Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Identification and Validation of Radiographic Enhancement for Reliable Differentiation of CD117(+) Benign Renal Oncocytoma and Chromophobe Renal Cell Carcinoma.

Purpose: The diagnostic differential for CD117/KIT(+) oncocytic renal tumor biopsies is limited to benign renal oncocytoma versus chromophobe renal cell carcinoma (ChRCC); however, further differentiation is often challenging and requires surgical resection. We investigated clinical variables that might improve preoperative differentiation of CD117(+) renal oncocytoma versus ChRCC to avoid the need for benign tumor resection.Experimental Design: A total of 124 nephrectomy patients from a single institute with 133 renal oncocytoma or ChRCC tumors were studied. Patients from 2003 to 2012 comprised a retrospective cohort to identify clinical/radiographic variables associated with renal oncocytoma versus ChRCC. Prospective validation was performed among consecutive renal oncocytoma/ChRCC tumors resected from 2013 to 2017.Results: Tumor size and younger age were associated with ChRCC, and multifocality with renal oncocytoma; however, the most reliable variable for ChRCC versus renal oncocytoma differentiation was the tumor:cortex peak early-phase enhancement ratio (PEER) using multiphase CT. Among 54 PEER-evaluable tumors in the retrospective cohort [19 CD117(+), 13 CD117(-), 22 CD117-untested], PEER classified each correctly as renal oncocytoma (PEER >0.50) or ChRCC (PEER ≤0.50), except for four misclassified CD117(-) ChRCC variants. Prospective study of PEER confirmed 100% accuracy of renal oncocytoma/ChRCC classification among 22/22 additional CD117(+) tumors. Prospective interobserver reproducibility was excellent for PEER scoring (intraclass correlation coefficient, ICC = 0.97) and perfect for renal oncocytoma/ChRCC assignment (ICC = 1.0).Conclusions: In the largest clinical comparison of renal oncocytoma versus ChRCC to our knowledge, we identified and prospectively validated a reproducible radiographic measure that differentiates CD117(+) renal oncocytoma from ChRCC with potentially 100% accuracy. PEER may allow reliable biopsy-based diagnosis of CD117(+) renal oncocytoma, avoiding the need for diagnostic nephrectomy. Clin Cancer Res; 24(16); 3898-907. ©2018 AACR.

Early identification of asymptomatic brain metastases from renal cell carcinoma.

Current guidelines for metastatic renal cell carcinoma (mRCC) do not recommend routine brain imaging as part of the surveillance protocol unless central nervous system (CNS) symptoms or abnormal laboratory values suggest brain involvement. We hypothesized that strict adherence to these guidelines will delay diagnosis and management of RCC brain metastases. Retrospective review of our IRB-approved kidney cancer database examined a consecutive series of subjects from 1995 to 2012. We identified all mRCC patients with radiographic evidence of renal cell brain metastasis (RCCBM). RCCBM patients were divided into two cohorts: CNS symptoms present at RCCBM diagnosis and those without symptoms present at diagnosis. Fifty-two patients within our database met criteria; CNS symptoms were present at RCCBM diagnosis in 73 % (36) of patients. Median size of RCCBM on presentation was smaller in the asymptomatic verses the symptomatic cohort (0.83 vs. 1.7 cm, p = 0.003). Multivariate analysis demonstrated presence of CNS symptoms and female gender as a survival advantage (p < 0.05) while poor performance status, history of tobacco abuse and coexistence of lung metastasis were poor indicators for survival (p < 0.05). Patients with pulmonary metastases and a history of tobacco abuse are more likely to harbor RCCBM and perhaps in the absence of CNS symptoms these subjects should have routine brain surveillance incorporated into the RCC follow up. Overall, the current urologic guidelines may be missing a subset of metastatic RCC patients who could potentially benefit from early radiation or neurosurgical intervention. This may result in improved overall survival.

Learning curves for robot-assisted and laparoscopic partial nephrectomy.

OBJECTIVES: To evaluate the learning curve of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) between two surgeons at a single institution. METHODS: A prospectively maintained, Institutional Review Board (IRB)-approved kidney surgery database was reviewed retrospectively and the first 116 consecutive LPNs performed by one surgeon (Hyung Kim) and 116 consecutive RPNs performed by a second surgeon (Thomas Schwaab) were identified. The learning curve was evaluated by examining the operative times, warm ischemia times (WITs), estimated blood loss, the postoperative estimated glomerular filtration rate (eGFR), and intra- and postoperative complications in the quartiles of 29 patients. The LPNs performed by Hyung Kim were done following completion of a minimally invasive fellowship. Thomas Schwaab had minimal experience with LPN and no fellowship training before starting RAPN. RESULTS: The RAPN and LPN groups had similar patient and tumor characteristics. The RAPN group had a higher preoperative eGFR (74.1±22.04 vs. 80.95±21.25 mL/minutes, p=0.015) and a worse Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 1+ in 12% vs. 2.6%, p<0.001) compared with the LPN group. Rates of intraoperative (p=0.203) and postoperative (p=0.193) complications were similar. In the RAPN group, operating room (OR) time (161±51 vs. 203±55 minutes, p<0.001) and WIT (17.7±14.8 vs. 21.8±9.1 minutes, p<0.001) were shorter. Postoperative stay was longer in the RAPN group (2.4±2.2 vs. 1.67±1.1 days, p<0.001). The percentage decrease in postoperative eGFR was lower in the RAPN group versus the LPN (9.6% vs. 10%). The learning curves differed for log tumor size, log WIT, and postoperative complications. CONCLUSIONS: The variables of the learning curve for RAPN can be obtained earlier than the same variables for LPN. RAPN had a shorter OR time and WITs. The shorter WITs, earlier in the series, led to consistently lower fluctuations in GFR and preservation of the renal function. The learning curves for each procedure need to be re-evaluated at longer intervals to ensure their accuracy.

