Fabio Muttin

When to perform preoperative chest computed tomography for renal cancer staging

To provide objective criteria for preoperative staging chest computed tomography (CT) in patients diagnosed with renal cell carcinoma (RCC) because, in the absence of established indications, the decision for preoperative chest CT remains subjective.

Pathological High-risk Renal Cell Carcinoma: Trends in Clinical Characteristics Over 25 Years

Background/Aim: The incidence of renal cell carcinoma (RCC) has been increasing mainly due to the increase in the incidental detection of small renal masses. The aim of this study was to verify whether the trend towards early diagnosis changed the clinical characteristics of pathologically-defined high-risk RCC patients over the last decades. Patients and Methods: A total of 741 patients with pathologically-confirmed high-risk RCC (pT1-4, and/or pN1 and/or Fuhrman grade 3-4 and/or all M1 patients) treated with radical (RN) or partial nephrectomy (PN) at a single tertiary referral center between 1987 and 2011 were included in the study. The temporal trends of pre-operative clinical and tumor characteristics were assessed relying on the lowess smoother weighted function with corresponding 95% confidence interval. Estimated annual percentage changes (EAPC) were evaluated using a log linear regression model. Results: The median age of patients increased from 57.5 to 67.3 years between 1987 and 2011 (EAPC 4.9%, p=0.002). Body mass index and gender rates remained stable during the study period. A constant trend towards patients with one or more comorbidity was observed. Moreover, the proportion of asymptomatic patients at diagnosis and of clinical T1 increased by 41.1 and 19.8%, respectively (all p≤0.007). The clinical tumor size dropped from 8.4 to 6.2 cm (EAPC -1.2%, p=0.001). This trend was accompanied by a clinically-relevant increase by 15.3% in the rate of patients without clinical metastases (p=0.07). Conversely, the rate of clinical lymphadenopathies remained stable over time. Finally, the rate of PNs performed increased by 23.3% (p<0.001). Conclusion: Over the years, pathologically-confirmed high-risk RCC patients are older, mostly asymptomatic, with smaller cancers, with a higher rate of tumors localized to the kidney and with a decreased rate of metastatic disease at diagnosis. These trends can explain the increasing number of PNs performed despite the presence of a high-risk cancer profile.

The Learning Curve for Robot-assisted Partial Nephrectomy: Impact of Surgical Experience on Perioperative Outcomes

Robot-assisted partial nephrectomy (RAPN) outcomes might be importantly affected by increasing surgical experience (EXP). The aim of the study is to investigate the effect of EXP on warm ischemia time (WIT), presence of at least one Clavien-Dindo ≥2 postoperative complication (CD ≥ 2), and positive surgical margins (PSMs) to define the learning curve for RAPN. We evaluated 457 consecutive patients diagnosed with a cT1-T2 renal mass were evaluated. EXP was defined as the total number of RAPNs performed by each surgeon before each patients operation. Median WIT was 14min and the rate of CD ≥ 2 and PSMs was 15% and 4%, respectively. At multivariable regression analyses adjusted for case mix, EXP resulted associated with shorter WIT (p<0.0001) and higher probability of CD ≥ 2-free postoperative course (p=0.001), but not with PSMs (p=0.7). The relationship between EXP and WIT emerged as nonlinear, with a steep slope reduction within the first 100 cases and a plateau observed after 150 cases. Conversely, the relationship between EXP and CD ≥ 2-free course resulted linear, without reaching a plateau, even after 300 cases. Patient summary: Perioperative outcomes after robot-assisted partial nephrectomy (RAPN) are importantly and individually affected by surgeons experience. After 150 RAPNs, no further improvement is observed with respect to ischemia time, but the learning curve appears endless with respect to complications.

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.

MP49-08 ON-CLAMP VERSUS OFF-CLAMP PARTIAL NEPHECTOMY: PROPENSITY SCORE MATCHED COMPARISON OF LONG TERM FUNCTIONAL OUTCOMES

clarify the effects of PN on the progression of HT, and investigate its risk factors in a larger cohort of patients with renal tumors. METHODS: Two hundred and ninety-five patients with renal tumors who underwent PN (N 1⁄4 188) or radical nephrectomy (RN) (N 1⁄4 107) between January 2012 and March 2016, and agreed to participate in this study, were enrolled. PN was carried out without vascular clamping in all but five patients (3%). We asked the participants to measure their home blood pressure (BP) in the morning and at bedtime for seven days, and to report these measurements and any use of antihypertensive medications at the time of the follow-up survey. Preand postoperative BP was calculated as the mean of the morning and bedtime BP measured on the day before the surgery, and the mean of all home BP measurements taken for postoperative seven days, respectively. The endpoint of this study was nephrectomy-related HT (NR-HT), defined as postoperative BP 140/90 mmHg with an increase of 20 mmHg from preoperative BP. RESULTS: In the PN and RN patients, the median age was 58 years and 62 years (p 1⁄4 0.042), and tumor size was 2.5 cm and 5.0 cm (p < 0.001), respectively. Before the surgery, 72 (38%) of the PN patients and 42 (39%) of the RN patients were taking antihypertensive medications (p 1⁄4 0.872). The median interval between the surgery and the follow-up survey was seven months. In the PN patients, mean preand postoperative BP was 125/74 mmHg and 129/79 mmHg, respectively, showing both systolic (p < 0.001) and diastolic BP (p < 0.001) increased significantly after the surgery. In the RN patients, there were no significant changes in BP after the surgery. Twenty (11%) of the PN patients and three (3%) of the RN patients developed NR-HT (p 1⁄4 0.009). Antihypertensive medications were added postoperatively in 23 (12%) of the PN patients and six (6%) of the RN patients (p 1⁄4 0.056). Multivariate analysis in the PN patients identified acute kidney injury (odds ratio (OR) 3.30, p 1⁄4 0.034) and higher postoperative peak serum C-reactive protein level (OR 3.01, p 1⁄4 0.026) as independent risk factors for NR-HT. CONCLUSIONS: Postoperative HT was more common in PN patients than in RN patients. Renal parenchymal damage during PN may contribute to the progression of HT.

MP55-14 THE ABILITY OF THREE COMORBITY INDECES TO PREDICT POSTOSPERATIVE MORTALITY IN RENAL CELL CARCINOMA PATIENTS: THE IMPENDING NEED OF A NEW DISEASE-SPECIFIC INDEX

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.

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.