Large Multi-institutional Cohort Research Articles

Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort.

Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albuminratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters. CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment. UMIN000040462.

Abstract PO5-05-12: Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a

Abstract Introduction: The impact of loco-regional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (BC) is controversial. The aim of this study is to assess the effect of LRT on survival utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with de novo metastatic BC with bone-only metastases were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Patients who received LRT were divided into two groups: those who received ST after LRT (LRT+ST arm) and those who received ST prior to LRT (ST+LRT arm). Solitary or multiple bone metastases were classified, and factors associated with disease progression were analyzed. Results: There were a total of 744 patients with de novo bone-only metastatic BC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32-66, 25-75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs 55 (44, 66), p=0.0001]. There were no significant differences in grade, Her2 neu and triple negative status, receipt of hormonal therapy and intervention to metastatic sites. During follow-up, 58% (n=217) of patients in ST arm and 32% (n=120) of patients in LRT arm died (p&amp;lt; 0.001). Local progression was observed in 20% of the patients in the ST arm whereas it was 9% in the LRT arm (p=0.0001). Systemic progression occurred more in ST arm; 66% (n=244) compared to 41% (n=152) of patients in LRT group (p&amp;lt; 0.001). The Hazard of death was 64% lower in LRT group than in ST group (HR: 0.36, 95% CI: 0.29-0.45), p&amp;lt;0.0001). The burden of metastatic disease was significantly different between groups with the solitary bone metastasis rate higher in LRT group than the ST only group (50% vs 24%, p&amp;lt; 0.001). However, the LRT group had better overall survival for both solitary (HR: 0.38, 95% Cl: 0.26-0.55) and multiple (HR: 0.38, 95% Cl: 0.29-0.51) bone metastases patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST.Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p&amp;lt; 0.05). Conclusion: Analysis of this large multi-institutional patient cohort provides further evidence that LRT improves overall survival and lowers loco-regional recurrence in patients with de novo bone-only metastatic BC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Didem Can Trabulus, Jamila El-Azrhi, Kazim Senol, Berk Goktepe, Shruti Zaveri, Salyna Meas, Umut Demirci, Hasan Karanlik, Aykut Soyder, Ahmet Dağ, Ahmet Bilici, Mutlu Dogan, Mehmet Ali Nahit Sendur, Hande Koksal, Mehmet Ali Gulcelik, Neslihan Cabıoğlu, Levent Yeniay, N. Zafer Utkan, Nuri Karadurmus, Gul Daglar, Turgay Simsek, Birol Yildiz, Cihan Uras, Mustafa Tukenmez, Cihangir Ozaslan, Niyazi Karaman, Arda Isik, Berkay Demirors, Efe Sezgin, Vahit Ozmen, Anthony Lucci. Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-12.

Leveraging radiomics and machine learning to differentiate radiation necrosis from recurrence in patients with brain metastases.

Radiation necrosis (RN) can be difficult to radiographically discern from tumor progression after stereotactic radiosurgery (SRS). The objective of this study was to investigate the utility of radiomics and machine learning (ML) to differentiate RN from recurrence in patients with brain metastases treated with SRS. Patients with brain metastases treated with SRS who developed either RN or tumor reccurence were retrospectively identified. Image preprocessing and radiomic feature extraction were performed using ANTsPy and PyRadiomics, yielding 105 features from MRI T1-weighted post-contrast (T1c), T2, and fluid-attenuated inversion recovery (FLAIR) images. Univariate analysis assessed significance of individual features. Multivariable analysis employed various classifiers on features identified as most discriminative through feature selection. ML models were evaluated through cross-validation, selecting the best model based on area under the receiver operating characteristic (ROC) curve (AUC). Specificity, sensitivity, and F1 score were computed. Sixty-six lesions from 55 patients were identified. On univariate analysis, 27 features from the T1c sequence were statistically significant, while no features were significant from the T2 or FLAIR sequences. For clinical variables, only immunotherapy use after SRS was significant. Multivariable analysis of features from the T1c sequence yielded an AUC of 76.2% (standard deviation [SD] ± 12.7%), with specificity and sensitivity of 75.5% (± 13.4%) and 62.3% (± 19.6%) in differentiating radionecrosis from recurrence. Radiomics with ML may assist the diagnostic ability of distinguishing RN from tumor recurrence after SRS. Further work is needed to validate this in a larger multi-institutional cohort and prospectively evaluate it's utility in patient care.

(181) Prior Radiation Therapy is Associated with Increased Risk of Intra-Operative Complications in Patients Undergoing Primary Inflatable Penile Prosthesis Placement: Results from a Large Multi-Institutional Collaborative

Abstract Introduction Radiation therapy (RT) can predispose the onset of corporal fibrosis and microvasculopathy. The impact of RT on intra-operative complications is not well described in the literature. Objective In this study, we assess intra-operative and post-operative outcomes among patients with or without prior history of RT following primary Inflatable Penile Prosthesis (IPP) implantation. Methods We performed a multicenter, retrospective analysis of men undergoing primary IPP placement between January 2015 and December 2022. A total of 3530 patients were identified, of which 3319 had no prior history of RT and 211 patients had history of RT. After 1:1 propensity score matching for all confounding variables, 211 patients with a history of RT were compared to 211 nonradiated patients for intra-operative and post-operative outcomes. Chi-square and Mann-Whitney tests were used for statistical analysis for categorial and continuous variables respectively. For multivariable analysis, we used a forward stepwise model and included significant variables found on pre-operative characteristics of patients. Kaplan-Meier time to event analysis were compared with Mantel-Cox log-rank test. Results Patients with history of RT encountered more intra-operative complications (4.3% vs 0.9%, p=0.032); specifically, these men experienced more distal crossover events (1.9% vs 0, p=0.044). On multivariable analysis, history of prior RT (OR 5.29, 95% CI 1.07-26.3, p=0.041) and diabetes mellitus (OR 10.5, 95% CI 2.58-43.5, p=0.01) were associated with increased risk of intra-operative complications. History of obesity (OR 0.11, 95% CI 0.01-0.91, p=0.040) reduced risk of intra-operative complications. There was no significant difference in early or late post-operative non-infectious complications between both groups and there was also no significant difference in risk of post-operative complications within 24 months on Kaplan Meier analysis (log rank p=0.9). Conclusions In this large multi-institutional cohort, history of RT is an independent predictor of intra-operative complications but not post-operative complications during primary IPP placement. These findings may help inform patient-specific counseling while guiding surgical planning to prevent untoward morbidity following surgery. Disclosure No.

Impact of Maintenance Rituximab Following First-Line Systemic Therapy on Outcomes in Patients with Marginal Zone Lymphoma: Real-World Evidence from 10 US Centers

Introduction First-line treatment options for patients (pts) with marginal zone lymphoma (MZL) include rituximab monotherapy (R) and immunochemotherapy (IC), such as bendamustine with rituximab (BR) or RCHOP/RCVP. The efficacy of maintenance rituximab (M-R) has been studied in splenic (SMZL) and nodal (NMZL) MZL, showing a benefit in progression-free survival (PFS) when M-R is administered after BR (Rummel et al., ASCO 2018). However, the role of M-R in pts with extranodal MZL (EMZL) of the mucosa-associated lymphatic tissue (MALT), or those receiving R or RCHOP/RCVP, remains uncertain. In this study, we analyzed the outcomes of pts with MZL who received M-R after their first-line systemic therapy (R or IC) using data from a large multi-institutional retrospective cohort. Methods Adult pts with MZL (SMZL, NMZL, or EMZL) who were treated at 10 US medical centers from 2010 onwards were included. Pts who had received first-line treatment with either R or IC and achieved a partial (PR) or complete (CR) response to the initial therapy were divided into groups based on whether they subsequently received M-R or not. To avoid immortal-time bias, we required a minimum follow-up of 6 months from diagnosis. Outcomes included PFS, overall survival (OS) and cumulative incidence of histologic transformation (HT). Because of non-proportional hazards, Wilcoxon test was used to compare survival curves, and Cox models (augmented by multiple imputation to account for missing data) were bounded by 6 years of follow up. Multivariable models adjusted for prognostic factors including age, sex, performance status, stage, baseline hemoglobin, albumin, LDH, type of IC and CR/PR status at the end of therapy. Results The study included 427 pts with a median age of 63 years. Of these pts, 53% were women, and 49% had EMZL, 27% had NMZL, and 23% had SMZL. The first-line therapies received were R (54%), BR (36%), RCHOP (7%), or RCVP (3%). A CR was achieved by 70% (n=298) of pts after the initial therapy. Overall, 33% (n=140) received M-R with a median of 8 cycles. Among pts who initially had PR, 39% converted to a CR during M-R therapy. The median follow-up period was 5 years. Factors associated with a higher likelihood of receiving M-R included achieving a PR instead of a CR after the first-line therapy (41% vs 29% receiving M-R, respectively; p=0.02) and having the SMZL subtype (p=0.03, Fig 1A). Pts treated with RCHOP were less likely to receive M-R compared to those receiving other regimens (p=0.049). There was also evidence of hospital-level preference to either prescribe M-R or not. We analyzed survival outcomes separately for pts who received first-line IC or R monotherapy, stratified further by MZL subtype and the type of IC regimen. Among pts who received IC (n=197), M-R was associated with longer PFS (median of 9.0 vs. 6.8 years, p=0.008, Fig 1B). However, the statistical significance was lost in the multivariable model (adjusted HR=0.52, 95%CI=0.25-1.10). When evaluated by MZL subtype, pts with EMZL had a significantly longer PFS with M-R (p=0.01), while those with NMZL and SMZL did not (p=0.41 and 0.10, respectively). When examining the type of first-line IC, pts receiving RCHOP/RCVP had a prolonged PFS with M-R (p=0.03), whereas the difference was not statistically significant after BR (p=0.12). There was no difference in OS overall (p=0.09; adjusted HR=0.55, 95%CI=0.12-2.60) or in any subgroup. Among pts who received first-line R, there were no statistically significant differences in PFS (p=0.70; adjusted HR=0.99, 95%CI=0.59-1.66) or OS (p=0.17) based on the receipt of M-R, either in the entire cohort or any subset. A total of 14 transformation events occurred during the study, including 3 in the M-R group. The cumulative incidence of HT did not significantly differ between the two groups (sub-HR=0.76, 95%CI=0.21-2.82, p=0.68). Discussion In this large retrospective cohort study, the use of M-R in MZL was primarily influenced by local preferences, the quality of response after initial treatment, and the type of IC regimen. Receipt of M-R was associated with a longer PFS for pts receiving first-line IC, especially for those with EMZL and those receiving RCHOP/RCVP. These findings suggest a PFS advantage of M-R in EMZL, which is a novel observation. However, this advantage was not observed in terms of OS or the rate of HT. M-R after initial R did not show any significant differences in outcomes for MZL.

