Sia Daneshmand

Super Extended Versus Extended Pelvic Lymph Node Dissection in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Comparative Study

PURPOSE There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. MATERIALS AND METHODS Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed. RESULTS Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%). CONCLUSIONS Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

Risk stratification of pT1-3N0 patients after radical cystectomy for adjuvant chemotherapy counselling

Background:In pT1-T3N0 urothelial carcinoma of the bladder (UCB) patients, multi-modal therapy is inconsistently recommended. The aim of the study was to develop a prognostic tool to help decision-making regarding adjuvant therapy.Methods:We included 2145 patients with pT1-3N0 UCB after radical cystectomy (RC), naive of neoadjuvant or adjuvant therapy. The cohort was randomly split into development cohort based on the US patients (n=1067) and validation cohort based on the Europe patients (n=1078). Predictive accuracy was quantified using the concordance index.Results:With a median follow-up of 45 months, 5-year recurrence-free and cancer-specific survival estimates were 68% and 73%, respectively. pT-stage, ge, lymphovascular invasion, and positive margin were significantly associated with both disease recurrence and cancer-specific mortality (P-values⩽0.005). The accuracies of the multivariable models at 2, 5, and 7 years for predicting disease recurrence were 67.4%, 65%, and 64.4%, respectively. Accuracies at 2, 5, and 7 years for predicting cancer-specific mortality were 69.3%, 66.4%, and 65.5%, respectively. We developed competing-risk, conditional probability nomograms. External validation revealed minor overestimation.Conclusion:Despite RC, a significant number of patients with pT1-3N0 UCB experience disease recurrence and ultimately die of UCB. We developed and externally validated competing-risk, conditional probability post-RC nomograms for prediction of disease recurrence and cancer-specific mortality.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma

BACKGROUND To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era

INTRODUCTION We sought to determine predictors for early and late biochemical recurrence following radical prostatectomy among localized prostate cancer patients. METHODS The study included localized prostate cancer patients treated with radical prostatectomy (RP) at the University of Southern California from 1988 to 2008. Competing risks regression models were used to determine risk factors associated with earlier or late biochemical recurrence, defined using the median time to biochemical recurrence in this population (2.9 years after radical prostatectomy). RESULTS The cohort for this study included 2262 localized prostate cancer (pT2-3N0M0) patients who did not receive neoadjuvant or adjuvant therapies. Of these patients, 188 experienced biochemical recurrence and a subset continued to clinical recurrence, either within (n=19, 10%) or following (n=13, 7%) 2.9 years after RP. Multivariable stepwise competing risks analysis showed Gleason score ≥7, positive surgical margin status, and ≥pT3a stage to be associated with biochemical recurrence within 2.9 years following surgery. Predictors of biochemical recurrence after 2.9 years were Gleason score 7 (4+3), preoperative prostate-specific antigen (PSA) level, and ≥pT3a stage. CONCLUSIONS Higher stage was associated with biochemical recurrence at any time following radical prostatectomy. Particular attention may need to be made to patients with stage ≥pT3a, higher preoperative PSA, and Gleason 7 prostate cancer with primary high-grade patterns when considering longer followup after RP.

Systematic Review of Comorbidity and Competing-risks Assessments for Bladder Cancer Patients

Context Radical cystectomy continues to be associated with a significant risk of morbidity and all-cause mortality (ACM). Practice pattern data demonstrating underuse of surgery for patients with muscle-invasive and high-risk non-muscle invasive bladder cancer (BC) have been linked to the advanced age and higher comorbidity status of such patients, which suggests that rates of ACM as well as cancer-specific mortality should be incorporated into patient counseling and guideline recommendations. Objective To review the literature on risk assessment tools for preoperative comorbidity in BC that may aid in treatment decision-making. Evidence acquisition A systematic search was conducted using Ovid and Medline according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2017 reporting on comorbidity risk assessment (CRA) tools for BC. Prospective and retrospective studies were included. Evidence synthesis There are no published randomized control trials comparing CRA tools for BC. Patients undergoing radical cystectomy with combined high-risk comorbidity and performance scores may face up to a sevenfold greater risk of other-cause mortality compared to those with low scores. The Charlson Comorbidity Index is one of the most widely studied indices for 90-d perioperative mortality and overall and cancer-specific survival, with an area under the receiver operating characteristic curve of up to 0.810. Prospective studies of CRA tools for BC have consistently shown that patients with higher comorbidity have worse outcomes. While not specific for BC, comorbidity indices provide useful assessment of competing risks. Competing-risks assessment tools are lacking, with limited studies assessing the impact of these tools on treatment decision-making by patients and providers. We provide the impetus for incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients. Conclusions CRA tools should be incorporated into preoperative treatment counseling and the assessment of postoperative outcomes. While retrospective evidence supports the use of CRA tools for BC, further comparative studies evaluating the effectiveness of these tools and identifying the patients most likely to benefit from a treatment according to competing-risks assessment are needed. Patient summary In this review we explored the clinical evidence for comorbidity risk assessment tools in bladder cancer. We found evidence to support incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.

Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank

The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts.

