Concordance of biopsy and pathologic ISUP grading in salvage radical prostatectomy patients for recurrent prostate cancer.

PURPOSE: To investigate the concordance of biopsy and pathologic International Society of Urological Pathology (ISUP) grading in salvage radical prostatectomy (SRP) patients for recurrent prostate cancer. METHODS: Within a high-volume center database, we identified patients who underwent SRP for recurrent prostate cancer (PCa) between 2004 and 2020. Upgrading, downgrading, concordance, and any discordance between posttreatment biopsy ISUP and ISUP at SRP were tested. Logistic regression models were used to predict ISUP upgrading and ISUP discordance. Models were adjusted for prostatic specific antigen before SRP, age at surgery, initial prostatic specific antigen (PSA), type of primary treatment, time from primary PCa diagnosis to SRP, number of positive cores at biopsy, and original Gleason score. RESULTS: Overall, 184 patients with available biopsy and pathologic ISUP grading were identified. Of those, 17.4% (n = 32), 40.8% (n = 75), 19.6% (n = 36), and 22.2% (n = 41) harbored biopsy ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading, respectively. Pathologic ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading was recorded in 6.0% (n = 11), 40.8% (n = 75), 32.1% (n = 59), and 21.2% (n = 39), respectively. Median PSA before SRP was 5.5 ng/ml (interquartile range [IQR]: 3.1-8.1 ng/ml), median age at SRP was 65.1 years (IQR:60.7-69.4 years) and median time from original PCa diagnosis to SRP was 47 months (IQR: 27.3-85.2 months). Concordance of biopsy and pathologic ISUP was identified in 45.1% (n = 83). Conversely, any ISUP discordance, upgrading and downgrading of at least one ISUP group was identified in 54.9% (n = 101), 35.3% (n = 65), and 19.6% (n = 36). In logistic models, none of the preoperative characteristics was associated with upgrading or ISUP discordance (all p > 0.1). CONCLUSION: Discordance between biopsy and pathologic ISUP grading is common at SRP. However, in 45% of SRP cases biopsy ISUP is capable to predict pathologic ISUP. Further studies are necessary to identify characteristics for ISUP upgrading at SRP.

The Will Rogers phenomenon, breast cancer and race.

BACKGROUND: The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients' group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP. METHODS: This is a retrospective analysis of 300 BC women (2007-2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS] was estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses was used to identify racial factors associated with outcomes. RESULTS: Our patient cohort included 30.3% Caucasians [Whites] and 69.7% African-Americans [Blacks]. Stages I, II, III, and IV were 46.2, 26.3, 23.1, and 4.4% of Whites; 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in anatomic staging (p = 0.043). In prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011). A total of Whites (45.05% vs. 47.85%) Blacks, upstaged. Whites (16.49% vs. 14.35%) Blacks, downstaged. The remaining, 38.46 and 37.79% patients had their stages unchanged. With a median follow-up of 54 months, the Black patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (p = 0.000). Among the Whites, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p = 0.000). The 8th showed complex results (p = 0.176) compared to DFS estimated using the 7th edition (p = 0.004). CONCLUSION: The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both White and Black patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data.

Prognostic value of FUS immunoexpression for Gleason patterns and prostatic adenocarcinoma progression.

BACKGROUND: Risk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. PATIENTS AND METHODS: Non-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. RESULTS: Our cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203-2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878-1.499]; p = 0.313). CONCLUSION: Non-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.

Extricating the Association Between the Prognostic Factors of Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is one of the recurring and lethal gastrointestinal tract disease rankings as the primary cause of worldwide morbidity and mortality. In general, the tumour node metastasis (TNM) and Dukes classification assist in diagnosis, prognosis and treatments of CRC along with haematological examinations and tumour demographic characterisations in patients. METHODS: The present investigation is carried out on clinically acknowledged sixty-five CRC patients based on haematological findings and are sorted into stages using TNM and Dukes. The present study is to find the association between haematological findings, demographic characters, differentiation position, lymph node invasion and tumour node metastasis in CRC patients in accordance with their age. RESULTS: We observed significant (p < 0.05) nexus between lymph node metastasis and tumour node metastasis on the basis of tumour's differentiation demographic positioning and age of the individuals. CONCLUSION: Earlier location tracing and medicinal treatment or surgery lessen the chance of CRC morbidity and mortality along with prolonging survival rate via prognostic factors and disease position determination.

HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status.

OBJECTIVES: To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy. METHODS: Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios. RESULTS: 9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p < 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p < 0.001. CONCLUSIONS: Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.

Screening of Clinical Factors Related to Prognosis of Breast Cancer Based on the Cox Proportional Risk Model.

Proper evaluation of the relevant clinical factors for the prognosis of breast cancer is particularly important in the selection of appropriate therapeutic strategies. To further screen and identify the clinically significant factors associated with breast cancer, the Cox risk regression model analysis was performed in this study. The follow-up data of intact breast cancer patients were downloaded from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) database, and the prognostic factors correlated with radiotherapy factors were screened using the Cox risk regression model analysis of prognostic factors. The response of different clinical features to radiotherapy was also evaluated by survival prognosis analysis and prediction. A total of 1980 breast cancer patients were enrolled in this study, including 1173 patients who received the radiotherapy treatment and 807 patients without radiotherapy treatment. To further study the correlation between the clinical prognostic factors and the overall survival, the single factor and multivariate Cox regression analysis were performed, and the clinical prognostic factors implied that the patients with age <60 years, receiving radiotherapy, grade 1, stage 0-1, or human epidermal growth factor receptor 2 (HER2) negative had a better overall clinical survival. The association analysis of the radiotherapy treatment and the clinical prognostic factors implied that the patients with younger age, stage lower, or HER2 negative showed a better overall clinical survival, and the patients who received radiotherapy had a better 3-year survival probability and 5-year survival probability. Screening and identifying the clinically significant factors associated with breast cancer can help predict the risk of disease. Age, stage, or HER2 status was the prognostic factors correlated with radiotherapy treatment.

The Long-Term Risks of Metastases in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: We assessd the long-term outcomes from a large prospective cohort of men diagnosed with prostate cancer managed with active surveillance and determined the clinical prognostic factors that may predict the risk of metastases. MATERIALS AND METHODS: We retrospectively reviewed data of men enrolled on active surveillance at our institution between 1990 and 2018 with low or intermediate risk disease (stage cT1-2, prostate specific antigen less than 20 ng/ml, and biopsy Grade Group [GG]1-2). Patients were classified into 3 groups by diagnostic GG and prostate specific antigen density. Primary outcome was metastatic prostate cancer detected on imaging or at prostatectomy. In addition, upgrade at surveillance biopsy, active treatment, and overall and prostate cancer specific survival outcomes were assessed. Cox proportional hazards regression models were used. RESULTS: A total of 1,450 men met the inclusion criteria. Median followup was 77 months (IQR 49-114). The 7-year metastasis-free survival rate was 99%. Metastases developed in 15 men at a median of 62 months (IQR 29-104), of which 69% were confined to lymph nodes. Men with GG2 had a lower metastasis-free survival rate compared to those with GG1 disease. GG2, prostate specific antigen velocity and PI-RADS® 4-5 lesions on multiparametric magnetic resonance imaging were associated with a higher risk of metastases. The 7-year prostate cancer specific survival was greater than 99%. CONCLUSIONS: Active surveillance seems to preserve favorable long-term prognosis, as metastases and prostate cancer specific death are rare. However, the higher risk of metastases associated with higher Gleason grade, prostate specific antigen velocity, and characteristics on multiparametric magnetic resonance imaging should be considered when selecting and counseling patients for active surveillance.

Accuracy of preoperative endometrial biopsy and intraoperative frozen section in predicting the final pathological diagnosis of endometrial cancer.

