Pathologic Upstaging Research Articles

Association of Time Between Radiation and Salvage APR and Margin Status in Patients With Anal Cancer Treated With Concurrent Chemoradiation.

There is a controversy regarding the optimal time to assess anal squamous cell carcinoma (SCC) response to chemoradiation and when salvage abdominoperineal resection (APR) should be offered. A retrospective cohort study was performed on patients with stage I-III anal SCC treated with chemoradiation in the National Cancer Database (2004-2015). The time between radiation and APR was recorded. Logistic regression and Cox proportional hazard analysis were used to determine predictors of resection margin status and overall survival. The cohort included 23 050 patients, of whom 545 (2.4%) underwent salvage APR. The median (IQR) time between radiation and resection was 3.8 (2.4-5.5) months. The rate of positive margins was 19.0%. Positive margins were more common in male, non-white patients with larger tumors, pathologic upstaging of T stage, and ≥3 months between chemoradiation and resection (all P < .05). Observing for ≥3 months between chemoradiation and APR remained associated with positive margins, even after adjusting for pretreatment tumor size (odds ratio = 2.56, 95% CI 1.46-4.47). Our data, based on the largest published cohort of anal SCC patients treated with chemoradiation and subsequent APR, suggest that patients at high risk of local treatment failure, particularly non-white men with large tumors, may benefit from early interim restaging and earlier consideration of salvage surgery.

Impact of socioeconomic disparities on upstaging for prostate cancer: A national cancer database analysis.

e17526 Background: Recent data suggest that socioeconomic disparities impact the outcome of oncologic disease. This retrospective analysis investigates the role of socioeconomic variables on clinical to pathologic staging of prostate cancer (PC). Methods: 455,773 males with stage 1-3 adenocarcinoma of prostate who underwent surgical intervention (96% radical prostatectomy) were extracted from the National Cancer Database from 2004-2016. Patients were stratified into age groups based on American Urologic Association PSA screening recommendations ( &lt; 40, 40-54, 55-69, &gt; 70 years). Changes from clinical to pathological staging were the primary outcomes. Demographics, income level, education status and distance to treatment facility ( &lt; 12.5, 12.5-49.9, &gt; 50 miles) were analyzed using Chi-square and logistic regression to find upstaging predictors. Results: Rates of stage changes are summarized in Table. Increased distance ( &gt; 50 vs &lt; 12.5 mi) was associated with upstaging in all age groups (40-54: OR 1.10 95%CI 1.05-1.16; 55-69: OR 1.20 95%CI 1.18-1.23; &gt; 70: OR 1.42 95%CI 1.35-1.50) except for &lt; 40 years (OR 1.15, 95%CI 0.60-2.21). Other predictors of upstaging included black or other race compared to white (OR 1.06 95%CI 1.04-1.09 and OR 1.10 95% CI 1.06-1.14, respectively) and in men with government insurance vs private insurance (OR 1.19 95%CI 1.17-1.21). Lower risk of upstaging was seen for those who were not insured vs private insurance (OR 0.70 95%CI 0.67-0.73), lived in areas with the highest vs lowest high school education rate (OR 0.95, 95%CI 0.92-0.98), or lived in the lowest vs highest income areas (OR 0.93, 95%CI 0.90-0.96). Conclusions: Socioeconomic disparities directly impact the outcome for prostate cancer. Our study suggests age, distance from treatment facility, and race are associated with a greater risk for clinical to pathologic upstaging. Investigation should continue to better understand at-risk populations. [Table: see text]