Leveraging Quantitative Imaging and Machine Learning to Differentiate Radionecrosis from Disease Recurrence in Patients with Brain Metastases

Radiation necrosis can be difficult to non-invasively discern from tumor progression after stereotactic radiosurgery (SRS). In this work, we investigate the utility of radiomics (computerized features) and machine learning to capture per-voxel lesion heterogeneity on routine MRI scans, to differentiate radionecrosis from tumor recurrence in patients with brain metastases treated with SRS. A retrospective analysis was conducted of patients with brain metastases treated with SRS. Eighty-three lesions (n = 56 intact; n = 27 surgical cavity) from 69 patients were identified with median age 68.8 years (range 40.2 - 91.0), of whom 53.6% were male and 33.3% received prior whole-brain radiotherapy (WBRT). Lesion histology included lung (60.2%), renal cell (15.7%), melanoma (10.8%), breast (9.6%), and other (3.6%). Pathologic confirmation was available in 73.5% of lesions. Both intact and resection cavity lesions were included and individually segmented. Image preprocessing and radiomic feature extraction were done using ANTsPy and open-source software. A total of 210 features were extracted from post-contrast T1-weighted (T1w) and T2/FLAIR MRIs. Highly correlated features were removed. Univariate logistic regression was conducted on the remaining T1w and T2/FLAIR features as well as on clinical variables. Multivariate analysis was implemented with various classifiers (Random Forest, Ridge, Lasso, Support Vector Machine [SVM]) on the top-performing features found on univariate logistic regression. Models were assessed using cross-validation to select the best model by area under ROC curve (AUC). Specificity and sensitivity were calculated. On univariate analysis, the top 10 radiomics features consisted of 6 T1w features and 4 T2/FLAIR features (4 GLCM, 3 first order, 1 GLSZM, 1 GLRLM, and 1 shape feature). Age, gender, disease site, prior WBRT, prior fractionated SRS, planning tumor volume, brain-GTV V12 Gy, and immunotherapy before or after SRS were not predictive (AUC less than 62.0%) on univariate analysis compared to radiomic features. Multivariate analysis of top performing radiomic features on both intact and surgical cavities yielded an AUC of 72.0% (standard deviation [SD] ±8.8%). Multivariate analysis of top features on intact lesions alone improved the AUC to 80.5% (SD ±10.8%), with sensitivity of 77.8%, specificity of 72.4%, and positive likelihood ratio of 2.82 in differentiating radionecrosis from recurrence. Radiomics and machine learning tools may improve diagnostic ability of distinguishing radiation necrosis from tumor recurrence after SRS. Further work is needed to deploy this in a larger multi-institutional cohort and prospectively evaluate its efficacy as a decision-support tool to personalize care in patients with brain metastases.

A multi-institutional study of 1,111 men with 4K score, multiparametric magnetic resonance imaging, and prostate biopsy

ObjectiveProstate magnetic resonance imaging (MRI) and biomarkers are often used in conjunction to enhance the selection process for prostate biopsy. However, the optimal sequence of ordering these tests has not been established. A comprehensive evaluation was conducted on a large multi-institutional cohort of patients who underwent MRI, 4K score, and biopsy of the prostate to examine the impact of utilizing both tests vs. either test alone and to determine if the order in which these tests are administered affects the ability to detect clinically significant prostate cancer (csCaP). Methods and materialsWe evaluated men from 8 different institutions who were referred for prostate cancer evaluation and underwent MRI, 4K score test, and prostate biopsy. The primary outcome was the presence of csCaP, defined as grade group 2 or higher cancer on a biopsy of the prostate. We used logistic regression, calibration plots, and decision curve analysis to evaluate using a 4K score or MRI alone vs. both tests together for detecting csCaP. In addition, we evaluated several strategies using one or both tests for selecting men for biopsy and compared them based on the proportion of biopsies avoided and the csCaP's missed. ResultsAmong the 1,111 men who formed the final cohort, 553 (49.8%) had prostate cancer, and 353 (31.8%) had csCaP. We found that using MRI and 4K score together had better discrimination, calibration, and a higher clinical utility on decision curve analysis compared to using either test individually. Using both tests together resulted in fewer biopsies avoided and missed cancers compared to using either test alone. Strategies that sequence MRI and 4K score tests resulted in the largest biopsy reduction, with no appreciable difference between starting with an MRI vs. a biomarker. ConclusionsWe found that using both an MRI and 4K score together was superior to using either test alone but found no appreciable difference between starting with an MRI vs. starting with a 4K score. Prospective studies are needed to identify the best strategy to sequence MRI and biomarkers in the evaluation of csCaP.

MP09-01 DETECTION OF CLINICALLY SIGNIFICANT PROSTATE CANCER ON MRI: A COMPARISON OF AN ARTIFICIAL INTELLIGENCE MODEL VERSUS RADIOLOGISTS

You have accessJournal of UrologyCME1 Apr 2023MP09-01 DETECTION OF CLINICALLY SIGNIFICANT PROSTATE CANCER ON MRI: A COMPARISON OF AN ARTIFICIAL INTELLIGENCE MODEL VERSUS RADIOLOGISTS Simon John Christoph Soerensen, Richard E. Fan, Indrani Bhattacharya, David S. Lim, Sarir Ahmadi, Xinran Li, Sulaiman Vesal, Mirabela Rusu, and Geoffrey A. Sonn Simon John Christoph SoerensenSimon John Christoph Soerensen More articles by this author , Richard E. FanRichard E. Fan More articles by this author , Indrani BhattacharyaIndrani Bhattacharya More articles by this author , David S. LimDavid S. Lim More articles by this author , Sarir AhmadiSarir Ahmadi More articles by this author , Xinran LiXinran Li More articles by this author , Sulaiman VesalSulaiman Vesal More articles by this author , Mirabela RusuMirabela Rusu More articles by this author , and Geoffrey A. SonnGeoffrey A. Sonn More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003224.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Automated detection of prostate cancer on magnetic resonance imaging (MRI) may help target biopsies and avoid unnecessary biopsies of false-positive lesions. We sought to develop an artificial intelligence (AI) model to rapidly and accurately identify cancer foci on MRI and compare its performance against radiologists. METHODS: A total of 1504 subjects underwent multiparametric MRI at more than 30 institutions in the US, followed by MRI-ultrasound fusion biopsy at one institution. We used T2-weighted images (T2WI), apparent diffusion coefficient maps (ADC), and diffusion-weighted imaging (DWI) from 1404 cases to train an AI model. MRI lesions were initially identified and outlined by a radiologist using T2WIs, DWIs, ADC, and contrast enhanced images (DCE). Cancers were confirmed by biopsy. Only lesions containing Gleason 3+3 (≥ 40% cancer core length) or Gleason ≥3+4 (any amount) in at least one targeted biopsy core were considered for training and testing the model. All other MRI lesions were removed. Systematic cores with significant cancer were also included for model training. We tested the AI model on 100 independent cases and compared it against trained radiologists. We computed lesion-level AUC, sensitivity, specificity, and negative predictive value (NPV). RESULTS: AI and radiologists had similar performances across all metrics, and all differences were non-significant. The AI model had an AUC of 0.79±0.22, NPV of 0.66±0.26, sensitivity of 0.34±0.41, and specificity of 0.99±0.05. Radiologists had an AUC of 0.81±0.22, NPV of 0.69±0.28, sensitivity of 0.37±0.45, and specificity of 0.99±0.05. CONCLUSIONS: In this study, we trained and tested an AI model on a large and diverse multi-institutional cohort of MRIs. The model matched the performance of radiologist experts. In future work, we envision comparing model performance against radiologists at different skill levels and comparing radiologist + AI vs radiologist performance alone. Source of Funding: Departments of Radiology and Urology, Stanford University, National Cancer Institute of the National Institutes of Health (R37CA260346 to M.R), and the generous philanthropic support of our patients (G.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e103 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Simon John Christoph Soerensen More articles by this author Richard E. Fan More articles by this author Indrani Bhattacharya More articles by this author David S. Lim More articles by this author Sarir Ahmadi More articles by this author Xinran Li More articles by this author Sulaiman Vesal More articles by this author Mirabela Rusu More articles by this author Geoffrey A. Sonn More articles by this author Expand All Advertisement PDF downloadLoading ...

MP29-03 MULTI-INSTITUTIONAL ANALYSIS OF METASTASIS DIRECTED THERAPY WITH OR WITHOUT ANDROGEN DEPRIVATION THERAPY IN OLIGOMETASTATIC CASTRATION SENSITIVE PROSTATE CANCER

MP29-03 MULTI-INSTITUTIONAL ANALYSIS OF METASTASIS DIRECTED THERAPY WITH OR WITHOUT ANDROGEN DEPRIVATION THERAPY IN OLIGOMETASTATIC CASTRATION SENSITIVE PROSTATE CANCER

MP80-14 EXTRAPERITONEAL SINGLE-PORT ROBOTIC RADICAL PROSTATECTOMY IN OVER 700 PATIENTS: UPDATED MULTI-INSTITUTIONAL COHORT STUDY FROM THE SPARC COLLABORATION