Stereotactic Body Radiotherapy for the Treatment of Renal Tumors.

The purpose of this study was to evaluate the response of actively growing renal masses to stereotactic body radiation therapy (SBRT). We retrospectively reviewed our institutional review board-approved kidney database and identified 4 patients who underwent SBRT, 15 Gy dose, for their rapidly growing renal masses. Three patients had a decreased tumor size after radiation treatment by 20.8%, 38.1%, and 20%. The other patient had a size gain of 5.6%. This patient maintained a similar tumor growth rate before and after SBRT. Mean follow-up time was 13.8 months. SBRT represents an effective management option in select patients with larger rapidly growing kidney masses.

High-dose interleukin-2 therapy for metastatic renal cell carcinoma: a contemporary experience.

OBJECTIVE: To present our experience of high-dose interleukin-2 (HDIL-2) in a high-volume National Cancer Institute-designated center for patients with metastatic renal cell carcinoma (mRCC). METHODS: Patients with mRCC who received HDIL-2 monotherapy as a first- or second-line therapy during 2004-2011 were identified. Demographics, pathologic variables, renal function, time until the start of HDIL-2 therapy, number of cycles (1-3), responses (complete response, partial response, stable disease, and progressive disease), and primary renal cell carcinoma treatment were analyzed. Progression-free survival and overall survival (OS) were determined. RESULTS: Of 906 patients in the kidney cancer database, 91 patients with mRCC were treated with HDIL-2 and 18 patients (20.5%) underwent prior cytoreductive nephrectomy. Median age was 51 years, and 73.9% were men. Median follow-up was 45 months. Pretreatment renal function impairment led to more treatment cycles (2-3) than in those with adequate initial kidney function (92.3% vs 50.6%, respectively; P = .002). Lower tumor stage correlated with a better response (P = .023) and with longer time from diagnosis to initiation of HDIL-2 (P = .011). Complications included hypotension (67.4%), renal impairment (63%), impaired liver function (42.4%), and thrombocytopenia (31.5%). Four patients (4.5%) had a complete response, 10 (11.4%) had a partial response, and 28 (31.8%) had a stable disease. Median progression-free survival and OS were 8.6 and 35.5 months, respectively. The estimated 2-year OS rate was 60.6%. CONCLUSION: Incorporating HDIL-2 therapy in the treatment strategies for mRCC added to the patients' survival in this series. HDIL-2 therapy is well tolerated in patients with pre-existing renal impairment with no long-term renal toxicity.

Health-related quality of life outcomes after robot-assisted and open radical cystectomy using a validated bladder-specific instrument: a multi-institutional study.

OBJECTIVE: To evaluate health-related quality of life (HRQL) using validated bladder-specific Bladder Cancer Index (BCI) and European Organization for Research and Treatment of Cancer Body Image scale (BIS) between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC). METHODS: This was a retrospective case series of all patients who underwent radical cystectomy. Patients were grouped based on surgical approach (open vs robot assisted) and diversion technique (extracorporeal vs intracorporeal). Patients completed BCI and BIS preoperatively and at standardized postoperative intervals (at least 2). The primary exposure variable was surgical approach. The primary outcome measure was difference in interval and baseline BCI and BIS scores in each group. The Fisher exact, Wilcoxon rank-sum, and Kruskal-Wallis tests were used for comparisons. RESULTS: Eighty-two and 100 patients underwent RARC and ORC, respectively. Compared with RARC, more patients undergoing ORC had an American Society of Anesthesiology score≥3 (66% vs 45.1% RARC; P=.007) and shorter median operative time (350 vs 380 minutes; P=.009). Baseline urinary, bowel, sexual function, and body image were not different between both the groups (P=1.0). Longitudinal postoperative analysis revealed better sexual function in ORC group (P=.047), with no significant differences between both the groups in the other 3 domains (P=.11, .58, and .93). Comparisons regarding diversion techniques showed similar findings in baseline and postoperative HRQL data, with no significant differences in the HRQL and body image domains. CONCLUSION: RARC has comparable HRQL outcomes to ORC using validated BCI and BIS. The diversion technique used does not seem to affect patients' quality of life.