Optimal PSA density threshold and predictive factors for the detection of clinically significant prostate cancer in patient with a PI-RADS 3 lesion on MRI.

INTRODUCTION: While Prostate Imaging Reporting and Data System (PI-RADS) 4 and 5 lesions usually justify prostate biopsy (PBx), the management of a PI-RADS 3 lesion can be discussed. The aim of our study was to determine the optimal prostate-specific antigen density (PSAD) threshold and predictive factors of clinically significant prostate cancer (csPCa) in patients with a PI-RADS 3 lesion on MRI. PATIENTS AND METHODS: Using our prospectively maintained database, we conducted a monocentric retrospective study, including all patients with a clinical suspicious of prostate cancer (PCa), all of them had a PI-RADS 3 lesion on the mpMRI prior to PBx. Patients under active surveillance or displaying suspicious digital rectal examination were excluded. Clinically significant (csPCa) was defined as PCa with any ISUP grade group ≥ 2 (Gleason ≥ 3 + 4). RESULTS: We included 158 patients. The detection rate of csPCa was 22.2%. In case of PSAD ≤ 0.15 ng/ml/cm3, PBx would be omitted in 71.5% (113/158) of men at the cost of missing 15.0% (17/113) of csPCa. With a threshold of 0.15 ng/ml/cm3, the sensitivity and the specificity were 0.51 and 0.78 respectively. The positive predictive value was 0.40 and the negative predictive value was 0.85. According to multivariate analysis, age (OR = 1.10, CI95% 1.03-1.19, P = 0.007), and PSAD ≥ 0.15 ng/ml/cm3 (OR = 3.59, CI95% 1.41-9.47, P = 0.008) were independent predictive factors of csPCa. Previous negative PBx was negatively associated with csPCa (OR = 0.24, CI 95% 0.07-0.66, P = 0.01). CONCLUSION: Our result suggests that the optimal PSAD threshold was 0.15 ng/ml/cm3. However, in this case omitting PBx in 71.5% of cases would be at the cost of missing 15.0% of csPCa. PSAD should not be used alone, other predictive factors as age and PBx history should also be considered in the discussion with the patient, to avoid PBx while missing few csPCa.

Reproducibility in PD-L1 Immunohistochemistry Quantification through the Tumor Proportion Score and the Combined Positive Score: Could Dual Immunostaining Help Pathologists?

We studied the pathologists' agreements in quantifying PD-L1 expression through the tumor proportion score (TPS) and the combined positive score (CPS) using single PD-L1 immunohistochemistry (S-IHC) and double immunohistochemistry (D-IHC) combining PD-L1 staining and tumor cell markers. S-IHC and D-IHC were applied to 15 cancer samples to generate 60 digital IHC slides (30 whole slides images and 30 regions of interest of 1 mm2) for PD-L1 expression quantification using both TPS and CPS, twice by four pathologists. Agreements were estimated calculating intraclass correlation coefficients (ICC). Both S-IHC and D-IHC slides analyses resulted in excellent (for TPS, ICC > 0.9) to good (for CPS, ICC > 0.75) inter- and intra-pathologist agreements with slightly higher ICC with D-IHC than with S-IHC. S-IHC resulted in higher TPS and CPS than D-IHC (+5.6 and +6.1 mean differences, respectively). High reproducibility in the quantification of PD-L1 expression is attainable using S-IHC and D-IHC.

Prognostic value of pre-therapeutic FDG-PET radiomic analysis in gastro-esophageal junction cancer.

The main aim of this study was to evaluate the prognostic value of radiomic approach in pre-therapeutic 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET/CT) in a large cohort of patients with gastro-esophageal junction cancer (GEJC). This was a retrospective monocenter study including 97 consecutive patients with GEJC who underwent a pre-therapeutic FDG-PET and were followed up for 3 years. Standard first-order radiomic PET indices including SUVmax, SUVmean, SUVpeak, MTV and TLG and 32 textural features (TFs) were calculated using LIFEx software on PET imaging. Prognostic significance of these parameters was assessed in univariate and multivariate analysis. Relapse-free survival (RFS) and overall survival (OS) were respectively chosen as primary and secondary endpoints. An internal validation cohort was used by randomly drawing one-third of included patients. The main characteristics of this cohort were: median age of 65 years [41-88], sex ratio H/F = 83/14, 81.5% of patients with a histopathology of adenocarcinoma and 43.3% with a stage IV disease. The median follow-up was 28.5 months [4.2-108.5]. Seventy-seven (79.4%) patients had locoregional or distant progression or recurrence and 71 (73.2%) died. In univariate analysis, SUVmean, Histogram-Entropy and 2 TFs (GLCM-Homogeneity and GLCM-Energy) were significantly correlated with RFS and OS, as well as 2 others TFs (GLRLM-LRE and GLRLM-GLNU) with OS only. In multivariate analysis, Histogram-Entropy remained an independent prognostic factor of both RFS and OS whereas SUVmean was an independent prognostic factor of OS only. These results were partially confirmed in our internal validation cohort of 33 patients. Our results suggest that radiomic approach reveals independent prognostic factors for survival in patients with GEJC.

Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

MiR-31-3p do not predict anti-EGFR efficacy in first-line therapy of RAS wild-type metastatic right-sided colon cancer.

BACKGROUND: Low miR-31-3p expression was identified as predictive of anti-EGFR efficacy in RAS-wt mCRC. Primary tumor side was also proposed as a predictive factor of anti-EGFR benefit. This retrospective multicentric study evaluated the predictive role of miR-31-3p in right-sided RAS-wt mCRC patients treated with first-line CT+anti-EGFR or CT+bevacizumab (Beva). METHODS: Seventy-two right-sided RAS-wt mCRC patients treated in first-line with CT+anti-EGFR (n = 43) or Beva (n = 29) were included. Overall survival (OS), progression-free survival (PFS) and response rate (RR) were analyzed and stratified according to tumor miR-31-3p expression level and targeted therapy (TT). RESULTS: BRAF V600E mutation was more frequent in high vs low miR-31-3p expressers (60.6% vs 15.4%, P < 0.001). PFS was significantly longer with CT+Beva than with CT+anti-EGFR (13 vs 7 months; P = 0.024). Among low miR-31-3p expressers, PFS, OS and RR were not significantly different between the two groups, while in high miR-31-3p expressers, only PFS was longer in the CT+Beva group (11 vs 6 months; P = 0.03). In patients treated with CT+anti-EGFR, low miR-31-3p expressers had a significantly longer OS (20 vs 13 months; P = 0.02) than high miR-31-3p expressers. ORR was not significantly different between the two groups of treatment, in both low and high miR-31-3p expressers. MiR-31-3p expression status was statistically correlated between primary tumors and corresponding metastases. CONCLUSION: In this study, miR-31-3p couldn't identify a subgroup of patients with right-sided RAS-wt mCRC who might benefit from anti-EGFR and suggest that Beva is the TT of choice in first-line treatment of these patients.

Impact of Multiparametric MRI and PSA Density on the Initial Indication or the Maintaining in Active Surveillance During Follow-Up in low-Risk Prostate Cancer.

INTRODUCTION: A greater selection of candidates for active surveillance (AS) of prostate cancer (PCa) may decrease the rate of delayed treatment. We aimed to study: 1) the impact of MRI and PSA density (PSAd) at baseline on the final status, and 2) the impact of bio-clinical features during the follow-up on pursuing AS. MATERIALS AND METHODS: This retrospective, monocentric study between June 2013 and July 2020, included 99 patients in AS (median follow-up: 19 months [18-92]). All MRI were reviewed by a single radiologist. Lost to follow-up were 17 patients and 6 patients chose treatment by themselves. Treatment was proposed in case of upgrading (≥ GG2) or increasing PCa volume. RESULTS: Impact of MRI and PSAd at baseline:  Combining PSAd ≤ 0.15 and PIRADS ≤ 3, the probability to remain in AS was 72%. This rate reached 83% when PSAd ≤ 0.10 was associated to normal MRI.  During follow-up:  One hundred fifty-seven prostatic biopsies (PBx) were performed and 38 (24%) found PCa upgrading. The association between negative MRI and PSAd ≤ 0.10, during follow-up, had an excellent NPV to predict treatment (95%). This combination concerned 25% (37/151) of surveillance biopsies that could have been avoided at the cost of delaying upgrading in 3% (1/37). In multivariate analysis, only PIRADS ≥ 4 before PBx was associated to a risk of treatment during follow-up (OR, 10.4 [95% CI, 4.2-25.8]; P < .0001). CONCLUSION: Using PSAd and MRI at baseline to select patients showed excellent performances to predict the maintenance in AS. During follow-up, MRI PIRADS ≥ 4 was associated to an increased risk of treatment.

Development of a Radiomic-Based Model Predicting Lymph Node Involvement in Prostate Cancer Patients.

Significant advances in lymph node involvement (LNI) risk modeling in prostate cancer (PCa) have been achieved with the addition of visual interpretation of magnetic resonance imaging (MRI) data, but it is likely that quantitative analysis could further improve prediction models. In this study, we aimed to develop and internally validate a novel LNI risk prediction model based on radiomic features extracted from preoperative multimodal MRI. All patients who underwent a preoperative MRI and radical prostatectomy with extensive lymph node dissection were retrospectively included in a single institution. Patients were randomly divided into the training (60%) and testing (40%) sets. Radiomic features were extracted from the index tumor volumes, delineated on the apparent diffusion coefficient corrected map and the T2 sequences. A ComBat harmonization method was applied to account for inter-site heterogeneity. A prediction model was trained using a neural network approach (Multilayer Perceptron Network, SPSS v24.0©) combining clinical, radiomic and all features. It was then evaluated on the testing set and compared to the current available models using the Receiver Operative Characteristics and the C-Index. Two hundred and eighty patients were included, with a median age of 65.2 y (45.3-79.6), a mean PSA level of 9.5 ng/mL (1.04-63.0) and 79.6% of ISUP ≥ 2 tumors. LNI occurred in 51 patients (18.2%), with a median number of extracted nodes of 15 (10-19). In the testing set, with their respective cutoffs applied, the Partin, Roach, Yale, MSKCC, Briganti 2012 and 2017 models resulted in a C-Index of 0.71, 0.66, 0.55, 0.67, 0.65 and 0.73, respectively, while our proposed combined model resulted in a C-Index of 0.89 in the testing set. Radiomic features extracted from the preoperative MRI scans and combined with clinical features through a neural network seem to provide added predictive performance compared to state of the art models regarding LNI risk prediction in PCa.

Tissue cholesterol metabolism and prostate cancer aggressiveness: Ethno-geographic variations.

BACKGROUND: Prostate cancer (PCa) is more frequent and more aggressive in populations of African descent than in Caucasians. Since the fatty acid composition of peri-prostatic adipose tissue (PPAT) has been shown to differ according to the ethno-geographic origin and is involved in PCa aggressiveness, we aimed to analyze the cholesterol content of PPAT from Caucasian and African-Caribbean patients, in correlation with markers of disease aggressiveness and cholesterol metabolism in cancer tissues. METHODS: The quantification of cholesterol in PPAT was analyzed in 52 Caucasian and 52 African-Caribbean PCa patients, with in each group 26 indolent tumors (ISUP Group1 and pT2) and 26 potentially aggressive tumors (ISUP Group 3-5 and/or pT3). The expression of proteins involved in cholesterol metabolism was analyzed by immunohistochemistry on cancer tissue samples included in tissue microarrays. RESULTS: The amount of cholesterol esters was lower in PPAT from African-Caribbean patients compared with Caucasians, without any correlation with markers of disease aggressiveness. In cancer tissues from African-Caribbean patients, the expression of ABCA1 (involved in cholesterol efflux) was decreased, and that of SREBP-2 (involved in cholesterol uptake) was increased. In both groups of patients, SREBP-2 expression was strongly associated with that of Zeb1, a key player in the epithelial-to-mesenchymal transition (EMT) process. CONCLUSION: These results suggest that cholesterol metabolism differs according to the ethno-geographic origin, in both PPAT and cancer tissues. In African-Caribbeans, the orientation towards accumulation of cholesterol in cancer cells is associated with a more frequent state of EMT, which may promote PCa aggressiveness in this population.

MSI-High RAS-BRAF wild-type colorectal adenocarcinomas with MLH1 loss have a high frequency of targetable oncogenic gene fusions whose diagnoses are feasible using methods easy-to-implement in pathology laboratories.

Targetable kinase fusions are extremely rare (<1%) in colorectal cancers (CRCs), making their diagnosis challenging and often underinvestigated. They have been shown particularly frequently among MSI-High, BRAF/KRAS/NRAS wild-type CRCs with MLH1 loss (MLH1loss MSI-High wild-type). We searched for NTRK1, NTRK2, NTRK3, ALK, ROS1, BRAF, RET, and NRG1 kinase fusions in CRCs using methods easy-to-implement in pathology laboratories: immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and fully automated real-time PCR targeted analyses. RNA-sequencing analyses were used for confirmation. Among 84 selected MLH1 deficient (IHC) CRCs cases, MLH1loss MSI-High wild-type CRCs consisted first in 19 cases after Idylla™ analyses and finally in 18 cases (21%) after RNA-sequencing (detection of one additional KRASG12D mutation). FISH (and when relevant, IHC) analyses concluded in 5 NTRK1, 3 NTRK3, 1 ALK, 2 BRAF, and 2 RET FISH positive tumors. ALK and NTRK1 rearranged tumors were IHC positive, but pan-TRK IHC was negative in the 3 NTRK3 FISH positive tumors. RNA-sequencing analyses confirmed 12 of 13 fusions with only one false positive RET FISH result. Finally, 12/18 (67%) of MLH1loss MSI-High wild-type CRCs contained targetable kinase fusions. Our study demonstrates the feasibility, but also the cost-effectiveness, of a multistep but rapid diagnostic strategy based on nonsequencing methods to identify rare and targetable kinase fusions in patients with advanced CRCs, as well as the high prevalence of these kinase fusions in MLH1loss MSI-High wild-type CRCs. Nevertheless, confirmatory RNA-sequencing analyses are necessary in case of low FISH positive nuclei percentage to rule out FISH false-positive results.

Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST).

Tyrosine kinase inhibitors have revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Nevertheless, some GISTs do not contain any targetable KIT or PDGFRA mutations classically encountered in this field. Novel approved therapies targeting TRK chimeric proteins products of NTRK genes fusions consist in a promising approach to treat some patients with GISTs lacking any identified driver oncogenic mutation in KIT, PDGFRA or BRAF genes. Thus, an adequate testing strategy permitting to diagnose the rare NTRK-rearranged GISTs is required. In this work, we studied about the performances of pan-TRK immunohistochemistry (IHC) and NTRK1/2/3 fluorescent in situ hybridization in a series of 39 GISTs samples. Among 22 patients with GISTs lacking KIT or PDGFRA mutations, BRAFV600E IHC permitted to diagnose 2/22 (9%) BRAFV600E-mutated GISTs and, among the 20 KIT, PDGFRA, and BRAF wild type tumors, 1/20 (5%), NTRK3-rearranged tumor was diagnosed using NTRK3 fluorescent in situ hybridization. Pan-TRK IHC using EPR17341 and A7H6R clones was negative in this NTRK3-rearranged sample. Pan-TRK IHC was frequently positive in NTRK not rearranged tumors without (24 samples analyzed) or with (15 samples analyzed) KIT or PDGFRA mutations with major discrepancies between the 2 IHC clones (intraclass correlation coefficient of 0.3042). Given the new therapeutic opportunity offered by anti-TRK targeted therapies to treat patients with advanced cancers including GISTs, it is worth to extend molecular analysis to NTRK fusions testing in KIT, PDGFRA, and BRAF wild type GISTs. Pan-TRK IHC appears not relevant in this field but performing a simple NTRK3 fluorescent in situ hybridization test consists in a valuable approach to identify the rare NTRK3-rearranged GISTs treatable using anti-TRK therapies.

Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network.

BACKGROUND: Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. METHODS: The nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. RESULTS: Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10-6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. CONCLUSIONS: This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials.

Clinicopathologic features of infection-related glomerulonephritis with IgA deposits: a French Nationwide study.

BACKGROUND: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. METHODS: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. RESULTS: Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. CONCLUSIONS: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Evaluation of KRAS, NRAS and BRAF mutational status and microsatellite instability in early colorectal carcinomas invading the submucosa (pT1): towards an in-house molecular prognostication for pathologists?

AIM: We aimed to study the prognostic value of KRAS, NRAS, BRAF mutations and microsatellite stable (MSS)/instable (MSI) in the field of colorectal cancer invading the submucosa (ie, pT1 colorectal cancer (CRC)). METHODS: We led a case-control study in tumour samples from 60 patients with pT1 CRC with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for KRAS, NRAS, BRAF mutations (Idylla testing and next generation sequencing, NGS) and MSS/MSI status (Idylla testing and expression of mismatch repair (MMR) proteins using immunohistochemistry). RESULTS: KRAS mutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (OR=1.11 (0.38 to 3.25), p=0.8548), NRAS mutations in 1/20 (5%) cases and 3/40 (7.5%) controls (OR=3.08 (0.62 to 15.39), p=0.1698) and BRAF mutations in 3/20 (15%) cases and 6/40 (15%) controls (OR=1.00 (0.22 to 4.5), p=1.00). A MSI status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (OR=1.2353 (0.26 to 5.79), p=0.7885). Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing KRAS, NRAS and BRAF mutations (Kappa value of 0.849 (0.748 to 0.95) between Idylla and NGS) and MSS/MSI (Idylla)-proficient MMR/deficient MMR (immunohistochemistry) status (Kappa value of 1.00). CONCLUSION: Although being feasible using the fully automated Idylla method as well as NGS, the molecular testing of KRAS, NRAS, BRAF and MSS/MSI status does not seem useful for prognostic purpose in the field of pT1 CRC.

External Validation of an MRI-Derived Radiomics Model to Predict Biochemical Recurrence after Surgery for High-Risk Prostate Cancer.

Adjuvant radiotherapy after prostatectomy was recently challenged by early salvage radiotherapy, which highlighted the need for biomarkers to improve risk stratification. Therefore, we developed an MRI ADC map-derived radiomics model to predict biochemical recurrence (BCR) and BCR-free survival (bRFS) after surgery. Our goal in this work was to externally validate this radiomics-based prediction model. EXPERIMENTAL DESIGN: A total of 195 patients with a high recurrence risk of prostate cancer (pT3-4 and/or R1 and/or Gleason's score > 7) were retrospectively included in two institutions. Patients with postoperative PSA (Prostate Specific Antigen) > 0.04 ng/mL or lymph node involvement were excluded. Radiomics features were extracted from T2 and ADC delineated tumors. A total of 107 patients from Institution 1 were used to retrain the previously published model. The retrained model was then applied to 88 patients from Institution 2 for external validation. BCR predictions were evaluated using AUC (Area Under the Curve), accuracy, and bRFS using Kaplan-Meier curves. RESULTS: With a median follow-up of 46.3 months, 52/195 patients experienced BCR. In the retraining cohort, the clinical prediction model (combining the number of risk factors and postoperative PSA) demonstrated moderate predictive power (accuracy of 63%). The radiomics model (ADC-based SZEGLSZM) predicted BCR with an accuracy of 78% and allowed for significant stratification of patients for bRFS (p < 0.0001). In Institution 2, this radiomics model remained predictive of BCR (accuracy of 0.76%) contrary to the clinical model (accuracy of 0.56%). CONCLUSIONS: The recently developed MRI ADC map-based radiomics model was validated in terms of its predictive accuracy of BCR and bRFS after prostatectomy in an external cohort.

MRI-Derived Radiomics to Guide Post-operative Management for High-Risk Prostate Cancer.

Purpose: Prostatectomy is one of the main therapeutic options for prostate cancer (PCa). Studies proved the benefit of adjuvant radiotherapy (aRT) on clinical outcomes, with more toxicities when compared to salvage radiotherapy. A better assessment of the likelihood of biochemical recurrence (BCR) would rationalize performing aRT. Our goal was to assess the prognostic value of MRI-derived radiomics on BCR for PCa with high recurrence risk. Methods: We retrospectively selected patients with a high recurrence risk (T3a/b or T4 and/or R1 and/or Gleason score>7) and excluded patients with a post-operative PSA > 0.04 ng/mL or a lymph-node involvement. We extracted IBSI-compliant radiomic features (shape and first order intensity metrics, as well as second and third order textural features) from tumors delineated in T2 and ADC sequences. After random division (training and testing sets) and machine learning based feature reduction, a univariate and multivariate Cox regression analysis was performed to identify independent factors. The correlation with BCR was assessed using AUC and prediction of biochemical relapse free survival (bRFS) with a Kaplan-Meier analysis. Results: One hundred seven patients were included. With a median follow-up of 52.0 months, 17 experienced BCR. In the training set, no clinical feature was correlated with BCR. One feature from ADC (SZEGLSZM) outperformed with an AUC of 0.79 and a HR 17.9 (p = 0.0001). Lower values of SZEGLSZM are associated with more heterogeneous tumors. In the testing set, this feature remained predictive of BCR and bRFS (AUC 0.76, p = 0.0236). Conclusion: One radiomic feature was predictive of BCR and bRFS after prostatectomy helping to guide post-operative management.

Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer.

The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.

High reproducibility is attainable in assessing histoprognostic parameters of pT1 colorectal cancer using routine histopathology slides and immunohistochemistry analyses.

Assessment of the risk of lymph node invasion and tumour recurrence is critical to determine whether additional surgery is required in patients with endoscopically-removed pT1 colorectal cancer (CRC). A reproducible assessment of this risk of recurrence based on histopathological parameters is crucial for relevant therapeutic decisions. The inter-observer reproducibility of these parameters was the subject of our study. Two pathologists independently analysed 163 endoscopically-removed pT1 CRC recorded in a local digestive cancer registry database (Finistère, France). Using haematoxylin-eosin-saffron (HES) and immunohistochemistry slides, they evaluated several parameters related to the risk of tumour recurrence according to the international pT1 CRC-dedicated guidelines. Based on Kappa and intra-class correlation coefficients, good to very good inter-observer agreement was obtained by analysing vertical and lateral margins, submucosal invasion, tumour differentiation and lymphovascular invasion. The reproducibility of tumour budding quantification was only fair on the basis of HES slides but reached a very good agreement using cytokeratin immunohistochemistry. Dual colour cytokeratin and podoplanin immunohistochemistry also improved inter-observer agreement for the detection of lymphovascular invasion. All patients with loco-regional nodal metastases (7 of 101 who underwent complementary surgery) or distant metastases (3 patients) were diagnosed as having a high risk of recurrence and requiring an additional surgery by the two observers. Our study showed that good to very good inter-observer agreement is achievable in evaluating the pathological parameters of recurrence risk in endoscopically-removed pT1 CRC. In addition to HES slides, the detection of lymphovascular invasion and tumour budding can benefit with more reproducible immunohistochemical analyses.