor prognosis, especially in cases of metastatic disease at the time of diagnosis. Surgery remains the standard of care, but it provides limited benefit to those with metastatic disease or as a consolidation therapy after partial response to systemic therapy.

Prospective evaluation of plasma kinetic bipolar resection of bladder cancer: comparison to monopolar resection and pathologic findings.

OBJECTIVE: To determine whether the Gyrus ACMI plasma kinetic bipolar device (Gyrus ACMI, Southborough, MA) improves pathologic specimen preservation and clinical outcomes compared to standard monopolar electrocautery. PATIENTS AND METHODS: In our prospective study, 83 patients underwent monopolar or bipolar transurethral resection of bladder tumors between April 2006 and February 2007 at Memorial Sloan-Kettering Cancer Center. Dedicated genitourinary oncology pathologists blinded to resection type and assessed pathologic features including stage and grade, presence of muscularis propria, fragment size, presence and thickness of thermal artifacts within the specimen, layer of tissue most affected, severity of tissue distortion, and diagnostic impact of thermal artifacts. Clinical outcomes including, perforation, obturator reflex, need for muscle paralysis, a catheter, or admission, were recorded. Clinical and pathologic outcomes between resection modality were compared. RESULTS: There were no significant thermal artifacts in 9/38 (23.7 %) and 11/45 (24.4 %) monopolar and bipolar specimens, respectively. The layer of bladder tissue most affected by thermal artifacts was readable in 18/38 (47.4 %) monopolar and 27/45 (60.0 %) bipolar specimens. Tissue distortion from thermal artifacts led to areas within 11/38 (28.9 %) monopolar and 7/45 (15.6 %) bipolar specimens being unreadable. Ultimately, thermal artifacts caused moderate diagnostic difficulty in 2/38 (5.3 %) specimens of the monopolar group and severe diagnostic difficulty in 1/45 (2.2 %) bipolar specimens. Clinically, there was no major difference between resection methods. CONCLUSION: Plasma kinetic bipolar equipment appears to cause less tissue distortion and has the potential to facilitate staging and grading of bladder tumors. No differences in clinical outcomes were appreciated between resection methods. If these results can be repeated in larger studies, the bipolar device represents a small advancement in transurethral resection.

Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma.

BACKGROUND: KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors. PATIENTS AND DESIGN: A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques. RESULTS: The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36 ± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1-negative group. CONCLUSION: Our small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses.