LN-positive Disease Research Articles

Development and multicenter validation of a nomogram for preoperative prediction of lymph node positivity in pancreatic cancer (NeoPangram)

BackgroundNeoadjuvant therapy is associated with nodal downstaging and improved oncological outcomes in patients with lymph node (LN)-positive pancreatic cancer. This study aimed to develop and validate a nomogram to preoperatively predict LN-positive disease. MethodsA total of 558 patients with resected pancreatic cancer were randomly and equally divided into development and internal validation cohorts. Multivariate logistic regression analysis was used to construct the nomogram. Model performance was evaluated by discrimination, calibration, and clinical usefulness. An independent multicenter cohort consisting of 250 patients was used for external validation. ResultsA four-marker signature was built consisting of carbohydrate antigen 19–9 (CA19–9), CA125, CA50, and CA242. A nomogram was constructed to predict LN metastasis using three predictors identified by multivariate analysis: risk score of the four-marker signature, computed tomography-reported LN status, and clinical tumor stage. The prediction model exhibited good discrimination ability, with C-indexes of 0.806, 0.742 and 0.763 for the development, internal validation, and external validation cohorts, respectively. The model also showed good calibration and clinical usefulness. A cut-off value (0.72) for the probability of LN metastasis was determined to separate low-risk and high-risk patients. Kaplan-Meier survival analysis revealed a good agreement of the survival curves between the nomogram-predicted status and the true LN status. ConclusionsThis nomogram enables the identification of pancreatic cancer patients at high risk for LN positivity who may have more advanced disease and thus could potentially benefit from neoadjuvant therapy.

Omission of Surgical Axillary Lymph Node Staging in Patients with Tubular Breast Cancer.

With more effective screening and treatment strategies, there is debate over whether surgical axillary staging should be deescalated for patients with small favorable breast cancers, such as tubular carcinoma (TC). We identified patients with TC [defined as > 90% tubular tubules (angulated, not multilayered)] and known surgical axillary staging from our institutional database (2000-2018). Using the National Cancer Database (NCDB) (2004-2015), we identified patients with TC, ductal carcinoma in situ (DCIS), and pT1 estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). We determined the rates of lymph node (LN) metastases, and the 5- and 10-year overall survival (OS) for patients with LN-negative versus LN-positive disease using the Kaplan-Meier method and propensity match analysis. In our institutional cohort, we identified 112 patients with T1 TC; only one (0.9%) patient had nodal involvement. In the NCDB cohort, we identified 6938 patients with T1 TC; 323 (4.7%) patients had axillary LN disease. The rate of axillary LN involvement for TC was comparable to that identified for patients with DCIS (4.2%), and much lower than that found for patients with grade I-III, T1, ER-positive IDC (20.5%), and patients with grade I, T1, ER-positive IDC (14.4%). There was no difference in 5-year (94.6% versus 95.4%, p = 0.67) and 10-year (83.9% versus 85.2%, p = 0.98) OS between TC patients with or without LN involvement. Kaplan-Meier survival curves even after propensity score matching suggest that tubular histology is independently associated with improved survival. T1 TC is an excellent starting point for deescalation of surgical axillary staging.

Multidisciplinary Approach in Improving Survival Outcome of Early-Stage Gastric Cancer

BackgroundThe necessity of extensive lymph node (LN) dissection/examination and adjuvant therapy for patients with early gastric cancer (EGC, Tis-T1, any N) remains controversial. We aim to refine treatment recommendations for patients with EGC through a reflective analysis for the survival gap between Eastern and Western countries. MethodsEGC patients diagnosed between 2004 and 2014 were identified from the National Cancer Database (NCDB) and a large medical center in China. Adequate LN yield was defined as ≥25 LNs examined. ResultsIn the US cohort, 14.4% of (1104/7641) patients with EGC had ≥25 LNs examined. The 5-y overall survival (OS) was significantly better than those with <25 LNs (78.9% versus 68.5%, P < 0.001). Examination of ≥25 LNs was an independent predictor of better OS after adjusting all known prognostic factors. Patients with ≥25 LNs examined had significantly higher chance of having LN-positive disease compared to patients with <25 LNs (14.9% versus 10.7%, P < 0.001). A similar stage migration phenomenon was observed in Chinese cohort (LN positive: 25.2% versus 18.4% in ≥25 LNs and <25 LNs examined group, respectively, P = 0.02). In the US cohort, adjuvant therapy was associated with a significant survival benefit for LN-positive patients (5-y OS: 71.0% versus 43.0% for with/without adjuvant therapy, respectively, P < 0.001) but not in LN-negative patients (5-y OS: 71.2% versus 71.5%, P = 0.90). ConclusionsAdequate lymphadenectomy and LN examination are critical components of EGC management. Adjuvant therapy should be strongly encouraged for all EGC patients with LN-positive disease in the United States.

