1993PROGNOSTIC ROLE OF MICROVASCULAR INVASION IN CLEARCELL RENAL CELL CARCINOMA: RESULTS OF THESATURN PROJECT

G. Novara*, Padua, Italy; A. Antonelli, Brescia, Italy; R. Bertini, Milan,Italy; G. Carmignani, Genova, Italy; S. Cosciani Cunico, Brescia,Italy; O. De Cobelli, Milan, Italy; A. Lapini, Florence, Italy; N. Longo,Naples, Italy; A. Minervini, Florence, Italy; F. Montorsi, Milan, Italy; S.Serni, Florence, Italy; A. Simonato, Genova, Italy; S. Siracusano,Trieste, Italy; A Volpe, Novara, Italy; F. Zattoni, V. Ficarra, Padua,Italy

INTRODUCTION AND OBJECTIVES: To evaluate the prog-nostic role of microvascular invasion in a large multi-institutional seriesof patients undergoing radical or partial nephrectomy for clear cell renalcell carcinoma (RCC).

METHODS: We collected retrospectively the data of 2083 pa-tients who were surgically treated for clear cell RCC in 16 academiccenters involved in the Surveillance And Treatment Update RenalNeoplasms (SATURN) project. Pathological slide review was not per-formed in these cases.

RESULTS: Microvascular invasion was present in 283 (14%)patients. Patients with microvascular invasion showed several unfavor-able clinical and pathologic characteristics, including symptoms atpresentation, higher nuclear grade, higher pathological tumor size,higher pathological T stage, higher prevalence of lymph node anddistant metastases (all p values �0.001).

At a median follow-up of 42 months (IQR 24–80), 393 patients(19%) had developed disease recurrence and 303 (15%) were dead ofRCC. Five and 10-year cancer-specific survival (CSS) estimates were88.7% (standard error [SE] 0.8%) and 82.3% (SE1.3%) in those pa-tients without microvascular invasion, respectively, compared with47.2% (SE 3.8%) and 36.2% (SE 4.7.4%), respectively, in patients withmicrovascular invasion (log rank p value �0.0001).

In univariable analysis, presence of microvascular invasion wassignificantly associated with CSS (H.R: 5.3; p�0.001). On multivariableCox regression analyses that adjusted for the effect of for age, gender,symptoms, type of surgery, histological subtype, TNM stage, andFuhrman grade, presence of microvascular invasion was an indepen-dent predictor of CSS (H.R. 1.4; p�0.027).

CONCLUSIONS: Microvascular invasion was an independentpredictor of CSS in patients with clear cell RCC, once adjusted for theeffect of all the major clinical and pathological variables.

Source of Funding: None

1994EXTERNAL VALIDATION OF THE PREOPERATIVEKARAKIEWICZ NOMOGRAM IN A MULTI CENTER SERIE OFPATIENTS WITH RENAL CELL CARCINOMA TREATED WITHRADICAL OR PARTIAL NEPHRECTOMY

P. Gontero*, Torino, Italy; G. Martorana, R. Schiavina, Bologna, Italy;A. Antonelli, C. Simeone, S. Cosciani Cunico, Brescia, Italy; A.Minervini, L. Masieri, Florence, Italy; A. Simonato, Genova, Italy; N.Longo, C. Imbimbo, Naples, Italy; F. Montorsi, Milan, Italy; G.Novara, Padua, Italy; A. Volpe, Novara, Italy; S. Siracusano, Trieste,Italy; R. Bertini, Milan, Italy; G. Carmignani, Genova, Italy; G. Morgia,Catania, Italy; V. Mirone, Naples, Italy; V. Ficarra, Padua, Italy

INTRODUCTION AND OBJECTIVES: To validate the Karakie-wicz nomogram using preoperative variables to predict cancer-specificsurvival of patients undergoing radical or partial nephrectomy for RCC.

METHODS: We collected retrospectively the data of 3364 pa-tients surgically treated for RCC in 16 academic centers involved in theSurveillance And Treatment Update Renal Neoplasms (SATURN) proj-ect. Univariable and multivariable Cox regression models addressedcancer-specific mortality. Concordance index was used to evaluate theprognostic accuracy of the nomogram 12, 24, 60, and 120 months aftersurgery.

RESULTS: All the variable included in the nomograms (age,gender, mode of presentation, clinical tumor size, clinical T stage,presence of metastasis) were independent predictor of CSS in multi-variable analysis (all p values �0.02). The prognostic accuracy of thenomogram was 87.8% (IC95% 84.4–91.4) at 12-mo; 87% (IC95%84.4–89.5) at 24-mo; 84% (IC95% 82.3–87.1) at 60-mo; and 85.9%(IC95% 83.2-88.6) at 120-mo from surgery. Calibrations curve showedthat the nomogram tended to significantly overestimate the rates offreedom from cancer-specific mortality a 60 and 120-mo, whereas thedifferences between estimates and observed rates at 12- and 24-mowere limited.

CONCLUSIONS: Karakiewicz nomograms has a high prognos-tic accuracy both in short and long term evaluation of cancer-relatedoutcome of patients with RCC. However, according to our series, thenomograms tend to underestimate the risk of cancer-specific deathsboth 60 and 120-mo after surgery.

Source of Funding: None

1995PREDICTIVE FACTORS FOR LATE RECURRENCE OF RENALCELL CARCINOMA

Yong Hyun Park*, Young Ju Lee, In-sung Kim, Ja Hyeon Ku, CheolKwak, Hyeon Hoe Kim, Seoul, Korea, Republic of

INTRODUCTION AND OBJECTIVES: We aimed to evaluatethe clinical and pathologic features and predictive factors for laterecurrence of RCC.

METHODS: A total of 747 patients who had undergone curativesurgery for RCC with follow up duration over 5 years or recurrencewithin 5 years were included in this study. Based on the recurrenceduration, the patients were stratified into 4 groups; group 1 (no recur-rence more than 5 years after surgery, n�425), group 2 (synchronousmetastasis, n�138), group 3 (recurrence within 5 years, n�143), andgroup 4 (recurrence after 5 years, n�41). Multivariate analysis withmultiple logistic regression analysis and Cox proportional hazardsregression model was used to identify the pathologic and clinicalfactors affecting the late recurrence more than 5 years after surgeryand its clinical outcome.

RESULTS: The subgroups based on the recurrence durationwere significantly different with respect to clinicopathologic parametersincluding age at initial diagnosis, preoperative hemoglobin, platelet,hs-CRP levels, pT stage, and nuclear grade. In multiple logistic regres-sion analysis, age at diagnosis (OR 1.085, 95% CI 1.012–1.163,p�0.022), and preoperative hs-CRP level (OR 6.211, 95% CI 1.590–24.270, p�0.009) were independent prognostic factors for late recur-rence more than 5 years after surgery. In group 2, 3, and 4, 5-yearcancer-specific survival after recurrence were 27.0%, 41.1%, 73.7%,respectively (p�0.001). Multivariate analysis by Cox proportional haz-ard model indicated that late recurrence (HR 0.487, 95% CI 0.274–0.864, p�0.014), as well as age at diagnosis, initial presenting symp-tom, pT stage, histologic subtype, sarcomatoid differentiation, andlymphovascular invasion, were independent predicting factors for can-cer-related death.

CONCLUSIONS: Late recurrence of RCC is not a rare event,and age and serum hs-CRP at initial diagnosis may be independentpredicting factors for late recurrence of RCC.

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Source of Funding: None

1996AGE AND GENDER PREDICTS RISK OF NON-LOCALIZEDDISEASE IN SMALL RENAL TUMORS <3CM IN SIZE IN THEUNITED STATES FROM 1988–2007

Max Kates*, Ruslan Korets, Neda Sadeghi, New York, NY; PhillipPierorazio, Baltimore, MD; James McKiernan, New York, NY

INTRODUCTION AND OBJECTIVES: It is thought that patientswith small renal masses (SRMs) have a negligible risk of metastases.However, recent publications have shown there to be a significantburden of metastatic RCC (mRCC) even in masses �3cm. The aim ofthis study was to assess the prevalence and characteristics of mRCCin the US population with SRMs to help identify patients at risk fornon-localized disease.

METHODS: Using the Surveillance, Epidemiology, and EndResults (SEER) registry we identified 14,962 patients diagnosed be-tween 1988-2007 with renal cell carcinoma (RCC) �3cm in size.Patients were separated by stage into metastatic, locally advanced,and localized disease. Differences in baseline characteristics amongstpatients in these 3 groups were assessed. After controlling for age, sex,grade, tumor size, and year of surgery, a logistic regression analysiswas performed to determine likelihood of having non-localized disease.

RESULTS: In the SEER cohort, 13,574 (90.7%) patients withRCC �3cm were diagnosed with localized disease, 938 (6.3%) patientshad invasion beyond the kidney into regional lymph nodes or nearbyorgans, and 450 (3.0%) patients had distant metastasis. Patients withmetastasis were older (65.9 years) compared to those with localizeddisease (59.5 years) (p�.001). The rate of metastatic disease was higherin patients with tumors 2.5–3.0cm (4.3%) compared with tumors �2.5cm(2.4%). Independent preoperative predictors of having more aggressivedisease at diagnosis (locally advanced/metastatic) included older age,particularly age �70 (OR: 2.46; 95% CI: 2.06–2.92), male sex(OR: 1.50;95% CI: 1.33–1.70), and tumor size �2.5 (OR: 1.41; 95% CI: 1.25–1.58).

CONCLUSIONS: A small subset (3%) of patients in the US withRCC �3cm have distant metastasis. Older patients, men, and thosewith tumors 2.5-3cm are more likely to present with regionally ad-vanced and metastatic disease despite having a mass �3cm. As theincidence of SRMs is increasing and active surveillance protocols are

becoming more commonplace, clinician’s should be aware of charac-teristics associated with advanced disease.

Source of Funding: The Doris Duke Charitable Foundation

1997NATURAL HISTORY OF PATIENTS WITH DISEASERECURRENCE AFTER NEPHRECTOMY FOR LOCALIZED RENALCELL CARCINOMA

Ari Adamy*, Shahrokh F. Shariat, Kian Tai Chong, Grace Russo,James Costaras, Melanie Bernstein, Paul Russo, New York, NY

INTRODUCTION AND OBJECTIVES: We investigated the natu-ral history of patients who experienced disease recurrence in a large singlecenter series of patients treated with nephrectomy for a clinically localizedRCC.

METHODS: We identified 2,368 patients with unilateral, clinicallylocalized RCC treated with either partial or radical nephrectomy betweenJanuary 1989 and October 2008. Overall, 256 patients who experienceddisease recurrence were included in the analysis. The previously pub-lished MSKCC prognostic scoring system was used to categorize patientsat the time of recurrence. Univariate and multivariable Cox regressionmodels were used to evaluate predictors of cancer-specific survival. Thepredictors included in the model were those present at the time of ne-phrectomy and those at the time of disease recurrence.

RESULTS: The median time from nephrectomy to disease recur-rence was 19.5 months. Overall, 146 patients died from RCC and 6patients died from other causes. The median follow-up from time ofdisease recurrence for those patients alive at the last follow-up was 28months. The 2- and 5-year survival probabilities from time of diseaserecurrence for the entire cohort were 64% (95% CI 58% – 70%) and 36%(29% – 43%). On univariate analyses, T4 stage at nephrectomy (HR 3.63;95%CI 1.78–7.40; p�0.001), presence of symptoms at recurrence (HR2.23; 95% CI 1.56–3.17; p�0.001), lack of metastasectomy (HR 2.02;95%CI 1.39–2.94; p�0.001), intermediate (HR 2.98; 95%CI 1.86 – 4.78;p�0.001) and poor risk score (HR 18.1; 95%CI 9.25 – 35.3; p�0.001),and shorter time from nephrectomy to recurrence (HR 0.99; 95%CI 0.98 –0.99; p�0.001) were significantly associated with worse cancer-specificsurvival. Age, gender, tumor size, T2 and T3 stage, N stage, and tumorhistology were not associated with cancer-specific survival. On multivari-able analysis, T4 stage (HR 4.03; 95%CI 1.49 – 10.8; p�0.006), presenceof symptoms at recurrence (HR 2.55; 95%CI 1.66 – 3.91; p�0.001), lackof metastasectomy (HR 1.77; 95%CI 1.14 – 2.77; p�0.011) and interme-diate (HR 2.52; 95%CI 1.50 – 4.24; p�0.001) and poor risk (HR 13.4;95%CI 6.25 – 28.8; p�0.001) remained independent predictors of cancer-specific survival.

CONCLUSIONS: We confirmed that intermediate and poorMSKCC risk score and the absence of metastasectomy are independentlyassociated with a higher risk of cancer-specific death. In addition, patientsdiagnosed with recurrence due to symptoms related to metastatic diseasehave also worst outcomes. Factors related to the primary tumor were notassociated with survival after the development of metastatic disease.

Source of Funding: None

1998EARLY PRIMARY TUMOR RESPONSE IS AN INDEPENDENTPREDICTOR OF OVERALL SURVIVAL IN PATIENTS WITHMETASTATIC RCC UNDERGOING TREATMENT WITH SUNITINIB

E Jason Abel*, Madison, WI; Stephen H Culp, Nizar M. Tannir, SurenaF. Matin, Pheroze Tamboli, Christopher G. Wood, Houston, TX

INTRODUCTION AND OBJECTIVES: In metastatic renal cellcarcinoma (mRCC) patients treated with sunitinib and the primarytumor in situ, there is minimal predictive data available to help guideclinicians during treatment with targeted therapy. In prior studies, earlyprimary tumor response (PTR) was associated with improved overallPTR, but the effect on overall survival (OS) is unknown. The purpose ofour study was to evaluate whether early PTR was associated withimproved OS in mRCC patients undergoing treatment with sunitinib.

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