Search

617 Background: Anxiety and depression are psychosocial factors which have been demonstrated to have mixed interactions with mortality across various malignancies. While these variables have been associated with poor overall survival for patients with metastatic RCC, the influence on outcomes for localized RCC has been poorly studied. We evaluated the association of anxiety or depression with survival in patients with surgically treated localized clear cell RCC (ccRCC). Methods: We performed retrospective review of our institutional nephrectomy registry to identify 1,990 patients who underwent radical or partial nephrectomy for unilateral, sporadic, non-metastatic ccRCC between 1995- 2011. Baseline anxiety and depression were identified using ICD-9 codes. Associations of anxiety or depression with outcomes of interest were evaluated using Cox proportional hazards models. Two propensity score (PS) techniques were used: adjusting for PS quintile and re-weighting by stabilized inverse probability weights. Results: A total of 197 (10%) patients had diagnoses of anxiety or depression (57 had anxiety alone, 107 had depression alone, and 33 had both anxiety and depression). Median follow-up among survivors was 10.0 (IQR 7.3-13.6) years, during which time 864 died, including 363 from RCC. Patients with anxiety or depression were younger (mean age 59 vs 62 years, p < 0.001) and had more recent operations (75% vs 47% in 2005-2011, p < 0.001) compared to those with neither diagnosis. After PS adjustment, all clinical and pathologic features were well balanced between groups. After PS adjustment, there were no significant differences in time to local ipsilateral recurrence, distant metastases, and death from RCC between groups. We did note a trend to poorer overall survival in patients with anxiety or depression (HR 1.29, 95%CI = 0.98-1.69, p = 0.065). Conclusions: Our results suggest that neither anxiety nor depression is significantly associated with oncologic outcomes among patients with localized surgically treated ccRCC. The trend toward worse overall survival among patients with anxiety or depression warrants further investigation.

672 Background: The optimal sequence of cytoreductive nephrectomy (CN) and targeted therapy (TT) for patients with metastatic renal cell carcinoma (mRCC) remains to be established. Herein, we compared overall survival (OS) between patients with mRCC receiving initial CN with or without subsequent TT versus initial TT with or without subsequent CN. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed between 2006-2013 with RCC that was metastatic at diagnosis who received CN, TT, or both. Those with other prior cancer history were excluded. The cumulative incidence of receiving TT after CN and CN after TT were evaluated, with death prior to second treatment as a competing risk. To account for treatment selection bias, inverse probability of treatment weighting (IPTW) was performed based on the propensity to receive initial CN or TT. OS from diagnosis was compared using Cox regression. Sensitivity analyses were performed. Results: The cohort included 15,068 patients, of whom 6,731 underwent initial CN and 8,337 underwent initial TT. At 6 months from diagnosis, the probability of receiving TT after CN was 46.2%, with 13.6% of patients having died after initial CN prior to receiving TT. Meanwhile, the probability at 6 months of undergoing CN after initial TT was 4.4%, with 38.3% of this group having died prior to undergoing CN. In the IPTW analysis, baseline characteristics were balanced (standardized difference < 0.1). Initial CN was associated with improved OS compared to initial TT (median 16.5 vs 9.2 months; HR 0.62; 95%CI 0.61-0.64; p < 0.001). Findings were similar in all sensitivity analyses (propensity score matching and adjustment; regression adjustment; 6-month landmark analysis; clear cell mRCC subset; exclusion of patients who had metastasectomy). Conclusions: Although initial CN was associated improved OS versus initial TT in this national dataset, initial CN was associated with delays in, and even death prior to, receipt of TT. As such, while the survival data here support initial CN in appropriate surgical candidates, continued efforts to develop the optimal multimodal approach to these patients are warranted.

703 Background: Clinical and pathologic factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). We sought to determine if tissue biomarkers, along with our previously reported clinical metastases score, can be used to predict cancer specific survival (CSS) in patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients, 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2,12.8) and 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44; 95%CI 1.16-1.78; p < 0.001), high survivin (HR 1.35; 95%CI 1.08-1.68; p = 0.008), and the metastases score (HR 1.13 per one point; 95%CI 1.10-1.16; p < 0.001) were retained as independent predictors in the final multivariable model (c-index 0.69). Conclusions: We created a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy. External validation will be required prior to clinical use.

704 Background: While the probability of benign versus malignant histology based on renal tumor size has been described, this alone does not sufficiently inform decision-making in the modern era since indolent malignant tumors can be surveilled. Thus, we sought to characterize the probability of indolent versus aggressive histology based on radiographic tumor size. Methods: We evaluated patients who underwent radical or partial nephrectomy at Mayo Clinic for a pT1-2, pNx/0, M0 solid renal tumor between 1990-2010. Pathology was reviewed by one genitourinary pathologist. Benign tumors, low grade (1-2) clear cell and papillary renal cell carcinoma (RCC), and any chromophobe, clear cell papillary, mucinous tubular and spindle cell, SDH-B deficient, and tubulocystic RCC were considered indolent. All other histologies were considered aggressive, as were any malignancies with necrosis or sarcomatoid differentiation. Cancer-specific survival (CSS) was estimated using the Kaplan Meier method. Logistic regression models were used to estimate the probability of malignant and aggressive histology based on tumor size. Sex-stratified analyses were also performed. Results: Of the 2650 patients included, there were 1773 patients with indolent tumors (303 benign; 1470 malignant) and 877 with aggressive tumors. Ten-year CSS was 96% for indolent malignant tumors and 82% for aggressive tumors. The predicted probabilities of any malignant histology and aggressive malignant histology increased with tumor size (Table; 1-7cm point estimates shown). For example, a 3 cm tumor had an 87% probability of malignancy and a 27% probability of being aggressive. For any given tumor size, men had a greater probability of aggressive histology than women. Conclusions: We present tumor size-based estimates of the probability of aggressive histology for renal masses. This information should be useful for patient counseling and treatment decision-making. [Table: see text]

e13073 Background: We observed several patients with a personal history of both RCC and myeloid malignancy, and aimed to explore a possible association, especially given the similarity in their epigenetic landscape, with both being characterized by widespread aberrant hypermethylation (Hu C et al, CCR 2014; Jiang Y et al, Blood 2009). Methods: Mayo Clinic’s ‘Advanced Cohort Explorer’ database was used to identify patients with a history of both RCC and a myeloid malignancy - Acute Myelogenous Leukemia (AML), Myeloproliferative Neoplasms (MPN), Myelodysplastic syndromes (MDS) - and to determine the clinical characteristics. The incidence of MDS in patients ≥65 years with a history of RCC was compared to that in the general population ≥65 years (SEER- Medicare database) as well as the general patient population at Mayo Clinic, using one sample test of proportions. Results: A total of 59 patients were identified, with both biopsy proven RCC and a myeloid malignancy during their life time (12 AML, 9 MPN, 9 low risk MDS and 29 intermediate- high risk MDS). The cohort was characterized by marked male predominance (4.4: 1). Median age at RCC diagnosis was 64 years (range 37-87) and myeloid malignancy was 75 years (range 44-90). 46/59 patients had the RCC antecedent, 10/59 concurrent and 3/59 subsequent to the myeloid malignancy with a median time of myeloid malignancy diagnosis after RCC diagnosis of 7.7 years. For patients ≥65 years, the risk of developing MDS with a history of stage I/II RCC and nephrectomy was 5.26 times that of the general population based on the SEER-Medicare database (Cogle, Blood 2011)(395/100,000 vs 75/100,000; p value < 0.001), and 3.07 times that of the general population at Mayo Clinic (395/100,000 vs 128.4/100,000; p value < 0. 001). Conclusions: We observed an association between RCC and myeloid malignancies, particularly MDS; with a history of RCC conferring a substantially increased risk of developing MDS. We hypothesize that the perturbation of epigenetic landscape in the form of widespread hypermethylation may explain, in part, the association between the two malignancies; and aim to explore the potential aberrancy of epigenetic regulators in our patient cohort with a genomic, epigenomic and transcriptomic analysis.

312 Background: Radical cystectomy (RC) is a preferred option for high−grade non−muscle invasive bladder cancer (HG NMIBC), particularly after failure of intravesical therapy. However, clinicians may be reluctant to offer surgery to older patients with NMIBC given concerns regarding morbidity. We therefore sought to evaluate the association of age with use of RC and clinicopathologic outcomes after RC for HG NMIBC. Methods: The National Cancer Data Base was queried to identify patients diagnosed with HG NMIBC between 2004−2013. Patients were stratified according to age at diagnosis: 80 years. Multivariable logistic regression was performed to assess the associations of age group with utilization of RC and with pathologic upstaging (pT2−4 or pN+). Overall survival (OS) was evaluated using unadjusted and inverse propensity score weighted (IPTW) Kaplan−Meier methods and compared with the log-rank test. Results: RC was performed in 3,641 (5.7%) of 63,402 patients with HG NMIBC. Utilization of RC remained relatively constant over the study period (4.3%−6.8%; p=0.44). On multivariable analysis, increasing age was inversely associated with RC utilization, with the lowest utilization in those >80 (2.1% rate; OR 0.24; p 15 cases/year), academic centers, and for patients with cT1 disease. Among patients who underwent RC, pathologic upstaging was identified in 1,445 (43.6%), and no significant association was noted with age. NMIBC pathologic tumor stage was associated with improved OS compared to progression to pT2−4 or N+ disease at RC for all age groups: median OS improvement not reached in those under 60; 32 months in those 61−70; 55 months in those 71−80; and 34 months in those over 80 (all p

433 Background: Current guidelines suggest that percutaneous thermal ablation (PTA) can be utilized in those with significant comorbidity who are unable to tolerate surgery (radical or partial nephrectomy). However, the use of PTA in healthy patients, who are otherwise candidates for surgery, has been limited. Here, we reviewed our institutional experience in healthy patients electing to undergo PTA, specifically cryoablation. Methods: We identified patients ≤65 years undergoing percutaneous cryoablation for solitary, non-metastatic renal masses 60. Clincopathologic characteristics and recurrence patterns (local recurrence within the kidney versus metastatic disease) were evaluated. Results: Between March 2003 and December 2015, 705 patients underwent cryoablation, of whom 43 (6.1%) were deemed to be “healthy”. Median age of this cohort was 57 years (IQR 52−62), with pre-ablation eGFR of 75.6 (IQR 69.0-86.3). Seven patients (16.3%) had a prior partial nephrectomy, and 5 (11.6%) had a solitary kidney. The majority (40, 93.0%) of ablated masses were cT1a, with 3 (7.0%) being cT1b. Median tumor size was 2.0 cm. 27 masses (63.7%) were biopsy-proven renal cell carcinoma (RCC) and 6 (13.6%) were benign; histology was unknown in 10 (22.7%). Follow-up imaging was available for 37 patients. Median radiological follow-up was 22 months (IQR 9-42), during which time 2 patients developed metastatic disease and 1 developed local recurrence; all events were in patients with biopsy-proven RCC. No patients died from RCC during this time period. Conclusions: In this single institution cohort of “healthier” patients with cT1 solitary renal masses, cryoablation offered reasonable short term oncologic control. While longer follow-up data are needed to evaluate for durability, cryoablation in healthy patients, particularly those with challenging surgical anatomy, warrants further study.

308 Background: Receipt of pelvic radiotherapy (PRT) prior to radical cystectomy (RC) has unclear association on oncologic outcomes. Methods: The Mayo Clinic Cystectomy Registry was queried to review 2139 patients undergoing RC for M0 bladder cancer between 1990 and 2010. We then identified patients receiving PRT prior to RC, and matched these cases to non-radiated controls (~1:2) on the basis of age, sex, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Cancer-specific survival (CSS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Of 2139 patients undergoing RC, 104 (4.9%) had received PRT prior to surgery. These patients were matched to 191 non-radiated control patients (no PRT). Overall, patients were well-matched on disease and patient characteristics. Median follow-up was 9.6 years (IQR 6.0, 14.8). During this time, 108 patients experienced disease recurrence and 218 died, including 122 who died from bladder cancer. Five-year CSS among patients who did versus did not receive PRT was 55% versus 63% (p=0.10), while the 5-year PFS was 55% versus 61% (p=0.32). Furthermore, the pattern of disease recurrence (abdominal/visceral, urothelial, local/pelvic, thoracic, soft tissue/other) did not differ between the no PRT and PRT groups (all p>0.05). Conclusions: Receipt of PRT prior to RC is not associated with worse oncologic outcomes. While prior PRT may increase surgical complexity, CSS, PFS, and patterns of recurrence are similar to patients who have not received PRT.

456 Background: Renal medullary carcinoma (RMC) is a rare, aggressive malignancy for which relatively limited characterization exists to date. We evaluated clinicopathologic features, treatment patterns, and variables associated with outcomes for patients with RMC. Methods: We reviewed the National Cancer Database to identify patients diagnosed with RMC between 1998-2012. Overall survival (OS) was estimated using the Kaplan-Meier method. Clinicopathologic features associated with all-cause mortality (ACM) were assessed using Cox regression analysis. Results: We identified 153 patients with RMC, comprising approximately 0.04% of renal malignancies during this time period. Median age at diagnosis for RMC was 24 years (IQR 20, 31). The majority of RMC patients were black (135; 88%), male (108; 71%), and presented with unilateral, right-sided tumors (101; 66%). Notably, nearly half (72; 48.9%) presented with metastatic disease. A total of 92 (64.3%) patients underwent radical nephrectomy (RN), and 2 (1.3%) were treated with partial nephrectomy. Pathologic stage at nephrectomy was ≤pT2 in 30 patients (32.6%), pT3 in 43 (46.7%), pT4 in 7 (7.6%), and N+ in 50 (55.6%). Of the patients who underwent RN, 60 (65.2%) received multimodal therapy (MMT), including radiation (3; 3.3%), systemic therapy (49; 53.3%), and radiation + systemic therapy (8; 8.7%). Of the 59 patients who did not undergo surgical resection, the majority (46; 77.8%) presented with M1 disease. Median OS was 7.8 months for the entire RMC cohort, with 1- and 3-year OS of 34% and 11%, respectively. Notably, median OS for patients presenting with M1 and M0 disease was 5.2 months versus 11.2 months, respectively (p< 0.01). On multivariable analysis, treatment with RN (HR 0.40; p=0.003) or RN+MMT (HR 0.44; p

355 Background: While neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) improves survival compared to RC alone for urothelial carcinoma of the bladder (UCB), the bulk of this survival benefit has been attributed to patients who achieve ypT0 status at RC. The implications of having residual UCB (rUCB) at RC after NAC are less clear. As such, we evaluated whether the outcomes for patients with rUCB after NAC differ from stage-matched RC patients who did not receive NAC. Methods: Patients undergoing RC for UCB between 1981-2010 at Mayo Clinic were identified. All RC pathology was re-reviewed by a single genitourinary pathologist. Patients who received NAC were matched 1:2 to patients not exposed to NAC based on pT and pN-stage, margin status, and year of RC. Kaplan Meier and Cox regression analyses were used to evaluate the associations between NAC and cancer-specific (CSS) and overall survival (OS), stratified by presence of rUCB (i.e. (y)pT0N0 and non-(y)pT0N0). Results: We matched 111 patients who underwent NAC + RC to 222 RC-alone patients. Median age was 68 years (IQR 60,74); 59 (18%) were female. Median follow-up among survivors was 7.2 years (IQR 6,16). A total of 248 patients died; 148 died from UCB. In patients without rUCB at RC, there were no differences in 5-yr CSS (86% vs. 90%, p=0.85) or OS (82% vs. 84%, p=0.46) between patients who did and did not receive NAC. Moreover, on multivariable analysis, NAC exposure was not associated with CSS (HR=1.0; 95%CI 0.3-3.1; p=0.9) or OS (HR=0.9; 95%CI 0.4-1.9; p=0.8) in this subgroup. Among patients with rUCB, receipt of NAC was associated with significantly worse 5-yr CSS (32% vs. 56%, p

367 Background: While neoadjuvant chemotherapy (NAC) for muscle−invasive bladder cancer (MIBC) is recognized as the standard of care, the management of patients with locally advanced and/or nodal disease after NAC and radical cystectomy (RC) is not well defined. We sought to evaluate the association of adjuvant chemotherapy (AC) and overall survival (OS) among patients with adverse pathology after NAC and RC. Methods: The National Cancer Database was reviewed to identify patients with adverse pathology (pT3N0, pT4N0, or pTanyN1−3) at RC following NAC from 2006−2012. Patients were stratified by receipt of AC. Clinical and pathologic variables were abstracted. OS was the primary end−point and differences on the basis of AC were assessed by the Kaplan−Meier method and log−rank test. Multivariable Cox proportional hazards regression was used to assess the association of AC with OS controlling for age, sex, race, Charlson score, year of diagnosis, pathologic stage, and receipt of adjuvant radiotherapy. Results: Adverse pathology following NAC and RC was identified in 1,361 patients from 2006−2012, of whom 328 (24.1%) received AC. Staging was pT3N0 in 444 (32.6%), pT4N0 in 162 (11.9%), and pTanyN1−3 in 755 (55.5%). Median OS for the entire cohort was 22.9 months, which differed by pathologic stage: 34.6 months (pT3N0), 21.4 months (pT4N0), and 19.3 months (pTanyN1-3)(p < 0.01). No difference in OS was noted by receipt of AC in the overall cohort (median OS 24.6 months with AC vs 22.0 months without AC; p = 0.18), or when stratified by pathologic stage. On multivariable analysis, receipt of AC was not significantly associated with overall mortality (HR 0.86; 95%CI 0.74−1.01; p = 0.06) for all patients. When stratified by stage, AC was associated with a significantly decreased risk of mortality among patients with pT4N0 disease (HR 0.56; 95%CI 0.33−0.97; p = 0.04), but not pT3N0 or pTanyN1−3 (p > 0.05). Conclusions: Patients with adverse pathology at RC after NAC have a median OS of approximately 2 years. AC was not associated with improved survival, except in the subgroup with pT4N0 disease. Clinical trials with newer systemic therapies are warranted for patients in this setting.

