Frank, Igor

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]

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.

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<0.001) and OS (25% vs. 48%, p<0.001). NAC exposure remained independently associated with worse CSS (HR=2.2; 95%CI 1.6-3.1; p<0.001) and OS (HR=2.0; 95%CI 1.5-2.7; p<0.001) among these patients. Conclusions: While patients who achieve a complete response to NAC have excellent survival outcomes, patients with residual UCB at RC after NAC have a worse prognosis compared to stage-matched RC patients not exposed to NAC. Such patients should be considered for enrolment in novel adjuvant therapy trials.

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.

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.