MP57-12 CANCER-SPECIFIC SURVIVAL AND PREDICTORS IN PATIENTS WITH CT3B KIDNEY CANCER: DATA OF THE IRCVT RCC VENOUS THROMBUS CONSORTIUM

(P 1⁄4 0.180) or when adjusting for thrombus level, age, sex, T stage, N stage, presence of metastasis, and time under surgery (P 1⁄4 0.734). Median cancer-specific survival was 29.1 months (95% CI [21.2, 48.3]) in non-CPB patients and 39.4 months in CPB patients (95% CI [29.3, 80.0]). Cancer-specific survival did not differ significantly based on CPB, either in the univariate analysis (P 1⁄4 0.704) or in the multivariate analysis (P 1⁄4 0.888). In univariate analysis, length of stay (LOS) was estimated to be 26% higher in CPB patients (P 1⁄4 0.002) and the complication rate was marginally lower in CPB patients (P 1⁄4 0.053). However, in multivariable analysis, no significant difference was seen in hospital LOS (P 1⁄4 0.439) or complication rate with the use of CPB (P 1⁄4 0.457). CONCLUSIONS: In our multi-institutional analysis, the use of cardiopulmonary by-pass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Higher surgical complications or longer hospital stay were not independently associated with the used of CPB.

1699 IDENTIFYING NOVEL DNA METHYLATION MARKERS TO MONITOR BLADDER CANCER RECURRENCE IN URINE SEDIMENTS FROM TURBT PATIENTS

logic subtype, carcinoma in situ (i.e., Tis), is present in 40% of total bladder cancers diagnosed. However, there is currently no ability at the time of initial diagnosis to identify which of these patients will respond to standard-of-care treatment, intravesical administration of Bacillus Calmette-Guerin (BCG). Thus, Tis bladder cancer patients are often treated subjectively using a “one size fits all” approach with only about a 60% success rate (i.e., tumor-free) among treated patients. The aim of the present study was is to correlate the BCG responsiveness of patients with Tis bladder cancer with measures of the tumor immune microenvironment at the time of initial diagnosis. METHODS: The immune microenvironments of tumor biopsies of 20 Tis bladder cancer patients responsive to BCG therapy (BCG ) were assessed relative to biopsies derived from 18 non-responsive patients (BCG-). Each tumor immune microenvironment was determined as a function of two immunohistochemical metrics: (i) The level of tumor eosinophil infiltration as well as the extent of eosinophil degranulation (i.e. Th2 effector arm) and (ii) The relative number of tumor-infiltrating GATA-3 (i.e., Th2-polarized) vs. T-bet (i.e., Th1 polarized) lymphocytes. RESULTS: The bladder biopsies of “normal” subjects displayed only a nominal eosinophil infiltrate with no evidence of degranulation or infiltrating lymphocytes. In contrast, Tis bladder tumors often displayed a robust tissue eosinophilia accompanied by degranulation. The tumor immune microenvironments were decidedly Th2 polarized with 3-fold more GATA-3 relative to T-bet lymphocytes. More importantly, each of these immune biomarkers had prognostic value in the evaluation of bladder cancer patients. Specifically, the data showed that the levels of each immune biomarker were statistically higher in patients subsequently shown to be BCG relative to BCGsubjects. In addition, an algorithm integrating these immune metrics (i.e., Th2 Signature) provided an unambiguous biomarker that stratifies bladder cancer patients prior to treatment decisions with a high degree of specificity. CONCLUSIONS: The immunohistochemical assessments of the Tis immune tumor microenvironment represents a clinically-relevant screening strategy of cancer patients as to their subsequent responsiveness to the standard-of-care treatment.

1868 PROGNOSTIC VALUE OF BAJORIN CRITERIA FOR CANCER-SPECIFIC SURVIVAL IN PATIENTS WHO HAVE DISEASE RECURRENCE AFTER RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

Luis A Kluth*, Evanguelos Xylinas, New York, NY; Michael Rink, Hamburg, Germany; Matt Kent, Dan Sjoberg, New York, NY; Marek Babjuk, Antonin Brisuda, Prague, Czech Republic; Atiqullah Aziz, Hans-Martin Fritsche, Regensburg, Germany; Evi Comploj, Armin Pycha, Bolzano, Italy; Debasish Sundi, Trinity Bivalacqua, Baltimore, MD; Giacomo Novara, Padua, Italy; Jack Baniel, Roy Mano, Petah-Tikva, Israel; Paolo Gontero, Torino, Italy; Robert S Svatek, San Antonio, TX; Lukas Lusuardi, Salzburg, Austria; Anirban Mitra, Sia Daneshmand, Los Angeles, CA; Matthew D. Galsky, New York, NY; Yair Lotan, Dallas, TX; Douglas S Scherr, Shahrokh F Shariat, New York, NY

943 PROGNOSTIC FACTORS AND OUTCOMES AFTER DEFINITIVE TREATMENT FOR PRIMARY URETHRAL CANCER: RESULTS FROM THE INTERNATIONAL COLLABORATION ON PRIMARY URETHRAL CARCINOMA

Georgios Gakis*, Tuebingen, Germany; Sia Daneshmand, Los Angeles, CA; Jason A. Efstathiou, Boston, MA; Bedeir Ali-El-Dein, Mansoura, Egypt; Jan Hrbacek, Prague, Czech Republic; Kirk A. Keegan, Nashville, TN; Sigolene Galland, Rebecca Clayman, Boston, MA; Lars Weissbach, Hamburg, Germany; Johannes Brunner, Regensburg, Germany; Harras B. Zaid, Nashville, TN; Tilman Todenhofer, Tuebingen, Germany; Michael Rink, Hamburg, Germany; Hans-Martin Fritsche, Regensburg, Germany; Sam S. Chang, Nashville, TN; Marko Babjuk, Prague, Czech Republic; George Thalmann, Bern, Switzerland; Arnulf Stenzl, Tuebingen, Germany