Abstract Background Focal therapy has been introduced for the treatment of localised prostate cancer (PCa). To provide the necessary data for consistent assessment, all focal therapy trials should be ...performed according to uniform, systematic pre- and post-treatment evaluation with well-defined end points and strict inclusion and exclusion criteria. Objective To obtain consensus on trial design for focal therapy in PCa. Design, setting, and participants A four-staged consensus project based on a modified Delphi process was conducted in which 48 experts in focal therapy of PCa participated. According to this formal consensus-building method, participants were asked to fill out an iterative sequence of questionnaires to collect data on trial design. Subsequently, a consensus meeting was held in which 13 panellists discussed acquired data, clarified the results, and defined the conclusions. Outcome measurements and statistical analysis A multidisciplinary board from oncologic centres worldwide reached consensus on patient selection, pretreatment assessment, evaluation of outcome, and follow-up. Results and limitations Inclusion criteria for candidates in focal therapy trials are patients with prostate-specific antigen <15 ng/ml, clinical stage T1c–T2a, Gleason score 3 + 3 or 3 + 4, life expectancy of >10 yr, and any prostate volume. The optimal biopsy strategy includes transrectal ultrasound-guided biopsies to be taken between 6 mo and 12 mo after treatment. The primary objective should be focal ablation of clinically significant disease with negative biopsies at 12 mo after treatment as the primary end point. Conclusions This consensus report provides a standard for designing a feasible focal therapy trial. Patient summary A variety of ablative technologies have been introduced and applied in a focal manner for the treatment of prostate cancer (PCa). In this consensus report, an international panel of experts in the field of PCa determined pre- and post-treatment work-up for focal therapy research.
•Clinically available AI software allows automatic quantification of lung involvement on chest CT scans for COVID-19 patients.•CT findings combined with clinical variables allow better intensive care ...unit admission and death prediction.
We evaluated the contribution of lung lesion quantification on chest CT using a clinical Artificial Intelligence (AI) software in predicting death and intensive care units (ICU) admission for COVID-19 patients.
For 349 patients with positive COVID-19-PCR test that underwent a chest CT scan at admittance or during hospitalization, we applied the AI for lung and lung lesion segmentation to obtain lesion volume (LV), and LV/Total Lung Volume (TLV) ratio. ROC analysis was used to extract the best CT criterion in predicting death and ICU admission. Two prognostic models using multivariate logistic regressions were constructed to predict each outcome and were compared using AUC values. The first model (“Clinical”) was based on patients’ characteristics and clinical symptoms only. The second model (“Clinical+LV/TLV”) included also the best CT criterion.
LV/TLV ratio demonstrated best performance for both outcomes; AUC of 67.8% (95% CI: 59.5 - 76.1) and 81.1% (95% CI: 75.7 - 86.5) respectively. Regarding death prediction, AUC values were 76.2% (95% CI: 69.9 - 82.6) and 79.9% (95%IC: 74.4 - 85.5) for the “Clinical” and the “Clinical+LV/TLV” models respectively, showing significant performance increase (+ 3.7%; p-value<0.001) when adding LV/TLV ratio. Similarly, for ICU admission prediction, AUC values were 74.9% (IC 95%: 69.2 - 80.6) and 84.8% (IC 95%: 80.4 - 89.2) respectively corresponding to significant performance increase (+ 10%: p-value<0.001).
Using a clinical AI software to quantify the COVID-19 lung involvement on chest CT, combined with clinical variables, allows better prediction of death and ICU admission.
This study evaluated a computer-assisted diagnosis (CADx) system for determining a likelihood measure of prostate cancer presence in the peripheral zone (PZ) based on multiparametric magnetic ...resonance (MR) imaging, including T2-weighted, diffusion-weighted and dynamic contrast-enhanced MRI at 1.5 T. Based on a feature set derived from grey-level images, including first-order statistics, Haralick features, gradient features, semi-quantitative and quantitative (pharmacokinetic modelling) dynamic parameters, four kinds of classifiers were trained and compared: nonlinear support vector machine (SVM), linear discriminant analysis, k-nearest neighbours and naïve Bayes classifiers. A set of feature selection methods based on t-test, mutual information and minimum-redundancy-maximum-relevancy criteria were also compared. The aim was to discriminate between the relevant features as well as to create an efficient classifier using these features. The diagnostic performances of these different CADx schemes were evaluated based on a receiver operating characteristic (ROC) curve analysis. The evaluation database consisted of 30 sets of multiparametric MR images acquired from radical prostatectomy patients. Using histologic sections as the gold standard, both cancer and nonmalignant (but suspicious) tissues were annotated in consensus on all MR images by two radiologists, a histopathologist and a researcher. Benign tissue regions of interest (ROIs) were also delineated in the remaining prostate PZ. This resulted in a series of 42 cancer ROIs, 49 benign but suspicious ROIs and 124 nonsuspicious benign ROIs. From the outputs of all evaluated feature selection methods on the test bench, a restrictive set of about 15 highly informative features coming from all MR sequences was discriminated, thus confirming the validity of the multiparametric approach. Quantitative evaluation of the diagnostic performance yielded a maximal area under the ROC curve (AUC) of 0.89 (0.81-0.94) for the discrimination of the malignant versus nonmalignant tissues and 0.82 (0.73-0.90) for the discrimination of the malignant versus suspicious tissues when combining the t-test feature selection approach with a SVM classifier. A preliminary comparison showed that the optimal CADx scheme mimicked, in terms of AUC, the human experts in differentiating malignant from suspicious tissues, thus demonstrating its potential for assisting cancer identification in the PZ.
Abstract Background High-intensity focused ultrasound (HIFU) is a nonsurgical therapy for selected patients with localized prostate cancer (PCa). Objective The long-term oncologic and morbidity ...outcomes of primary HIFU therapy for localized PCa were evaluated in a prospective, single-arm, single-institution cohort study. Design, setting, and participants Participants were patients treated with HIFU for localized PCa from 1997 to 2009. Excluded were patients with local recurrence following radiotherapy. A second HIFU session was systematically performed in patients with biopsy-proven local recurrence. Intervention Whole-gland prostate ablation with transrectal HIFU. Outcome measurements and statistical analysis Incontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the five-item version of the International Index of Erectile Function (IIEF-5) scores. Primary outcomes were survival rates (biochemical-free, cancer-specific, metastasis-free, and overall survival). Secondary outcomes were morbidity rates. Median follow-up was 6.4 yr (range: 0.2–13.9). The Kaplan-Meier method was used to determine survival estimates, and multivariate analysis was used to determine predictive factors of biochemical progression. Results and limitations A total of 1002 patients were included. The median nadir prostate-specific antigen (PSA) was 0.14 ng/ml, with 63% of patients reaching a nadir PSA ≤0.3 ng/ml. Sixty percent of patients received one HIFU session, 38% received two sessions, and 2% received three sessions. The 8-yr biochemical-free survival rates (Phoenix definition) were 76%, 63%, and 57% for low-, intermediate-, and high-risk patients, respectively ( p < 0.001). At 10 yr, the PCa-specific survival rate and metastasis-free survival rate (MFSR) were 97% and 94%, respectively. Salvage therapies included external-beam radiation therapy (EBRT) (13.8%), EBRT plus androgen-deprivation therapy (ADT) (9.7%), and ADT alone (12.1%). Severe incontinence and bladder outlet obstruction decreased with refinement in the technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively. Limitations included the fact that the study was a single-arm study without a comparison group, technological improvements, changes in surgical protocol during the study, and the use of ADT to downsize the prostate in 39% of patients. Conclusions HIFU is a potentially effective treatment of localized PCa, with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity.
The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial.
To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) ...to formulate clinical practice recommendations.
A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance AS, radical prostatectomy RP, or external beam radiotherapy EBRT) was undertaken. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised.
Out of 1119 articles identified, four primary studies (1 randomised controlled trial RCT and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed.
The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies.
We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.
Our systematic review did not find any robust data demonstrating superiority or equivalence of focal therapy over standard management options for patients with localised prostate cancer. Consequently, focal therapy should only be performed within clinical trials or prospective comparative studies.
Background: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance ...imaging- (MRI) derived data. Methods: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. Results: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models (p < 0.001 for all). Conclusions: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.
In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological outcomes.
To perform a systematic review of the ...existing literature on BCR after treatment with curative intent for nonmetastatic PCa. Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR. Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes.
Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. For objective 1, prospective and retrospective studies comparing survival outcomes of patients with or without BCR following radical prostatectomy (RP) or radical radiotherapy (RT) were included. For objective 2, all studies with at least 100 participants and reporting on prognostic patient and tumor characteristics in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies tool. Both a narrative synthesis and a meta-analysis were undertaken.
Overall, 77 studies were included for analysis, of which 14 addressed objective 1, recruiting 20 406 patients. Objective 2 was addressed by 71 studies with 29 057, 11 301, and 4272 patients undergoing RP, RT, and a mixed population (mix of patients undergoing RP or RT as primary treatment), respectively. There was a low risk of bias for study participation, confounders, and statistical analysis. For most studies, attrition bias, and prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with short prostate-specific antigen doubling time (PSA-DT) and a high final Gleason score after RP, or a short interval to biochemical failure (IBF) after RT and a high biopsy Gleason score.
BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. Short PSA-DT and a high final Gleason score after RP, and a short IBF after RT and a high biopsy Gleason score are the main factors that have a negative impact on survival. These factors may form the basis of new BCR risk stratification (European Association of Urology BCR Risk Groups), which needs to be validated formally.
This review looks at the risk of death in men who shows rising prostate-specific antigen (PSA) in the blood test performed after curative surgery or radiotherapy. For many men, rising PSA does not mean that they are at a high risk of death from prostate cancer in the longer term. Men with PSA that rises shortly after they were treated with radiotherapy or rapidly rising PSA after surgery and a high tumor grade for both treatment modalities are at the highest risk of death. These factors may form the basis of new risk stratification (European Association of Urology biochemical recurrence Risk Groups), which needs to be validated formally.
In patients who underwent radical prostatectomy as primary treatment and who subsequently developed biochemical recurrence (BCR), the main prognostic factor for distant metastases, prostate cancer-specific mortality, and overall mortality is short prostate-specific antigen doubling time (ie, <1yr), and to a lesser extent an increasing pathological Gleason score (GS) and a short interval to biochemical failure (IBF). The main prognostic factors for patients developing BCR following primary radiotherapy are a short IBF (<18mo) and to a lesser extent an increasing biopsy GS.
Objective
To train and to test for prostate zonal segmentation an existing algorithm already trained for whole-gland segmentation.
Methods
The algorithm, combining model-based and deep learning–based ...approaches, was trained for zonal segmentation using the NCI-ISBI-2013 dataset and 70 T2-weighted datasets acquired at an academic centre. Test datasets were randomly selected among examinations performed at this centre on one of two scanners (General Electric, 1.5 T; Philips, 3 T) not used for training. Automated segmentations were corrected by two independent radiologists. When segmentation was initiated outside the prostate, images were cropped and segmentation repeated. Factors influencing the algorithm’s mean Dice similarity coefficient (DSC) and its precision were assessed using beta regression.
Results
Eighty-two test datasets were selected; one was excluded. In 13/81 datasets, segmentation started outside the prostate, but zonal segmentation was possible after image cropping. Depending on the radiologist chosen as reference, algorithm’s median DSCs were 96.4/97.4%, 91.8/93.0% and 79.9/89.6% for whole-gland, central gland and anterior fibromuscular stroma (AFMS) segmentations, respectively. DSCs comparing radiologists’ delineations were 95.8%, 93.6% and 81.7%, respectively. For all segmentation tasks, the scanner used for imaging significantly influenced the mean DSC and its precision, and the mean DSC was significantly lower in cases with initial segmentation outside the prostate. For central gland segmentation, the mean DSC was also significantly lower in larger prostates. The radiologist chosen as reference had no significant impact, except for AFMS segmentation.
Conclusions
The algorithm performance fell within the range of inter-reader variability but remained significantly impacted by the scanner used for imaging.
Key Points
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Median Dice similarity coefficients obtained by the algorithm fell within human inter-reader variability for the three segmentation tasks (whole gland, central gland, anterior fibromuscular stroma)
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The scanner used for imaging significantly impacted the performance of the automated segmentation for the three segmentation tasks
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The performance of the automated segmentation of the anterior fibromuscular stroma was highly variable across patients and showed also high variability across the two radiologists
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