Unfavorable Pathology Research Articles

MP15-13 PATHOLOGICAL FINDINGS IN PATIENTS FULFILLING THE EPSTEIN CRITERIA FOR INSIGNIFICANT PROSTATE CANCER AND HAVING A NEGATIVE MPMRI

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II1 Apr 2016MP15-13 PATHOLOGICAL FINDINGS IN PATIENTS FULFILLING THE EPSTEIN CRITERIA FOR INSIGNIFICANT PROSTATE CANCER AND HAVING A NEGATIVE MPMRI Nicolas Branger, Thomas Maubon, Miriam Traumann, Jeanne Thomassin-Piana, Maria Paciencia, Serge Brunelle, Naji Salem, Gwenaelle Gravis, and Jochen Walz Nicolas BrangerNicolas Branger More articles by this author , Thomas MaubonThomas Maubon More articles by this author , Miriam TraumannMiriam Traumann More articles by this author , Jeanne Thomassin-PianaJeanne Thomassin-Piana More articles by this author , Maria PacienciaMaria Paciencia More articles by this author , Serge BrunelleSerge Brunelle More articles by this author , Naji SalemNaji Salem More articles by this author , Gwenaelle GravisGwenaelle Gravis More articles by this author , and Jochen WalzJochen Walz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2537AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It is known that the Epstein criteria, defining insignificant prostate cancer based on randomized biopsy data, are associated with a risk of underestimation of the true cancer grade and the true cancer extent. Recent literature suggests that a negative multiparametric MRI (mpMRI) allows to rule out significant prostate cancer. It is also known that such a negative MRI is associated as well with a risk to underestimate the true cancer grade and the true cancer extent. Little is known about the systematic combination of both criteria to select patients who are candidates for active surveillance. The objective of our study was to evaluate the histopathological findings after radical prostatectomy in patients fulfilling the Epstein criteria and having a normal preoperative mpMRI and to test if those patients indeed had favorable pathology METHODS We retrospectively identified 28 patients who underwent radical prostatectomy in our centre and who fulfilled the Epstein criteria for insignificant cancer and who had a preoperative negative MRI. The Epstein criteria were: no more than 2 biopsies positive, less than 50% core involvement, no Gleason pattern 4-5. The MRIs were considered negative when no suspicious lesion was seen or when the PI-RADS V1 score was less than 9. All MRIs were done before or at least 6 weeks after prostate biopsy. The whole mount section pathology reports after radical prostatectomy were used to obtain information about pTNM stage, Gleason score and maximal tumor diameter. RESULTS Mean PSA of the 28 patients’ cohort was 7.6ng/ml, clinical stage was T1c in 79%, and T2a 21%. In accordance with the Epstein criteria, biopsy Gleason was 6 in all patients. Final pathology showed that 7% had pT3a disease. Regarding the Gleason score, 1 patient (4%) had primary Gleason pattern 4 (4+3), 9 patients (32%) had secondary Gleason pattern 4 (3+4). Regarding the maximal tumor diameter 37% had a diameter <10mm, and 70% < 20mm. Overall, 36% of all patients had unfavorable pathology defined as Gleason pattern4-5 or extracapsular extension. CONCLUSIONS Even when combining biopsy data and imaging data in the process to select patients for active surveillance, there is a persisting risk to underestimate the true cancer grade as well as the true cancer extension. Despite this, active surveillance should be a standard treatment strategy to offer to low risk prostate cancer patients. During the decision process the risk of prostate cancer underestimation needs to be discussed with the patient. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e156 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Nicolas Branger More articles by this author Thomas Maubon More articles by this author Miriam Traumann More articles by this author Jeanne Thomassin-Piana More articles by this author Maria Paciencia More articles by this author Serge Brunelle More articles by this author Naji Salem More articles by this author Gwenaelle Gravis More articles by this author Jochen Walz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma.

PurposeThe purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.Materials and MethodsTH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated.ResultsTH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS.ConclusionThe treatment intensity should be tailored according to TH expression in PB at diagnosis.

Importance of Reporting the Gleason Score at the Positive Surgical Margin Site: Analysis of 4,082 Consecutive Radical Prostatectomy Cases

Since 2010 pathologists at our institution have routinely been documenting the Gleason score at the margin and length of the positive surgical margin after prostatectomy. In this study we evaluate how the Gleason score and positive surgical margin length correlate with the grade and adverse pathological characteristics of the final specimen, and whether the positive surgical margin Gleason score affects the risk of early biochemical recurrence. A total of 4,082 consecutive patients undergoing radical prostatectomy and pelvic lymph node dissection between 2010 and 2014 for localized prostate cancer were included in the study, of whom 405 had a Gleason score of 7 or greater of the primary nodule and a positive surgical margin with the length and Gleason score recorded at the margin. Concordance rates between the Gleason score at the margin and the final pathological specimen were compared. Logistic regression models were used to predict the risk of unfavorable pathology. Cox proportional hazards models controlling for Gleason score, preoperative prostate specific antigen, pathological stage and adjuvant radiation were used to predict biochemical recurrence, and Kaplan-Meier estimates of recurrence-free survival were calculated by Gleason score. Among patients with positive margins biochemical recurrence was identified in 22% (vs 5.6% without positive margins), metastases in 3% (vs 0.5%) and adjuvant radiation in 30% (vs 4.1%). Mean followup was 22 months (range 12 to 48). The Gleason score at the positive surgical margin was the same as the final pathology specimen in 44% of patients, and a lower Gleason score in 56% of patients. A shorter positive surgical margin was independently associated with a lower Gleason score at the margin (p=0.02). Kaplan-Meier estimates demonstrated improved freedom from biochemical recurrence among patients with a lower Gleason score at the margin. In multivariate Cox models having a lower grade margin was associated with a decreased risk of biochemical recurrence (HR 0.50, OR 0.25-0.97). A lower Gleason score at the positive surgical margin is independently associated with a shorter margin length and a decreased risk of early biochemical recurrence. Thus, the Gleason score at the margin should be documented.

Clinico-epidemiology of neuroblastoma in north east Egypt: A 5-year multicenter study.

Neuroblastoma, an embryonal malignancy of the sympathetic nervous system, is the most frequent extracranial solid tumor The clinico-epidemiological features of neuroblastoma in infants and children were investigated between January 2005 and January 2010 at the Pediatric Oncology units of Mansoura, Zagazig, and Tanta University Children's Hospitals (Egypt). Of 142 cases of neuroblastoma, 10 were omitted from the study due to defective data. The median age of the patients was 30 months, with 75.8% aged ≥1 year and 24.2% aged <1 year at time of diagnosis. The male-to-female ratio was 1.06. Suprarenal glands were the most common primary tumor site (72.7%). The majority of the patients (76.7%) had stage IV disease. Favorable pathology was observed in 43.8% of patients, while 56.2% exhibited unfavorable pathology. The estimated survival rate of patients was 30.7±10.0%, and mean survival time was 24.2±5.2 months. The rate of mortality was 28.6% for patients aged <1 year, and 81.8% for those aged ≥1 year (P=0.005). For patients with favorable pathology, the rate of mortality was significantly lower (28.6%) compared with that of patients with unfavorable pathology (77.8%; P=0.049). Although the association between outcome and each of the primary tumor sites, children's oncology group risk and gender was statistically insignificant, a large effect size was identified between outcome and primary tumor site, as well as children's oncology group risk and a medium effect size was identified between outcome and gender. Additionally, an age of ≥1 year was associated with unfavorable pathology (P=0.024), stage IV disease (P=0.026) and a suprarenal primary tumor site (P=0.001).

Outcomes following immediate versus delayed radical prostatectomy among men on active surveillance for prostate cancer.

40 Background: Little is known about the risk of delaying radical prostatectomy (RP) until biopsy progression following active surveillance (AS) for prostate cancer. This study examines the pathological outcomes associated with surgery following AS compared to immediate treatment of prostate cancer with similar grades. Methods: Men who underwent RP between 1997-2013 at University of California San Francisco were included. The first comparison consisted of men who met strict AS inclusion criteria (Gleason Score ≤ 6, PSA ≤ 10, clinical stage &lt;T3, ≤ 33% biopsy cores positive, and &lt;= 50% of any single core positive) at diagnosis and underwent AS prior to RP (AS+RP) compared to men who met strict AS criteria and underwent RP within 6 monts (immediate RP). The second comparison consisted of men who met strict AS criteria and were upgraded on follow-up biopsy compared to a cohort of men matched on the basis pre-treatment biopsy pathology. Logistic regression was used to determine associations of RP group with adverse pathology (stage ≥pT3/N1, positive margins, and/or upgrade to Gleason &gt;=4+3), adjusting for clinical and demographic factors. Results: We identified 241 men who underwent RP after a period of AS, 157 of whom initially met strict AS criteria. The median time to RP was 20 months (IQR 14-36). Men who met strict criteria and underwent immediate RP were less likely to have unfavorable pathology than those who underwent AS+RP (OR 0.39, 95% CI 0.24-0.62). Fifty-four of the men who underwent AS+RP did so have upgrading to Gleason 3+4 disease. These patients were matched with 154 men based on their pre-treatment biopsy features. After appropriate matching, the timing of RP was not associated with adverse pathology (OR 1.27, 9% CI 0.65-2.49). Conclusions: Men who undergo surgery following AS are a selected subset of men with low risk prostate cancer. The surgical pathology features of these patients are more similar to men undergo surgery after diagnosis with intermediate risk prostate cancer than those diagnosed with very low risk disease. Additional follow-up of this and other cohorts is needed to assess long term clinical outcomes following delayed RP.

Impact of Race on Selecting Appropriate Patients for Active Surveillance With Seemingly Low-risk Prostate Cancer

To evaluate active surveillance (AS) criteria on their ability to predict favorable pathology at prostatectomy within a low-risk African American (AA) cohort. The sensitivity, specificity, positive predictive value, receiver operator curve, and area under the curve (AUC) were compared for 6 published AS criteria (National Comprehensive Cancer Network; Memorial Sloan-Kettering Cancer Center; Prostate Cancer Research International: Active Surveillance Study; Johns Hopkins-Epstein; University of California at San Francisco; and University of Miami) to predict organ-confined Gleason score 6 disease at prostatectomy in AAs and white Americans (WAs) with low-risk cancer. We also compared clinical parameters for AAs with favorable prostatectomy pathology with those for AAs with unfavorable pathology, and then used preoperative variables associated with unfavorable pathology as an additional exclusion criteria for AS. Of 468 patients with low-risk disease, 308 of 402 (76.6%) WAs and 55 of 66 (83.3%) AAs were eligible for AS by one or more criteria (P = .23). For WAs, Prostate Cancer Research International: Active Surveillance Study criteria had the highest rate of favorable pathology (81.7%) and the best performance (AUC = 0.70) in determining appropriate candidates for AS. However, all 6 AS criteria performed poorly for AA patients, with all AUCs ≤0.52. When comparing AAs with favorable pathology with AAs with unfavorable pathology, only family history of prostate cancer was statistically significant (11 of 25 [47.8%] vs. 8 of 41 [22.2%]; P = .04). When adjusting AS criteria in AAs to exclude those with a positive family history, the AUC increased most for the University of California at San Francisco (from 0.52 to 0.6) and Memorial Sloan-Kettering Cancer Center criteria (from 0.50 to 0.58). Current criteria underperform in appropriately selecting AAs for AS. AAs considering AS should be counseled about their increased risk for occult adverse pathology, particularly if a family history of prostate cancer is present.

Aurora kinase A is superior to Ki67 as a prognostic indicator of survival in neuroblastoma.

To compare the expression and prognostic value of the cell cycle markers Aurora kinase A (AURKA) and Ki67 in neuroblastoma, because AURKA expression levels have greater prognostic significance than those of Ki67 in some cancers. Eighty-eight neuroblastomas were immunostained with anti-AURKA and Ki67 antibodies. Digitally scanned slides were scored using imaging analysis software. Median AURKA and Ki67 proliferation indices (PIs) were 1.5% and 26%, respectively. Higher than median AURKA and Ki67 levels were detected in the neuroblastomas from patients belonging to the high-risk group, those with MYCN amplification, and those with unfavourable pathology, including a high mitosis-karyorrhexis index (MKI). High AURKA and Ki67 levels were significantly associated with shorter overall survival (OS) and event-free survival (EFS) in univariate analyses. In multivariate analyses, high AURKA level was associated with significantly shorter OS and EFS, independently of risk group, and of MYCN amplification and MKI. High Ki67 level was not associated with shorter OS or EFS after adjustment for risk group or MYCN amplification and MKI. High AURKA and Ki67 levels were associated with adverse prognostic factors and shorter survival, but AURKA provides more valuable prognostic information than Ki67 in neuroblastoma.

Preoperative predictors of malignancy and unfavorable pathology for clinical T1a tumors treated with partial nephrectomy: A multi-institutional analysis

PurposeTo determine preoperative predictors associated with renal cell carcinoma (RCC) and unfavorable pathology in small renal masses treated with partial nephrectomy (PN). Materials and methodsPN records from 5 centers were retrospectively queried for patients with a clinically localized single tumor <4cm on imaging (clinical T1a). Between 2007 and 2013, 1,009 patients met the inclusion criteria. Unfavorable pathology was defined as any grade III or IV RCC or tumors upstaged to pathologic T3a disease. Logistic regression models were used to determine preoperative characteristics associated with RCC and with unfavorable pathology. ResultsA total of 771 (76.4%) patients were found to have RCC and 198 (19.6%) had unfavorable pathology. On multivariate, bootstrap-adjusted logistic regression analysis, factors associated with the presence of malignancy were imaging tumor size≥3cm (odds ratio [OR] = 1.46; P = 0.040), male sex (OR = 1.88; P<0.0001), and nephrometry score≥8 (OR = 1.64; P = 0.005). These same factors were independently associated with risk of unfavorable pathology: size≥3cm (OR = 1.46; P = 0.021), male sex (OR = 2.35; P<0.0001), and nephrometry score≥8 (OR = 1.49; P = 0.015). The c statistic was 0.62 for the predicting malignancy and 0.63 for unfavorable pathology. ConclusionsIn this multi-institutional cohort, male sex, imaging tumor size≥3cm, and nephrometry score≥8 were predictors of RCC and adverse pathology following PN. These factors may assist in risk stratification and selective renal mass biopsy before decision making. Further studies are necessary to validate these findings.

Multiparametric magnetic resonance imaging (MRI) and active surveillance for prostate cancer: future directions

A growing body of data exists suggesting an important role of MRI in selecting men with prostate cancer for active surveillance (AS). In the present study, Park et al. 1 show that a suspicious lesion on MRI was independently predictive of adverse pathology after radical prostatectomy (RP). This finding supports existing data suggesting that suspicious lesions on MRI confer an increased risk of disease reclassification among men enrolled in AS 2. Indeed, in our institutional AS experience we found that men with a suspicious lesion on MRI were more likely to have biopsy reclassification with extended follow-up 3. While these data are provocative, much work remains to be done before the adoption of MRI as a standard screening tool for entry into AS for men with very low-risk prostate cancer. Introduction of functional sequence imaging into multiparametric MRI protocols has resulted in improved detection and characterisation of clinically localised prostate cancer. However, before widespread implementation into AS protocols can occur, increased rigor and standardisation in image interpretation is needed. As in the present study, 5-point Likert scales have become an increasingly popular method of quantifying a lesions likelihood of representing cancer 1. Still other authors have quantified a lesions level of suspicion using both weighted and non-weighted scoring systems based on the number of positive MRI sequences 3, 4. While useful for statistical analysis, these reporting methods are fraught with concerns of inter-observer variability and generalizability. Additionally, a recent report by Lee et al. 5 found that a simple measurement of lesion diameter on diffusion-weighted MRI was predictive of insignificant disease after RP. Combining the plethora of functional and morphological data obtained by multiparametric MRI into a standardised, reproducible tool will greatly facilitate implementation of MRI into current AS screening protocols. As a step in the right direction, Stamatakis et al. 4 recently generated a nomogram for predicting biopsy reclassification in men on AS after taking into consideration both functional and morphological characteristics of MRI lesions. Adding an additional layer of complexity, they also assessed the utility of calculated values, e.g. lesion density (lesion volume/prostate volume), in predicting biopsy reclassification. Briefly, their analysis showed that the number of lesions, lesion suspicion, and lesion density were predictive of biopsy reclassification. While nomogram validation and testing of its predictive value on pathological outcomes is needed, this represents a major advance in the standardised application of MRI to AS cohorts. Despite great strides in the application of multiparametric MRI to AS cohorts, a significant concern about the false-negative rate exists. Considering the present report, of the 35 men with no visible lesion on MRI, 14.3% men had unfavourable pathology after RP 1. This is similar to previous studies reporting disease reclassification rates of <18% 2, 6. These men with normal imaging and high-grade cancer highlight the importance of incorporating imaging and clinical data when selecting men for AS. Better defining the false-negative rate of multiparametric MRI, and effectively identifying men with a normal MRI and high-grade disease remain major challenges. Considering all of the available data, it is becoming increasingly clear that MRI has the potential for improving the identification of patients for whom AS would be safe. It is currently the practice at our institution to refer eligible men for multiparametric MRI before enrolment in AS. Our future scholarly efforts should be directed at the standardisation of reporting MRI data and the development of user-friendly AS criteria that synthesise MRI results with clinicopathological data. None declared.

MP40-09 PREOPERATIVE PREDICTORS OF MALIGNANCY AND UNFAVORABLE PATHOLOGY FOR CLINICAL T1A RENAL TUMORS TREATED WITH PARTIAL NEPHRECTOMY

You have accessJournal of UrologyKidney Cancer; Evaluation/Staging IV1 Apr 2014MP40-09 PREOPERATIVE PREDICTORS OF MALIGNANCY AND UNFAVORABLE PATHOLOGY FOR CLINICAL T1A RENAL TUMORS TREATED WITH PARTIAL NEPHRECTOMY Mark Ball, Michael Gorin, Sam Bhayani, Craig Rogers, Michael Stifelman, Jihad Kaouk, Homayoun Zargar, Susasn Marshall, Jeffrey Larson, Phillip Pierorazio, and Mohamad Allaf Mark BallMark Ball More articles by this author , Michael GorinMichael Gorin More articles by this author , Sam BhayaniSam Bhayani More articles by this author , Craig RogersCraig Rogers More articles by this author , Michael StifelmanMichael Stifelman More articles by this author , Jihad KaoukJihad Kaouk More articles by this author , Homayoun ZargarHomayoun Zargar More articles by this author , Susasn MarshallSusasn Marshall More articles by this author , Jeffrey LarsonJeffrey Larson More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , and Mohamad AllafMohamad Allaf More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1344AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Surgical treatment of clinical T1a (cT1a) renal tumors is on the rise and preoperative risk stratification remains imperfect. Following partial nephrectomy (PN), 20-30% of masses are benign, and even when renal cell carcinoma (RCC) is diagnosed, upwards of 50% are indolent. We sought to determine preoperative predictors associated with RCC and unfavorable pathology using a large database of renal tumors treated with PN. Methods Partial nephrectomy records from 5 centers were queried for patients with a single tumor < 4 cm on imaging without known metastases. Between 2007 and 2013, 1097 patients met these inclusion criteria. Unfavorable pathology was defined as any grade III or IV RCC, any type II papillary RCC, pathologic T3 disease, or undifferentiated RCC. Uni- and multivariable logistic regression was used to determine preoperative characteristics associated with RCC and with unfavorable pathology. Results A total of 828 (75.5%) patients were found to have RCC and 219 (20.0% of total cohort) had unfavorable pathology. On multivariate logistic regression analysis, factors associated with presence of malignancy were imaging tumor size > 2.5 cm (OR 1.46, p = 0.009), male sex (OR 1.83, p < 0.0001)and nephrometry score > 6 (OR 1.64, p = 0.002). These same factors were independently associated with risk of unfavorable pathology: size > 2.5 cm (OR 1.53, p=0.006), male sex (OR 1.90, p < 0.0001)and nephrometry score > 6 (OR 1.54, p =0.024) Tables 1 and 2 show the risk of RCC and unfavorable pathology, respectively. Conclusions The treatment of cT1a renal masses must include a discussion of the likely pathologic outcome for each patient. In this multi-institutional cohort, imaging tumor size >2.5 cm, male sex and nephrometry score > 6 were predictors of RCC and adverse pathology following PN. These factors may assist in risk stratification and selective renal mass biopsy prior to decisionmaking. Further studies are necessary to validate these findings. Table 1. Proportion of RCC after RPN by size, nephrometry score and sex Female, % Nephrometry < 6 Nephrometry ≥ 6 Size < 2.5 cm 50.0 67.4 Size ≥ 2.5 cm 63.4 80.7 Male, % Nephrometry < 6 Nephrometry ≥ 6 Size < 2.5 cm 74.6 80.4 Size ≥ 2.5 cm 80.0 82.6 Table 2. Proportion of Unfavorable pathology after RPN by size, nephrometry score and sex Female, % Nephrometry < 6 Nephrometry ≥ 6 Size < 2.5 cm 9.5 11.8 Size ≥ 2.5 cm 11.9 19.3 Male, % Nephrometry < 6 Nephrometry ≥ 6 Size < 2.5 cm 13.2 23.4 Size ≥ 2.5 cm 25.5 28.7 © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e437-e438 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Mark Ball More articles by this author Michael Gorin More articles by this author Sam Bhayani More articles by this author Craig Rogers More articles by this author Michael Stifelman More articles by this author Jihad Kaouk More articles by this author Homayoun Zargar More articles by this author Susasn Marshall More articles by this author Jeffrey Larson More articles by this author Phillip Pierorazio More articles by this author Mohamad Allaf More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP40-10 DOES THE PREDICTIVE ACCURACY OF THE NEPHROMETRY SCORE FOR COMPLICATIONS FOLLOWING PARTIAL NEPHRECTOMY DIFFER BY SURGEON?

p 1⁄4 0.009), male sex (OR 1.83, p 6 (OR 1.64, p 1⁄4 0.002). These same factors were independently associated with risk of unfavorable pathology: size > 2.5 cm (OR 1.53, p1⁄40.006), male sex (OR 1.90, p 6 (OR 1.54, p 1⁄40.024) Tables 1 and 2 show the risk of RCC and unfavorable pathology, respectively. CONCLUSIONS: The treatment of cT1a renal masses must include a discussion of the likely pathologic outcome for each patient. In this multi-institutional cohort, imaging tumor size >2.5 cm, male sex and nephrometry score > 6 were predictors of RCC and adverse pathology following PN. These factors may assist in risk stratification and selective renal mass biopsy prior to decisionmaking. Further studies are necessary to validate these findings.

MP79-12 KI-67 PROLIFERATION ON PROSTATE BIOPSY IS ASSOCIATED WITH UNFAVORABLE PATHOLOGY AT PROSTATECTOMY AND BIOCHEMICAL RECURRENCE AMONG LOW RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2014MP79-12 KI-67 PROLIFERATION ON PROSTATE BIOPSY IS ASSOCIATED WITH UNFAVORABLE PATHOLOGY AT PROSTATECTOMY AND BIOCHEMICAL RECURRENCE AMONG LOW RISK PROSTATE CANCER John Knoedler, Karnes R. Jeffrey, Boyd Viers, Laureano Rangel, Eric Bergstralh, and Matthew Tollefson John KnoedlerJohn Knoedler More articles by this author , Karnes R. JeffreyKarnes R. Jeffrey More articles by this author , Boyd ViersBoyd Viers More articles by this author , Laureano RangelLaureano Rangel More articles by this author , Eric BergstralhEric Bergstralh More articles by this author , and Matthew TollefsonMatthew Tollefson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2515AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Active surveillance is a management option for patients with localized prostate cancer. However, even with rigorous selection criteria (Gleason 6, PSA <10 ng/ml, clinical stage ≤pT2a), certain patients progress while on surveillance. Therefore, additional tools are needed to improve prediction of cancer outcomes. Herein, we evaluate the association of Ki-67 proliferation index with pathologic upstaging/upgrading at radical prostatectomy (RP) and its association with biochemical recurrence among patients with low-risk prostate cancer. METHODS Since 1993, our institution has performed assessment of cellular proliferation (Ki-67) on all prostate cancer biopsies. We identified 809 patients who met NCCN criteria for low-risk disease (Gleason≤6, PSA <10, clinical stage ≤T2a) and underwent both biopsy and radical prostatectomy at our institution. Ki-67 proliferation was assessed by the nuclear antibody MIB-1 and reported as a percent positive. Clinicopathologic data were correlated to Ki-67 proliferation. Kaplan-Meier analysis estimated survival, and multivariable Cox proportional hazard regression models evaluated the association of Ki-67 with upstaging/upgrading at prostatectomy and biochemical recurrence. RESULTS Among 809 patients 126 (15.6%) had Ki-67 expression >5%, while 683 (84.4%) had expression ≤5%. Median follow up was 10.4 years after surgery. Overall 131 patients (16.2%) experienced biochemical recurrence, 15 (1.9%) experienced systemic progression, and 6 (0.7%) died from prostate cancer. Patients with a biopsy Ki-67 proliferation >5% were significantly more likely to be upstaged/upgraded at surgery (pathologic Gleason ≥7, stage ≥pT3, or N+) compared to patients with proliferation ≤5% (35.7% vs 18.2%; p<0.0001). On multivariate analysis. Ki-67 proliferation (as a continuous variable) was significantly associated with upstaging at RP (HR 1.14; p<0.0001), as well as biochemical recurrence (HR 1.07; p= 0.04). CONCLUSIONS Among patients with low-risk prostate cancer, Ki-67 proliferation is predictive of unfavorable pathology at RP as well as biochemical recurrence after RP. In fact, for each percent increase in Ki-67 index there was a 14% increase risk of upstaging/upgrading. Given its low cost and wide availability, Ki-67 is a biomarker that may help stratify and counsel patients with low-risk prostate cancer considering treatment options. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e934 Advertisement Copyright & Permissions© 2014MetricsAuthor Information John Knoedler More articles by this author Karnes R. Jeffrey More articles by this author Boyd Viers More articles by this author Laureano Rangel More articles by this author Eric Bergstralh More articles by this author Matthew Tollefson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The impact of pathologic staging on the long‐term oncologic outcomes of patients with clinically high‐risk prostate cancer

In the prostate-specific antigen (PSA) screening era, approximately 15% of US men still present with clinically high-risk prostate cancer (PC). However, high-risk PC may be downgraded/downstaged at radical prostatectomy (RP), making additional therapy unnecessary. The authors tested the oncologic outcomes in men with clinically high-risk disease stratified on RP pathology. A total of 611 men with high-risk PC (PSA level > 20 ng/mL, biopsy Gleason sum [bGS] ≥ 8, or clinical classification of ≥ T3) underwent RP and pelvic lymphadenectomy between 1998 and 2011. Outcomes included biochemical disease recurrence (BCR), receipt of androgen deprivation therapy (ADT), metastases, and PC-specific and overall survival. RP pathology was classified as unfavorable (pathologic Gleason sum ≥ 8, pathologic classification of ≥ T3, or lymph node-positive disease), or favorable (no unfavorable features). Multivariable analyses tested oncologic outcomes stratified by pathologic classification. Overall, 527 men had complete pathologic data and were included in the current analysis. Of the cohort, 206 of 527 men (39%) had favorable pathology. This finding was more common in men with only 1 clinical high-risk feature, and a lower body mass index, PSA level, bGS, and percentage positive biopsy cores. Favorable pathology was associated with decreased BCR (hazards ratio [HR], 0.34), metastases (HR, 0.17), and PC death (HR, 0.17). After a median follow-up of 82 months (range, 49 months-131 months), 193 of the 527 men (37%) received ADT, including only 35 of the 206 men with favorable pathology (17%). Unfavorable pathology was associated with early (≤ 5 years) but not late treatment with ADT. In a large cohort of men with high-risk PC who were managed with RP, 39% had favorable pathology and superior oncologic outcomes.

Completion surgery following transanal endoscopic microsurgery: assessment of quality and short‐ and long‐term outcome

Patients with unfavourable pathology after transanal endoscopic microsurgery (TEM) should be offered completion surgery (CS) if appropriate. The aim of this retrospective cohort study was to assess the short-term outcome and long-term oncological results of CS and identify factors compromising the quality of resection specimens. Data were retrieved and analysed on patients who underwent CS from a comprehensive national TEM database (1992-2008) and the institutional prospective database from the Oxford University Hospitals (2008-2011). There were 36 patients eligible for analysis. Postoperative complications occurred in 19 and were minor (grade I-II) in 13 and major (grade III-V) in six patients. The quality of the resected specimen was graded as good in 23 (64%), moderate in six (16.6%) and poor in seven (19.4%). Full-thickness excision by TEM (P = 0.03), an interval to CS greater than 7 weeks (P = 0.05) and distally located lesions (P = 0.04) were associated with increased risk for an inferior surgical specimen. Overall survival after CS was 91% at 1 year and 83% at 5 years. Patients with a 'good' TME specimen had significantly improved disease-free survival compared with patients with an 'inferior' specimen (100 vs 51%, P = 0.001). Patients having full-thickness TEM excision, distally placed lesions and a long interval (> 7 weeks) to CS were likely to have an inferior TME specimen. The results confirm that CS after TEM does not negatively influence local recurrence and survival, but the reduced disease-free survival in patients with an inferior specimen is of concern.

368 OPTIMAL DEFINITION OF BIOCHEMICAL RECURRENCE (BCR) AFTER RADICAL PROSTATECTOMY (RP) DEPENDS ON PATHOLOGICAL RISK FACTORS

You have accessJournal of UrologyProstate Cancer: Staging (II)1 Apr 2013368 OPTIMAL DEFINITION OF BIOCHEMICAL RECURRENCE (BCR) AFTER RADICAL PROSTATECTOMY (RP) DEPENDS ON PATHOLOGICAL RISK FACTORS Maria Carmen Mir, Joseph C Klink, Eric Klein, and Andrew J Stephenson Maria Carmen MirMaria Carmen Mir Cleveland, OH More articles by this author , Joseph C KlinkJoseph C Klink Cleveland, OH More articles by this author , Eric KleinEric Klein Cleveland, OH More articles by this author , and Andrew J StephensonAndrew J Stephenson Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1756AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The optimal definition of BCR to administer secondary therapy for recurrent prostate cancer after radical prostatectomy is poorly defined. In general, the outcome of postoperative radiotherapy (PORT) is improved the lower the pre-radiotherapy PSA. However, administering PORT for all patients with PSA levels at the threshold of detection risks over-treatment as many of these patients may be at low risk for subsequent biochemical (BCP) and clinical progression (CP). We analyzed 14 BCR definitions for their association with subsequent BCP and CP among sub-groups of patients at varying risk of PCSM. METHODS Of 9534 patients whom underwent RP at our institution since 1987, 2649 (27.7 %) had a detectable PSA (iÝ 0.03 ng/mL) recorded at least 6 weeks after surgery. Using 14 BCR definitions, the subsequent risk of BCP (defined as a subsequent PSA > 0.1 ng/mL above the PSA at BCR at any point in time or secondary therapy after the initial detectable rise) was analyzed using Kaplan-Meier analysis. Endpoints were also analyzed according to favorable pathology (FP; pT2N0/Gleason 6/SM+/− or pT2N0/Gleason 3+4/SM-) and unfavorable pathology (UFP; pT3B or pTanyN1 or Gleason 8-10). RESULTS The 5-year BCP for patients with a single PSA iÝ 0.03 ng/mL was 30%, but was 10% for those with FP vs. 73% for those with UFP. Patients with evidence of BCR by all widely-accepted definitions (PSA iÝ 0.2, PSAiÝ 0.2 and rising, PSA iÝ 0.4, PSA iÝ 0.4 and rising) had a risk of subsequent BCP at 5 years > 90%, regardless of the presence of FP or UFP. Considering all patients, a single detectable PSA iÜ 0.1 ng/mL was associated with BCP in only 30-38% of patients. However, this risk ranged from 10-15% for those with FP versus 70-80% for those with UFP. For BCR definitions requiring successive PSA rises at levels < 0.2 ng/mL, the 5-year risk of subsequent BCP ranged from 80-81% for those with FP and 95-96% for those with UFP. CONCLUSIONS For patients with UFP, any detectable PSA iÝ 0.03 ng/mL is associated with a high probability of subsequent PSA progression and is a reliable indicator of recurrent prostate cancer. For patients with FP, a more stringent definition requiring successive PSA measurements above a given threshold should be used. These findings have important implications for the patient selection and timing of secondary therapy after radical prostatectomy. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e149 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maria Carmen Mir Cleveland, OH More articles by this author Joseph C Klink Cleveland, OH More articles by this author Eric Klein Cleveland, OH More articles by this author Andrew J Stephenson Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MYCN gene monitoring in children's malignant solid tumors

Although the incidence of malignant solid tumors in children is not high,it is one of the major death causes in children.MYCN gene amplification is an independent poor prognosis factor of neuroblastoma.MYCN gene involves in neuroblastoma tumorgenesis and is the major evidence of treatment.MYCN gene amplification could be detected in other children's solid tumor.It is associated with unfavorable medulloblastoma pathology,poor outcome of Wilms' tumor and alveolar rhabdomyosarcomas.This review compares different MYCN gene detection methods,makes a summary about the clinical relationship between MYCN gene and children's solid tumor and investigates the possibility of increasing cure rate of malignant solid tumors through molecular specificity treatment. Key words: MYCN gene; Solid tumors; Neuroblastoma

Podoplanin Lymphatic Density and Invasion Correlate With Adverse Clinicopathologic and Biological Factors and Survival in Neuroblastomas

Neuroblastoma (NB) is a challenging problem in oncology, as the majority of patients have lymphatic and/or hematogenous metastases at diagnosis. We investigated the prognostic significance of lymphatic density (LD) and invasion (LI) in NBs using the lymphatic endothelial marker podoplanin (PDPN). A total of 77 neuroblastic tumors and 9 ganglioneuromas (GNs) were immunostained for PDPN using D2-40 antibody. Intratumoral lymphatics were identified in 87% (67/77) of NBs and 7/9 GNs. The LD counts were significantly higher (P<0.01) in NBs (median=19.6, range=0.00 to 89.3) than in GNs (median=10.2, range=0 to 18.7). LI, assessed in D2-40-stained lymphatics, was present in 52/67 (78%) NBs. LDs were significantly higher in NBs from patients with adverse clinical factors (advanced-stage, high-risk group, primary abdominal compared with extra-abdominal sites), biological factors (MYCN amplification, 1p deletion, 17q gain), and distant lymph node metastases. LDs and LI were also significantly higher in NBs belonging to an unfavorable pathology prognostic group and in those with a high mitosis-karyorrhexis index. High LD and the presence of LI correlated with a shorter event-free survival in univariable analyses. High LD and the presence of LI were also associated with worse overall survival, although the association was less strong. In conclusion, increased LDs and the presence of LI correlated with adverse clinicopathologic and biological factors and survival. These findings suggest that PDPN has the potential to provide valuable prognostic information to clinicians for risk assessment in NBs.

HIF‐1α up‐regulation is associated with adverse clinicopathological and biological factors in neuroblastomas

To study the expression of hypoxia-inducible factor 1α (HIF-1α) in clinical neuroblastoma (NB) samples and its association with the clinicopathological features, biological features and survival of NB patients. Immunohistochemistry indicated that elevated HIF-1α expression was present in 30 of 90 (33%) NBs. This expression was correlated significantly and positively with higher clinical stage (P = 0.002), ≥18 months of age at presentation (P = 0.020), high-risk group (P = 0.005), unfavourable pathology (P = 0.002), MYCN amplification (P < 0.001), 1p deletion (P = 0.004) and 17q gain (P = 0.002). Enzyme-linked immunosorbent assays showed that total HIF-1α protein was significantly higher in NBs of patients with all examined adverse prognostic factors except for age. Univariate survival analysis revealed that higher-than-median HIF-1α total protein levels were associated significantly with a decrease in event-free survival (EFS) (P = 0.017), but not in overall survival (OS) (P = 0.12). HIF-1α immunoexpression by ≥10% of tumour cells was associated significantly with decreased OS and EFS (P = 0.002 and P = 0.004, respectively), but not in multivariate analysis after adjusting for the high-risk group (P = 0.16 and P = 0.19, respectively). HIF-1α was increased significantly in patients with NB associated with unfavourable characteristics. HIF-1α is a prognostic indicator of poor OS and EFS and defines subgroups of NBs with aggressive clinical behaviour.

1455 EARLY REPEAT BIOPSY AS A PART OF AN ACTIVE SURVEILLANCE PROTOCOL

You have accessJournal of UrologyProstate Cancer: Detection and Screening II1 Apr 20121455 EARLY REPEAT BIOPSY AS A PART OF AN ACTIVE SURVEILLANCE PROTOCOL Ahmed El-Shafei, Ayman Moussa, Ranko Miocinovic, Jianbo Li, Khaled Fareed, Ryan Berglund, Levy David, Andrew Stephenson, and J.Stephen Jones Ahmed El-ShafeiAhmed El-Shafei Cleveland, OH More articles by this author , Ayman MoussaAyman Moussa Cleveland, OH More articles by this author , Ranko MiocinovicRanko Miocinovic Cleveland, OH More articles by this author , Jianbo LiJianbo Li Cleveland, OH More articles by this author , Khaled FareedKhaled Fareed Cleveland, OH More articles by this author , Ryan BerglundRyan Berglund Cleveland, OH More articles by this author , Levy DavidLevy David Cleveland, OH More articles by this author , Andrew StephensonAndrew Stephenson Cleveland, OH More articles by this author , and J.Stephen JonesJ.Stephen Jones Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1949AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Repeat or “re-staging” prostate biopsy is used to identify disease progression in patients with prostate cancer managed with active surveillance. Our aim is to evaluate ability to identify unfavorable pathology on early repeat biopsy for patients considering active surveillance for proper patient selection. METHODS We performed office-based repeat transrectal ultrasound guided biopsy (TRUBP) on all 137 patients who were diagnosed with prostate cancer and were being considered for active surveillance (AS). We performed restaging biopsy within the first 7 months after diagnostic biopsy. All patients were diagnosed using a minimum of 12 cores biopsy. Demographic, clinical & pathological data from both biopsies were reviewed including age, race, family history, total PSA, PSA slope, number of cores obtained, number of positive cores, % of positive cores/number of cores, number of positive cores to total cores, Gleason sum, total gland volume, PSA density, max cancer% per core & clinical stage. Statistical comparison was performed using the Wilcoxon rank sum for continuous variables & McNeMar's Chi-square test for categorical variables. RESULTS Mean age was 65 years; 85% were Caucasian, 13% had positive family history & 92% had stage T1c. Among variables analyzed we found only the mean maximum cancer % per core (20.1% for initial & 27.2 for restaging biopsies) & presence of coexistent atypia or PIN demonstrated statistical significance, while there is no statistical significance found regarding the number of positive cores & Gleason sum (table 1). Table 1. Statistical analysis of different variables Variables P value Number of positive cores 0.0710 Positive cores/number of cores 0.03697⁎ Gleason sum 0.2596 Total volume 0.6394 PSA density 0.6477 Max cancer% 0.0268⁎ (PIN) 0.0012⁎ Atypia 0.0123⁎ ⁎ Statistically significant. CONCLUSIONS Our analysis shows that identification of adverse (unfavorable) pathological findings on restaging biopsy which indicate disease upgrading are maximum cancer % per core & coexistence of PIN or atypia. The number of positive cores on initial biopsy was marginally associated with unfavorable pathology on restaging biopsy. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e589-e590 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmed El-Shafei Cleveland, OH More articles by this author Ayman Moussa Cleveland, OH More articles by this author Ranko Miocinovic Cleveland, OH More articles by this author Jianbo Li Cleveland, OH More articles by this author Khaled Fareed Cleveland, OH More articles by this author Ryan Berglund Cleveland, OH More articles by this author Levy David Cleveland, OH More articles by this author Andrew Stephenson Cleveland, OH More articles by this author J.Stephen Jones Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Preoperative characteristics of high‐Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

What's known on the subject? and What does the study add? Men with high-risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high-grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low- and intermediate-risk features; there is a paucity of data about preoperative criteria to identify men with high-grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high-grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high-grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate-specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high-grade prostate cancer as to their risk of favourable or unfavourable disease at RP. To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8-10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP). The Institutional Review Board-approved institutional RP database (1982-2010) was analysed for men with high-Gleason prostate cancer on biopsy; 842 men were identified. The 10-year biochemical-free (BFS), metastasis-free (MFS) and prostate cancer-specific survival (CSS) were calculated using the Kaplan-Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8-10 and pT3b or N1. Preoperative characteristics were compared using appropriate comparative tests. Logistic regression determined preoperative predictors of unfavourable pathology. There was favourable pathology in 656 (77.9%) men. The 10-year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively. In contrast, men with unfavourable pathological findings had significantly worse 10-year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001). In multivariable logistic regression, a prostate-specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38-3.62, P = 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55-4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59-4.09, P < 0.001), increasing number of cores positive with high-grade cancer (OR 1.16, 95% CI 1.01-1.34, P = 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17-4.35, P = 0.015) were predictive of unfavourable pathology. Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis. Among men with high-Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high-grade cancer and >50% core involvement are predictive of unfavourable pathology.