Interaction of race and pathology for neuroendocrine tumors: Epidemiology, natural history, or racial disparity?

Although minority race has been associated with worse cancer outcomes, the interaction of race with pathologic variables and outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is not known. Patients from the US Neuroendocrine Study Group (2000-2016) undergoing curative-intent resection of GEP-NETs were included. Given few patients of other races, only Black and White patients were analyzed. A total of 1143 patients were included. Median age was 58 years, 49% were male, 14% Black, and 86% White. Black patients were more likely to be uninsured (7% vs 2%, P = .011), and to have symptomatic bleeding (13% vs 7%, P = .009), emergency surgery (7% vs 3%, P = .006), and positive lymph nodes (LN) (47% vs 36%, P = .021). However, Black patients had improved 5-year recurrence-free survival (RFS) (90% vs 80%, P = .008). Quality of care was comparable between races, seen by similar LN yield, R0 resections, postoperative complications, and need for reoperation/readmission (all P > .05). While both races were more likely to have pancreas-NETs, Black patients had more small bowel-NETs (22% vs 13%, P < .001). LN positivity was prognostic for pancreas-NETs (5-year RFS 67% vs 83%, P = .001) but not for small-bowel NETs. Black patients with GEP-NETs had more adverse characteristics and higher LN positivity. Despite this, Black patients have improved RFS. This may be attributed to the epidemiologic differences in the primary site of GEP-NETs and variable prognostic value of LN-positive disease.

Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group.

Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined. Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined. Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n = 158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p < 0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size ≥ 2cm (odds ratio [OR] 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate versus well-differentiation (OR 2.1; p = 0.006), and Ki-67 ≥ 3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2cm (9%), distal location (19%), well-differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p = 0.198; seven or more LNs: 67% vs. 86%; p = 0.002). Tumor size ≥ 2cm, proximal location, moderate differentiation, and Ki-67 ≥ 3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9-23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.

Abstract P2-07-07: Development of a machine learning-based classifier for Oncotype DX® category prediction in a population of lymph node positive breast carcinoma patients

Abstract INTRODUCTION: Oncotype DX® (ODX) Assay is a valuable prognostic and predictive tool in ER+, Her2- invasive breast cancer (IBC). Initially tested and validated in lymph node (LN) negative patients, the indications of this test have been expanded to include patients with limited LN-positive disease. Several prediction systems have been developed to predict the ODX Recurrence Score (RS) with substantial performance in predicting a high vs low RS score but with low performance when predicting the 3 classes that compose the standard ODX. Additionally, many of these prediction systems have not been developed and/or tested for a population of LN+ patients. OBJECTIVES: The primary objective of this study was to evaluate the performance of several previously published ODX RS predictive systems in a population of LN+ patients. Furthermore, we developed a machine-learning based classification system to accurately predict the ODX 3 category RS for this specific population. METHODS: We conducted a retrospective search of Stanford's pathology database for all patients with LN+ IBC diagnosed between January 2013 and December 2017 with an ODX RS available. A total of 119 patients were identified for inclusion in this cohort. Our multivariate pathologic feature-based discriminatory model aimed to classify each case as belonging to the low, intermediate or high ODX RS category. We performed model validation by the 10-fold cross validation (10F-CV) method. The model's performance was assessed by comparing simple accuracy, balanced accuracy, F1 score (harmonic average of the precision and recall) and several concordance classification metrics. RESULTS: Of the evaluated methods, Magee equations performed well in this population of LN+ patients with the modified Magee equation 2 displaying the best accuracy (70.9%) which was surprisingly better than originally reported (55.8%, in Klein et al. Mod Path. 2013). After an initial screen of methods and tuning of the best performing model, our model achieved an overall accuracy of 78.1% on 10F-CV with a 79.1 % balanced accuracy and no two-step discordances. This corresponded to an increase of weighted Cohen's kappa of 30% versus the best performing Magee equation in this cohort and an increase of 103% versus the modified Magee 1 equation (which uses the same features as our model except for tumor grade). DISCUSSION: Classifiers aimed at providing an alternative to Oncotype DX testing are available and perform consistently across datasets. We are currently validating our approach in a population of 1000 LN-negative patients from the MSKCC and the SEER database. Due to the substantial performance of our machine learning-based classifier based on standard reported pathologic features, our model may be considered an alternative to the ODX standard testing or a screening method for ODX testing, especially for cases with where the cost and availability of the ODX test are a concern. Citation Format: Beca F, Yang S-R, Gruber JG, Barry-Holson K, West R, Wen HY, Allison KH. Development of a machine learning-based classifier for Oncotype DX® category prediction in a population of lymph node positive breast carcinoma patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-07.

The Impact of Lymphovascular Invasion on Risk of Upstaging and Lymph Node Metastasis at the Time of Radical Cystectomy

BackgroundLymphovascular invasion (LVI) in muscle-invasive bladder cancer is associated with a poor prognosis when identified from radical cystectomy (RC) specimens. However, LVI is not clearly emphasized in any risk models to guide clinical decision-making. The impact of LVI on the risk of lymph node (LN) metastasis after a transurethral resection of bladder tumor (TURBT) specimen is less understood. ObjectiveThe goal was to describe the impact of LVI and the risk of LN metastasis at each clinical stage of urothelial carcinoma of the bladder (UC). Design, setting, and participantsThe National Cancer Database was queried for patients with bladder cancer who underwent RC with LN dissection from 2004 to 2014. Patients with non-bladder primary, non-UC histology, clinical metastatic disease, and having received chemotherapy/radiation were excluded. Pathologic LN positive rates at RC were determined. Outcome measurements and statistical analysisThe primary outcome was pathologic upstaging at RC and pathologic node positivity. Secondary outcomes included determining overall survival (OS). All hypotheses testing were two-sided and a p value of <0.05 was considered statistically significant. All statistical analyses were performed using Stata version 13.1. Results and limitationsA total of 3007 patients with UC underwent RC with pelvic LN dissection. In patients with LVI, the risk of LN metastasis was significantly higher at each clinical stage as was the rate of pathologic upstaging. Patients with LVI on TURBT had worse OS stage for stage in pure UC (p<0.001). Limitations include that there was no central pathologic review and the number of TURBTs per patient was not known. ConclusionsPatients with UC with LVI had worse OS and are at higher risk for LN-positive disease and pathologic upstaging at surgery than patients without LVI. Patient summaryIn this report we examined the impact of lymphovascular invasion (LVI) at transurethral resection of bladder tumor on pathologic upstaging and lymph node metastasis at radical cystectomy using the National Cancer Database. We identified LVI as being prognostic at each stage of urothelial carcinoma.

Patterns of lymph node sampling and the impact of lymph node density in favorable histology Wilms tumor: An analysis of the national cancer database

There is controversy about the role of lymph node (LN) sampling or dissection in the management of favorable histology (FH) Wilms tumor (WT), specifically how it performed and how it may impact survival. The objective of this study was to analyze factors affecting LN sampling patterns and the impact of LN yield and density (number of positive LNs/LNs examined) on overall survival (OS) in patients with advanced-stage favorable histology Wilms tumor (FHWT). The National Cancer Database (NCDB) was queried for patients with FHWT during 2004-2013. Demographic, clinical and OS data were abstracted for those who underwent surgical resection. Poisson regression was performed to analyze how factors influenced LN yield. Patients with positive LNs had LN density calculated and were further analyzed. A total of 2340 patients met criteria, with a median age at diagnosis of 3 years (range 0-78 years). The median number of LNs examined was three (range 0-87). Lymph node yield was affected by age, race, insurance, tumor size, laterality, advanced stage, LN positivity, and institutional volume. A total of 390 (16.6%) patients had LN-positive disease. Median LN density for these LN-positive patients was 0.38 (range 0.02-1) (Summary Figure). Estimated 5-year OS was significantly improved for those with LN density ≤0.38 vs. >0.38 (94% vs. 84.6%, P=0.012). In this population, on multivariate analysis, age and LN density were significant predictors of OS. It is difficult to compile large numbers of cases in rare diseases like WT, and fortunately a large administrative database such as the NCDB can serve as a great resource. However, administrative data come with inherent limitations such as missing data and inability to account for a variety of factors that may influence LN yield and/or OS (specimen designation, pathologist experience, surgeon experience/volume, institutional Children's Oncology Group (COG) association, etc.). In this specific disease, the American Joint Committee on Cancer staging (captured by the NCDB) is different than the COG WT staging system that is used clinically, and the NCDB does not capture oncologic outcomes beyond OS. In a review of the NCDB, various factors associated with LN yield and observed LN density were identified to be significantly associated with OS in patients with LN-positive FHWT. This reinforces the need for adequate LN sampling at the time of WT surgery, to maximize surgical disease control. It was proposed that LN density as a metric may allow for improved risk-stratification, and possibly allow for therapeutic reduction in a sub-set of patients with low LN density.

The diagnosis of pancreatic mucinous cystic neoplasm and associated adenocarcinoma in males: An eight-institution study of 349 patients over 15 years.

Per WHO, 2000 classification, pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma, and are primarily located in the pancreatic body/tail of females. The incidence of MCN and associated malignancy in males, since, standardization of MCN diagnostic-criteria is unknown. MCN resections from 2000 to 2014 at eight institutions of the Central-Pancreas-Consortium were included, and divided into early (2000-2007) and late (2008-2014) time-periods. Primary aim was to characterize MCN and associated adenocarcinoma/high-grade-dysplasia (AC/HGD) in males versus females over time. Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had MCNs: 310 (89%) female, 39 (11%) male. Patients were equally divided between early (n = 173) and late (n = 176) time-periods. MCN in male-patients decreased over time (early: 15%, late: 7%; P = 0.036), as did pancreatic head/neck location (early: 22%, late: 11%; P = 0.01). MCN-associated AC/HGD was more frequent in males versus females (39 vs. 12%; P < 0.001). The overall rate of MCN-associated AC/HGD remained stable (early: 17%, late: 13%; P = 0.4), and was identical in males (39%) over both time-periods. Males with AC/HGD had more LN-positive disease versus females (57 vs. 22%; P = 0.039). As the diagnostic-criteria of MCN have standardized over time, MCN diagnosis has decreased in males and head/neck location. Despite this, MCN-associated adenocarcinoma/high-grade dysplasia has been stable and remains high in males. Any male with suspected MCN, regardless of location, should undergo resection.

Next Generation intraoperative Lymph node staging for Stratified colon cancer surgery (GLiSten): a multicentre, multinational feasibility study of fluorescence in predicting lymph node-positive disease

Background5-aminolevulinic acid (5-ALA) is used for fluorescence diagnosis (FD) in neurological, gynaecological and urological malignancies. The Medical Research Council/Efficacy and Mechanism Evaluation (EME) programme/National Institute for Health Research’s Next Generation intraoperative Lymph node staging for Stratified colon cancer surgery (GLiSten) study investigated its use to predict lymph node (LN)-positive disease in colon cancer as an aid to stratified surgery.ObjectivesThe primary objective was to optimise the dose of oral 5-ALA for intraoperative FD of metastatic LNs in colon cancer. Secondary objectives included standardisation of pre-operative computerised tomography (CT) LN reporting, intraoperative fluorescence detection, surgical resection with D3 lymphadenectomy and histopathological examination of resected specimens.DesignThis was a feasibility study to determine optimal strategies for 5-ALA positive LN detection. Patients with locally advanced disease identified using the Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer (FOxTROT) criteria were recruited from two sites between October 2013 and June 2015. Cohort 1 received 20 mg/kg and cohort 2 received 30 mg/kg of oral 5-ALA, 1–6 hours preoperatively. Laparoscopic assessment of fluorescence was performed using the Storz D-Light system (KARL STORZ GmbH &amp; Co. KG; Tuttlingen, Germany), with marking of fluorescent LNs, followed by oncological resection. The specimen was subjected to histological analysis with step sectioning of marked fluorescent LNs. Progression to an evaluation phase using the optimal dosing schedule was dependent on positively identifying at least 2 out of 10 patients with metastatic LN disease in either cohort.ResultsA total of 44 patients were recruited with a male to female ratio of 26 : 18 and a mean age of 71 years (range 52–88 years). Cohort 1 consisted of 18 patients, of whom six had fluorescent primary cancers and three of these had fluorescent LNs. One out of 10 patients with metastatic LN disease had a fluorescent involved LN. Cohort 2 consisted of 26 patients, of whom eight had fluorescent primary cancers and four of these had fluorescent LNs. None of the fluorescent LNs contained disease in this cohort. No serious adverse events (SAEs) occurred but two mild, self-limiting, photosensitivity reactions were observed in cohort 2. The sensitivity and specificity for 5-ALA detection of LN-positive disease were: cohort 1 11.1%, 75%; and cohort 2 0%, 75%.LimitationsThis was a feasibility study exploring the use of 5-ALA for LN disease in a select cohort of patients with advanced colorectal cancer. The study population was small and generalisation to other cancers is not possible. The study was limited by the ability to determine LN-positive patients on the basis of pre-operative CT staging, which is often inaccurate, resulting in our cohorts containing several patients without LN disease.Conclusions5-ALA fluorescent diagnosis has poor sensitivity for discriminating LN-positive colon cancer. Its use as an aid to stratified colon cancer surgery is not supported. No SAEs were observed, suggesting that photosensitisers may be useful for intraoperative FD.Future work5-ALA has poor sensitivity for detecting LN metastases and cannot be recommended for intraoperative staging. Other, more sensitive fluorescent probes are required if this strategy is to be used.Study registrationCurrent Controlled Trials ISRCTN79949827 and EudraCT number 2012–002623–15.Funding detailsThis project was funded by the EME programme, a Medical Research Council and National Institute for Health Research partnership.

Abstract P1-09-08: Does adverse tumour biology contribute to inferior outcomes for Indigenous Australians diagnosed with breast cancer?

