A preoperative magnetic resonance imaging can aid in staging and treatment choice for upper tract urothelial carcinoma.

Objectives: The aim was to investigate the predictive abilities of a preoperative diffusion-weighted MRI (dwMRI) among patients with surgically treated upper tract urothelial carcinoma (UTUC). Materials and methods: Written consent was obtained from all participants in this prospective and ethically approved study. Thirty-five UTUC patients treated with radical surgery were examined with a preoperative dwMRI and prospectively included during 2017-2022. Two radiologists examined the CT scans and dwMRIs for radiological stage, and the apparent diffusion coefficient (ADC) in the tumours at the dwMRI was registered. The radiologists were blinded for patient history, final histopathology and the readings of the other radiologist. The radiological variables were analysed regarding their abilities to predict muscle-invasive disease (MID, T2-T4) and tumour grade at final pathology after radical surgery. The predictive abilities were assessed using chi-square tests, Student's t-test and calculating the area under the curve in a receiver operating characteristic (ROC) curve. Correlation between the two radiologists was quantified calculating the intra-class correlation coefficient. P-values <0.05 were considered statistically significant. Results: Mean age was 72 years, 20 had high-grade tumour, and 13 patients had MID. The ADC values at the dwMRI were significantly lower among patients with MID compared to patients with non-muscle-invasive disease (930 vs 1189, p = <0.001). The area under the ROC curve (AUC) in an ROC curve to predict MID was 0.88 (CI 0.77-0.99, p = <0.001). The ADC values were significantly lower among patients with high-grade tumours compared to low-grade tumours (1005 vs 1210, p = 0.002). The correlation of the ADC measurements between the two radiologists was of 0.93 (CI 0.85-0.96, p < 0.001). Conclusion: Tumour ADC at the MRI emerges as a potential biomarker for aggressive disease. The results are promising but should be validated in a larger, multicentre study.

Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up.

PURPOSE: There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years. MATERIALS AND METHODS: From 2013 to 2017, 38 patients with biopsy-proven locally recurrent PCa >2 years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included. The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation. The Phoenix criteria defined biochemical recurrence-free survival (bRFS), and toxicity was scored according to Radiation Therapy Oncology Group criteria. RESULTS: Median age was 70 years, and median time from primary radiation to prostate-specific antigen (PSA) recurrence was 83 months. The actuarial 2-year and 5-year bRFS were 81% (95% CI, 69 to 94) and 58% (95% CI, 49 to 74), respectively. The actuarial 5-year local recurrence-free survival was 93% (95% CI, 82 to 100), metastasis-free survival was 82% (95% CI, 69 to 95), and overall survival was 87% (95% CI, 76 to 98). Two patients (5%) had durable grade 3 genitourinary toxicity, one combined with GI grade 3 toxicity. A PSA doubling time ≤6 months at salvage, a Gleason score >7, and a PSA nadir ≥0.1 ng/mL predicted a worse outcome. CONCLUSION: Reirradiation with EBRT for locally recurrent PCa after primary curative radiation therapy is clinically feasible and demonstrated a favorable outcome with acceptable toxicity in this prospective study with long-term follow-up.

Transitioning from transrectal to transperineal prostate biopsy using a freehand cognitive approach.