BACKGROUND: Histotype and grade of endometrial cancer (EC) are prognostic factors of nodal involvement and thus of survival. Preoperative biopsy (PB) and intraoperative frozen section (FS) are usually used to guide surgical staging on which the choice of adjuvant therapy will be based successively. OBJECTIVE: The aim of this study was to assess the agreement rate between PB and FS with final diagnosis (FD) in a series of surgically resected EC. MATERIALS: All patients submitted to hysterectomy for EC or atypical endometrial hyperplasia in the Reggio Emilia Province hospitals from 2007 to 2018 were included. Concordance rate differences in histotype, grading, myoinvasion, risk of recurrence between PB, FS and FD were assessed with Fisher's exact test and Mc Nemar contingency test. RESULTS: A total of 352 patients were identified. For 345 patients it was possible to compare PB and FD results. FS examination was performed in 201/352 (57%) cases, while for 21/352 (6%) patients only an intraoperative macroscopic evaluation was done; in the remaining women, FS-exam was omitted. In 14/201 (7%) cases the tumor wasn't grossly identifiable and the random FS-sampling wasn't able to find the tumor site. High diagnostic concordance of tumor type between PB and FD was observed: no significant differences were registered in type 1 and type 2-endometrial cancer identification (83%, 73%, p = 0.121). Significant differences (p = 0.005) were observed comparing FS and FD results: 95% of type 1-ECs were correctly diagnosed by FS, while only 76% of type 2-ECs received a correct diagnosis on FS. PB showed a concordance with FD among tumor grading close to 55% whilst concordance achieved 71% grouping low grade (G1-G2) EC. No significant differences in FS and FD concordance rate were observed between tumor grades. Concordance for low grade was significantly higher than for high grade ECs (89% vs 50%, respectively, p value = 0.014). The concordance rate in evaluating the myoinvasion status between FS and FD was 80% (n: 199 patients), reaching 99% after combining the first 2 groups (0-49% vs ≥ 50%). Twenty-two cases underwent only intraoperative macroscopic evaluation of the myoinvasion, with an accuracy of 91%: only in 1 case the invasion of the cervical stroma was not detected (Stage II), and 1 case the patient was overstaged as Ib. Discrepancies were observed in FS capacity to correctly predict the final ESMO risk group in stage I patients: FS resulted particularly reliable in predicting a low-risk (concordance with FD: 91%) while the accuracy sharply decreased for intermediate- and high-risk patients (62% and 40%, respectively). To investigate the usefulness of FS in EC management, we compared patients who underwent FS (FS-group) or not (no-FS-group). Especially for low risk patients, the FS significantly increased the adequacy of surgical treatment from 53% (no-FS-group) to 72% (FS-group) (p = 0.016). CONCLUSIONS: FS remains a useful tool to tailor surgery in EC-patients, avoiding secondary surgery to complete staging particularly in patients with AH + AHBA, low and intermediate risk ECs that could benefit from adjuvant therapy.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

BACKGROUND: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. RESULTS: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96). CONCLUSION: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

PI-RADS® Category as a Predictor of Progression to Unfavorable Risk Prostate Cancer in Men on Active Surveillance.

PURPOSE: We identified baseline imaging and clinical characteristics of patients that may improve risk stratification among patients being evaluated for active surveillance. MATERIALS AND METHODS: From July 2007 to January 2020 patients referred to our institution for prostate cancer were evaluated and those who remained on active surveillance were identified. Men underwent multiparametric magnetic resonance imaging upon entry into our active surveillance protocol during which baseline demographic and imaging data were documented. Patients were then followed and outcomes, specifically progression to Gleason Grade Group (GG)3 or greater disease, were recorded. RESULTS: Of the men placed on active surveillance 344 had at least 1 PI-RADS score documented. For those with an index lesion PI-RADS category of 5, 33% (17/51) had progression to GG3 or greater on active surveillance with a median time to progression of 31 months. When comparing the progression-free survival times and progression rates in each category, PI-RADS category was found to be associated with progression to GG3 or greater on active surveillance (p <0.01). On univariable analysis factors associated with progression included an index lesion PI-RADS category of 5, prostate specific antigen density and the size of the largest lesion. On multivariable analysis only PI-RADS category of 5 and prostate specific antigen density were associated with progression on active surveillance. CONCLUSIONS: PI-RADS lesion categories at baseline multiparametric magnetic resonance imaging during active surveillance enrollment can be used to predict cancer progression to GG3 or greater on active surveillance. This information, along with other clinical data, can better assist urologists in identifying and managing patients appropriate for active surveillance.

Improving the accuracy of gastrointestinal neuroendocrine tumor grading with deep learning.