PD11-05 MULTICENTER COMPARISON OF OUTCOMES FOR CLINICAL AND PATHOLOGIC T3A RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy II (PD11)1 Apr 2020PD11-05 MULTICENTER COMPARISON OF OUTCOMES FOR CLINICAL AND PATHOLOGIC T3A RENAL CELL CARCINOMA Aaron Bradshaw*, Robert Uzzo, Umberto Capitanio, Brian Lane, Dattatraya Patil, Kazutaka Saito, Fady Ghali, Alexander Kutikov, Alessandro Larcher, Sabrina Noyes, Raksha Dutt, Cathrine Keiner, Nathan Miller, Fang Wan, Margaret Meagher, Devin Patel, Yasuhisa Fujii, Francesco Montorsi, Viraj Master, and Ithaar Derweesh Aaron Bradshaw*Aaron Bradshaw* More articles by this author , Robert UzzoRobert Uzzo More articles by this author , Umberto CapitanioUmberto Capitanio More articles by this author , Brian LaneBrian Lane More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Kazutaka SaitoKazutaka Saito More articles by this author , Fady GhaliFady Ghali More articles by this author , Alexander KutikovAlexander Kutikov More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Sabrina NoyesSabrina Noyes More articles by this author , Raksha DuttRaksha Dutt More articles by this author , Cathrine KeinerCathrine Keiner More articles by this author , Nathan MillerNathan Miller More articles by this author , Fang WanFang Wan More articles by this author , Margaret MeagherMargaret Meagher More articles by this author , Devin PatelDevin Patel More articles by this author , Yasuhisa FujiiYasuhisa Fujii More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Viraj MasterViraj Master More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000845.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The identification of imaging characteristics associated with T3a renal cell carcinoma (RCC) can may be challenging on pre-operative imaging. A substantial number of patients are upstaged to T3a following intervention. The impact of upstaging to pT3a disease on ultimate outcomes in comparison with clinical T3a RCC is unclear. We compared survival outcomes between patients with clinical T3a versus those upstaged to pT3a RCC. METHODS: This is a retrospective, multicenter analysis of patients with RCC of cT3a or pT3a staging who underwent operative management. Primary outcome was recurrence-free survival (RFS). Secondary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression multivariable analysis (MVA) was utilized for primary outcome. Kaplan-Meier analyses (KMA) were conducted to describe RFS, OS, and CSS with log-rank test comparing survival between clinical and upstaged T3a groups. RESULTS: 1314 patients were included in analysis (cT3a 309, pT3a 1005). Upstaged pT3a patients were more likely to be female (p=0.02) and have a higher BMI (p<0.01). Average tumor size was similar between groups (cT3a 7.7 vs. pT3a 7.2 cm, p=0.26), however a higher proportion of cT3a underwent radical nephrectomy (90.9% vs. 56.7% pT3a, p<0.01). Positive surgical margin rate was higher among pT3a (9.6% vs 2.3% cT3a, p<0.01) with a similar proportion having pathologically positive nodes (11.5% pT3a vs. 11.7% cT3a, p=0.96). MVA for RFS revealed increasing age (HR 1.01, p=0.03), clear cell RCC (HR 1.32, p=0.03), and positive node status (HR 3.83, p<0.01) to be independent risk factors of recurrence while sex (p=0.13), cT3a vs. pT3a staging (p=0.08), positive surgical margins (p=0.30), and type of surgery (p=0.95) were not significant. KMA demonstrated 5-year RFS of 52.2% and 55.6% for cT3a and pT3a respectively (p=0.04). KMA demonstrated 5-year OS rates of 69.0% and 59.0% (p=0.20) and 5-year CSS of 76.7% and 72.6% for cT3a and pT3a respectively (p=0.70) (Figure). CONCLUSIONS: Pathologic upstaging was not an independent risk factor for recurrence in T3a RCC. Despite an increased recurrence rate in clinical T3a RCC versus pathologically upstaged T3a, no difference in oncological outcomes were noted and pathologic upstaging does not compromise oncologic outcomes compared to clinical T3a disease. Source of Funding: Stephen Weissman Kidney Cancer Research Fund © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e254-e255 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aaron Bradshaw* More articles by this author Robert Uzzo More articles by this author Umberto Capitanio More articles by this author Brian Lane More articles by this author Dattatraya Patil More articles by this author Kazutaka Saito More articles by this author Fady Ghali More articles by this author Alexander Kutikov More articles by this author Alessandro Larcher More articles by this author Sabrina Noyes More articles by this author Raksha Dutt More articles by this author Cathrine Keiner More articles by this author Nathan Miller More articles by this author Fang Wan More articles by this author Margaret Meagher More articles by this author Devin Patel More articles by this author Yasuhisa Fujii More articles by this author Francesco Montorsi More articles by this author Viraj Master More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF downloadLoading ...

Predictive model using prostate MRI findings can predict candidates for nerve sparing radical prostatectomy among low-intermediate risk prostate cancer patients.

BackgroundIn order to improve postoperative functional outcome, including urinary continence and erectile function, nerve sparing surgery is recommended for patients with clinically localized prostate cancer (PCa). However, due to poor diagnosis accuracy at the preoperative stage, upstaging occurs in a considerable proportion of patients. Multiparametric magnetic resonance imaging (mpMRI) and the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) have recently shown excellent performance in diagnosis and staging of PCa. The aim of this study was to develop a predictive model based on PI-RADS v2 for postoperative upstaging in patients with low-intermediate risk PCa.MethodsThe medical records of 314 patients with low-intermediate risk PCa [prostate-specific antigen (PSA) level ≤20 ng/mL, Gleason score (GS) <8, and clinical stage < T3] who underwent preoperative mpMRI and radical prostatectomy in the Department of Urology, Peking University First Hospital between January 2012 and July 2019 were reviewed retrospectively. Clinicopathological characteristics were collected. All MRI reports were done at our institution as part of routine clinical practice before prostate biopsy and there was no re-reporting occurred. Using PI-RADS v2, the mpMRI results were assigned to three groups: “negative”, “suspicious”, and “positive”. Multivariate logistic regression analysis was used to assess factors associated with postoperative pathological upstaging, defined as the presence of pT3 at final pathology. A regression coefficient based model for predicting postoperative upstaging was constructed and internally validated using 1,000 bootstrap resamples. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC). With the optimal cutoff point the performance of the model was assessed through analysis of sensitivity, specificity, positive predictive value, and negative predictive value.ResultsUpstaging was observed in 119 (37.9%) patients. The univariate and multivariate analyses revealed that PSA density, biopsy Gleason grade group (GGG), and mpMRI findings were significantly independent predictors for postoperative upstaging (all P<0.05). A predictive model showing very favorable calibration characteristics and higher accuracy than the single variables was constructed (AUC =0.74; P<0.001). At the optimal cutoff point, the model demonstrated a sensitivity and negative predictive value of 87.4% and 87.0%, respectively.ConclusionsPI-RADS v2 assessment proved to be one of the most valuable predictors for postoperative upstaging in patients with low-intermediate risk PCa. The predictive model, based on PI-RADS v2 assessment, PSA density, and biopsy GGG, may help to select suitable candidates for nerve sparing radical prostatectomy among patients with low-intermediate risk PCa.