Abstract Background: Analyses across multiple Australian states have consistently demonstrated significantly inferior breast cancer survival for Indigenous patients (IPs). Studies compensating for increased remoteness, socioeconomic disadvantage and later presentation demonstrate a residual unexplained detriment. This survival disadvantage is confined to the first five years, akin to the inferior outcomes demonstrated by higher risk biological breast cancer subtypes. We postulated that a preponderance of such higher risk subtypes could explain the disparate mortalities. Methods: The distribution of breast cancer subtypes in Western Australian IPs diagnosed between 2001 and 2010 was assessed to explore the contribution of adverse prognostic subtypes to poorer outcome. This was a retrospective cohort study of Indigenous women (n=114) and 3:1 age and remoteness matched non-Indigenous women (n=310) diagnosed with invasive, non-metastatic, unilateral breast cancer, who underwent definitive local treatment. Subtypes were assigned as luminal A, B, HER2 enriched and triple negative by ER, PR, HER2 and tumour grade comparisons. Differences in basic tumour demographics and biological sub-types were analysed and racial survival discrepancies explored within biological subtype cohorts. Results: Hazards for overall and breast cancer-specific mortality in IPs were 4.07 (95% CI 2.55-6.49) and 4.19 (95% CI 2.42-7.25). IPs were significantly more likely to have grade 3 tumours (41 v 25%, p&amp;lt;0.001), LN positive disease (39 v 27%, p&amp;lt;0.001) and larger tumours (median 20 v 10 mm, p&amp;lt;0.001). No significant differences in proportions of classical histological sub-types (ductal v lobular) or in tumours showing ER, PR or HER2 positivity were observed. There were no significant differences in biological sub-type proportions although IPs were diagnosed with numerically more non-Luminal A subtypes (56 v 44%, p=0.08), accounted for by increased Luminal B (21 v 15%) and HER2 enriched (10 v 5%) sub-types. The significant relative five-year survival deficit for IPs noted overall (94 v73%, p&amp;lt;0.0001) was observed for each sub-type with the exception of HER2 positive patients. This extended from the relatively low risk luminal A sub-type where oral anti-estrogens are the mainstay of treatment (98 v 82%, p=0.0002) to the high risk triple negative sub-type where intravenous chemotherapy is the standard adjuvant therapy (94 v 50%, p=0.0014). Conclusions: The contribution of adverse tumour biological subtype to poorer outcomes for Indigenous women is modest. Indigenous women with almost all biological subtypes fare significantly worse than their non-Indigenous contemporaries. Ongoing work includes more detailed biological comparisons of RNA expression and DNA mutation between groups as well as an exploration of potentially disparate treatment patterns. Citation Format: Redfern A, Lee E, Bulsara M, Threlfall T, Harvey J, Cordell D. Does adverse tumour biology contribute to inferior outcomes for Indigenous Australians diagnosed with breast cancer?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-08.

Small bowel neuroendocrine tumors: A critical analysis of diagnostic work-up and operative approach.

203 Background: Small bowel neuroendocrine tumors (SB-NET) are rare, and often small and multifocal. They are difficult to localize preoperatively and can be overlooked during operative exploration. The optimal work-up and operative approach is not known. Methods: Patients who underwent resection of SB-NET at a single institution from 2000-2014 were included. Primary aim was to describe the diagnostic work-up, pathologic characteristics, and compare minimally-invasive (MIS) to open resection. Results: 93pts underwent resection for SB-NET. Median age was 61yrs; 52% were male. On presentation, 71% of pts were symptomatic and underwent an average of 3 diagnostic tests prior to resection: 45% had octreoscans, which identified the region of primary disease in 85%; 11% had small bowel enteroscopy, with a 10% diagnostic yield; 19% had capsule endoscopy, which saw a lesion in 83%, but in only 21% was the correct number of tumors seen. The diagnostic yield of capsule was 28% overall, but 82% in pts presenting with GI bleeding. 79pts (85%) underwent curative-intent resections. Median tumor size was 1.8cm and multiple primary tumors were seen in 34pts(42%), of whom 50% had &gt; 3 tumors. 37% had metastatic and 70% had LN positive disease. 27pts underwent MIS resections vs 66 open. MIS pts were younger (56vs61yrs;p0.035) and less likely to have obstructive symptoms (4vs24%;p = 0.19) and metastatic disease at resection (19vs44%;p = 0.038). Compared to open, the MIS group had smaller (1.7vs2.4cm;p = 0.03) and fewer tumors resected (2vs5;p = 0.049), but similar LN yield (13vs12;p = 0.7). In pts without metastases undergoing curative-intent resection, MIS approach was still associated with fewer tumors removed compared to open (1.5vs4;p = 0.034). Conclusions: Capsule endoscopy appears to be better than small bowel enteroscopy at identifying occult small bowel neuroendocrine tumors, particularly when pts present with bleeding, but still may underestimate tumor burden. While MIS may be appropriate in select patients, recognizing the limitations of preoperative evaluation is critical when selecting the operative approach for these tumors, as heightened operative vigilance is often required.