The Ki-67 index is an established prognostic factor in gastrointestinal neuroendocrine tumors (GI-NETs) and defines tumor grade. It is currently estimated by microscopically examining tumor tissue single-immunostained (SS) for Ki-67 and counting the number of Ki-67-positive and Ki-67-negative tumor cells within a subjectively picked hot-spot. Intraobserver variability in this procedure as well as difficulty in distinguishing tumor from non-tumor cells can lead to inaccurate Ki-67 indices and possibly incorrect tumor grades. We introduce two computational tools that utilize Ki-67 and synaptophysin double-immunostained (DS) slides to improve the accuracy of Ki-67 index quantitation in GI-NETs: (1) Synaptophysin-KI-Estimator (SKIE), a pipeline automating Ki-67 index quantitation via whole-slide image (WSI) analysis and (2) deep-SKIE, a deep learner-based approach where a Ki-67 index heatmap is generated throughout the tumor. Ki-67 indices for 50 GI-NETs were quantitated using SKIE and compared with DS slide assessments by three pathologists using a microscope and a fourth pathologist via manually ticking off each cell, the latter of which was deemed the gold standard (GS). Compared to the GS, SKIE achieved a grading accuracy of 90% and substantial agreement (linear-weighted Cohen's kappa 0.62). Using DS WSIs, deep-SKIE displayed a training, validation, and testing accuracy of 98.4%, 90.9%, and 91.0%, respectively, significantly higher than using SS WSIs. Since DS slides are not standard clinical practice, we also integrated a cycle generative adversarial network into our pipeline to transform SS into DS WSIs. The proposed methods can improve accuracy and potentially save a significant amount of time if implemented into clinical practice.

Risk Factors for Biopsy Reclassification over Time in Men on Active Surveillance for Early Stage Prostate Cancer.

PURPOSE: Few validated clinical tools currently exist to standardize the frequency of biopsies for men on active surveillance for low risk prostate cancer. We determined predictors of biopsy reclassification at specific time points after enrollment on active surveillance. MATERIALS AND METHODS: We identified men with clinically low risk prostate cancer prospectively enrolled on active surveillance at the University of California, San Francisco between 2000 and 2016. Biopsy reclassification was defined as Gleason Grade Group 2 or greater on subsequent biopsy. Multivariable Cox proportional hazards regression models were used to identify factors associated with risk of biopsy reclassification at first surveillance biopsy and 1 to 3, 3 to 5 and 5 to 10 years after enrollment, adjusting for clinicodemographic factors, PI-RADS® (Prostate Imaging Reporting and Data System) score and genomic testing. RESULTS: A total of 1,031 men were included in the study. On multivariable analysis biopsy reclassification was associated with prostate specific antigen density 0.15 or greater (HR 3.37, 95% CI 1.83-6.21), percentage biopsy cores positive (HR 1.27, 95% CI 1.05-1.54) and high genomic score (HR 2.81, 95% CI 1.21-6.52) at first surveillance biopsy and also at 1 to 3 years, after adjustment. Prostate specific antigen density 0.15 or greater (HR 2.36, 95% CI 1.56-3.56) and prostate specific antigen kinetics (HR 2.19, 95% CI 1.43-3.34) were associated with reclassification at 3 to 5 years. A PI-RADS 4-5 score was not associated with biopsy reclassification at any time point. CONCLUSIONS: High genomic score, prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater were associated with reclassification within 3 years of commencing active surveillance, and prostate specific antigen kinetics and prostate specific antigen density 0.15 or greater remained associated with reclassification at 5 years after diagnosis.

Differentiating Grade in Breast Invasive Ductal Carcinoma Using Texture Analysis of MRI.

PURPOSE: The objective of this study is to investigate the use of texture analysis (TA) of magnetic resonance image (MRI) enhanced scan and machine learning methods for distinguishing different grades in breast invasive ductal carcinoma (IDC). Preoperative prediction of the grade of IDC can provide reference for different clinical treatments, so it has important practice values in clinic. METHODS: Firstly, a breast cancer segmentation model based on discrete wavelet transform (DWT) and K-means algorithm is proposed. Secondly, TA was performed and the Gabor wavelet analysis is used to extract the texture feature of an MRI tumor. Then, according to the distance relationship between the features, key features are sorted and feature subsets are selected. Finally, the feature subset is classified by using a support vector machine and adjusted parameters to achieve the best classification effect. RESULTS: By selecting key features for classification prediction, the classification accuracy of the classification model can reach 81.33%. 3-, 4-, and 5-fold cross-validation of the prediction accuracy of the support vector machine model is 77.79%~81.94%. CONCLUSION: The pathological grading of IDC can be predicted and evaluated by texture analysis and feature extraction of breast tumors. This method can provide much valuable information for doctors' clinical diagnosis. With further development, the model demonstrates high potential for practical clinical use.

