Microvascular proliferation is associated with high tumour blood flow by mpMRI and disease progression in primary prostate cancer.

Active angiogenesis may be assessed by immunohistochemistry using Nestin, a marker of newly formed vessels, combined with Ki67 for proliferating cells. Here, we studied microvascular proliferation by Nestin-Ki67 co-expression in prostate cancer, focusing on relations to quantitative imaging parameters from anatomically matched areas obtained by preoperative mpMRI, clinico-pathological features and prognosis. Tumour slides from 67 patients (radical prostatectomies) were stained for Nestin-Ki67. Proliferative microvessel density (pMVD) and presence of glomeruloid microvascular proliferation (GMP) were recorded. From mpMRI, forward volume transfer constant (Ktrans), reverse volume transfer constant (kep), volume of EES (ve), blood flow, and apparent diffusion coefficient (ADC) were obtained. High pMVD was associated with high blood flow (p = 0.008) and low ADC (p = 0.032). High Ktrans, kep, and blood flow were associated with high Gleason score. High pMVD, GMP, and low ADC were associated with most adverse clinico-pathological factors. Regarding prognosis, high pMVD, Ktrans, kep, and low ADC were associated with reduced biochemical recurrence-free- and metastasis-free survival (p ≤ 0.044) and high blood flow with reduced time to biochemical- and clinical recurrence (p < 0.026). In multivariate analyses however, microvascular proliferation was a stronger predictor compared with blood flow. Indirect, dynamic markers of angiogenesis from mpMRI and direct, static markers of angiogenesis from immunohistochemistry may aid in the stratification and therapy planning of prostate cancer patients.

Preoperative predictors of pathological tumour stage and prognosis may be used when selecting candidates for intensified treatment in upper tract urothelial carcinoma.

PURPOSE: Intensified treatment such as extended lymph node dissection (LND) and/or perioperative chemotherapy in addition to radical nephroureterectomy (RNU) has been suggested for high-risk cases of upper tract urothelial carcinoma (UTUC). We aimed to identify preoperative predictors of tumour stage and prognosis in the diagnostic work-up before RNU. Further to evaluate if our findings could be used in selecting patients for intensified treatment. PATIENTS AND METHODS: A total of 179 patients treated with RNU for UTUC at Haukeland University Hospital (HUS) and Vestfold Hospital Trust (VHT) during 2005-2017 were included in this retrospective study. All relevant preoperative variables regarding the patient, the CT and the ureteroscopy (URS) were registered and analysed regarding their ability to predict non-organ confined disease (NOCD, pT3+ and/or N+) at final pathology after RNU. The prognosis was assessed calculating survival for the cohort and stratified by preoperative variables. RESULTS: Local invasion and pathological lymph nodes at CT predicted NOCD in uni and multivariate regression analyses (OR 3.36, p=.004 and OR 6.21, p=.03, respectively). Reactive oedema surrounding the tumour (OR 2.55, p=.02), tumour size (4.8 vs. 3.9 cm, p=.006) and high-grade tumour at URS biopsy (OR 3.59, p=.04) predicted NOCD at univariate regression analyses. The 5-year CSS and OS for the entire cohort was 79% and 60%. ECOG, local invasion, pathological lymph nodes and reactive oedema surrounding the tumour at CT predicted CSS. CONCLUSIONS: Several variables at the CT predicted both stage and survival. Local invasion at CT seems the most promising feature for selecting patients for intensified treatment.

Magnetic resonance radiomics for prediction of extraprostatic extension in non-favorable intermediate- and high-risk prostate cancer patients.

BACKGROUND: To investigate whether magnetic resonance (MR) radiomic features combined with machine learning may aid in predicting extraprostatic extension (EPE) in high- and non-favorable intermediate-risk patients with prostate cancer. PURPOSE: To investigate the diagnostic performance of radiomics to detect EPE. MATERIAL AND METHODS: MR radiomic features were extracted from 228 patients, of whom 86 were diagnosed with EPE, using prostate and lesion segmentations. Prediction models were built using Random Forest. Further, EPE was also predicted using a clinical nomogram and routine radiological interpretation and diagnostic performance was assessed for individual and combined models. RESULTS: The MR radiomic model with features extracted from the manually delineated lesions performed best among the radiomic models with an area under the curve (AUC) of 0.74. Radiology interpretation yielded an AUC of 0.75 and the clinical nomogram (MSKCC) an AUC of 0.67. A combination of the three prediction models gave the highest AUC of 0.79. CONCLUSION: Radiomic analysis combined with radiology interpretation aid the MSKCC nomogram in predicting EPE in high- and non-favorable intermediate-risk patients.

Assessing Extraprostatic Extension with Multiparametric MRI of the Prostate: Mehralivand Extraprostatic Extension Grade or Extraprostatic Extension Likert Scale?

Purpose: To validate the MRI grading system proposed by Mehralivand et al in 2019 (the "extraprostatic extension [EPE] grade") in an independent cohort and to compare the Mehralivand EPE grading system with EPE interpretation on the basis of a five-point Likert score ("EPE Likert"). Materials and Methods: A total of 310 consecutive patients underwent multiparametric MRI according to a standardized institutional protocol before radical prostatectomy was performed by using the same 1.5-T MRI unit at a single institution between 2010 and 2012. Two radiologists blinded to clinical information assessed EPE according to standardized criteria. On the basis of the readings performed until 2017, the diagnostic performance of EPE Likert and Mehralivand EPE score were compared using receiver operating characteristics (ROC) and decision curve methodology against histologic EPE as standard of reference. Prediction of biochemical recurrence-free survival (BRFS) was assessed by Kaplan-Meier analysis and log rank test. Results: Of the 310 patients, 80 patients (26%) had EPE, including 33 with radial distance 1.1 mm or greater. Interrater reliability was fair (weighted κ 0.47 and 0.45) for both EPE grade and EPE Likert. Sensitivity for identifying EPE using EPE grade versus EPE Likert was 0.83 versus 0.86 and 0.86 versus 0.91 for radiologist 1 and 2, respectively. Specificity was 0.48 versus 0.58 and 0.39 versus 0.70 (P < .05 for radiologist 2). There were no significant differences in the ROC area under the curve or on decision curve analysis. Both EPE grade and EPE Likert were significant predictors of BRFS. Conclusion: Mehralivand EPE grade and EPE Likert have equivalent diagnostic performance for predicting EPE and BRFS with a similar degree of observer dependence.© RSNA, 2020Keywords: MR-Imaging, Neoplasms-Primary, Observer Performance, Outcomes Analysis, Prostate, StagingSupplemental material is available for this article.See also the commentary by Choyke in this issue.

Tumour architecture, grade and location remain predictors of non-organ-confined upper tract urothelial carcinoma at time of radical nephroureterectomy: results from a multicenter Norwegian external validation study.

PURPOSE: Selecting patients for intensified treatment for upper tract urothelial carcinoma can be challenging, partly due to the lack of accurate preoperative staging tools. Several preoperative staging models for upper tract urothelial carcinoma have been presented, but none have been externally validated. The aim of the current study was to perform an external validation of the Margulis nomogram for predicting non-organ-confined upper tract urothelial carcinoma at time of nephroureterectomy. METHODS: 209 patients from two high-volume centres in Norway were treated with radical nephroureterectomy during the period 2005-2017. 163 patients with complete data necessary for external validation of the Margulis nomogram were included in the study. All relevant covariates were analysed with uni- and multivariate regression analysis to assess their ability to predict non-organ-confined disease. The Margulis nomogram was applied on the present cohort to calculate predicted risk of non-organ-confined disease. This was compared to the observed risk to assess model calibration. The Margulis nomogram accuracy was measured as the area under the curve in a receiver operator characteristics curve to evaluate model discrimination. RESULTS: Tumour grade (OR 28.1, p = 0.001) and architecture (OR 4.72, p < 0.001) were independent predictors of non-organ-confined disease. There was a high concordance between predicted and observed risk quantified with a Cronbach alpha of 0.96. The Margulis nomogram had an area under the curve of 0.83 in predicting non-organ-confined disease when applied on the current cohort. CONCLUSIONS: We consider the Margulis nomogram validated for clinical use.

Optimising preoperative risk stratification tools for prostate cancer using mpMRI.

PURPOSE: To improve preoperative risk stratification for prostate cancer (PCa) by incorporating multiparametric MRI (mpMRI) features into risk stratification tools for PCa, CAPRA and D'Amico. METHODS: 807 consecutive patients operated on by robot-assisted radical prostatectomy at our institution during the period 2010-2015 were followed to identify biochemical recurrence (BCR). 591 patients were eligible for final analysis. We employed stepwise backward likelihood methodology and penalised Cox cross-validation to identify the most significant predictors of BCR including mpMRI features. mpMRI features were then integrated into image-adjusted (IA) risk prediction models and the two risk prediction tools were then evaluated both with and without image adjustment using receiver operating characteristics, survival and decision curve analyses. RESULTS: 37 patients suffered BCR. Apparent diffusion coefficient (ADC) and radiological extraprostatic extension (rEPE) from mpMRI were both significant predictors of BCR. Both IA prediction models reallocated more than 20% of intermediate-risk patients to the low-risk group, reducing their estimated cumulative BCR risk from approximately 5% to 1.1%. Both IA models showed improved prognostic performance with a better separation of the survival curves. CONCLUSION: Integrating ADC and rEPE from mpMRI of the prostate into risk stratification tools improves preoperative risk estimation for BCR. KEY POINTS: • MRI-derived features, ADC and EPE, improve risk stratification of biochemical recurrence. • Using mpMRI to stratify prostate cancer patients improves the differentiation between risk groups. • Using preoperative mpMRI will help urologists in selecting the most appropriate treatment.

National Norwegian Practice Patterns for Surgical Treatment of Kidney Cancer Tumors ≤7cm: Adherence to Changes in Guidelines May Improve Overall Survival.

BACKGROUND: Guidelines on surgical treatment for kidney cancer (KC) have changed over the last 10 yr. We present population-based data for patients with KC tumors ≤7cm from 2008 to 2013 to investigate whether surgical practice in Norway has changed according to guidelines. OBJECTIVE: To assess the predictors of treatment and survival after KC surgery. DESIGN, SETTING, AND PARTICIPANTS: We identified all surgically treated KC patients with tumors ≤7cm without metastasis diagnosed during 2008-2013 (2420 patients) from the Cancer Registry of Norway. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcomes were analyzed using joinpoint regression, multivariate logistic regression, Kaplan-Meier survival estimates, Cox regression, relative survival (RS), and competing-risk analyses. RESULTS AND LIMITATIONS: The mean follow-up was 5.2 yr. There was a 28% increase in the number of patients undergoing surgical treatment over the study period. Joinpoint regression revealed a significant annual increase in partial nephrectomy (PN) and a small reduction in radical nephrectomy (RN). PN increased from 43% to 66% for tumors ≤4cm and from 10% to 18% for tumors of 4.1-7cm. Minimally invasive (MI) RN increased from 53% to 72% and MI PN from 25% to 64%, of which 55% of procedures were performed with robotic assistance in 2013. The geographical distribution of treatment approaches differed significantly. Both PN and MI approaches were more frequent in high-volume hospitals. Cox regression analysis revealed that PN, age, and Fuhrman grade and stage were independent predictors of survival. There were no significant differences in cancer-specific survival (p=0.8). The 5-yr RS for T1a disease was higher after PN than after RN. CONCLUSIONS: The rate of PN for tumors ≤7cm increased in the 6-yr study period. MI approaches increased for both RN and PN. This treatment shift coincides with the new guideline recommendations in 2010. The possible better survival for patients undergoing PN compared to RN indicates the importance of following evidence-based guidelines. PATIENT SUMMARY: The use of partial nephrectomy and minimally invasive surgery for kidney cancer tumors increased in Norway from 2008 to 2013 according to population-based data, coinciding with guideline changes. The study illustrate that adherence to guidelines may improve patient outcomes.

A prospective risk-stratified follow-up programme for radically treated renal cell carcinoma patients: evaluation after eight years of clinical use.

PURPOSE: In mid-2007, we introduced a new risk-stratified follow-up programme (FUP) for surgically treated localized renal cell carcinoma. After inclusion, the patients have been followed prospectively. In this study, we present the results in regard to stratification, completeness of the FUP and recurrences. METHODS: The FUP consists of three risk groups: low risk (LR), intermediate risk (IR) and high risk (HR), based on the risk stratification model introduced by Leibovich et al. (Cancer 97(7):1663-1671, 2003). In all risk groups, the patients are scheduled for ten follow-up visits (FUV) over 5 years, but seven, five and three FUVs, respectively, are outsourced to the patient's general practitioner (GP). Chest X-ray and abdomen CT are the imaging modalities used in the FUP. RESULTS: Of 312 included patients, 195 (62.5 %) had a complete FUP. However, in 86 patients the scheduled FUP had to be reduced, leaving 86.3 % of the remaining patients with a complete FUP. By including GPs, the number of FUVs at the hospital was reduced by ~60 %. The 5-year probability for freedom of recurrence is 0.98, 0.84 and 0.52 for the LR, IR and HR groups, respectively. Of 31 recurrences, 20 patients (65 %) were diagnosed within the FUP. Eleven patients (35 %) were diagnosed due to symptoms, and five of these had recurrences in locations not covered by standard imaging. Patients diagnosed within the FUP showed a better prognosis for survival and could in greater part receive tumour-directed treatment. CONCLUSIONS: After 8 years of clinical use, the outcome measures of the FUP seem to be within acceptable ranges.

Contemporary external validation of the Leibovich model for prediction of progression after radical surgery for clear cell renal cell carcinoma.

OBJECTIVE: The aim of this study was to externally validate in an up-to-date setting the predictive ability of the model for recurrence after radical treatment of clear cell renal cell carcinoma (CCRCC) published by Leibovich in 2003. MATERIALS AND METHODS: The study included a total of 386 consecutive patients with CCRCC between January 1997 and May 2013, treated with partial or radical nephrectomy. All patients were scored with points between 0 and 11, and further subdivided into low-, intermediate- and high-risk groups according to the original paper. Well-recognized statistical methods for the evaluation of Cox's proportional hazard-based prognostic models were applied. To validate the discriminative ability, Harrell's concordance (c) index and hazard ratios (HRs) between risk groups were used, and calibration was graphically explored. RESULTS: The 10 year recurrence-free survival rates for the low-, intermediate- and high-risk groups were 87.3%, 63.8% and 19.8%, respectively Harrell's c index was 0.864. The HRs across risk groups for the intermediate- and high-risk groups were 5.29 and 21.56, respectively, with the low-risk group as a reference category. A gross comparison of the survival estimates between the patients showed an overall similarity. However, differences within the intermediate- and high-risk groups were seen in the first year of follow-up. CONCLUSIONS: The Leibovich model seems to discriminate well between risk groups, but for the intermediate- and high-risk groups the calibration is not optimal. This study validates the model in a present-day Nordic patient population. The model can be used as a risk stratification tool for follow-up after radical treatment of CCRCC.

Observation should be considered as an alternative in management of renal masses in older and comorbid patients.

BACKGROUND: Renal masses diagnosed in older and comorbid patients represent a challenge with regard to treatment. OBJECTIVE: To evaluate clinical outcome and tumor progression in patients with renal masses managed by observation due to age and comorbidity. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 63 consecutive patients with renal masses primarily managed by observation during 2002-2007 were reviewed retrospectively and analyzed. The mean age for all patients at diagnosis was 76.6 yr, and 59% were male. Mean tumor size was 4.3 cm in diameter at diagnosis. Of these, 30% had Eastern Cooperative Oncology Group performance status (PS) of 2 or 3, 78% were American Society of Anesthesiologists (ASA) class 3, and the patients had a mean of 2.8 other medical conditions. MEASUREMENTS: Registration of age, ASA class, PS, comorbid conditions, computed tomography scans, primary tumor size, tumor growth rate, pathology parameters, observation time, survival time. RESULTS AND LIMITATIONS: Five-year overall survival (OS) and cancer-specific survival (CSS) rates were 42.8% and 93.3%, respectively. For tumors < or =4.0 cm in size, 5-yr CSS was 100%. Nine patients received delayed radical treatment, none of whom had later progression of the disease. In 18 patients histopathologic diagnosis of the renal masses were available, and in 15 patients (83%) renal cell carcinoma (RCC) was verified. The annual growth rate was <1cm/yr in 85.4% of the cases. In tumors < or =4.0 cm, only 1 of 27 tumors (3.7%) grew faster than 1cm/yr. CONCLUSIONS: Management of renal masses by observation among older and comorbid patients seems to give acceptable results with regard to OS and CSS rates after 5 yr. The risk of disease progression is significantly higher in patients with larger sized renal masses (>4 cm). Thus, selection for observation in this group has to be stricter than in a group of patients with smaller sized renal masses (< or =4.0 cm).