Validation of 3 T MRI including diffusion-weighted imaging for nodal staging of newly diagnosed intermediate- and high-risk prostate cancer

To prospectively validate 3T magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) for preoperative lymph node (LN) staging in a clinical setting, in intermediate- and high-risk prostate cancer (PCa) patients using laparoscopic extended LN dissection (ePLND) as the reference standard. Between August 2011 and May 2013, 40 newly diagnosed intermediate and high-risk PCa patients underwent preoperative LN staging with 3T MRI DWI using histopathology of ePLND as the reference standard. The sensitivity, specificity, and accuracy of MRI DWI were calculated. A subgroup analysis of proven LN-positive patients was made to investigate differences in PSA, Gleason score, number, and size of LN metastases, estimated risk of LN involvement, and if curative treatment was indicated, between the true-positive and the false-negative groups. A total of 728 LN were harvested from six anatomical regions per patient (external, obturator, internal) with a mean number of 18 LNs per patient (range 11-40). Twenty patients had histologically proven LN-positive disease. MRI DWI was true positive in 11 patients, false negative in nine patients, false positive in two patients, and true negative in 18 patients, resulting in 90% specificity, 55% sensitivity, and 72.5% accuracy. The true-positive patients had significantly more involved LNs (mean 6.9 versus 2.7, p=0.017), with larger diameter (mean 12.3 versus 5.2mm, p=0.048) and fewer were treated with curative intent (six versus nine, p=0.03), compared with the false-negative group. MRI DWI LN staging has a low sensitivity but high specificity. The true-positive patients have a considerably higher burden of LN metastases compared to false-negative patients.

Adjuvant therapy in the treatment of gallbladder cancer: a meta-analysis.

BackgroundThe benefit of adjuvant therapy (AT) for gallbladder cancer (GBC) is unclear as evidenced by conflicting results from nonrandomized studies. Here we aimed to perform a meta-analysis to determine the impact of AT on overall survival (OS).MethodsWe used data from MEDLINE, EMBASE and the Cochrane Collaboration Library and published between October 1967 and October 2014. Studies that evaluated AT compared with curative-intent surgery alone for resected GBC were included. Subgroup analyses of benefit based on node status, margins status, and American Joint Committee on Cancer (AJCC) staging were prespecified. Data were weighted and pooled using random-effect modeling.ResultsTen retrospective studies involving 3,191 patients were analyzed. There was a nonsignificant improvement in OS with AT compared with surgery alone (hazard ratio [HR], 0.76; 95 % confidence interval [CI], 0.56–1.03). A significant improvement was observed in OS with chemotherapy (CT) compared with surgery alone (HR, 0.42; 95 % CI, 0.22–0.80) by sensitivity analysis. The greatest benefit for AT was also observed in those with R1 disease (HR, 0.33; 95 % CI, 0.19–0.59), LN-positive disease (HR, 0.71; 95 % CI, 0.63–0.81), and AJCC staging meeting or exceeding tumor Stage II (HR, 0.45; 95 % CI, 0.26–0.79), but not in those with LN-negative or R0 disease.ConclusionOur results strongly support the use of CT as an AT in GBC. Moreover, patients with node positivity, margin positivity, or non-stage I disease are more likely to benefit from AT.

Lymph node density as a prognostic variable in node-positive bladder cancer: a meta-analysis.

BackgroundAlthough lymph node (LN) status and the LN burden determine the outcome of bladder cancer patients treated with cystectomy, compelling arguments have been made for the incorporation of LN density into the current staging system. Here, we investigate the relationship between LN density and clinical outcome in patients with LN-positive disease, following radical cystectomy for bladder cancer.MethodsPubMed, SCOPUS, the Institute for Scientific Information Web of Science, and the Cochrane Library were searched to identify relevant published literature.ResultsFourteen studies were included in the meta-analysis, with a total number of 3311 patients. Of these 14 publications, 6 studies, (533 patients), 10 studies (2966 patients), and 5 studies (1108 patients) investigated the prognostic association of LN density with disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS), respectively. The pooled hazard ratio (HR) for DFS was 1.45 (95 % confidence interval [CI], 1.10–1.91) without heterogeneity (I2 = 0 %, p = 0.52). Higher LN density was significantly associated with poor DSS (pooled HR, 1.53; 95 % CI, 1.23–1.89). However, significant heterogeneity was found between studies (I2 = 66 %, p = 0.002). The pooled HR for OS was statistically significant (pooled HR, 1.45; 95 % CI, 1.11–1.90) without heterogeneity (I2 = 42 %, p = 0.14). The results of the Begg and Egger tests suggested that publication bias was not evident in this meta-analysis.ConclusionsThe data from this meta-analysis indicate that LN density is an independent predictor of clinical outcome in LN-positive patients. LN density may be useful in future staging systems, thus allowing better prognostic classification of LN-positive bladder cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1448-x) contains supplementary material, which is available to authorized users.

Lymph node status predicts the benefit of adjuvant chemoradiotherapy for patients with resected pancreatic cancer

BackgroundThe role of adjuvant chemoradiotherapy in pancreatic cancer remains limited. The primary aim of this study was to determine the prediction of lymph node (LN) status to the benefit of adjuvant chemoradiotherapy for patients with resected pancreatic adenocarcinoma. MethodsBetween December 2010 and December 2012, a total of 152 patients undergoing curative R0 resection for pancreatic adenocarcinoma from multi-institutions were retrospectively analyzed. ResultsOverall median survival was 16.3 months. Sixty-four patients (42.1%) received adjuvant chemoradiotherapy, whereas 88 (57.9%) did not receive adjuvant therapy after surgery. Patients who received chemoradiotherapy could achieve an improved median OS compared with surgery alone (20.3 versus 13.9 months, p=0.027). Stratified by different lymph node status, multivariate analysis demonstrated the benefit of adjuvant chemoradiotherapy was only seen among patients with lymphatic positive disease (HR = 0.54, 95% CI, 0.33–0.88; p=0.014), not lymphatic negative disease (HR = 0.80, 95% CI, 0.44–1.46; p=0. 468). ConclusionsThis study suggests adjuvant chemoradiotherapy is associated with a significant improvement of survival only in patients with LN-positive disease, while the effects of chemoradiotherapy on patients with LN-negative disease may be limited. This study may add incremental knowledge of the role of lymph node status in offering treatment with adjuvant chemoradiotherapy.

MP67-19 ONCOLOGICAL OUTCOMES OF TOTALLY INTRACORPOREAL ROBOT-ASSISTED RADICAL CYSTECTOMY: RESULTS FROM THE ERUS SCIENTIFIC WORKING GROUP.

ABSTRACT: INTRODUCTION AND OBJECTIVES Data on the oncological outcomes in patients undergoing robot-assisted radical cystectomy (RARC) is limited. Globally extracorporeal urinary diversion following RARC remains the most common approach despite potential advantages of a completely minimally invasive approach. We report oncological outcomes and associated prognostic factors from a multi-institutional European database focusing on the centres performing totally intracorporeal RARC. METHODS In the ERUS scientific working group database, 467 patients underwent totally intracorporeal RARC for bladder cancer between 2003 and 2014. Clinical and pathological data at the time of the latest follow-up was reviewed. Recurrence free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were the outcomes of interest and evaluated using the Kaplan Meier estimator. Multivariable Cox regression analysis was performed to identify factors associated with outcomes of interest. RESULTS Mean age was 67 years, 80% were men. 384 (82%) patients were alive at the time of the analysis. Median follow-up was 17.9 months (range 1-130 months). 87 patients (19%) had undergone surgery 3 or more years' ago. Median follow-up of patients alive was 16 months. 31% patients had pathological non organ-confined disease. Positive surgical margins were present in 5%; median lymph node yield was 18 with 19% of patients having positive lymph nodes. The 3-year RFS, CSS and OS were 73%, 75% and 73% respectively. On multivariable analysis, non-organ confined disease was found to impact RFS, CSS and OS (HR 4.0, 4.3 and 4.2 respectively) and LN positive disease was associated with poorer RFS (HR 2.1). Histopathology stage pT0 was a positive prognostic indicator associated with better RFS, CSS and OS (HR 0.15, 0.16 and 0.74 respectively). CONCLUSIONS This is the largest reported multi-institutional cohort of totally intracorporeal RARC showing acceptable medium term survival outcomes comparable to open radical cystectomy series. The ERUS scientific working group database indicates that a totally intracorporeal approach is replicable.

221 Prostate sparing cystectomy: 20 years single center experience

INTRODUCTION AND OBJECTIVES: Patients who experience disease recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) have a very poor prognosis. Most recurrences occur during the first two years following RC. The incidence, patterns, and prognosis of late recurrences (LRs) following RC have not been well described. METHODS: We queried our prospectively maintained institutional database and identified 1953 consecutive patients who underwent RC for UCB from 1995-2010. We identified patients who experienced disease recurrence following RC and analyzed both nonurothelial tract disease recurrence and urothelial recurrence. Late recurrence was defined as a non-urothelial tract recurrence occurring three or more years following RC. RESULTS: Of 648 UCB patients who experienced non-urothelial tract disease recurrence following RC, 93 (14%) occurred greater than 3 years following RC, and 42 (6%) occurred after 5 years (range 3.01 e 12.89 years). Of these 93 LRs, 22 (24%) were local, 54 (58%) were distant, and 17 (18%) were both local and distant. Sites of metastasis in patients with LRs included 21 (23%) lung, 20 (22%) bone, 47 (51%) lymphatic, 18 (19%) liver, 20 (22%) pelvis, and 5 (5%) other. Urothelial tract recurrences were identified in 44 of 93 patients with LR, 30 upper tract and 18 urethral. After excluding 17 patients in whom the LR could be ascribed to an invasive upper tract second primary tumor, 76 LR patients were left for analysis. The stage distribution at RC for LR patients was pT0 (7%), pTa (5%), pTis (18%), pT1 (12%), pT2 (26%), pT3 (21%), and pT4 (8%). Twelve LR patients (16%) had LN-positive disease. Eleven LR patients had received pre-operative cisplatin-based chemotherapy and 8 received adjuvant chemotherapy. LR patients were more likely to have organ-confined disease at RC (62% vs. 21%, p<0.001) and concomitant CIS (78% vs. 61%, p1⁄40.02) than patients experiencing recurrence within 3 years. However, the prognosis following recurrence was similarly poor for patients experiencing LR as it was for early recurrence, although LR patients had a slightly longer time from recurrence to death (p1⁄40.002). CONCLUSIONS: Bladder cancer patients treated with RC remain at risk for disease recurrence for many years, although the majority of patients who will recur do so within the first two years. Patients who experience late recurrence have different disease characteristics than those who experience early recurrence. Continued surveillance for detection of local, distant, and urothelial recurrences following RC may be beneficial.

MP55-05 LATE RECURRENCE FOLLOWING RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

INTRODUCTION AND OBJECTIVES: Patients who experience disease recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) have a very poor prognosis. Most recurrences occur during the first two years following RC. The incidence, patterns, and prognosis of late recurrences (LRs) following RC have not been well described. METHODS: We queried our prospectively maintained institutional database and identified 1953 consecutive patients who underwent RC for UCB from 1995-2010. We identified patients who experienced disease recurrence following RC and analyzed both nonurothelial tract disease recurrence and urothelial recurrence. Late recurrence was defined as a non-urothelial tract recurrence occurring three or more years following RC. RESULTS: Of 648 UCB patients who experienced non-urothelial tract disease recurrence following RC, 93 (14%) occurred greater than 3 years following RC, and 42 (6%) occurred after 5 years (range 3.01 e 12.89 years). Of these 93 LRs, 22 (24%) were local, 54 (58%) were distant, and 17 (18%) were both local and distant. Sites of metastasis in patients with LRs included 21 (23%) lung, 20 (22%) bone, 47 (51%) lymphatic, 18 (19%) liver, 20 (22%) pelvis, and 5 (5%) other. Urothelial tract recurrences were identified in 44 of 93 patients with LR, 30 upper tract and 18 urethral. After excluding 17 patients in whom the LR could be ascribed to an invasive upper tract second primary tumor, 76 LR patients were left for analysis. The stage distribution at RC for LR patients was pT0 (7%), pTa (5%), pTis (18%), pT1 (12%), pT2 (26%), pT3 (21%), and pT4 (8%). Twelve LR patients (16%) had LN-positive disease. Eleven LR patients had received pre-operative cisplatin-based chemotherapy and 8 received adjuvant chemotherapy. LR patients were more likely to have organ-confined disease at RC (62% vs. 21%, p<0.001) and concomitant CIS (78% vs. 61%, p1⁄40.02) than patients experiencing recurrence within 3 years. However, the prognosis following recurrence was similarly poor for patients experiencing LR as it was for early recurrence, although LR patients had a slightly longer time from recurrence to death (p1⁄40.002). CONCLUSIONS: Bladder cancer patients treated with RC remain at risk for disease recurrence for many years, although the majority of patients who will recur do so within the first two years. Patients who experience late recurrence have different disease characteristics than those who experience early recurrence. Continued surveillance for detection of local, distant, and urothelial recurrences following RC may be beneficial.

Outcomes of radical cystectomy with extended lymphadenectomy alone in patients with lymph node‐positive bladder cancer who are unfit for or who decline adjuvant chemotherapy

To analyse the long-term outcomes of patients with lymph node (LN)-positive bladder cancer, who did not receive any adjuvant therapy after radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND). We conducted a retrospective, combined cohort analysis based on two prospectively maintained cystectomy databases from the University of Southern California and the University of Bern. Eligible patients underwent RC with ePLND for cN0M0 disease but were found to have LN-positive disease. No patient had neoadjuvant therapy, and all had negative surgical margins. Kaplan-Meier plots were used to estimate recurrence-free survival (RFS) and overall survival (OS). Subgroup comparisons were performed using log-rank tests, and multivariable analysis was based on Cox proportional hazard models. Of 521 patients with LN-positive disease, 251 (48%) never received adjuvant therapy. Although the pathological stage distribution was similar, the 251 patients who did not receive adjuvant therapy were older and had both fewer total and positive LNs than those who underwent adjuvant therapy. The median RFS for patients treated with RC alone was 1.6 years. Recurrences mainly occurred <2 years after RC, resulting in 5- and 10-year RFS rates of 32 and 26%, respectively. Pathological T stage, the total number of LNs and the number of positive LNs detected were independent predictors of RFS and OS. In this study, 25% of patients with documented LN metastases who did not receive adjuvant therapy were cured with RC and ePLND; however, a few relapses may occur later than 3 years. Predictors of survival were pathological T stage, the number of total LNs and the number of positive LNs identified.