The Impact of Prostate Cancer Upgrading and Upstaging on Biochemical Recurrence and Cancer-Specific Survival.

Background and Objectives: Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes. Materials and Methods: Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), metastasis-free survival (MFS), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging. Results: Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5 times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1 times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p <0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p <0.001). Grade and stage increase after RP were associated with inferior MFS rates and ten-year CSS: 89% vs. 98% for upgrading (p = 0.039) and 87% vs. 98% for upstaging (p = 0.008). Conclusions: Currently used risk stratification models are associated with substantial misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, which should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

Clinicopathologic features and outcomes of anterior-dominant prostate cancer: implications for diagnosis and treatment.

OBJECTIVE: This study aims to describe the pathological features and clinical outcomes in anterior-dominant prostate cancer (APCA) compared to posterior/posterolateral-dominant prostate cancer (PPCA) among men treated with radical prostatectomy for localized prostate cancer. METHODS: This is a single-institution, matched case-control analysis of short-term clinical outcomes stratified by pathologic tumor location at radical prostatectomy. Pathologic data extracted by expert genitourinary pathologists on tumor location was linked to clinical and oncologic outcomes data from a prospective institutional database for analysis. RESULTS: From 2005 to 2013, 1580 patients were identified for analysis with 150 (9.5%) having APCA. One-hundred and thirty two of these APCA men had complete clinical data and were matched to 353 men with PPCA (~1:3 ratio) by GrdGrp at surgery, margin status, and pathologic T stage. There were no racial/ethnic differences between APCA and PPCA (p = 0.13). Men with APCA demonstrated a higher median PSA at diagnosis (6.4 [4.6-9.1] ng/mL vs 5.6 [4.4-8.1] ng/mL; p = 0.04), a higher rate of GrdGrp 1 disease at diagnosis (57.7% vs. 40.0%, p = 0.003), and lower rates of abnormal digital rectal examination (DRE) (10.1% vs. 23.2%, p = 0.003) when compared to PPCA. The rate of surgical upgrading was higher among men with APCA vs. PPCA (55.3% vs 42.0%, p = 0.015). Freedom from biochemical failure (BF) at 5-years was 85.1% (95% CI 73.1-98.9) for APCA and 82.9% (95% CI 69.2-99.5) for men with PPCA (p = 0.70, log-rank test). CONCLUSIONS: The majority of anterior tumors were undetectable by DRE and were associated with higher PSA at diagnosis. Despite presenting mostly as low/intermediate grade cancers, more than half of the men with APCA had upgrading at surgery and slightly more than 40% had positive margins and/or extraprostatic disease. When matched to a cohort of posterior predominant tumors, no differences were seen in the rate of biochemical-failure after prostatectomy.

Impact of MRI and Targeted Biopsies on Eligibility and Disease Reclassification in MRI-positive Candidates for Active Surveillance on Systematic Biopsies.

OBJECTIVE: To assess the impact of concomitant targeted biopsies (TB) for predicting final disease reclassification in MRI-positive low-risk prostate cancer patients eligible for active surveillance (AS) on systematic biopsies (SB). MATERIALS AND METHODS: From a prospective database, we included all prebiopsy MRI-positive men fulfilling AS criteria at diagnosis (Toronto [n = 114], UCSF [n = 82], or PRIAS [n = 60] criteria) on SB. All patients underwent a combination of SB and software-based fusion TB, and an immediate radical prostatectomy. The primary endpoints were the pathologic upgrading and upstaging rates. RESULTS: Biopsy grade group was upgraded to grade group (GG) 2 and to GG≥3 on TB in 65.9%-76.7% and in 12.2-16.7%, respectively. The rate of GG ≥3 in radical prostatectomy specimens varied from 31.6% to 43.3% with no relation between strictest criteria and lower upgrading rates. The proportion of not organ-confined disease (35%-39%) was comparable among the AS cohorts. Negative TB was strongly associated with the absence of final GG ≥3. Tumor grade on TB was significantly correlated with the risk of final GG ≥3 in both Toronto and UCSF cohorts, not in the PRIAS cohort. In the PRIAS cohort, the only independent predictive factor for GG ≥3 disease was the maximal tumor length in any core (P = .034). CONCLUSION: In MRI-positive patients, the risk of disease reclassification was comparable whatever the SB-based AS criteria used. TB were predictive of final upgrading, with a varied impact according to the AS criteria. SB features remained relevant for reclassification prediction even in case of positive TB. The risk of upstaged disease remains important, approximately one third, and neither TB/SB parameters nor MRI findings could accurately predict it.

Adherence to guidelines for baseline staging in newly diagnosed localized breast cancer.

RATIONALE, AIMS, AND OBJECTIVES: Different health agencies in Canada including Cancer Care Ontario (CCO) have developed guidelines for the baseline staging of newly diagnosed breast cancer patients but adherence to them is unknown. We sought to investigate adherence to CCO staging guidelines in a single cancer center in addition to the factors that influence this adherence. METHOD: A retrospective chart review was conducted on 212 newly diagnosed breast cancer patients between 2015 and 2017. Baseline patient demographic and disease characteristics as well as radiologic staging studies and subsequent treatments were recorded. The group of patients in whom the guidelines were observed was compared to the group of patients in whom the guidelines were not followed. RESULTS: Staging guidelines were not followed in 46.7% of the patients in the cohort (99 of 212 patients). In most cases, deviations from the guidelines consisted of performing more than the recommended baseline screening, most commonly in the form of a computerized tomography (CT) scan or a bone scan and chest x-ray (CXR)/ ultrasound (US) of the liver. Less commonly, a recommended staging evaluation was omitted or the suggested timing of the staging procedure (i.e., pre-operatively versus post-operatively) was not followed. Higher stage and grade of the disease and subsequent chemotherapy administration were associated with higher guideline non-adherence. CONCLUSIONS: Low adherence to staging guidelines for newly diagnosed breast cancer according to CCO is shown in a community cancer center. Incorporation of arising prognostic factors to staging procedure determination may increase acceptance and adherence to guidelines in the future.

Evaluación semicuantitativa de gliomas cerebrales en adultos: un enfoque de las características neuropatológicas.

INTRODUCTION: Gliomas are neoplasms with high recurrence and mortality. Due to the difficulty to apply the World Health Organization (2016) classification, developing countries continue to use histological evaluation to diagnose and classify these neoplasms. OBJECTIVE: To develop a semi-quantitative scale to numerically grade gliomas morphological characteristics. METHOD: A cohort of patients with gliomas was assessed and followed for 36 months. Tumor tissue sections were analyzed and graded, including aspects such as cell line, cellularity, nuclear pleomorphism, mitosis, endothelial hyperplasia, hypoxic changes, apoptotic bodies, necrosis, hemorrhage and proliferation index. RESULTS: 58 cases were analyzed. Low-grade gliomas median score was 12 points (9 and 13.5 for percentiles 25 and 75, respectively), whereas for high-grade gliomas it was 17 points (16 and 20.5 for percentiles 25 and 75, respectively) (p < 0.0001). Thirty-six-month survival of patients with low (13/17) and high grade gliomas (6/41) was also significantly different (p < 0.0001). CONCLUSIONS: The semi-quantitative morphological scale allows an objective evaluation of gliomas, with an adequate correlation between the score, tumor grade and survival time.

INTRODUCCIÓN: Los gliomas son neoplasias con alta recurrencia y mortalidad. Por la dificultad para aplicar la clasificación de la Organización Mundial de la Salud (2016), los países en desarrollo siguen utilizando la evaluación histológica para diagnosticarlos y clasificarlos. OBJETIVO: Desarrollar una escala semicuantitativa para calificar numéricamente las características morfológicas de los gliomas. MÉTODO: Cohorte de pacientes con gliomas evaluada y seguida durante 36 meses. Se analizaron y calificaron cortes del tejido tumoral, incluyendo aspectos como estirpe celular, celularidad, pleomorfismo nuclear, mitosis, hiperplasia endotelial, cambios hipóxicos, cuerpos apoptóticos, necrosis, hemorragia e índice de proliferación. RESULTADOS: Se analizaron 58 casos. La mediana de la calificación de los gliomas de bajo grado fue de 12 puntos (percentiles 25 y 75 de 9 y 13.5, respectivamente) y la de los gliomas de alto grado fue de 17 puntos (percentiles 25 y 75 de 16 y 20.5, ­respectivamente) (p < 0.0001). La supervivencia a 36 meses de los pacientes con gliomas de bajo (13/17) y alto grado (6/41) también fue significativamente diferente (p < 0.0001). CONCLUSIONES: La escala morfológica semicuantitativa permite una evaluación objetiva de los gliomas, con una adecuada correlación entre la calificación, el grado del tumor y el tiempo de supervivencia.

Value of Intravoxel Incoherent Motion for Hepatocellular Carcinoma Grading.

BACKGROUND: To evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) parameters in estimation of hepatocellular carcinoma (HCC) grading. MATERIALS AND METHODS: Twenty-nine patients with histopathologically diagnosed as 42 HCC at explant were included in this retrospective study. All patients were examined by 1.5T magnetic resonance imaging with the use of 4-channel phased array body coil. In addition to routine pre- and postcontrast sequences, IVIM (16 different b factors varying from 0 to 1300 s/mm2) and conventional diffusion-weighted imaging (3 different b factors of 50, 400, 800 s/mm2) were obtained with single-shot echo planar spin echo sequence. Apparent diffusion coefficient (ADC) and IVIM parameters including mean D (true diffusion coefficient), D* (pseudo-diffusion coefficient associated with blood flow), and f (perfusion fraction) values were calculated. Histopathologically, HCC was classified as low (grade 1, 2) and high (grade 3, 4) grade in accordance with the Edmondson-Steiner score. Quantitatively, ADC, D, D*, and f values were compared between the low- and high-grade groups by Student t test. The relationship between the parameters and histologic grade was analyzed using the Spearman's correlation test. To evaluate the diagnostic performance of the parameters, receiver operating characteristic analysis was performed. RESULTS: High-grade HCCs had significantly lower ADC and D values than low grade groups (P = .005 and P = .026, retrospectively); ADC and D values were inversely correlated with tumor grade (r = -0.519, P = .011, r = -0.510, P = .026, respectively). High-grade HCCs had significantly higher f values when compared with the low-grade group (P = .005). The f values were positively correlated with tumor grade (r = 0.548, P = .007). The best discriminative parameter was f value. Cut-off value of 32% of f values showed sensitivity of 75.6% and a specificity of 73.5%. CONCLUSION: ADC values and IVIM parameters such as f values appear to reflect the grade of HCCs.

Prostate cancer upgrading or downgrading of biopsy Gleason scores at radical prostatectomy: prediction of "regression to the mean" using routine clinical features with correlating biochemical relapse rates.

Recommendations for managing clinically localized prostate cancer are structured around clinical risk criteria, with prostate biopsy (PB) Gleason score (GS) being the most important factor. Biopsy to radical prostatectomy (RP) specimen upgrading/downgrading is well described, and is often the rationale for costly imaging or genomic studies. We present simple, no-cost analyses of clinical parameters to predict which GS 6 and GS 8 patients will change to GS 7 at prostatectomy. From May 2006 to December 2012, 1590 patients underwent robot-assisted radical prostatectomy (RARP). After exclusions, we identified a GS 6 cohort of 374 patients and a GS 8 cohort of 91 patients. During this era, >1000 additional patients were enrolled in an active surveillance (AS) program. For GS 6, 265 (70.9%) of 374 patients were upgraded, and the cohort included 183 (48.9%) patients eligible for AS by the Prostate Cancer Research International Active Surveillance Study (PRIAS) standards, of which 57.9% were upgraded. PB features that predicted a >90% chance of upgrading included ≥ 7 cores positive, maximum foci length ≥ 8 mm in any core, and total tumor involvement ≥ 30%. For GS 8, downgrading occurred in 46 (50.5%), which was significantly higher for single core versus multiple cores (80.4% vs 19.6%, P = 0.011). Biochemical recurrence (BCR) occurred in 3.4% of GS 6 upgraded versus 0% nonupgraded, and in GS 8, 19.6% downgraded versus 42.2% nondowngraded. In counseling men with clinically localized prostate cancer, the odds of GS change should be presented, and certain men with high-volume GS 6 or low-volume GS 8 can be counseled with GS 7-based recommendations.