Francesco Ripa

When to Perform Preoperative Bone Scintigraphy for Kidney Cancer Staging: Indications for Preoperative Bone Scintigraphy

OBJECTIVE To identify an objective and reproducible strategy for preoperative staging bone scintigraphy (BS) in patients diagnosed with renal cell carcinoma (RCC), because in the absence of objective criteria, the decision to perform preoperative BS remains a subjective practice. PATIENTS AND METHODS The study included a total of 2008 patients with RCC treated with surgery and prospectively included into an institutional database. The study outcome was the presence of 1 or more bone lesions suspicious for metastases at staging BS. A multivariable logistic regression model predicting a positive BS was fitted. The predictors consisted of the preoperative clinical tumor (cT) and clinical nodal (cN) stages, the presence of systemic symptoms, and the platelet-to-hemoglobin (PLT/Hb) ratio. RESULTS The rate of positive BS was 4% (n = 81). At the multivariable logistic regression analysis, cT2, cN1, the presence of systemic symptoms, and the PLT/Hb ratio were all associated with am increased risk of positive BS (P <.05). Following the 2000-sample bootstrap validation, the concordance index was 0.77 (proposed model) vs 0.63 (decision making based on symptoms only). At the decision curve analysis, the proposed strategy was associated with a higher net benefit. If BS is performed when the risk of positive result is >5%, a negative BS is spared in 80% and a positive BS is missed in 2% of the population only. CONCLUSION Using preoperative variables, it is possible to accurately estimate the risk of positive BS at RCC staging using preoperative characteristics. Compared with the strategy supported by available guidelines, the proposed model was more objective, statistically more accurate, and clinically associated with higher net benefit.

Lymph node dissection should not be dismissed in case of localized renal cell carcinoma in the presence of larger diseases

OBJECTIVE To assess whether even in the group of localized renal cell carcinoma (RCC), some patients might harbor a disease with a predilection for lymph node invasion (LNI) and/or lymph node (LN) progression and might deserve lymph node dissection (LND) at the time of surgery. MATERIALS AND METHODS Between 1990 and 2014, 2,010 patients with clinically defined T1-T2N0M0 RCC were treated with nephrectomy and standardized LND at a single tertiary care referral center. The endpoint consists of the presence of LNI and/or nodal progression, defined as the onset of a new clinically detected lymphadenopathy (>10mm) in the retroperitoneal lymphatic area with associated systemic progression or histological confirmation or both. We tested the association between clinical characteristics and the endpoint of interest. Predictors consisted of age at surgery, clinical tumor size, preoperative hemoglobin, and platelets levels. Multivariable logistic regression model and smoothed Lowess method were used. RESULTS LNI was recorded in 14 cases (2.2%). The median follow-up after surgery was 68 months. During the study period, 23 patients (1.1%) experienced LN progression; 91% of those patients experienced LN progression within 3 years after surgery. Combining the 2 endpoints, 36 patients (1.8%) had LNI and/or LN progression. Clinical tumor size was the only independent predictors of LNI and/or LN progression (OR = 1.25). A significant increase of the risk of LNI and/or LN progression was observed in RCC larger than 7cm (cT2a or higher). CONCLUSIONS LNI and/or LN progression is a rare entity in patients with localized RCC. Nonetheless, patients with larger tumors might still benefit from LND because of a non-negligible risk of LNI and/or LN progression.

MP22-14 PREOPERATIVE HAEMATOLOGICAL PARAMETERS AS PREDICTORS OF LONG-TERM SURVIVAL IN RENAL CELL CARCINOMA

onset in adults 46 years of age. Limited data exists regarding patients with early onset RCC. Our objective was to investigate the clinical and pathologic characteristics within this unique subset of patients with RCC. METHODS: We retrospectively reviewed our surgical pathology database from 2011-2016 for patients with RCC. The clinical and pathologic characteristics of patients 46 years were compared to the overall population. RESULTS: We identified 98/604 (16%) cases of RCC in patients 46 years. The median age of patients with early onset RCC compared to our control group was 38.6 (range 19-46) vs. 64.4 (range 47-89) years, respectively. Early onset RCC patients included Caucasians (55%), African Americans (40%), Latino (4%), and Asian (1%). Histologic subtypes, included clear cell (54%), papillary (29%), unclassified (7%), chromophobe (5%), clear cell papillary (3%), multilocular cystic neoplasm (1%), and carcinoid (1%). 20/28 (71%) of early onset papillary RCCs occurred in African Americans. Risk factors for RCC included hypertension (47%), smoking (22%), obesity (12%), diabetes mellitus (9%), and chronic kidney disease (CKD) or end-stage renal disease (ESRD) (16.3%). Known genetic syndromes prior to diagnosis were identified in 7/98 (7%) patients (1 Von Hippel Lindau, 2 Familial Adenomatous Polyposis, 1 Marfan, 1 Tuberous Sclerosis, 1 Birt-Hogg-Dube). There was no significant difference between the two groups in terms of tumor size, focality, margin status, presence of necrosis, or sarcomatoid features. Non-Caucasians were more likely to develop early onset RCC (OR 1.98; p1⁄40.001). Patients with early onset RCC were more likely to receive a radical nephrectomy (OR 1.98; p1⁄40.001), have lower grade tumors (OR 0.69; p1⁄40.033) and present with organ confined disease (p1⁄40.008). CONCLUSIONS: Despite having more indolent tumor characteristics and organ confined disease, early onset RCC patients were more likely to undergo a radical nephrectomy. In addition, a high percentage of these patients had either concurrent, or risk factors for developing, CKD/ESRD. These findings suggest that this population is potentially being over treated and should undergo nephron sparing surgery if surgically feasible.

PD52-05 WHEN TO PERFORM PREOPERATIVE BONE SCINTIGRAPHY FOR KIDNEY CANCER STAGING

disease may have worse survival than those without nodal disease, although they are currently all considered stage III. Our aim was to compare the survival of stage III RCC patients with pathologic nodal disease (pT123N1M0) to stage III patients without nodal disease (pT3N0M0), and stage IV patients. METHODS: We retrospectively studied a cohort of patients who underwent retroperitoneal lymph node dissection at the time of nephrectomy from 1993 to 2012. Stage III with (pT123N1M0) and without (pT3abcN0M0) pathologic nodal disease was noted in 115 (7.7%) and 275 (18.4%) patients. In order to compare outcomes of stage III patients to those with stage IV disease, we included 523 pT123N0M1 and 222 pTanyN1M1 patients. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier Method. Univariate and multivariate Cox proportional hazards regression models were fit to identify factors significantly associated with clinical outcomes. RESULTS: Clear cell RCC was present in 86.9% and 60.0%, and high grade tumor (grade 4) was present in 26.5% and 50.4% of pT3N0 and pT123N1, respectively. Median tumor size was 9 cm and 10 cm in pT3N0 and pT123N1 patients, and median number of lymph nodes removed was 6 (range1-45) and 8 (range1-37), respectively. Cancer-specific survival was better in patients with pT3abcN0M0 than those with pT123N1M0 (5-year CSS rate: 74.8% vs 38.6%, p<0.001); however, similar 5-year CSS rates were noted in pN1M0 and pN0M1 (38.6% vs 29.8%, p1⁄40.13), while pTanyN1M1 had the worst 5-year CSS (7%). On multivariate Cox regression analysis, high-grade tumor (HR 2.96, 95% CI 2.11-4.14, p<0.0001), and pathologic lymph node involvement (HR 2.83, 95% CI 2.03-3.95, p<0.0001) were significantly associated with cancer-specific survival. CONCLUSIONS: Patients with pN1M0 disease have significantly worse survival than those with pT3N0M0 disease, although both groups are currently classified as stage III. In addition, patients with pN1M0 have survival similar to those with pN0M1 disease (stage IV), suggesting that pN1M0 patients should be reclassified as stage IV.

MP55-15 IMPACT OF INTRAOPERATIVE BLOOD TRANSFUSIONS ON SURVIVAL AFTER SURGERY FOR RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: To date no studies assessed whether Charlson Comorbidy Index (CCI), American Society of Anesthesiologists score (ASA) and Eastern Cooperative Oncology Group performance status (ECOG) have the same ability to predict postoperative mortality in renal cell carcinoma (RCC) patients who undergo radical (RN) or partial nephrectomy (PN). The aim of the study was to assess the predictive ability of these indeces on other cause mortality (OCM) in patients treated with surgery for kidney cancer. METHODS: We identified 2,648 T1-T4 patients treated with RN or PN for RCC between 1987 and 2014 at a single centre. Patients with distant metastases at diagnosis, with multiple lesions and with Von Hippel Lindau were excluded. Four multivariable Cox regression analyses (MVA) were performed to assess OCM predictors. Predictors included in Model 1 were age at surgery and gender (basic model). Predictors in Model 2, 3 and 4 were the same included into Model 1 plus CCI, ASA and ECOG, respectively. The discrimination of the accuracy of each model was quantified using the receiver operating characteristic-derived area under the curve with a time frame at 3-year. Decision curve analyses were performed to evaluate and compare the netbenefit associated with the use of the 3 indeces relative to the basic model. RESULTS: 249 patients (9.4%) died of other causes. Overall, 82 (3.1%) patients died within 3 years after surgery. The median followup in patients who survived was 63 months (IQR 30-118). At MVA of Model 1, age (HR 1.1) and gender (HR 1.5) were independent predictors of OCM (all p0.004). At MVA of Model 2, 3 and 4, age and gender remained independent predictors of OCM (all p0.04). Furthermore, at MVA of model 2, 3 and 4 CCI (HR 1.3), ASA (HR 1.09) and ECOG (HR 1.9) reached the independent predictor status (all p<0.001). The accuracy of Model 1, 2, 3 and 4 were 74.5 vs 77.6 vs 76.3 vs 76.3. After decision curve analyses, there was no superior net-benefit of one model relative to the others. CONCLUSIONS: We provided evidence that the difference in accuracy between the CCI, ASA and ECOG is clinically negligible. Interestingly, the increase in accuracy relative to the basic model of all three index is limited and there is no superior net-benefit of any of the examined indeces relative to the basic model. These findings suggest that there is an impending need of a disease-specific index to predict OCM in RCC patients submitted to surgery. At the moment, clinicians may use any of these indeces for RCC patients counselling to predict postoperative mortality after surgery.

PD59-08 PROPOSAL AND VALIDATION OF A DYNAMIC CRITERION FOR PATIENT INCLUSION IN KIDNEY CANCER ACTIVE SURVEILLANCE PROTOCOLS

INTRODUCTION AND OBJECTIVES: Renal mass biopsy (RMB) can be employed as an adjunct to the decision-making process for patients with small renal masses. It is hypothesized that the pathological diagnosis provided by RMB purports a QOL advantage by alleviating cancer-related uncertainty and anxiety. This study evaluates the influence of RMB on QOL in a large prospective registry of patients with SRM. METHODS: The DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry is a multi-institutional study that prospectively follows patients with SRM who elect primary intervention (PI) or active surveillance (AS). Patients complete SF12 QOL questionnaire at enrollment, 6 and 12 months, and subsequently on an annual basis. SF12 scores, MCS (Mental Component Summary) and PCS (Physical Component Summary) were compared between patients who had RMB versus those who did not in the PI, AS, and crossover groups separately using ANOVA and linear regression mixed modeling. RESULTS: 619 patients were identified in the DISSRM Registry, of whom 320 were in the AS arm and 299 in the PI arm. 84 patients (13.6%) underwent biopsy, 34 (40.6%) in the PI group, 35 (41.6%) in the AS group, and 15 (17.8%) in the AS group who crossed over. Median age, ECOG performance status and Charlson comorbidity Index (CCI) were similar regardless of biopsy status among the AS and PI groups. In PI patients, there were no significant differences between SF12, MCS or PCS (p>0.092) or changes in SF12, MCS, or PCS (p>0.162) in patients who underwent biopsy and those who did not across all time points up to 84 months. In the AS patients who did not crossover, no differences in SF12, MCS and PCS were seen between patients who had biopsy and those who did not (p>0.0564). PCS declined over time in patients who stayed on AS without biopsy (p<0.001), but all other measures were unchanged over time (p>0.7291). In the crossover group, SF12, MCS, and PCS were lower at 24 and 48 months in patients who had not undergone biopsy (p1⁄40.002). These patients were older (72.5 vs 67.2, p1⁄40.003), had higher CCI (p1⁄40.004), and lower ECOG performance status (p1⁄40.045). There were no changes to SF12, MCS, or PCS scores in crossover patients regardless of biopsy status over time (p>0.1513). CONCLUSIONS: AS and PI patients who underwent RMB during follow-up in DISSRM did not have significant changes in quality of life scores over time, nor did they have worse scores than their counterparts who did not undergo biopsy. A pathological diagnosis through RMB did not appear to have a beneficial or detrimental effect on QOL while on AS.

MP67-17 IS A PREOPERATIVE LOW EJECTION FRACTION A RISK FACTOR FOR COMPLICATIONS AND IMPAIRED SURVIVAL IN RENAL CANCER PATIENTS WHO UNDERGO SURGERY? RESULTS FROM A PROPENSITY-SCORE MATCHING WITH NON CARDIOPATHIC COUNTERPARTS

INTRODUCTION AND OBJECTIVES: Little is known about the impact of reduced left ventricular ejection fraction (rLVEF) on outcomes of patients undergoing surgery for renal cell carcinoma (RCC). The aim of our study was to compare complication rate, perioperative mortality, other-cause mortality (OCM) and overall mortality (OM) between cardiopathic patients (rLVEF) and matched controls. METHODS: Between 1990 and 2016, 2,974 consecutive patients treated with surgery for RCC were collected into an institutional database. When LVEF was <50% at preoperative transthoracic cardiac ultrasound, patients were classified as rLVEF, according to European Society of Cardiology Guidelines. Propensity-score matching was performed between patients with rLVEF and controls without rLVEF with a 1-to-4 ratio, after adjusting for age, body mass index, comorbidities (diabetes, hypertension and Charlson Comorbidity Index) and tumour characteristics (TNM classification). RESULTS: After matching 1:4, 175 patients (35 rLVEF vs. 140 controls) were included in the analyses. In the matched cohort, no differences were recorded in terms of baseline clinical features and tumor characteristics. Low grade complications (Clavien-Dindo I-II) were reported in 20% of controls vs. 41% of rLVEF patients (p<0.01). High grade complications (Clavien-Dindo III-IV) were reported in 4% vs. 2.5% (p1⁄40.6) in the control vs. rLVEF groups, respectively. Thirty-day and 90day mortality rates were 1.3% and 1.4% in the control group vs. 0% and 0% in rLVEF counterparts (all p1⁄40.9). At 1, 5 and 10 years after surgery, OCM resulted 3.2%, 12.5% and 26% vs. 0%, 17.8% and 38.3% in controls vs. rLVEF (p1⁄40.2). Correspondingly, at 1, 5 and 10 years after surgery, OM resulted 4.9%, 22.8% and 40.4% vs. 3.3%, 34.2% and 76.7% in controls vs. rLVEF (p1⁄40.6). CONCLUSIONS: After matching, patients with rLVEF experienced more frequently minor complications (Clavien-Dindo I-II) relative to controls. However, no differences in terms of high grade complications (Clavien-Dindo III-IV) and perioperative mortality were observed after surgery when patients with preoperative rLVEF were compared to equivalent non cardiopathic counterparts. When long-term survival outcomes were taken into consideration, no difference was recorded according to cardiopathic status.

MP55-12 LONG-TERM ASSESSMENT OF MORTALITY PATTERNS AFTER SURGICAL TREATMENT FOR NON-METASTATIC KIDNEY CANCER: A COMPETING RISK ANALYSIS

INTRODUCTION AND OBJECTIVES: Accurate estimation of long-term risk of cancer-specific [CSM] and other-cause mortality [OCM] is of utmost importance for clinical management of patients diagnosed with kidney cancer. The aim of the study is to assess longterm mortality rates of a contemporary cohort of patients surgically treated for non-metastatic kidney cancer. METHODS: 1,704 patients with non-metastatic kidney cancer treated with either radical or partial nephrectomy between 1987 and 2015 in a prospectively collected institutional database were assessed. Outcomes of the study were the 10-year rates of CSM and OCM. A multivariable competing risk regression model was fitted to predict CSM and OCM. Covariates consisted of age, gender, Charlson comorbidity index [CCI], pre-operative estimated glomerular filtration rate, haemoglobin and platelets, clinical tumour size, clinical tumour [cT] and nodal stage [cN], presence of local symptoms at diagnosis and year of surgery. Smoothed Poisson’s incidence plots were used to estimate 10-year CSM and OCM rates in the overall population as well as in 4 sub-cohorts defined as: A.age 1⁄460 and stage T1; B.age >60 and stage T1; C.age 1⁄460 and stage >T1; D.age >60 with stage >T1. RESULTS: At a median follow-up of 72 months, 10-year rates of CSM and OCM were 11 and 14%, respectively. At competing risk regression analysis, age, platelets, cT and cN resulted associated with higher risk of CSM (all p<0.05). Conversely, female gender and year of diagnosis were associated with lower risk of CSM (all p<0.05). Moreover, age, CCI and tumour size resulted associated with higher risk of OCM (all p<0.05). Conversely, female gender and year of diagnosis were associated with lower risk of OCM (all p<0.05). After stratification according to age and cT (Figure 1), the 10-year CSM and OCM rates resulted 3.4 and 5% in group A; 8 and 24% in group B; 22 and 7.7% in group C and 31 and 24% in group D, respectively. CONCLUSIONS: The relative impact on CSM and OCM in patients treated with surgery for kidney cancer is extremely heterogeneous according to host and cancer characteristics. The 10-years rates of CSM and OCM resulted 3.4 and 5% in younger patients with cT1 and 31 and 24% in older patients with cT2 or higher stage. These figures can aid clinical decision making providing a precise long-term mortality risk estimation. Source of Funding: none

MP59-05 CRITICAL ANALYSIS AND ASSESSMENT OF CLINICAL UTILITY OF NEPHROMETRY SCORES FOR THE PREDICTION OF COMPLICATIONS AFTER NEPHRON SPARING SURGERY

Brian Chun*, Deepansh Dalela, Mouafak Tourojman, Detroit, MI; Ronney Abaza, Dublin, OH; Rajesh Ahlewat, Gurgaon, India; James Adshead, Stevenage, United Kingdom; Benjamin Challacombe, Prokar Dasgupta, London, United Kingdom; Daniel Moon, Melbourne, Australia; Giacomo Novara, Padua, Italy; Francesco Porpiglia, Orbassano, Italy; Mahendra Bhandari, Detroit, MI; Alexander Mottrie, Aalst, Belgium; Craig Rogers, Detroit, MI

The Association of Uromodulin Genotype with Renal Cancer Aggressiveness

The aim of the study was to investigate the association of the uromodulin (UMOD) genotype with patient health status and with renal cell carcinoma (RCC) aggressiveness. The UMOD genotype at the top single nucleotide variant rs4293393 was determined in a cohort of 211 patients diagnosed with a renal mass and treated with surgery. Clinical data were prospectively collected. Due to the higher frequency of allele T relative to the lower frequency of allele C, recessive homozygous (CC), and heterozygous (TC) patients were grouped together and compared with homozygous (TT) patients. Mann-Whitney and chi-square tests were used to compare clinical characteristics after stratification for the UMOD genotype. UMOD genotype frequencies resulted TT and TC-CC in 67% (n=141) and 33% (n=70) of the population, respectively. The rate of cM1 RCC at clinical staging was higher in patients with genotype TT relative to patients with genotype TC-CC (18% vs 1%, p=0.001). Similarly, the rate of pT3-pT4 (41% vs 25%, p=0.047) and lymphovascular invasion (29% vs 13%, p=0.02) RCC at final pathology were higher in patients with genotype TT relative to patients with genotype TC-CC. PATIENT SUMMARY: In patients diagnosed with renal cell carcinoma and treated with surgery, uromodulin homozygous genotype is associated with more aggressive renal cell carcinoma clinical and pathological characteristics.