Impact of radiological morphology of clinical T1 renal cell carcinoma on the prediction of upstaging to pathological T3.

Previous studies have reported that cases with clinical T1 renal cell cancer upstaging to pathological T3 are a risk factor to predicting postoperative recurrence after partial nephrectomy. The aim of our study was to investigate the impact of the radiological morphology of the enhanced CT scan of clinical T1 renal cell cancer on predicting upstaging to pathological T3. Three hundred sixty-seven cases with clinical T1 renal cell cancer diagnosed from enhanced CT scans were enrolled in this study. Based on the findings from the enhanced CT scan, the cases were classified into 'round', the margins of which were smooth and round; 'lobular', one or more findings of smooth dent and no spiky dent were identified on the margin of the tumor; and 'irregular', one or more spiky dent were identified on the margin of the tumor. The association of postoperative upstaging with these radiological morphology and other clinical characteristics of each case was analyzed. Eighteen cases (4.9%) pathologically upstaged to T3a. Two round case (0.7%), 3 lobular cases (10.0%) and 13 irregular cases (22.0%) pathologically upstaged (P<0.001, round + lobular versus irregular). Four of 17 cases (23.5%) with hilar tumors pathologically upstaged, while 14 of 350 cases (4%) with tumors pathologically upstaged in other sites (P<0.001). Multivariate analysis revealed that irregular case was an independent factor in predicting upstaging to pathological T3a (P<0.001). Evaluation of the radiological morphology of clinical T1 renal cell cancer based on enhanced CT scans is useful for predicting pathological upstaging.

Does pathologic upstaging to PT3A portend a worsened prognosis when compared to non-upstaged PT3A renal cell carcinoma: Analysis of the National Cancer Database.

624 Background: Pathological T3a (pT3a) renal cell carcinoma (RCC) is often diagnosed at the time of final pathological analysis, though impact of lack pre-treatment detection on surgical outcomes is unclear. We sought to compare outcomes of pathologically upstaged pT3a RCC with pT3a RCC recognized clinically. Methods: We queried the National Cancer Database for incident cases of pT3a pN0/x pM0/x renal cell carcinoma (RCC) treated with radical (RN) or partial nephrectomy (PN) between 2009-2015. Tumors were staged using the AJCC staging system, 7th edition. Pathologically upstaged tumors were defined as those that had a clinical stage of T1 or T2. Non-upstaged tumors had a clinical stage of T3a. Multivariable Cox proportional hazards and Kaplan-Meier survival analysis were performed to study the impact of clinical to pathological upstaging in pT3a tumors on overall survival (OS) in patients treated with RN and PN. Results: A total of 19,538 pT3a tumors were identified of which 7,231 (37%) had concordant clinical stage (non-upstaged) and 12,307 (63%) had lower clinical stage (upstaged). Patients with upstaged tumors had longer time from diagnosis to surgery (31.5 vs. 23.8 days; p&lt;0.001), smaller tumor size (6.7 vs. 7.4 cm; p&lt;0.001), higher rates of treatment with partial nephrectomy (18% vs. 11%; p&lt;0.001), and higher rates of negative margins (92% vs. 89%; p&lt;0.001). On multivariate analysis, age (HR 1.06; p&lt;0.001), Charlson Comorbidity Index (HR 1.51; p=0.006) and positive margin status (HR 1.55; p&lt;0.001) were associated with worse OS. Pathological upstaging was an independent predictor of improved OS following both PN (HR 0.74; 95% CI 0.59-0.91; p=0.006) and RN (HR 0.87; 95% CI 0.82-0.93; p&lt;0.001). Kaplan-Meier analysis showed higher OS for tumors that were upstaged following both PN (5-year OS 73 vs. 70%; p=0.0083) and RN (5-year OS 67 vs. 64%; p&lt;0.001). Conclusions: Most pT3a RCC are pathologically upstaged. Pathological pT3a tumors that were correctly detected clinically were associated with worsened outcomes. While our findings require further confirmation, they call for consideration and refinement of risk stratification protocols in pT3a RCC.

Improving detection of higher-risk or locally advanced disease features in stage I and II renal cell carcinoma.

625 Background: Pathologically upstaged T3a renal cell carcinoma (RCC) carries higher oncologic risk than corresponding preoperative clinical stage and presents unique risks from a treatment planning standpoint due to reduced clinician awareness of locally aggressive disease. We sought to identify imaging criteria that predict risk of pathological upstaging of clinical T1 and T2 RCC to T3a and to assess accuracy of CT in detecting T3a RCC. Methods: Single institution retrospective analysis of patients who underwent surgery for RCC. A propensity-score matching process was used to match upstaged patients with non-upstaged (control) patients in a 1:2 fashion. Preoperative CT images were reviewed in a blinded fashion by 2 radiologists for presence of T3a stage imaging criteria. Multivariable analyses assessed risk conferred by imaging features and sensitivity analysis assessed accuracy in detecting T3a RCC. Results: After exclusions, 231 patients were analyzed (mean age 61 years, upstaged 83/control 148, mean tumor size 6.4 cm). In 71/83 (86%) of upstaged tumors, the presence of sinus fat invasion (SFI), perinephric fat invasion (PFI), or venous invasion (VI) was found. The presence of all three was not observed in any non-upstaged tumor. The following features were associated with upstaging: tumor necrosis (OR 2.1, p=0.017), irregular tumor edge (OR 2.9, p&lt;0.001), thickened perirenal fascia (OR 2.6, p=0.001), perinephric stranding (OR 1.8, p=0.043), increased perinephric vascularity (OR 2.02, p=0.021), and perinephric nodules (OR 3.4, p=0.020). The SE/SP for tumor necrosis, irregular tumor edge, thickened perirenal fascia, perinephric stranding, increased perinephric vascularity, and perinephric nodules were 42%/74%, 74%/50%, 48%/74%, 70%/44%, 70%/46%, and 13%/96%, respectively. Conclusions: Upstaged T3a RCC contained several preoperative imaging attributes which were 2-3 times more likely to be present than in non-upstaged tumors. Of these, irregular tumor edge had highest sensitivity, and perinephric nodules had highest specificity. These features should elevate clinical suspicion for T3a disease and may be used to develop a novel risk scoring system. Further investigation is requisite.

A Multi-Institutional Analysis of the Effect of Positive Surgical Margins Following Robot-Assisted Partial Nephrectomy on Oncologic Outcomes.

Objective: To determine the effect of positive surgical margins (PSMs) on oncologic outcomes following robot-assisted partial nephrectomy (RAPN) and to identify factors that increase the likelihood of adverse oncologic outcomes. Methods: A multi-institutional database of patients who underwent RAPN with complete follow-up data was used to compare recurrence-free survival (RFS) and overall survival (OS) between 42 (5.1%) patients with a PSM and 797 (94.9%) patients with a negative surgical margin. Analysis was performed with univariable and multivariable Cox proportional hazard regression models adjusting for confounding variables. A Kaplan-Meier method was used to evaluate the relationship between PSM and oncologic outcomes (RFS and OS), and the equality of the curves was assessed using a log-rank test. Results: The rate of PSM was 5.1%. RFS at 12, 24, and 36 months was 97.8%, 95.2%, and 92.9%. OS at 12, 24, and 36 months was 98.6%, 97.7%, and 93.3%. PSM was not associated with worse RFS in both univariable and multivariable analyses (hazard ratio [HR] = 1.43; 95% confidence interval [CI] = 0.37, 5.55; p = 0.607). Factors associated with worse RFS include pT3a upstaging (HR = 4.97; 95% CI = 1.63, 15.12; p = 0.005), a higher Charlson comorbidity index (HR = 1.68; 95% CI = 1.20, 2.34; p = 0.002); and advanced clinical stage (cT1a vs cT1b, HR = 4.22; 95% CI = 1.84, 9.68; p = 0.001 vs cT2a, HR = 14.09; 95% CI = 3.85, 51.53; p < 0.001). PSM was not associated with worse OS in both univariable and multivariable analyses (HR = 0.87; 95% CI = 0.26, 2.94; p = 0.821). Higher R.E.N.A.L. nephrometry score was found to be associated with worse OS (HR = 1.26; 95% CI = 1.01, 1.57; p = 0.041). Conclusions: Given the absence of association between PSM and worse oncologic outcomes, patients with PSM following RAPN should be carefully monitored for recurrence rather than undergo immediate secondary intervention. As advanced clinical stage (cT1b, cT2a) and pathologic upstaging (pT3a) were independently associated with disease recurrence, their presence may warrant more attentive postoperative surveillance.

Clinicopathologic factors associated with pathologic upstaging in patients clinically diagnosed stage T2N0M0 squamous cell esophageal carcinoma.

Even with the use of contrast-enhanced thin-layer chest computed tomography (CT) and endoscopic ultrasonography (EUS), the likelihood of cT2N0M0 squamous cell esophageal cancer correlating with the final pathologic outcome is exceedingly low. We therefore sought to investigate the associations between different risk factors and pathologic upstaging in stage T2N0M0 esophageal cancer patients who underwent esophagectomy. We retrospectively reviewed the clinicopathological characteristics of 224 stage T2N0M0 squamous cell esophageal cancer patients who underwent complete resection over a 2-year period (October 2016-September 2018). The tumor volume (TV) was automatically measured from thin-layer chest CT scans using imaging software. Univariate and multivariate analyses were performed to identify the risk factors associated with upstaging. A receiver operating characteristic (ROC) curve was plotted, and its ability to identify pathological upstaging was assessed. A total of 224 patients with clinical stage T2N0M0 squamous cell esophageal carcinoma (SCEC) underwent esophagectomy; of these patients, 96 (42.86%) had a more advanced stage during the final pathologic review than during the initial diagnosis. The risk factors for pathologic upstaging included a large TV, high total cholesterol (TC), high triglycerides (TGs), high platelet-to-lymphocyte ratio (PLR), and high number of lymph nodes examined. The ROC analysis demonstrated an area under the curve of 0.845 (95% confidence interval 0.794-0.895). In SECC diagnosed as stage T2N0M0 by CT and EUS, the incidence of postoperative pathologic upstaging increases with a large TV, high TC, high TGs, high PLR, and high number of lymph nodes examined.

Simplified, standardized methods to assess the accuracy of clinical cancer staging

BackgroundHospitals lack intuitive methods to monitor their accuracy of clinical cancer staging, which is critical to treatment planning, prognosis, refinements, and registering quality data. MethodsWe introduce a tabulation framework to compare clinical staging with the reference-standard pathological staging, and quantify systematic errors. As an example, we analyzed 9,644 2016 U.S. National Cancer Institute SEER surgically-treated non-small cell lung cancer (NSCLC) cases, and computed concordance with different denominators to compare with incompatible past results. ResultsThe concordance for clinical versus pathological lymph node N-stage is very good, 83.4 ± 1.0%, but the tumor length-location T-stage is only 58.1 ± 0.9%. There are intuitive insights to the causes of discordance. Approximately 29% of the cases are pathological T-stage greater than clinical T-stage, and 12% lower than the clinical T-stage, which is due partly to the fact that surgically-treated NSCLC are typically lower-stage cancer cases, which results in a bounded higher probability for pathological upstaging. Individual T-stage categories Tis, T1a, T1b, T2a, T2b, T3, T4 invariant percent-concordances are 85.2 ± 9.7 + 10.3%; 72.7 ± 1.6 + 11.3%; 46.6 ± 1.8 + 10.9%; 54.6 ± 1.6 – 20.5%; 41.6 ± 3.3 – 0.1%; 54.7 ± 2.8 – 24.1%; 55.2 ± 4.7 + 2.6%, respectively. Each percent-concordance is referenced to an averaged number of pathological and clinical cases. The first error number quantifies statistical fluctuations; the second quantifies clinical and pathological staging biases. Lastly, comparison of over and under staging versus clinical characteristics provides further insights. ConclusionsClinical NSCLC staging accuracy and concordance with pathological values can improve. As a first step, the framework enables standardizing comparing staging results and detecting possible problem areas. Cancer hospitals and registries can implement the efficient framework to monitor staging accuracy.

Influence of preoperative hydronephrosis and ureteral orifice involvement in the survival of patients undergoing radical cystectomy: A retrospective comparative study.

The aim of the present study was to evaluate the influence of preoperative hydronephrosis and ureteral orifice involvement (UOI) on survival of patients undergoing radical cystectomy (RC) for bladder cancer (BC). A total of 162 patients with BC underwent RC between January 2006 and March 2017. Patients were divided into two groups for both presences of preoperative hydronephrosis and orifice involvement at final pathology. Additionally, tumors with orifice involvement were subgrouped histopathologically after RC as those with only UOI and those with invasive to the ureter with an additional concurrent site at final pathology. Preoperative hydronephrosis was detected in 57 patients. Preoperative and postoperative creatinine on month 3 were higher in the preoperative hydronephrosis (+) group (p<0.001). In addition, postoperative T stage, surgical margin positivity, invasion of urethra, and pathological upstaging were higher in this group. Cancer-specific survival (CSS) and overall survival (OS) were better in the hydronephrosis (-) group than in the hydronephrosis (+) group (p=0.001 and p=0.001, respectively). Preoperative hydronephrosis was found to be an independent factor in pathological upstaging. Patients were divided into two groups according to the presence of UOI. Group 1 consisted of patients without UOI, and group 2 with UOI. Preoperative hydronephrosis, hydronephrosis grade, and T stage were statistically higher in tumors with UOI. Moreover, CSS and OS were lower in group 2 than in group 1. Preoperative hydronephrosis and UOI are predicting factors on survival of patients undergoing RC for BC. Preoperative hydronephrosis was found to be an independent factor in pathological upstaging.

Renal Mass Biopsy is Associated with Reduction in Surgery for Early-Stage Kidney Cancer

To determine whether use of renal mass biopsy may be associated with a reduction in surgery for patients with small, localized renal cell carcinoma (cT1aN0M0), especially among older patients and patients with greater comorbidity burden. A total of 106,258 patients with cT1aN0M0 renal cell carcinoma from 2004 to 2015 were analyzed in the National Cancer Data Base. Multivariable logistic regression identified independent associations with nonsurgical management, receipt of biopsy, and pathologic upstaging. Marginal effects were derived by age and comorbidity. A sensitivity analysis was conducted in years identifying patients undergoing active surveillance (2010-2015). There was increased use of biopsy (8.0%-15.3%) and nonsurgical management (11.7%-15.6%) over time. Biopsy was significantly associated with use of nonsurgical management (OR 4.80 [95%CI 4.58-5.02], P <.001) as well as active surveillance (OR 1.87 [1.69-2.07], P <.001) in the sensitivity analysis. Individual predicted probability of undergoing nonsurgical management ranged from 3% to 92% (median 31.4% with use of biopsy) and increased with age and comorbidity. Pathologic tumor upstaging (≥pT3a) occurred more frequently for patients receiving biopsy compared to no biopsy (5.8% vs 3.3%, P <.001). After adjustment, biopsy remained a statistically significant predictor of upstaging (OR 1.31 [95%CI 1.24-1.38], P <.001). Overall, biopsy demonstrated a strong, independent association with reduced use of surgery for cT1aN0M0 kidney cancer, especially with increasing age and comorbidity. The potential association of renal mass biopsy with upstaging warrants caution, but it is uncertain whether it impacts prognosis relative to true perinephric fat invasion.

Risk Factors of Pathological Upstaging for Patients with Clinical T2N0M0 Esophageal Squamous Cell Carcinoma

Risk Factors of Pathological Upstaging for Patients with Clinical T2N0M0 Esophageal Squamous Cell Carcinoma

Urinary DNA methylation biomarkers for prediction of prostate cancer upgrading and upstaging

BackgroundSignificant numbers of prostate cancer (PCa) patients experience tumour upstaging and upgrading in surgical specimens that cause serious problems in timely and proper selection of the treatment strategy. This study was aimed at the evaluation of a set of established epigenetic biomarkers as a noninvasive tool for more accurate PCa categorization before radical prostatectomy (RP).MethodsQuantitative methylation-specific PCR was applied for the methylation analysis of RARB, RASSF1, and GSTP1 in 514 preoperatively collected voided or catheterized urine samples from the single-centre cohort of 1056 treatment-naïve PCa patients who underwent RP. The rates of biopsy upgrading and upstaging were analysed in the whole cohort.ResultsPathological examination of RP specimens revealed Gleason score upgrading in 27.2% and upstaging in 20.3% of the patients with a total misclassification rate of 39.0%. DNA methylation changes in at least one gene were detected in more than 80% of urine samples. Combination of the PSA test with the three-gene methylation analysis in urine was a significant predictor of pathological upstaging and upgrading (P < 0.050), however, with limited increase in overall accuracy. The PSA test or each gene alone was not informative enough.ConclusionsThe urinary DNA methylation assay in combination with serum PSA may predict tumour stage or grade migration post-RP aiding in improved individual risk assessment and appropriate treatment selection. Clinical utility of these biomarkers should be proven in larger multi-centre studies.

Oncological outcomes and pathological characteristics of cT1 upstaging to pT3a renal cell carcinoma compared with de novo pT3a tumours

IntroductionThe significance of upstaging of cT1 renal tumors to pT3a is not clear. We evaluate the incidence of upstaging, identify predictors and analyze oncological outcomes of these patients versus those who did not upstage. We also compared the oncological outcomes of cT1 upstaging to pT3a with de novo pT3a renal tumors. MethodsFrom a database of 1021 renal tumors with complete available follow-up data, 517 patients had cT1. Patients upstaging to pT3a were compared to those who did not. Baseline clinical, perioperative, histopathologic features and oncological outcomes were analysed. ResultsOut of 517 cT1 patients, 105 (20.3%) upstaged to pT3a and 412 (79.7%) did not. Proportion of patients in each group undergoing partial and radical nephrectomy, postoperative tumor size, histology, margin status and lymph node involvement were similar. Among upstaged, 9 patients (8.6%) developed first recurrence as compared to only 3 (0.7%) in those not upstaging (p<0.001). The median time to recurrence (57 vs. 107 months; p<0.001) was lesser in de novo pT3a renal tumors. ConclusionsPathological upstaging from cT1 to pT3a and necrosis on histopathology were associated with recurrence.Advanced age, smoking, necrosis on histopathology, clear cell histology and higher Fuhrman grades contributed to pathological upstaging of cT1 tumors. De novo pT3a RCC had worse survival when compared to cT1 patients upstaging to pT3a RCC.

Patient (pt) characteristics, treatment patterns, outcomes and prognostic factors in plasmacytoid urothelial carcinoma (PUC).

e16007 Background: PUC is uncommon and highly aggressive, with limited data on treatment patterns, outcomes and prognostic factors. We hypothesized that PUC is associated with clinical under-staging, poor outcomes and lack of chemotherapy (CT) response. Methods: We conducted a retrospective review of pts with UC and plasmacytoid component (PUC), seen in our institution (2000 - 2018). Demographic and clinicopathologic data, treatment modalities, pathologic complete/partial response (pCR, pPR) to neoadjuvant CT (NAC), and overall survival (OS) from diagnosis and surgery (Sx) were captured. T-test, chi-square, and Cox-regression were used to explore potential prognostic associations. OS was estimated with KM method. Results: We identified 63 consecutive pts (51 men) with available data for analysis. Median age at diagnosis was 67 (44-89). During initial diagnostic workup, 32 (51%) pts had extravesical disease (cT3:24, cT4:8) and 23 (36.5%) hydronephrosis at imaging. Overall, 39 (62%) pts underwent Sx with curative intent, 25 (39.6%) were pre-treated with cisplatin-based NAC; adjuvant CT was given to 15 (24%). The remaining pts pursued bladder-sparing and/or palliative approaches. At time of Sx, 17/39 (43.6%) pts had pathologic upstaging, 10 (25.6%) had positive margins and 19 (48.7%) pN+ stage. In the NAC pt subset (25 pts), 5 (20%) had progression on scans, 19 (76%) had Sx; 2 pts had pCR (10.5%), 1 had pPR, 6 (31.5%) had pathologic upstaging. In the entire cohort, median follow-up was 8 months. Median OS was 20.7 months from diagnosis and 23.6 months from Sx. NAC was not significantly associated with longer OS (from Sx) (HR 1.53, 95%CI 0.16-15, p = 0.715) and the same was true for adjuvant CT (HR 0.64, 95%CI 0.1-4, p = 0.630). 15/39 pts recurred after Sx (38.4%), with 9/15 (60%) having peritoneal/retroperitoneal involvement. Conclusions: PUC frequently presented with advanced stage at diagnosis and demonstrated poor NAC response, frequent upstaging, positive margins and pN+ stage at Sx. More than half of patients who recurred after Sx, presented with (retro)peritoneal disease. Studies evaluating molecular biomarkers and drivers in PUC, and prospective clinical trials are being pursued.

Prognostic implications of prostatic urethral involvement in non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer involving the prostatic urethra is associated with pathologic upstaging and shorter survival. We investigated the survival impact of prostatic urethral involvement in non-muscle-invasive patients who are not upstaged at cystectomy. From 2000 to 2016, 177 male patients underwent cystectomy for high-risk non-muscle-invasive bladder cancer and remained pT1, pTis, or pTa, and N0 on final pathology; 63 (35.6%) patients had prostatic urethral involvement and 114 (64.4%) did not. Prostatic involvement was non-invasive (Ta or Tis) in 56 (88.9%) patients and superficially invasive (T1) in 7 (11.1%) patients. No patient had stromal invasion. Log-rank and Cox regression analyses were used to evaluate survival. Compared to patients without prostatic urethral involvement, patients with involvement were more likely to have received intravesical therapy (84.6% vs. 64.4%, p < 0.01), have multifocal tumor (90.8% vs. 51.7%, p < 0.01), and have positive urethral margins (7.7% vs. 0%, p < 0.01) and ureteral margins (18.5% vs. 5.1%, p < 0.01). Log-rank comparison showed inferior recurrence-free, cancer-specific, and overall survival in patients with prostatic involvement (p = 0.01, p = 0.03, p < 0.01). Patients with prostatic urethral involvement were more likely to experience recurrence in the urinary tract (p < 0.01). On Cox regression, prostatic urethral involvement was an independent predictor of overall mortality (HR=2.08, p < 0.01). Prostatic urethral involvement is associated with inferior survival in patients who undergo cystectomy for non-muscle-invasive bladder cancer and remain pT1, pTis, or pTa on final pathology. Prostatic urethral involvement is thus an adverse pathologic feature independent of its association with upstaging.

Resultados oncológicos y características patológicas de la sobrestadificación de cT1 a carcinoma de células renales pT3a en comparación con los tumores pT3a de novo

IntroductionThe significance of upstaging of cT1 renal tumors to pT3a is not clear. We evaluate the incidence of upstaging, identify predictors and analyze oncological outcomes of these patients versus those who did not upstage. We also compared the oncological outcomes of cT1 upstaging to pT3a with de novo pT3a renal tumors. MethodsFrom a database of 1021 renal tumors with complete available follow-up data, 517 patients had cT1. Patients upstaging to pT3a were compared to those who did not. Baseline clinical, perioperative, histopathologic features and oncological outcomes were analysed. ResultsOut of 517 cT1 patients, 105 (20.3%) upstaged to pT3a and 412 (79.7%) did not. Proportion of patients in each group undergoing partial and radical nephrectomy, postoperative tumor size, histology, margin status and lymph node involvement were similar. Among upstaged, 9 patients (8.6%) developed first recurrence as compared to only 3 (0.7%) in those not upstaging (P <0.001). The median time to recurrence (57 vs. 107 months; P <0.001) was lesser in de novo pT3a renal tumors. ConclusionsPathological upstaging from cT1 to pT3a and necrosis on histopathology were associated with recurrence.Advanced age, smoking, necrosis on histopathology, clear cell histology and higher Fuhrman grades contributed to pathological upstaging of cT1 tumors. De novo pT3a RCC had worse survival when compared to cT1 patients upstaging to pT3a RCC.

Preoperative factors predictive of pathologic upstaging in clinical stage I gastric cancer patients.

39 Background: In patients with stage 1 gastric cancer, surgical resection without neoadjuvant therapy is offered as the first line treatment. However, some of these patients are found to have higher stage after resection and miss the opportunity for neoadjuvant therapy. Preoperative patient and tumor characteristics may be predictive of the likelihood of pathological upstaging in stage 1 gastric cancer patients who have not received neo-adjuvant therapy. Methods: The National Cancer Database was queried for patients diagnosed from 2004-2015 with clinical stage 1 gastric adenocarcinoma who had undergone surgical resection without neoadjuvant therapy. Univariate analysis and multivariable logistic regression were conducted to determine pre-operative factors associated with pathological upstaging. Candidate variables examined included age, sex, race, tumor size, histology, grade, tumor location, days to surgery, and lymphovascular invasion. Results: Analysis was conducted on 8,015 clinical stage 1 patients. Overall 1,981 (25%) patients were upstaged. On multivariable logistic regression analysis, significant predictors of upstaging included increasing tumor size [ref : size &lt; 1 cm, 1-2 cm aOR=3.8 (95% CI 2.3-6.1); 2-4 cm aOR=12.4 (7.9-19.5); &gt; = 4cm aOR=25.9 (22.9-56.4)], younger age [ref: &gt; = 75, &lt; 50 aOR=1.7 (1.4-2.1), 50-65 aOR=1.4 (1.2-1.6), 65-75 aOR=1.2 (1.1-1.5)], male gender [aOR=1.16 (1.0-1.3)], presence of diffuse type gastric cancer [aOR=2.3 (1.7-3.2)], mucinous type [aOR=1.7 (1.1-2.5)], or signet ring cell histology [aOR=1.6 (1.3-2.0)] compared to intestinal histology, presence of lymphovascular invasion [aOR=6.0 (5.0-7.1)], and increasing grade [ref: grade 1, grade 2 aOR=2.30 (1.7-3.5); grade 3 aOR=4.9 (3.6- 6.7)]. Conclusions: A quarter of all patients thought to have stage 1 gastric cancer prior to surgery had higher pathologic stage at time of resection. Patients with the above risk factors may be understaged with currently available diagnostic tools. The addition of neoadjuvant therapy should be considered when the above risk factors are present in clinical stage 1 patients.

A risk-stratified approach to neoadjuvant chemotherapy in muscle-invasive bladder cancer: implications for patients classified with low-risk disease.

To validate published risk criteria for informing use of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC), and to examine outcomes of low-risk (LR) patients treated with immediate radical cystectomy (RC). We identified 1931 patients who underwent RC for MIBC from 1980 to 2016. Patients were considered high risk (HR) with hydronephrosis, lymphovascular invasion, variant histology and/or cT3/4 disease. Kaplan-Meier survival estimates were compared to patients classified as LR, and logistic regression was used to examine factors associated with pathologic downstaging. A total of 1025 LR and 906 HR patients were identified. Median follow-up was 6.3years (IQR 2.6-12), during which time 1321 (68%) patients died, 753 (39%) from bladder cancer. HR patients had significantly lower 5-year CSS than LR patients (50% vs. 68%, p = 0.001). Of 561 cisplatin-eligible LR patients treated with RC without NAC, 293 (52%) had pathologic non-organ confined disease; of these, 81 (14%) received adjuvant chemotherapy; 78 (14%) did not due to a perioperative event, while 134 (24%) did not due to patient/provider choice. NAC in LR patients was associated with greater odds of pT0 (OR 3.05; p < 0.001) and < pT2 (OR 2.53; p < 0.001) disease, but was not significantly associated with CSS (p = 0.31). Our results validate the proposed risk groups. Among LR patients treated without NAC, 52% experienced pathologic upstaging, and 14% were unable to receive adjuvant chemotherapy due to a perioperative event. These data support offering NAC to both HR and LR MIBC patients, and may be useful for patient counseling.