OBJECTIVES: To report a single-centre experience of a complete transition from transrectal (TR) to transperineal (TP) prostate biopsy under local anaesthesia using a freehand cognitive coaxial approach and without use of antibiotic prophylaxis. PATIENTS AND METHODS: Analysis was performed of a prospective database of patients undergoing prostate biopsy performed by four surgeons between 1 June 2018 and 31 May 2022. Outcomes of interest were complications, cancer detection rate, inter-operator reliability, and tolerability. RESULTS: Overall, 1915 patients underwent 2337 separate prostate biopsy sessions. Only 2.4% patients in the TP group received antibiotic prophylaxis, while 100% received antibiotics in the TR group. The complication rate was significantly lower in the TP group compared to the TR group (0.3% vs 5.0%, P < 0.001). In contrast to the TR group, there were no cases of urosepsis or admissions to intensive care in the TP group. The total cancer detection rate by TP biopsy was 70% and the overall pathology detection rate was 88.4%. There was no difference in cancer or pathology detection between operators. A stable level of cancer detection was reached early on for both Prostate Imaging-Reporting and Data System 4 and 5 lesions. All cases performed were performed successfully without need for early termination. CONCLUSION: Implementing a complete transition from TR to TP biopsy can result in a significant reduction in complications and hospital re-admissions. A cognitive freehand coaxial technique is well tolerated by patients and achieves a high cancer detection rate.

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.

Impact of prebiopsy MRI on prostate cancer staging: Results from the Norwegian Prostate Cancer Registry.

Objectives: The aim of this study is to evaluate the 2015 introduction of prebiopsy magnetic resonance imaging of the prostate (MRI-P) as the standard of care for diagnosing prostate cancer (PCa) by the Norwegian public health care authorities. There were three specific objectives of this study: first, to evaluate the consequences of using different TNM manuals for clinical T-staging (cT-staging) in a national setting; second, to determine if the data reveals that MRI-P based cT-staging is superior to digital rectal examination (DRE)-based cT-staging compared with pathological T-stage (pT-stage) post radical prostatectomy; and third, to assess whether treatment allocations have changed over time. Materials and Methods: All patients registered in the Norwegian Prostate Cancer Registry between 2004 and 2021 were retrieved and 5538 were eligible for inclusion. Concordance between clinical T-stage (cT-stage) and pT-stage was assessed by percentage agreement, Cohen's kappa and Gwet's agreement. Results: MR visualisation of lesions influences reporting of tumour extension beyond DRE findings. Agreement between cT-stage and pT-stage declined from 2004 to 2009, which coincided with an increase in the percentage being pT3. From 2010, agreement increased, which aligned with changes in cT-staging and the introduction of MRI-P. From 2017, regarding the reporting of cT-DRE and cT-Total (overall cT-stage), agreement diminished for cT-DRE but remained relatively stable (>60%) for cT-Total. Regarding treatment allocation, the study suggests that staging with MRI-P has shifted treatment towards radiotherapy in locally advanced high-risk disease. Conclusion: Introduction of MRI-P has affected cT-stage reporting. Agreement between cT-stage and pT-stage appears to have improved. This study suggests that use of MRI-P influences treatment decisions in certain patient subgroups.

A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.

Enhancing PSMA-PET/CT with intravenous contrast: Improved tracer clearance in the prostate bed.

AIMS: We observed hitherto unreported layering of radioactivity in the bladder on PET/CT in prostate cancer (PC) when combined with contrast-enhanced CT (CECT). This effect facilitates assessment of the prostate bed in PC. METHODS: Among 128 patients imaged with [18F]PSMA-1007, we selected all 8 studies without and 28 studies with CECT. 20 patients also underwent PET/MR. As controls, we chose 20 and 16 males studied with [18F]FDG for extrapelvic disease with and without CECT. Posterior anterior (PA) ratio was calculated as SUVpost/SUVant * 100 % based on maximal standard uptake values (SUV) in 20 mm spheres in the anterior and posterior bladder. Four nuclear physicians scored assessibility of the bladder base on a 3-point Likert scale (3 = optimal, 1 = poor). We acquired serial PET/CT over 4 hours of a flask with layering of 100 ml intravenous contrast agent and 100 ml physiological saline with 40 MBq of [18F]PSMA-1007, while a control flask was shaken at the start of the experiment. RESULTS: Layering of tracer was observed in all PET/CT studies with CE-CT, but not in studies without contrast. Median PA ratios were 44 % (interquartile range 33-62) for [18F]PSMA-1007 and 73 % (52-67) for [18F]FDG, respectively. Intravenous contrast improved assessibility scores in PET of the bladder base, but the effect only reached significance in the PET/MR data. In the in vitro data, radioactivity was retained in the aqueous supernatant over the entire experiment whereas there was no separation of phases in the control flask over time. CONCLUSION: When performing PET combined with CECT, sedimentation of contrast agent in the bladder leads to upward displacement of radioactivity, enhancing clarity of PET images in the posterior bladder and the prostate bed on both PET/CT and PET/MR.