364 Background: Venous thromboembolism (VTE) has been reported to occur in 2-5% of patients undergoing radical cystectomy (RC). While VTE is an important cause of perioperative morbidity, the association of these events with long-term cancer prognosis has not been established. Herein, we evaluated the association of perioperative VTE with patients’ risk of subsequent disease recurrence and mortality. Methods: We reviewed 2889 patients undergoing RC between 1980−2009 at the Mayo Clinic to identify patients diagnosed with a VTE within 90 days of RC. These cases were then matched in a 1:2 fashion to control patients undergoing RC who did not develop VTE. Matching was performed on the basis of age, BMI, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) were estimated utilizing the Kaplan-Meier method and compared with the log-rank test. Results: A total of 132 patients with a VTE within 90 days of RC were identified, accounting for 4.6% of all patients analyzed. These cases were matched to 257 controls per criteria noted above, and were overall well-matched. Of the 389 patients in this study, median follow-up after RC was 9.2 years, during which time 152 (39%) patients experienced recurrence and 306 (78%) died, including 157 (40%) who died of bladder cancer. We found no significant difference in 5-year RFS (59% versus 61%; p = 0.75); CSS (57% versus 64%; p = 0.13); or OS (45% versus 50%; p = 0.15) between patients with versus without perioperative VTE, respectively. Conclusions: We found that VTE within 90 days of RC did not significantly impact long-term cancer outcomes. While these events represent an important cause of perioperative morbidity, no interaction with oncologic control was noted, and patients may be counseled accordingly.

255 Background: The purpose of this study was to identify site-specific recurrence patterns for patients (pts) with biochemical recurrence (BCR) after prostatectomy (RP) using C-11 Choline PET/CT (C11Ch) and 3T pelvic MRI with endorectal coil (pMRI). Methods: Between 2008 and 2006, 2,466 men underwent C11Ch and pMRI for BCR after RP. From this cohort, we identified 261 pts who received no adjuvant or salvage therapy (androgen deprivation or radiation). Suspected radiographic relapse was confirmed by biopsy (46%) or progression/response to treatment in concordance with subsequent rise/decline in PSA (54%). Results: Of the 261 men evaluated, 202 (75%) had positive pMRI, C11Ch or both. Seventy nine (39%), 105 (52%) and 18 (9%) pts had high, intermediate, and low risk CaP, respectively at RP. Median PSA at the time of positive scan was 2.3 ng/mL, with a median time from BCR to radiographic disease identification of 15 months. Of these 202 men, 67 (33%) harbored prostate fossa recurrence only, 44 (22%) had a combination of local and metastatic disease and 91 (45%) had metastatic disease without local recurrence. Forty (20%) pts had pelvic nodal recurrence only and 18 (9%) had perirectal nodal involvement. Median PSA for pts with local only recurrence, distant metastases only, and local + distant disease was 2.3, 2.7 and 2.2 ng/mL, respectively, with a median interval from BCR to positive scan of 16.7, 7.9 and 11 months. Imaging revealed that 33% to 66% of our cohort would have all sites of disease treated by salvage RT depending on the extent of the treatment field Conclusions: C11Ch and pMRI were used to identify recurrence patterns in pts with BCR after RP only. At median PSA of 2.3 ng/ml, our study demonstrates a low rate of local-only recurrence, higher than anticipated frequency of metastatic recurrence with peak frequency within the pelvic lymph nodes, and substantial perirectal recurrences. Despite the high rates of distant recurrences, 2/3 of our cohort had their disease limited to the pelvis and could be potential candidates for local therapies, including salvage radiation.

513 Background: Chromophobe renal cell carcinoma (chRCC) is the third most common histologic subtype of kidney cancer. While most of these tumors have an indolent behavior, 7% of patients with chRCC develop metastases, with no currently available standard of care. The Cancer Genome Atlas characterized chRCC, highlighting pathognomonic single copy chromosomal losses of 1, 2, 6, 10, 13 and 17, as well as a minimal mutation burden distinguishing it from all other cancer types. However, only 15% of the analyzed patients had advanced disease. We analyzed metastatic chRCC to further characterize these tumors and elucidate mechanisms leading to aggressive disease using a variety of next generation and whole genome sequencing. Methods: Our cohort of metastatic chRCC consisted of 40 patients with available clinical and pathologic data. Whole genome sequencing (WGS) was performed on 6 patients (4 primary tumors and 2 metastases), 42 additional samples from 33 patients were analyzed using targeted next-generation sequencing (MSK-IMPACT). Notably, we were able to collect and analyze matched primary and metastatic tumors from 7 patients. As control cohort 27 non-metastatic chRCC tumors were sequenced with MSK-IMPACT. Copy number patterns were computed with OncoSNP seq and FACETS. Results: The most commonly mutated genes in the aggressive chRCC tumors were TP53 and PTEN (WGS: TP53 67 %, PTEN 33%; MSK-IMPACT: TP53 61%, PTEN 27%). No other genes were mutated frequently. Primary tumor samples of chRCC did show the typical pattern of chromosomal losses in 1, 2, 6, 10, 13 and 17. Interestingly, these canonical losses could not be detected in the metastases even when accounting for tumor purity. Conclusions: TP53 and PTEN mutations are highly enriched in both primary and metastatic tumors of aggressive chRCC compared to the non-aggressive tumors and likely play a critical role in disease progression. More intriguingly, the observation of differential copy numbers in matched primary and metastatic tumors suggest whole genome or whole chromosome events in these samples. We are currently employing different bioinformatic and cytogenetic platforms to validate our novel hypothesis of chromosomal events as driver for metastatic development in chRCC.

389 Background: Venous thromboembolism (VTE) has been reported in approximately 5-7% of patients undergoing radical cystectomy (RC). While extended-duration pharmacologic prophylaxis (EDPP) has been investigated following surgery for a variety of malignancies, limited data exist in bladder cancer. Herein, we evaluated the efficacy and safety of EDPP after RC. Methods: We instituted a change in our clinical practice beginning in May 2014 such that patients undergoing RC were prescribed 30 days of enoxaparin at discharge. We recorded symptomatic VTE and lymphocele rates within 30 days of RC among patients treated from 5/14-6/15, and compared these outcomes to the cohort of all patients who underwent RC at our institution in the year prior to EDPP implementation. Patients in both groups received subcutaneous unfractionated heparin and mechanical prophylaxis during hospitalization. Patients with a history of VTE prior to surgery (n = 24) were excluded from study. Unadjusted descriptive statistics and univariate analyses were performed using the Pearson or Fisher chi-square test for categorical variables and Wilcoxon rank-sum test for continuous variables. Results: In total, 58 patients who received EDPP and 82 patients who had not received EDPP after RC were included for analysis. Baseline clinicopathologic demographics were similar between the cohorts. We found that only 1 patient (1.9%) discharged with EDPP was diagnosed with a VTE within 30 days of RC, compared to 5 (6.1%) who had not received EDPP. Mean time to VTE was 18.0 days after RC (range 9-28 days). Events consisted of DVT alone (n = 2), DVT and PE (n = 2), and PE alone (n = 2). The odds ratio for VTE in the absence of EDPP was 3.31 (95% CI 0.38, 29.2). Overall, 3 patients developed a symptomatic lymphocele within 30 days of RC: 1 (1.9%) who received EDPP and 2 (2.4%) who had not (p = 0.84). No patient in either cohort was rehospitalized for bleeding complications. Conclusions: Our initial experience suggests that EDPP was associated with a lower rate of VTE following RC, and does not increase the risks of bleeding or symptomatic lymphocele. Future evaluation in a larger-scale prospective clinical trial setting is needed to confirm the benefit of EDPP in RC patients.

e15590 Background: Peripheral blood counts (PBC) such as anemia and elevated platelets are associated with a worse prognosis in patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC...

447 Background: Components of the peripheral blood counts (PBC) are associated with poor prognosis in patients diagnosed with non-metastatic clear cell renal cell carcinoma (ccRCC). Related to this, higher tumor expression of programmed death ligand one (PDL1) is also associated with poor ccRCC prognosis. Herein, we utilize a large cohort of patients undergoing nephrectomy for localized ccRCC to evaluate the association of PBC with tumor expression of PDL1. Secondarily, we examine the association of PBC and relapse free survival (RFS) after adjusting for age and PDL1 expression. Methods: Through chart review, we obtained PBC values at time of nephrectomy for patients enrolled in the Mayo Clinic Renal Registry from 1990-2009 who were treated for localized (M0) ccRCC including the following: hemoglobin (HGB), white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), and platelets (PLT). We determined tumor PDL1 expression as a continuous variable (% of positive PDL1 tumor cells) using the 5H1 antibody on archived tissues. We analyzed the correlation of PBC values with PDL1 expression as a continuous variable using a linear estimate. To evaluate the association of PBC values with RFS after adjusting for PDL1 expression, we employed multivariate Cox regression models. Results: A total of 706 ccRCC patients had available PDL1 expression and PBC. PDL1 expression was inversely associated with HGB (linear estimate of -0.02, p

420 Background: Cytoreductive nephrectomy (CN) has been associated with significant morbidity, but there is little data identifying patients at increased risk. We evaluated the association of clinicopathologic features with early post-operative complications and prolonged length of stay (pLOS) among CN patients. Methods: We identified 294 patients treated with radical nephrectomy for M1 renal cell carcinoma between 1990 and 2009 at the Mayo Clinic. All complications within 30 days of surgery were reported using standardized methodology according to the Clavien classification. Associations with the presence of any early complication and pLOS (defined as ≥8 days, the top 25th percentile) were evaluated using logistic regression models. Results: Thirty-five (12%) patients experienced at least one early complication and 15 (5%) patients experienced at least one Clavien grade ≥3 early complication. The median LOS was 6 days (IQR 5-7), and 68 (23%) patients had a pLOS. On univariate analysis, liver metastases, symptomatic presentation, intraoperative transfusion, and pathologic nodal stage were significantly associated with both early complications and pLOS (Table). Two multivariate models were constructed. In Model 1 (limited to pre-operative features), only liver metastases (p

494 Background: Renal cell carcinoma (RCC) with rhabdoid differentiation is thought to portend a poor prognosis, similar to RCC with sarcomatoid differentiation. Both rhabdoid and sarcomatoid differentiation are classified as grade 4 RCC based on the most recent International Society of Urological Pathology (ISUP) grading system. We sought to determine the prognostic value of rhabdoid differentiation in comparison to RCC with sarcomatoid differentiation, grade 4 RCC without rhabdoid or sarcomatoid differentiation, and grade 3 RCC. Methods: Using the Mayo Clinic Nephrectomy Registry, we identified 406 patients with ISUP grade 4 RCC and 1,758 patients with grade 3 RCC. A urologic pathologist reviewed all specimens to determine the presence of both rhabdoid and sarcomatoid differentiation. Associations of clinical and pathologic features with death from RCC were evaluated using Cox models. Results: Among the 406 grade 4 RCC tumors, 111 (27%) had rhabdoid differentiation and 189 (47%) had sarcomatoid differentiation, although only 28 (7%) demonstrated both rhabdoid and sarcomatoid differentiation. In multivariable analysis of grade 4 RCC tumors, the presence of rhabdoid differentiation was not associated with death from RCC (HR 0.95, p=0.75); in contrast, sarcomatoid differentiation was significantly associated with death from RCC (HR 1.63, p

4530 Background: A subset (10-20%) of clear cell renal cell carcinoma (ccRCC) tumors evades the immune system through expression of programmed death ligand 1 (PDL1), and these tumors are associated...

e15598 Background: Although targeted agents have drastically changed clinical practice for metastatic renal cell carcinoma (mRCC), the variations in out-of-pocket costs for these expensive agents r...

503 Background: We evaluated temporal patterns in the utilization of systemic therapy among patients undergoing cytoreductive nephrectomy (CN) for metastatic Renal Cell Carcinoma (mRCC) from a large national cancer registry and assessed patient characteristics associated with receipt of systemic treatment. Methods: We reviewed the National Cancer Database to identify patients with stage IV RCC who underwent CN between 1998-2010. Systemic therapy was defined as any treatment with immunotherapy and/or chemotherapy (including targeted agents). We evaluated the association between clinicopathologic features and receipt of systemic therapy using multivariable logistic regression with generalized estimating equations, and assessed the interaction of treatment with time, stratified as immunotherapy (1998-2004) versus targeted-therapy (2005-2010) eras. Results: Of 22,409 patients with mRCC undergoing CN, 8,830 (39%) received systemic therapy. Receipt of systemic therapy increased from 32% in 1998 to 49% in 2010 (p

402 Background: The American Urological Association (AUA) and the National Comprehensive Cancer Network (NCCN) are highly utilized sources for surveillance strategies following surgical treatment for renal cell carcinoma (RCC). However, the duration of follow-up may be inadequate to capture the majority of recurrences. Herein, we assess the ability of these guidelines to effectively capture recurrences of RCC following primary surgical resection. Methods: We reviewed our institutional database of 3,725 patients treated with radical or partial nephrectomy for M0 sporadic RCC between 1970-2008. For comparison to the AUA guidelines, patients were stratified into low risk following partial nephrectomy (LRp) or radical nephrectomy (LRr) = pT1N0, and moderate/high risk (M/HR) = pT2-4 N0-1. Guideline effectiveness was assessed by calculating the percentage of recurrences detected within the prescribed follow-up periods given for site-specific recurrence: AUA—LRp: 3yrs for all sites; LRr: 1yr for abdominal and 3yrs for chest/bone/other sites; M/HR: 5yrs for all sites; NCCN—6 months for abdominal/chest sites and 5yrs for bone/other sites. Results: Of the 3,725 patients, 2721 (73.1%) underwent radical nephrectomy, 2,210 (59.3%) were classified as pT1 NX-0 and 2,910 (78.1%) as clear cell RCC. Median postoperative follow-up was 8.9yrs (IQR 5.5-14.2) during which 1,114 (29.9%) patients developed recurrence. Of these recurrences, 760 (68.2%) would have been detected using the AUA guidelines and 432 (38.8%) by NCCN recommendations. Within AUA risk groups, 37.2% recurrences were captured in LRp, 31.4% in LRr and 80.2% in M/HR. Capture of 90% of recurrences in the abdomen and chest would require surveillance for 9yrs and 8 yrs, respectively in LRp, 15yrs and 12yrs in LRr and 11yrs and 10yrs in M/HR. Conclusions: Duration of follow-up recommended by current surveillance algorithms by the AUA and NCCN do not adequately capture many recurrences in RCC following radical or partial nephrectomy. Guidelines using risk stratification and site-specific recurrence parameters to assign length of surveillance may allow providers to better individualize surveillance regimens.

310 Background: The European Association of Urology (EAU) and the National Comprehensive Cancer Network (NCCN) provide general guidelines for bladder cancer (BC) surveillance following radical cystectomy (RC). However, it is unclear how well these guidelines capture recurrences after surgery. Herein, we assess the ability of current guidelines to effectively capture BC recurrence following RC and propose a risk stratified and recurrence site-specific surveillance strategy. Methods: We reviewed our institutional database of 1,800 patients who underwent primary RC between 1980-2007. Guideline effectiveness was assessed by calculating the percentage of recurrences detected within the prescribed follow-up periods: EAU—5yrs; NCCN—2yrs. Patients were then stratified according to stage: < = pT1Nx-0, > = pT2Nx-0, pN+, and recurrence site: urothelium, abdomen, chest, other. Recurrence free survival estimates for stage groups and recurrence site were assessed with Kaplan Meier models. Results: Of the 1,800 patients, 634 (35.2%) were classified as > pT2Nx-0 and 234 (13%) as pN+ and overall 228 (12.7%) received perioperative chemotherapy. Median postoperative follow-up was 10.6yrs (IQR 6.8-15.2), during which 716 (39.8%) patients developed recurrence. Of these recurrences, 492 (68.7%) would have been detected using the NCCN guidelines and 644 (89.8%) by EAU recommendations. However, ending oncologic surveillance at 5 years would only capture 81.7% of all recurrences for < = pT1Nx-0 patients and 83% of urothelial specific recurrences across all stage groups. Capture of 90% of recurrences, by stage group, in the urothelium, abdomen and chest would require surveillance for 8yrs, 8yrs and 4yrs, respectively in < = pT1Nx-0, 6yrs, 4yrs and 3yrs in > = pT2Nx-0 and 3yrs, 3yrs and 2yrs for pN+ patients. Conclusions: Duration of surveillance recommended for BC following RC by the EAU and NCCN do not comprehensively capture recurrences seen, specifically, in low risk patients and in cases of urothelial recurrence. Guidelines using risk stratification and site-specific recurrence patterns to assign length of surveillance may allow providers to better individualize surveillance regimens.

4567 Background: Trials combining anti-PDL1 and anti-VEGF therapies for clear cell renal cell carcinoma (ccRCC) are underway; however the relationship between the expression of PDL1 and genes in the VEGF pathway is poorly understood. Using the Affymetrix platform, we observed an inverse association between the expression of PDL1 and key genes in the VEGF pathway. Herein, we validate this inverse association using an independent set of 100 primary ccRCC tumors. Methods: From our registry database we sampled 100 ccRCC tumors with varying PDL1 protein expression (0%-100%) determined by immunohistochemistry (IHC). We extracted RNA from FFPE slides and performed RT-PCR to quantify gene expression of PDL1, VEGF, VEGFR1, and VEGFR2. All genes were normalized to the POLR2a gene. We evaluated the association of PDL1 protein expression and VEGF gene expression using Spearman rank correlation. In addition, we employed a linear mixed effects model to compare the fold-change in expression of VEGF genes between PDL1 low (0-5%, n=68) and PDL1 high (>5%, n=32) tumors. Results: As expected, PDL1 protein expression positively correlates with PDL1 geneexpression (corr=0.42, p

359 Background: Sarcomatoid renal cell carcinoma (RCC) is an aggressive form of RCC and is associated with a poor prognosis. Standard therapies tend to be less effective in this subset of patients. Methods: Using the Mayo Clinic Nephrectomy Registry, 206 patients with sarcomatoid RCC treated with partial or radical nephrectomy were identified. These patients were characterized based on extent of disease, treatment response and survival. Results: Of these 206, there was no evidence of distant metastases in 110 patients at the time of surgery and the estimated distant metastases-free survival at one year was 44%. The estimated cancer-specific survival rate at one and five years was 56% and 20%, respectively. Compared to patients with grade 4 RCC without sarcomatoid features, those with sarcomatoid RCC were more likely to develop distant metastases following surgery (hazard ratio 1.49). Considering those with metastatic sarcomatoid RCC, 96 patients had metastases at the time of surgery and 77 with no metastases at the time of surgery subsequently developed distant metastases (n=173). Of these, 156 died at a mean of 1.0 years from time of first evidence of distant metastases with a median cancer-specific survival of 0.6 years. Estimated cancer-specific survival rates from time of first metastases at one year and five years were 34% and 4%, respectively. The most common metastatic sites: lung (46%), bone (15%), liver (13%), non-regional lymph nodes (9%), and brain (5%). Patients who received targeted systemic therapy (10%) with either sunitinib (n=14), sorafenib (2) or pazopanib (1) for their first occurrence of distant metastases had an estimated cancer-specific survival rate at one year of 69%, compared to 30% for patients who did not. Median cancer-specific survival for those receiving targeted therapy as first-line was 2.2 years compared to 0.6 years for those patients who did not. Conclusions: Sarcomatoid RCC is an aggressive subtype of kidney cancer as evidenced by poor survival rates. The patients in this registry with metastatic sarcomatoid RCC who received targeted therapy as first-line treatment had improved cancer-specific survival rates.

321 Background: Factors that determine renal function after partial nephrectomy (PN) are not well defined, including the impact of cold vs. warm ischemia and the relative importance of modifiable and non-modifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing PN. Methods: In 1980–2009, 660 PN were performed at 4 centers for tumor in a solitary-functioning kidney under cold (n=300) or warm (n=360) ischemia. Data were collected in IRB-approved registries; follow- up averaged 4.5 years. Pre- and postoperative glomerular filtration rates (GFR) were estimated via CKD-EPI equation. Results: At 3 months after PN, median GFR decreased by equivalent amounts with cold or warm ischemia (21% vs. 22%, respectively, p=0.7) although median cold ischemic times were much longer (45 vs. 22 min. respectively, p Conclusions: This non-randomized comparative study suggests that long-term renal function after PN is determined primarily by the quantity and quality of renal parenchyma that can be preserved. Within the relatively strict parameters of conventional practice, i.e. predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after PN. Nevertheless, type and duration of ischemia remain the most important modifiable factors during PN, and mandate further study. [Table: see text]

354 Background: Partial nephrectomy (PN) has demonstrated equivalent cancer control to radical nephrectomy (RN) and has been associated with lower rates of all-cause mortality. Nevertheless, there continues to be wide variability in practice pattern in the treatment of renal masses. Specifically, the decision to perform PN or RN often depends on patient, surgeon and renal mass characteristics. By quantifying the renal tumor using the R.E.N.A.L. nephrometry scoring system, collecting surgeon information, and providing defined clinical scenarios we attempt to evaluate factors important in surgeon decision-making. Methods: In June 2009, all members of the American Urological Association with a listed email address were invited to participate in a survey evaluating the management of renal masses. Respondents were asked their preferred treatment for 8 clinical scenarios. Each of these renal masses was given a nephrometry score (NS). The propensity to offer PN was evaluated by NS and surgical volume. High volume was defined as > 50 renal cases per year and low volume was defined as £ 10 cases per year. Results: 764 attending level urologic surgeons responded to each of the 8 scenarios providing 6112 evaluable clinical scenarios. NS ranged from 4-10; each unit increase was associated with 2-fold increased odds of a surgeon offering radical nephrectomy (OR 1.99, 95% CI: 1.93,2.06). PN was the preferred treatment for approximately 95% of patients with low complexity tumors (NS < 8) regardless of surgical volume. However, proposed treatment of high complexity tumors (NS ³ 8) demonstrated considerable heterogeneity in treatment choice. Controlling for all patient characteristics, high surgical volume significantly predicted whether PN would be offered to patients with high complexity tumors (OR 3.04 95% CI: 2.34,9.95), but not those with low complexity tumors (OR 1.95 95% CI: 0.87,4.38) compared to low volume surgeons. Conclusions: Increasing NS correlated with increased use of radical nephrectomy, particularly after a score of 8 among all surgeons. As renal surgical volume increased, surgeons were more willing to offer PN in high complexity tumors. No significant financial relationships to disclose.

324 Background: The indications for the removal of the ipsilateral adrenal gland in patients with renal cell cancer (RCC) have not been well defined. Most continue to advocate ipsilateral adrenalectomy in patients with risky features such as a tumor thrombus, large, locally advanced tumors, and/or upper pole tumors. We evaluated the oncologic outcomes of concurrent adrenalectomy with either partial (PN) or radical nephrectomy (RN) in a large single institution cohort. Methods: From 1970–2006, 4,019 consecutive patients with RCC treated by RN (n=3,107) or PN (n=912) from Mayo Clinic were studied for adrenal involvement. Risk of asynchronous adrenal metastasis and cancer specific survival (CS) were also compared between those who underwent concomitant adrenalectomy (n=1,464) and those who did not (n=2,555) using multivariate cox models. Results: Median postoperative follow-up was 6 years. Synchronous ipsilateral adrenal involvement was rare even for those with large (>7cm) tumors (2.5%), upper pole (1.3%), and locally advanced (pT3/4) tumors (3.5%). The development of asynchronous adrenal metastasis occurred in 109 patients (2.7%) at a median of 3.7 years after initial surgery. The risk of developing an ipsilateral (1.4% 95% CI 0.8, 2.0) vs. contralateral (1.8% 95% CI 1.0, 2.6) asynchronous adrenal metastasis was equivalent at 10 years, in those who did not undergo adrenalectomy at initial surgery. At 10 years, 7.3% (99% CI: 4.4, 10.2) of patients with higher stage tumors (pT3/4) are predicted to develop a contralateral adrenal metastasis. On multivariate analysis, routine adrenalectomy was associated with a decreased risk of subsequent adrenal metastasis (HR 0.88: 99% CI 0.81, 0.95), but did not significantly impact CS (HR 1.15: 99% CI 0.99, 1.34). Conclusions: Asynchronous metastasis can usually be salvaged without apparent effect on CS. Ipsilateral adrenal involvement from RCC was uncommon even in large, locally advanced, and/or upper pole tumors. Routine adrenalectomy in these high risk patients may lead to an unacceptably high rate of adrenal insufficiency when a significant subset develops a contralateral adrenal metastasis. No significant financial relationships to disclose.

348 Background: While the initial natural history after surgical resection for localized renal cell carcinoma (RCC) has been well-characterized, recurrence patterns for patients who experience late recurrence of disease continue to be defined. Here, we evaluated the clinical characteristics and survival of patients who experienced disease recurrence > 5 years following nephrectomy. Methods: We identified 1,454 patients who were treated with radical nephrectomy (RN) or nephron-sparing surgery (NSS) for unilateral, sporadic pT1-4NxM0 RCC between 1970-2000 and who had remained free of disease for 5 years after surgery. Late (> 5 years) recurrence was then recorded and was classified as renal (ipsilateral/contralateral kidney) recurrence and distant (all other sites) recurrence. The incidence of late recurrence was estimated using the Kaplan Meier method, and clinicopathological variables subsequent disease relapse were analyzed using Cox proportional hazard regression models. Results: Median follow-up after nephrectomy in the cohort here was 13.9 years (range 5.1-38.9). In total, 63 patients experience a late recurrence in the ipsilateral/contralateral kidney, at a median of 9.3 years (range 5.1-25.3) after surgery. 172 (11.8%) patients developed late distant metastases, at a median of 9.6 years (range: 5.1-26.6). Estimated recurrence-free survival at 10 and 15 years following nephrectomy was 97.3% and 95.2% for renal recurrence and 93.1% and 85.9% for distant recurrence, respectively. Increased tumor size (HR 1.1; p Conclusions: Patients undergoing surgery for localized RCC remain at life-long risk of disease recurrence. Approximately 5% experience renal recurrence and 15% demonstrate distant relapse, during the ensuing 10 years. Continued investigation to identify potential site-specific predictors of late recurrence is necessary to guide postoperative surveillance regimens. No significant financial relationships to disclose.

e16103 Background: At present, androgen ablation (AA) therapy ± radiation therapy represents a first-line treatment for patients with unresectable locally advanced prostate cancer (CAP), typically resulting in palliative disease control. Immunotherapy, in the form of CTLA-4 blockade, has been shown to potentiate T-cell responses, representing a potential antitumoral immunotherapy for treating CAP. Here, we discuss the outcomes of 5 locally advanced CAP patients treated with the monoclonal antibody MDX-CTLA-4 (MDX-010) + AA who subsequently underwent radical prostatectomy (RP), 2 of whom exhibited striking down-staging of their disease. Methods: A Phase II trial testing AA + MDX-010 therapy for treatment of locally or systemically advanced CAP is currently ongoing at our institution. To date, 5/85 patients have electively opted for off-study RP with extended pelvic lymphadenectomy after documentation of robust treatment response by PSA, staging digital rectal exam, and 3-D imaging. Results: All men had unresectable, locally advanced disease (stage T2c-T4) prior to treatment with AA + MDX-010 and subsequently underwent RP. Median blood loss was 400mL (400–900). All patients had negative surgical margins. Of the 5 patients, 2 exhibited dramatic and indisputable down-staging of their disease. These two patients presented with 80% of biopsies involved with cancer, extraprostatic extension, seminal vesicle (SV) invasion, and bladder base involvement. On final pathology, both exhibited extensive treatment effect, remission of SV involvement, and robust disaggregation of solid tumors resulting in only microscopic, non-contiguous foci of residual intraprostatic cancer. Both had T4 disease pre-treatment, and had stage T2c on final pathology. One patient is free of disease with undetectable PSA for 19 months following adjuvant radiation treatment but no further therapy, while the other patient is awaiting follow-up. Conclusions: We have been able to demonstrate true down-staging of locally advanced prostate cancer with neoadjuvant AA + MDX-010 therapy. This therapeutic modality exhibits significant promise for men with unresectable disease and may provide durable and potentially curative cancer control. No significant financial relationships to disclose.

5052 Background: Discovered in 2003, B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently descri...