You have accessJournal of UrologyCME1 Apr 2023MP80-14 EXTRAPERITONEAL SINGLE-PORT ROBOTIC RADICAL PROSTATECTOMY IN OVER 700 PATIENTS: UPDATED MULTI-INSTITUTIONAL COHORT STUDY FROM THE SPARC COLLABORATION Ethan Ferguson, Jennifer L. Nguyen, Roxana Ramos, Grace Chen, Kennedy Okhawere, Samantha Wilder, Ruth Sanchez De La Rosa, Jaya Chavali, Indu Saini, James Peabody, Ketan K. Badani, Craig Rogers, Jeffrey Nix, Jean Joseph, Michael Stifelman, Simone Crivellaro, Mutahar Ahmed, Moses Kim, and Jihad Kaouk Ethan FergusonEthan Ferguson More articles by this author , Jennifer L. NguyenJennifer L. Nguyen More articles by this author , Roxana RamosRoxana Ramos More articles by this author , Grace ChenGrace Chen More articles by this author , Kennedy OkhawereKennedy Okhawere More articles by this author , Samantha WilderSamantha Wilder More articles by this author , Ruth Sanchez De La RosaRuth Sanchez De La Rosa More articles by this author , Jaya ChavaliJaya Chavali More articles by this author , Indu SainiIndu Saini More articles by this author , James PeabodyJames Peabody More articles by this author , Ketan K. BadaniKetan K. Badani More articles by this author , Craig RogersCraig Rogers More articles by this author , Jeffrey NixJeffrey Nix More articles by this author , Jean JosephJean Joseph More articles by this author , Michael StifelmanMichael Stifelman More articles by this author , Simone CrivellaroSimone Crivellaro More articles by this author , Mutahar AhmedMutahar Ahmed More articles by this author , Moses KimMoses Kim More articles by this author , and Jihad KaoukJihad Kaouk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003357.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: An extraperitoneal approach to single-port (SP) robot-assisted radical prostatectomy has been demonstrated with proposed benefits in decreased morbidity, single incision, and same-day discharge. We sought to determine the perioperative and early postoperative outcomes in a large, multi-institutional setting. METHODS: SP extraperitoneal radical prostatectomy was performed in 712 patients between February 2019 and October 2022. All procedures were performed by experienced robotic surgeons from eight tertiary medical centers. Data from baseline demographics, perioperative and early postoperative outcomes were collected prospectively and analyzed retrospectively RESULTS: All reported procedures were completed without open conversion, blood transfusions, or intraoperative complications. The median follow-up time was 11.7 months for the entire cohort. The median age, BMI and preoperative PSA were 64 years, 27.9kg/m2, and 6.4 ng/mL, respectively. About 30% of the patients had at least one previous abdominal surgery. On pathology, high risk disease was noted in 12% and lymph node involvement on final pathology was present in 5.8%. Extraprostatic extension was noted in 38% and positive surgical margins were present in 30.2% of cases. Lymphadenectomy was performed in 85% of patients and the median lymph node yield was 5 nodes. There were no intraoperative complications and inadvertent peritoneal entry with insufflation was rare (0.6%) and managed conservatively. Postoperative complications occurred in 11.8%. The median length of stay and foley catheter duration were 8 hours and 7 days, respectively. Postoperative recovery of continence was 69% at 3 months and 88% at 6 months. Recovery of potency was 35.6% at 6 months. CONCLUSIONS: Single-port extraperitoneal robotic radical prostatectomy is safe and feasible for management of clinically localized prostate cancer. Analysis from a large multi-institutional cohort shows promising single incision and short hospital length of stay without compromise in early functional or oncologic outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1157 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ethan Ferguson More articles by this author Jennifer L. Nguyen More articles by this author Roxana Ramos More articles by this author Grace Chen More articles by this author Kennedy Okhawere More articles by this author Samantha Wilder More articles by this author Ruth Sanchez De La Rosa More articles by this author Jaya Chavali More articles by this author Indu Saini More articles by this author James Peabody More articles by this author Ketan K. Badani More articles by this author Craig Rogers More articles by this author Jeffrey Nix More articles by this author Jean Joseph More articles by this author Michael Stifelman More articles by this author Simone Crivellaro More articles by this author Mutahar Ahmed More articles by this author Moses Kim More articles by this author Jihad Kaouk More articles by this author Expand All Advertisement PDF downloadLoading ...

Outcomes for patients with dementia undergoing emergency and elective colorectal surgery: A large multi-institutional comparative cohort study

BackgroundAlzheimer's Disease and Related Dementias (ADRD) may result in poor surgical outcomes. The current study aims to characterize the risk of ADRD on outcomes for patients undergoing colorectal surgery. MethodsColorectal surgery patients with and without ADRD from 2007 to 2017 were identified using electronic health record-linked Medicare claims data from two large health systems. Unadjusted and adjusted analyses were performed to evaluate postoperative outcomes. Results5926 patients (median age 74) underwent colorectal surgery of whom 4.8% (n = 285) had ADRD. ADRD patients were more likely to undergo emergent operations (27.7% vs. 13.6%, p < 0.001) and be discharged to a facility (49.8% vs 28.9%, p < 0.001). After multi-variable adjustment, ADRD patients were more likely to have complications (61.1% vs 48.3%, p < 0.001) and required longer hospitalization (7.1 vs 6.1 days, p = 0.001). ConclusionsThe diagnosis of ADRD is an independent risk factor for prolonged hospitalization and postoperative complications after colorectal surgery.

P53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR]=2.18, 95% confidence interval [CI] 1.36-3.47, p=0.0011) and with CCC (HR=1.57, 95% CI 1.11-2.22, p=0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer.

Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

Racial disparities in the pharmacological treatment of insomnia: A time-to-event analysis using real-world data

ObjectiveExamine the association between race and time to pharmacologic treatment of insomnia in a large multi-institutional cohort. MethodsRetrospective analysis of electronic medical records from a regional health information exchange. Eligible patients included adults with at least one healthcare visit per year from 2010 to 2019, a new insomnia diagnosis code during the study period, and no prior insomnia diagnosis codes or medications. A Cox frailty model was used to examine the association between race and time to an insomnia medication after diagnosis. ResultsIn total, 9557 patients were analyzed, 7773 (81.3%) of whom where White, 1294 (13.5%) Black, 238 (2.5%) Other, and 252 (2.6%) unknown race. About 6.2% of Black and 8% of Other race patients received an order for a Food and Drug Administration-approved insomnia medication after diagnosis compared with 13.5% of White patients. Black patients were significantly less likely to have an order for a Food and Drug Administration-approved insomnia medication at all time points (adjusted hazard ratio [aHR] range: 0.37-0.73), and patients reporting Other race were less likely to have received an order at 2 (aHR 0.51, 95% confidence interval [CI] 0.28-0.94), 3 (aHR 0.33, 95% CI 0.13-0.79), and 4 years (aHR 0.21, 95% CI 0.06-0.71) of follow-up. Similar results were observed in a sensitivity analysis including off-label medications. ConclusionsPatients belonging to racial minority groups are less likely to be prescribed an insomnia medication than White patients after accounting for sociodemographic and clinical factors. Further research is needed to determine the extent to which patient preferences and physician perceptions affect these prescribing patterns and investigate potential disparities in nonpharmacologic treatment.

RBIO-06. CLINICAL AND MOLECULAR PREDICTORS OF RADIATION RESPONSIVENESS IN MENINGIOMAS: A MULTICENTER RETROSPECTIVE COHORT STUDY

Abstract BACKGROUND Aside from surgery, radiotherapy (RT) remains the only standard of care treatment for meningiomas. However, few studies have identified clinical/molecular biomarkers associated with responsiveness to RT and the optimal timing of RT after surgery remains controversial. We aimed to assess outcomes in a large multi-institutional cohort of RT-treated meningiomas to identify clinical factors and DNA methylation and RNA expression markers associated with progression-free survival (PFS) post-RT. METHODS Patients with intracranial meningiomas who underwent treatment with fractionated RT between 1997-2018 were included. DNA-methylation using the Illumina 850K EPICArray and RNA-sequencing were performed on tumours with sufficient tissue. Primary endpoints were radiographic recurrence of progression and time to progression from the time of RT completion. RESULTS 404 meningiomas were included for analysis. Of these, 167 (41.3%) recurred post-RT, usually within 5-years of RT. Previous RT to the meningioma, having a WHO grade 3 meningioma, and older age at diagnosis were independently associated with poorer PFS post-RT. Following propensity score matching, patients that received adjuvant RT had significantly better PFS post-RT compared to those that received salvage RT after recurrence (p=0.04). DNA methylation on 220 of these meningiomas segregated tumours into two distinct methylation groups (RT-resistant and RT-sensitive) based on unsupervised consensus clustering. DNA methylation were able to independently predict PFS post-RT better than all clinical factors. Differential RNA-expression analysis of these groups showed up-regulation of pathways involved in chromosome segregation and mitotic cell cycle and down-regulation of fatty acid metabolism pathways in RT-resistant meningiomas. CONCLUSION While there are a paucity of clinical factors that can reliably predict a meningioma’s response to RT, DNA methylation and RNA expression biomarkers may aid in differentiating RT-resistant meningiomas from RT-sensitive tumours. Patients that receive adjuvant RT may have prolonged PFS post-RT compared to those that receive salvage RT only after recurrence has already occurred.

Characterization of pediatric brain tumors using pre-diagnostic neuroimaging.

To evaluate for predictive neuroimaging features of pediatric brain tumor development and quantify tumor growth characteristics in patients who had neuroimaging performed prior to a diagnosis of a brain tumor. Retrospective review of 1098 consecutive pediatric patients at a single institution with newly diagnosed brain tumors from January 2009 to October 2021 was performed to identify patients with neuroimaging prior to the diagnosis of a brain tumor. Pre-diagnostic and diagnostic neuroimaging features (e.g., tumor size, apparent diffusion coefficient (ADC) values), clinical presentations, and neuropathology were recorded in those patients who had neuroimaging performed prior to a brain tumor diagnosis. High- and low-grade tumor sizes were fit to linear and exponential growth regression models. Fourteen of 1098 patients (1%) had neuroimaging prior to diagnosis of a brain tumor (8 females, mean age at definitive diagnosis 8.1 years, imaging interval 0.2-8.7 years). Tumor types included low-grade glioma (n = 4), embryonal tumors (n = 2), pineal tumors (n=2), ependymoma (n = 3), and others (n = 3). Pre-diagnostic imaging of corresponding tumor growth sites were abnormal in four cases (28%) and demonstrated higher ADC values in the region of high-grade tumor growth (p = 0.05). Growth regression analyses demonstrated R2-values of 0.92 and 0.91 using a linear model and 0.64 and 0.89 using an exponential model for high- and low-grade tumors, respectively; estimated minimum velocity of diameter expansion was 2.4 cm/year for high-grade and 0.4 cm/year for low-grade tumors. High-grade tumors demonstrated faster growth rate of diameter and solid tumor volume compared to low-grade tumors (p = 0.02, p = 0.03, respectively). This is the first study to test feasibility in utilizing pre-diagnostic neuroimaging to demonstrate that linear and exponential growth rate models can be used to estimate pediatric brain tumor growth velocity and should be validated in a larger multi-institutional cohort.

Second-stage cesarean delivery and preterm birth in subsequent pregnancy: A large multi-institutional cohort study

Objective: To estimate the risk of preterm birth associated with mode of delivery in a previous pregnancy.Patients and Methods: This was a multicenter retrospective cohort study. Women who had two consecutive deliveries in the participating hospitals between January 2012 and January 2022 were included in this study. They were divided into three groups according to the mode of delivery in a previous pregnancy: vaginal birth (group A), cesarean section before the second stage of labor (group B), and second stage cesarean section (group C). Data were extracted from the medical records. The primary outcome was the risk of spontaneous preterm birth in the subsequent pregnancy. The secondary outcomes were the risk of early spontaneous preterm birth (< 34 weeks) and the medically indicated preterm birth in the subsequent pregnancy. The logistic regression was employed to estimate odds and adjust for confounders.Results: 18,253 women were included. Among them, 10,951 women were in group A, 5111 women in group B, and 2191 women in group C. The rates of spontaneous preterm birth in groups A, B, and C were 5.5%, 7.3%, and 15.1%, respectively. The rates of early spontaneous preterm birth in groups A, B, and C were 2.3%, 3.4%, and 8.2%, respectively. When compared with vaginal birth, second-stage cesarean section significantly increased the risk of spontaneous preterm birth (aOR, 3.23; 95% CI, 2.02–5.17; P = 0.003) and early spontaneous preterm birth (aOR, 3.59; 95% CI, 2.01–5.19; P <0.001) in the subsequent pregnancy. The rates of medically indicated preterm birth in groups A, B, and C were 2.3%, 2.8%, and 2.2%, respectively. There was no statistical difference across the three groups.Conclusion: History of cesarean section at full dilation is independently associated with an increased risk of spontaneous preterm birth in the subsequent pregnancy.

Abstract 1722: Role of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer (NSCLC)

Abstract The rapid clinical expansion of immune checkpoint blockers (ICB) has transformed the therapeutic arsenal for non-small cell lung cancer (NSCLC). However, only a relatively small fraction of patients benefits from these treatments and those who respond can develop acquired resistance. This underlines the need to identify factors or biomarkers associated with treatment sensitivity and resistance to guide clinical decisions. It has been proposed that elevated levels of tumor infiltrating lymphocytes (TIL) in the tumor microenvironment could be associated with favorable clinical outcomes after treatment with ICB. However, few studies have explored this relationship and they used semi-quantitative scoring methods and/or analyzed small tumor areas. Here, we used multiplexed quantitative immunofluorescence (QIF) panels to study major TIL subsets (DAPI, CK, CD4, CD8 and CD20) and T-cell exhaustion markers (DAPI, CD3, LAG-3, PD-1, TIM-3) in full-face baseline whole-tumor slides from a large multi-institutional patient cohort (n=179). The analysis of numerous fields of view per case allowed us to examine the spatial distribution of immune cells and spatial immune heterogeneity. Our results demonstrate that CD8+ effector T-cells are the largest TIL subpopulation and that they are preferentially located in the stromal compartment. We also show that tertiary lymphoid structures have limited association with survival and their detection depends on the size of the tissue area analyzed. Additionally, higher levels of baseline CD8+ T-cells in the stroma were significantly associated with better survival in PD-L1 positive patients but not in PD-L1 negative. To validate these results, we used whole-exome sequencing to analyze the TCR-burden in an independent cohort of ICI-treated NSCLC patients. Increased expression of the exhaustion markers LAG-3 and TIM-3 in CD3 positive T-cells was associated with reduced survival. Finally, we used a novel multiparametric heterogeneity metric termed Rao’s quadratic entropy that enabled us to measure the spatial immune heterogeneity and was associated with worse survival. In summary, we quantitatively measured the density, functional properties, and spatial distribution of major TIL subsets in a large cohort of NSCLC patients treated with ICB. Our results highlight the prominent role of TILs in NSCLC and their potential role as a biomarker. These results could be easily translated into the clinic and used to guide optimal treatment options. Citation Format: Miguel Lopez de Rodas Gregorio, Venkata Nagineni, Arvind Ravi, Ila J. Datar, Mari Mino-Kenudson, German Corredor, Cristian Barrera, Lindsey Behlman, David L. Rimm, Roy S. Herbst, Anant Madabhushi, Jonathan W. Riess, Vamsidhar Velcheti, Matthew Hellmann, Justin F. Gainor, Kurt A. Schalper. Role of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1722.

PD18-02 EXTERNAL VALIDATION OF THE ASSURE MODEL TO PREDICT ONCOLOGICAL OUTCOMES AFTER RESECTION OF HIGH-RISK RENAL CELL CARCINOMAS

You have accessJournal of UrologyCME1 May 2022PD18-02 EXTERNAL VALIDATION OF THE ASSURE MODEL TO PREDICT ONCOLOGICAL OUTCOMES AFTER RESECTION OF HIGH-RISK RENAL CELL CARCINOMAS Zine-Eddine Khene, Alessandro Larcher, Jean-Christophe Bernhard, Nicolas Doumerc, Romain Boissier, Idir Ouzaid, Philippe Barthelemy, Morgan Roupret, Francesco Montorsi, Pierre Bigot, and Karim Bensalah Zine-Eddine KheneZine-Eddine Khene More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Jean-Christophe BernhardJean-Christophe Bernhard More articles by this author , Nicolas DoumercNicolas Doumerc More articles by this author , Romain BoissierRomain Boissier More articles by this author , Idir OuzaidIdir Ouzaid More articles by this author , Philippe BarthelemyPhilippe Barthelemy More articles by this author , Morgan RoupretMorgan Roupret More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Pierre BigotPierre Bigot More articles by this author , and Karim BensalahKarim Bensalah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002556.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A prognostic model based on the population of the ASSURE phase III trial has recently been described. The ASSURE model stratifies patients into risk groups to predict survival after surgical resection of intermediate and high-risk localized kidney cancer. Our objective was to validate the ASSURE model in a large independent multi-institutional cohort of patients treated in a “real life” setting outside of a clinical trial. METHODS: Data of patients from ten institutions who underwent radical or partial nephrectomy for a non-metastatic RCC between 2013 and 2019 were analyzed. We exclusively focused on patients with pT1b and ISUP 3-4, pT2, pT3, pT4, and N1 (i.e., those classified as intermediate and high risk according to the ASSURE model). The performance of the ASSURE model was evaluated in terms of discrimination and calibration. In addition, decision curve analysis (DCA) was used to determine whether the clinical value of the new model increased the net benefit over a realistic range of threshold probabilities. Finally, DCA of the ASSURE model was compared with that of older UCLA Integrated Staging System (UISS) and Leibovich 2018 score. RESULTS: 1372 patients were included in the analysis. Median age was 64 years (IQR 55-72). Median tumor size was 6.5 cm (IQR 5-9). The majority of tumors were clear cell RCCs (77%), of high ISUP grade (72% of grade 3 and 4), with 45% exhibiting tumor necrosis and 5% harboring nodal involvement. Median follow up was 54 months (IQR 32-75). Regarding disease-free survival, the ASSURE model showed modest discrimination (65%), miscalibration and poor net benefit compared with UCLA Integrated Staging System (UISS) and Leibovich 2018 models. Similarly, the ability of the ASSURE model to predict overall survival was poor in terms of discrimination (63%), with an overestimation on calibration plots and a modest net benefit for probability threshold between 10-40%. CONCLUSIONS: The ASSURE model is the last reported prognostic model that evaluates survival after surgical resection of a non-metastatic renal cell carcinoma. An improvement of patient classification was not clearly established when compared with available models, and implementation of this model in this setting still needs to be clarified. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e342 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zine-Eddine Khene More articles by this author Alessandro Larcher More articles by this author Jean-Christophe Bernhard More articles by this author Nicolas Doumerc More articles by this author Romain Boissier More articles by this author Idir Ouzaid More articles by this author Philippe Barthelemy More articles by this author Morgan Roupret More articles by this author Francesco Montorsi More articles by this author Pierre Bigot More articles by this author Karim Bensalah More articles by this author Expand All Advertisement PDF DownloadLoading ...

External validation of the VENUSS prognostic model to predict recurrence after surgery in non-metastatic papillary renal cell carcinoma: A multi-institutional analysis.

Recently, VENUSS (VEnous extension, NUclear Grade, Size, Stage), as a prognostic model, was defined to predict disease recurrence (DR) after curative surgery of non-metastatic papillary renal cell carcinoma (papRCC). This study aimed to validate the VENUSS prognostic model in a large multi-institutional European cohort of patients with histopathologically proven papRCC after curative surgery for non-metastatic disease. Overall, 980 patients undergoing partial or radical nephrectomy for sporadic, unilateral and non-metastatic papRCC between 1987 and 2020 were included from 7 European tertiary institutions. The primary outcome was the prediction of DR by VENUSS score and VENUSS risk groups. Chi-square, Kruskal-Wallis, Cox-regression and Kaplan-Meier survival analyses were used in statistical methods. The Concordance (C) Index was calculated to assess model's discriminatory power. The median age was 64 (IQR:55-70) years and 82.6 % (n = 809) of patients were male. Median VENUSS score was 2 (IQR: 0-4), and 62.9 % (n = 617), 23.9 % (n = 234) and 13.2 % (n = 129) of patients was classified into low, intermediate and high risk according to the VENUSS model, respectively. At a median follow-up of 48 (IQR:23-88) months, the disease recurred in 6.6%, 18.8% and 63.8%, and the 5-year recurrence-free survival was 93.8%, 80.7% and 26.7% in low, intermediate and high-risk groups, respectively. (P < 0.001) Each increase in VENUSS score had 1.52-fold (95%CI:1.45-1.60, P < 0.001) DR risk. Compared with the VENUSS low risk, the intermediate risk had a 2.91-fold increased DR risk (95%CI:1.90-4.46, P < 0.001) and 17.9-fold (95%CI:12.25-26.25, P < 0.001) in high risk, while it was 6.07-fold greater in high risk vs. intermediate risk (95%CI:4.17-8.83, P < 0.001). The discrimination was 81.2% (95%CI:77.5%-84.8%) for the VENUSS score, and 78.6% (95%CI:74.8%-82.4%) for VENUSS risk groups, respectively. Both the VENUSS score and groups were well calibrated. This contemporary multi-institutional European large dataset validated the use of VENUSS score and VENUSS risk groups on the prediction of DR after curative surgery in patients with non-metastatic papRCC. The VENUSS prognostic model can provide valuable information for patient counselling, follow-up and patient selection for adjuvant trials.