The levels of IL-6 and soluble IL-33R are increased in the renal vein during surgery for clear cell renal cell carcinoma.

PURPOSE: The main aim was to map serum levels of IL-1/IL-6 family cytokines and relevant receptors from serum samples taken across treatment in patients with Renal Cell Carcinoma (RCC). Additionally, we explored the possible interactions between these measurements, immunohistochemistry and intratumoral blood flow. METHODS: We included 40 patients undergoing open surgery for renal tumors. Blood samples were collected before, during (taken simultaneously from a peripheral site and the renal vein (RV) before clamping) and after surgery. Samples were analyzed for IL-6, IL-27, IL-31, OSM, TNF-α, serum (s)-gp130, s-IL-6Rα, s-IL-33R, IL-1Rα and VEGF. All 35 RCC tumors were histologically subtyped as clear cell (CCRCC), papillary or chromophobe. Immunohistochemistry for the CCRCC group included expression of IL-6/IL-6R. Intratumoral blood flow was determined by calculating intratumoral contrast enhancement on preoperative computerized tomography (CT) imaging. RESULTS: In the CCRCC patients, the intraoperative RV concentration of IL-6 was significantly higher than in both the preoperative and postoperative samples (p = 0.005 and p = 0.032, respectively). Furthermore, the intraoperative ratio showed significantly higher levels of IL-6 in the RV than in the simultaneously drawn peripheral sample. Immunohistochemistry showed general expression of IL-6 (23/24) in both tumor cells and the vasculature (20/23). Moreover, s-IL-6R was expressed in tumor cells in 23/24 studied patients. Increased blood flow in the CCRCC tumors predicted increased IL-6 levels in the RV (p < 0.001). The other cytokines and receptors showed an overall stability across the measurements. However, the intraoperative ratios of IL-33R and gp130 showed significantly higher levels in the RV. CONCLUSION: Serum levels of IL-6 increased during surgery. Intraoperative IL-6 and s-IL-33R values were higher in the RV compared to the periphery, suggesting secretion from the tumor or tumor microenvironment itself. Supportive of this is an almost general expression of IL-6/s-IL-6R in tumor cells and IL-6 in vasculature in the tumor microenvironment. Other studied cytokines/receptors were remarkably stable across all measurements.

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.

Ten-Year Results From a Phase II Study on Image Guided, Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in High-Risk Prostate Cancer.

PURPOSE: There is no consensus on how to treat high-risk prostate cancer, and long-term results from hypofractionated radiation therapy are lacking. We report 10-year results after image guided, intensity modulated radiation therapy with hypofractionated simultaneous integrated boost and elective pelvic field. METHODS AND MATERIALS: Between 2007 and 2009, 97 consecutive patients with high-risk prostate cancer were included, treated with 2.7 to 2.0 Gy × 25 Gy to the prostate, seminal vesicles, and elective pelvic field. Toxicity was scored according to Radiation Therapy Oncology Group criteria and biochemical disease-free survival (BFS) defined by the Phoenix definition. Patients were subsequently divided into 3 groups: high risk (HR; n = 32), very high risk (VHR; n = 50), and N+/s-prostate-specific antigen (PSA) ≥100 (n = 15). Differences in outcomes were examined using Kaplan-Meier analyses. RESULTS: BFS in the patients at HR and VHR was 64%, metastasis-free survival 80%, prostate cancer-specific survival 90%, and overall survival (OS) 72%. VHR versus HR subgroups demonstrated significantly different BFS, 54% versus 79% (P = .01). Metastasis-free survival and prostate cancer-specific survival in the VHR group versus HR group were 76% versus 87% (P = .108) and 74% versus 100% (P = .157). Patients reaching nadir PSA <0.1 (n = 80) had significantly better outcomes than the rest (n = 17), with BFS 70% versus 7% (P < .001). Acute grade 2 gastrointestinal tract (GI) and genitourinary tract (GU) toxicity occurred in 27% and 40%, grade 3 GI and GU toxicity in 1% and 3%. Late GI and GU grade 2 toxicity occurred in 1% and 8%. CONCLUSIONS: High-risk prostate cancer patients obtained favorable 10-year outcomes with low toxicity. There were significantly better results in the HR versus the VHR group, both better than the N+/PSA ≥100 group. A nadir PSA value < 0.1 predicted good prognosis.

