Parker, William P.

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<0.001) were associated with decreased ACM, whereas the presence of metastatic disease at diagnosis remained associated with an increased risk of ACM (HR 1.74; p=0.02). Conclusions: The prognosis for patients with RMC is dismal, with a median OS under 8 months. Further studies, including the development of novel therapies, are needed to establish the optimal multimodal management approach for these patients.

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 <7cm (cT1). We further limited our cohort to patients with an ASA score of 1 or 2, and in whom pre-operative eGFR was >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.

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.

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: <60, 61−70, 71−80, >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<0.01). Similar associations of age with RC were observed at high volume centers (> 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<0.01). Similar improvements in survival were noted after IPTW. Conclusions: Older patients are significantly less likely to receive RC for HG NMIBC, despite a similar risk of upstaging and an improved survival when pathologic NMIBC is found at RC. These data support the use of RC for HG NMIBC in well selected patients across age strata.

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.

445 Background: Radical cystectomy (RC) is the gold standard treatment for muscle-invasive and high-risk non-muscle invasive bladder cancer. However, the procedure has been associated with a high complication rate, including perioperative infection. In addition to resulting in patient morbidity, infections have been suggested as a quality metric. We sought to evaluate the incidence, risk factors, and timing of infection following RC. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried to identify patients undergoing RC for bladder cancer from 2005-2013 using CPT procedure and ICD-9 diagnosis codes. Infections (urinary tract infection (UTI), surgical site infection (SSI), and sepsis) within 30 days of RC were recorded. Characteristics including age, gender, ethnicity, body-mass index, diabetes, smoking status, renal function, steroid usage, albumin, receipt of perioperative transfusion, and operative time were abstracted, and relative risk of infection was assessed in univariate chi-squared analysis. Results: A total of 3,187 patients were identified, of whom 2604 (81.8%) were male, with a median age of 68.8 years (IQR 62, 77). Postoperative infection was diagnosed in 766 (24%) patients, at a median of 13 days (IQR 8, 19) after RC, with 44.4% occurring prior to hospital discharge. The most common type of infection was SSI (404; 12.7%), followed by sepsis (315; 9.9%), and UTI (309; 9.7%). Factors associated with increased overall infection risk were obesity (RR 1.32; 1.20-1.46; p < 0.001), receipt of a blood transfusion (RR 1.20; 1.10-1.31; p < 0.001), and increased operative time (RR for > 450 min 1.46; 1.26-1.70; p < 0.001). Risk factors for UTI in particular included obesity (RR 1.28; 1.11-1.47; p < 0.001), diabetes (RR 1.38; 1.09-1.75; p = 0.009), and increased operative time (RR for > 450 min 1.45; 1.18-1.78; p < 0.001). Conclusions: Approximately 25% of patients undergoing RC experience an infection within 30 days of surgery, most commonly SSI. Several modifiable risk factors were identified, including blood transfusion and prolonged operative time, that represent potential targets for care improvement.

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.