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.

Intensity-based volumetric registration of magnetic resonance images and whole-mount sections of the prostate.

OBJECTIVE: Magnetic Resonance Imaging (MRI) of the prostate provides useful in vivo diagnostic tissue information such as tumor location and aggressiveness, but ex vivo histopathology remains the ground truth. There are several challenges related to the registration of MRI to histopathology. We present a method for registration of standard clinical T2-weighted MRI (T2W-MRI) and transverse histopathology whole-mount (WM) sections of the prostate. METHODS: An isotropic volume stack was created from the WM sections using 2D rigid and deformable registration combined with linear interpolation. The prostate was segmented manually from the T2W-MRI volume and registered to the WM section volume using a combination of affine and deformable registration. The method was evaluated on a set of 12 patients who had undergone radical prostatectomy. Registration accuracy was assessed using volume overlap (Dice Coefficient, DC) and landmark distances. RESULTS: The DC was 0.94 for the whole prostate, 0.63 for the peripheral zone and 0.77 for the remaining gland. The landmark distances were on average 5.4 mm. CONCLUSION: The volume overlap for the whole prostate and remaining gland, as well as the landmark distances indicate good registration accuracy for the proposed method, and shows that it can be highly useful for registering clinical available MRI and WM sections of the prostate.

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.

Real-life use of diagnostic biopsies before treatment of kidney cancer: results from a Norwegian population-based study.

OBJECTIVE: Interest in renal mass biopsies (RMBs) has increased in recent years. However, most publications are low-volume and/or single-center studies, so their generalizability is questionable. The aim of this study was to describe population-based, real-life use of diagnostic RMBs for localized and advanced kidney cancer (KC). MATERIALS AND METHODS: All KC patients diagnosed during 2008-2013 extracted from the database at the Cancer Registry of Norway were included. Relationships with outcome were analyzed using multivariate logistic regression and competing risks analyses. RESULTS: Of patients treated radically for localized KC, a pretreatment RMB was used in 8.4%. For similar patients treated by observation only, the rate increased from 29.3% to 60.7% during the study period. Tumor size ≤4 cm, another malignancy, multiple tumors, old age (≥ 80 years) and second study half were independent RMB predictors. Competing risks analysis showed that among radically treated patients with localized KC, those who had undergone an RMB had a higher risk of dying of other diseases. In patients with advanced KC, biopsy was used in 54.5%, and is increasing. Study limitations include a lack of data on benign tumors, comorbidity and performance status. CONCLUSIONS: For localized KC, the use of RMBs in Norway is in line with current guidelines. Because real-world data on RMB use are scarce, this study is useful for benchmarking in future studies. Furthermore, the study shows that fewer patients with advanced KC are treated without histopathological verification, and biopsies seem to have an increasing role in tailoring 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.

F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis.

BACKGROUND: Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC). PURPOSE: To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy. MATERIAL AND METHODS: A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma's bivariate model. RESULTS: Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9-84.1) and 79.4% (95% CI, 71.2-85.4), respectively, with an area under the curve of 0.858. CONCLUSION: F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy.