Diagnostic performance of MRI and endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy: a systematic review of the literature.

BACKGROUND: The diagnostic performance of magnetic resonance imaging (MRI) modalities and/or endoscopy for assessing complete response in rectal cancer after neoadjuvant chemoradiotherapy (nCRT) is unclear. PURPOSE: To summarize existing evidence on the diagnostic performance of diffusion-weighted MRI, perfusion-weighted MRI, T2-weighted MR tumor regression grade, and/or endoscopy for assessing complete tumor response after nCRT. MATERIAL AND METHODS: MEDLINE and Embase databases were searched. The PRISMA guidelines were followed. Sensitivity, specificity, negative predictive, and positive predictive values were retrieved from included studies. RESULTS: In total, 81 studies were eligible for inclusion. Evidence suggests that combined use of MRI and endoscopy tends to improve the diagnostic performance compared to single imaging modality. The positive predictive value of a complete response varies substantially between studies. There is considerable heterogeneity between studies. CONCLUSION: Combined re-staging tends to improve diagnostic performance compared to single imaging modality, but the vast majority of studies fail to offer true clinical value due to the study heterogeneity.

Ethical Principles in the Analysis of Prostate Cancer Diagnostics.

Recent developments in prostate cancer diagnostics call for appropriate tools to frame the ethical assessment of diagnostic practice. The first aim is to identify ethically important features and ethical principles of key importance for prostate cancer diagnostics. Next, we need to argue which ethical theory justifies these principles and can therefore be used for ethical assessment in the field. The standard medical procedure for prostate cancer diagnostics offered by the Danish health care system is used as an example.

Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density.

PURPOSE: Tumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na+/K+-ATPase density, which is relevant as 82Rb is transported intracellularly via the Na+/K+-ATPase. METHODS: One hundred and two patients were included for pelvic 82Rb PET scan prior to magnetic resonance imaging (MRI)-guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82Rb PET for TBF measurement. Immunohistochemical Na+/K+-ATPase staining was subsequently performed on biopsies. RESULTS: TBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = -0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na+/K+-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na+/K+-ATPase density determined tumour 82Rb uptake. CONCLUSION: TBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.

Risk stratification in men with a negative prostate biopsy: an interim analysis of a prospective cohort study.

OBJECTIVE: To investigate whether a risk score for prostate cancer (PCa) lifetime risk can be used to optimise triaging of patients with a negative prostate biopsy, but under sustained suspicion of PCa. PATIENTS AND METHODS: In this prospective clinical study, we included, and risk scored patients who had a PCa-negative transrectal ultrasonography (TRUS)-guided prostate biopsy, but elevated prostate-specific antigen (PSA), a suspicious prostate digital rectal examination and/or a positive family history (FH) of PCa. The risk score estimated individual lifetime risk of PCa, based on a polygenic risk score (33 single nucleotide polymorphisms), age, and FH of PCa. Patients were followed, under urological supervision, for up to 4 years with annual controls, always including PSA measurements. Multiparametric magnetic resonance imaging (mpMRI) and/or prostate biopsy was performed at selected annual controls depending on risk score and at the urologist's/patient's discretion, which means that the follow-up differed based on the risk score. RESULTS: We included 429 patients. After risk scoring, 376/429 (88%) patients were allocated to a normal-risk group (<30% PCa lifetime risk) and 53/429 (12%) to a high-risk group (≥30% PCa lifetime risk). The high-risk group had significantly different follow-up, with more biopsy and mpMRI sessions compared to the normal-risk group. PCa was detected in 89/429 (21%) patients, with 67/376 (18%) patients diagnosed in the normal-risk group and 22/53 (42%) in the high-risk group. There was no statistically significant difference in the cumulative incidence of PCa between the normal-risk group and the high-risk group after 4 years of follow-up. Currently, 67/429 (16%) patients are still being followed in this ongoing study. CONCLUSION: In a 4-year perspective, our PCa lifetime risk score did not demonstrate significant prognostic value for triaging patients, with a negative TRUS-guided biopsy and sustained suspicion of PCa.

Effectiveness of infliximab treatment of complex idiopathic anal fistulas.

OBJECTIVES: To investigate the effects of infliximab treatment in patients with complex idiopathic anal fistulas refractory to standard surgical treatment. MATERIALS AND METHODS: We retrospectively evaluated the effects ofinfliximab treatmentin patients with complex idiopathic anal fistulas refractory to standard surgical intervention. The primary outcome was achievement of substantial clinical improvement defined as sustained, reduced inflammatory activity at perioperativeevaluation, i.e., only minimal-to-moderate secretion and induration and a reduction of fistula size of a magnitude that would make it possible to perform a lay-open or sphincter-sparring closure procedure. Secondary outcomes weresymptom improvement, adverse treatment events and fistula healing after the surgical procedure in those achieving the primary outcome. RESULTS: Twenty-two patients were included (18 high transsphincteric, 3complex low transsphincteric, 1 suprasphincteric fistula). Fistulas had been present for a median of 24 [interquartile range, IQR: 12-33] months. In total, 16 patients (73%) achieved the primary outcome of substantial clinical improvement. Median time from infliximab initiation to patients achieved the primary outcome was 11 [IQR: 8-22] months. Sixteen of the patients responding to infliximab received subsequent lay-open or sphincter-sparring closure procedure surgery. Of these, ten (63%) achieved fistula healing. No serious infectious complications to infliximab treatment were seen. One patient developed a new abscess. One patient developed psoriasis (pustolosispalmoplantaris). CONCLUSIONS: Infliximab treatment may be considered a supplement to repeated curettage and setondrainage in the management of selected, complex idiopathic anal fistulas. Such combined treatment may make otherwise refractory fistulas amenable to definitive closure attempts.

Efficacy of Injection of Freshly Collected Autologous Adipose Tissue Into Perianal Fistulas in Patients With Crohn's Disease.

BACKGROUND & AIMS: Perianal fistulas are common in patients with Crohn's disease (CD). Injections of cultured autologous and allogeneic adipose tissue-derived stem cells have been shown to heal CD-associated fistulas. Unfortunately, this treatment is time consuming and expensive. We investigated the effects of injecting freshly collected autologous adipose tissue into perianal fistulas in patients with CD. METHODS: In a prospective interventional study, freshly collected autologous adipose tissues were injected into complex perianal fistulas of 21 patients with CD, from March 2015 through June 2018. The primary endpoint was complete fistula healing (no symptoms of discharge, no visible external fistula opening in the perineum, and no internal opening detected by rectal digital examination) 6 months after the last injection. We performed pelvic magnetic resonance imaging to confirm fistula resolution in patients with intersphincter and transsphincter fistulas who showed complete healing at clinical examination. Patients without complete fistula healing after 6 weeks and those with later relapse were offered additional injections. No control individuals were included. RESULTS: Six months after the last adipose tissue injection, 12 patients (57%) had complete fistula healing. Three patients (14%) had ceased fistula secretion, and 1 patient (5%) reported reduced secretion. Among 10 patients with trans-sphincter or inter-sphincter fistulas, magnetic resonance imaging showed complete fistula resolution in 9 patients and a markedly reduced gracile fistula in the remaining patient. Of the 12 patients with complete fistula healing, 9 (43%) required 1 injection, 2 (10%) required 2 injections, and 1 (5%) required 3 injections. The predominant adverse effect was postprocedure proctalgia lasting a few days. Two patients developed small abscesses, 1 had urinary retention, and 1 had minor bleeding during liposuction. CONCLUSION: In a study of 21 patients with CD and perianal fistulas, we found injection of recently collected autologous adipose tissue to be safe and to result in complete fistula healing in 57% of patients. ClinicalTrials.gov, Number: NCT03803917.

Prospective evaluation of paravaginal defect repair with and without apical suspension: a 6-month postoperative follow-up with MRI, clinical examination, and questionnaires.

INTRODUCTION AND HYPOTHESIS: Paravaginal defect (PVD) has been suggested as one of the main contributors to the development of prolapse in the anterior vaginal wall (AVW). We aimed to evaluate the descent of pelvic organs, presence of vaginal H configuration, and pubococcygeus (PC) muscle defect by pelvic magnetic resonance imaging (MRI), together with subjective symptoms of prolapse, before and 6 months after PVD repair. We also aimed to evaluate risk factors of recurrence. METHODS: Fifty women with PVD diagnosed by gynecological examination and scheduled for vaginal PVD repair were planned for enrollment. Preoperatively and 6 months postoperatively, subjective symptoms were evaluated using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) together with MRI of the pelvis to evaluate defects in the PC muscle, vaginal shape, and pelvic organ descent. RESULTS: Forty-six women completed the study. Twenty had PVD repair alone, whereas 26 also had concomitant surgery performed. Prolapse grade, subjective symptoms, sexual problems, and quality of life (QoL) were significantly improved at follow-up. Missing vaginal H configuration was observed in 21 women before operation and was correlated with PC muscle defect. Recurrence rate was 39%, and significantly more women with recurrence had PC muscle defects and missing H configuration. CONCLUSION: Vaginal PVD repair alone or combined with concomitant surgery significantly reduces objective prolapse and subjective symptoms. We could not demonstrate MRI findings of missing H configuration to be a sign of PVD but, rather, a sign of defect in the PC muscle. Risk of recurrence is significantly higher in women with major PC muscle defects and missing H configuration.

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance imaging (MRI) and clinical measures of disease progression in people with MS. METHODS: This study was a 24-week randomised controlled cross-over trial, including a Training ( n = 18, 24 weeks of PRT followed by self-guided physical activity) and Waitlist group ( n = 17, 24 weeks of habitual lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did not differ between groups. PBVC tended to differ between groups and higher absolute cortical thickness values were observed in 19 of 74 investigated cortical regions after PRT. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups for four areas: anterior cingulate gyrus, temporal pole, orbital sulcus and inferior temporal sulcus. CONCLUSION: PRT seem to induce an increase in cortical thickness, indicating that PRT have a neuroprotective or even neuroregenerative effect in relapsing-remitting MS.

Prostate cancer: in-bore magnetic resonance guided biopsies at active surveillance inclusion improve selection of patients for active treatment.

Background Active surveillance (AS) of low-risk prostate cancer (PCa) is an accepted alternative to active treatment. However, the conventional diagnostic trans-rectal ultrasound guided biopsies (TRUS-bx) underestimate PCa aggressiveness in almost half of the cases, when compared with the surgical specimen. Purpose To investigate if additional multi-parametric magnetic resonance imaging (mpMRI) of the prostate and MRI-guided in-bore biopsies (MRGB) at AS inclusion would improve selection of patients for active treatment. Material and Methods All patients enrolled in AS programs at two Danish centers, from October 2014 to January 2016, were offered an mpMRI 8-12 weeks after the initial diagnostic TRUS-bx. Candidates had low-risk disease (PSA < 10 ng/mL, 6 or GS 6 (3 + 3) lesions with ≥ 6 mm maximal cancer core length (MCCL). Results A total of 78 patients were included and in 21 patients a total of 22 PIRADS-score 4 or 5 lesions were detected. MRGB pathology revealed that 17 (81%) of these and 22% of the entire AS population harbored significant cancers at AS inclusion. In eight (38%) cases, the GS was upgraded. Also, nine patients (43%) had GS 6 (3 + 3) foci with MCCL ≥ 6 mm. Conclusion In an AS cohort based on TRUS and TRUS-bx diagnostic strategies, supplemental mpMRI and in-bore MRGB were able to efficiently reclassify a substantial number of patients as candidates for immediate active treatment.

Paravaginal defect: anatomy, clinical findings, and imaging.

INTRODUCTION AND HYPOTHESIS: The paravaginal defect has been a topic of active discussion concerning what it is, how to diagnose it, its role in anterior vaginal wall prolapse, and if and how to repair it. The aim of this article was to review the existing literature on paravaginal defect and discuss its role in the anterior vaginal wall support system, with an emphasis on anatomy and imaging. METHODS: Articles related to paravaginal defects were identified through a PubMed search ending 1 July 2015. RESULTS: Support of the anterior vaginal wall is a complex system involving levator ani muscle, arcus tendineus fascia pelvis (ATFP), pubocervical fascia, and uterosacral/cardinal ligaments. Studies conclude that physical examination is inconsistent in detecting paravaginal defects. Ultrasound (US) and magnetic resonance imaging (MRI) have been used to describe patterns in the appearance of the vagina and bladder when a paravaginal defect is suspected. Different terms have been used (e.g., sagging of bladder base, loss of tenting), which all represent changes in pelvic floor support but that could be due to both paravaginal and levator ani defects. CONCLUSION: Paravaginal support plays a role in supporting the anterior vaginal wall, but we still do not know the degree to which it contributes to the development of prolapse. Both MRI and US are useful in the diagnosis of paravaginal defects, but further studies are needed to evaluate their use.

Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study.

OBJECTIVE: This study aimed to validate a magnetic resonance imaging (MRI) staging classification that preoperatively assessed the relationship between tumor and the low rectal cancer surgical resection plane (mrLRP). BACKGROUND: Low rectal cancer oncological outcomes remain a global challenge, evidenced by high pathological circumferential resection margin (pCRM) rates and unacceptable variations in permanent colostomies. METHODS: Between 2008 and 2012, a prospective, observational, multicenter study (MERCURY II) recruited 279 patients with adenocarcinoma 6 cm or less from the anal verge. MRI assessed the following: mrLRP "safe or unsafe," venous invasion (mrEMVI), depth of spread, node status, tumor height, and tumor quadrant. MRI-based treatment recommendations were compared against final management and pCRM outcomes. RESULTS: Overall pCRM involvement was 9.0% [95% confidence interval (CI), 5.9-12.3], significantly lower than previously reported rates of 30%. Patients with no adverse MRI features and a "safe" mrLRP underwent sphincter-preserving surgery without preoperative radiotherapy, resulting in a 1.6% pCRM rate. The pCRM rate increased 5-fold for an "unsafe" compared with "safe" preoperative mrLRP [odds ratio (OR) = 5.5; 95% CI, 2.3-13.3)]. Posttreatment MRI reassessment indicated a "safe" ymrLRP in 33 of 113 (29.2%), none of whom had ypCRM involvement. In contrast, persistent "unsafe" ymrLRP posttherapy resulted in 17.5% ypCRM involvement. Further independent MRI assessed risk factors were EMVI (OR = 3.8; 95% CI, 1.5-9.6), tumors less than 4.0 cm from the anal verge (OR = 3.4; 95% CI, 1.3-8.8), and anterior tumors (OR = 2.8; 95% CI, 1.1-6.8). CONCLUSIONS: The study validated MRI low rectal plane assessment, reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy. It also highlights the importance of posttreatment restaging.

Objective measurement of the distal resection margin by MRI of the fresh and fixed specimen after partial mesorectal excision for rectal cancer: 5 cm is not just 5 cm and depends on when measured.

BACKGROUND: Most studies have directly established the optimal perioperative in situ clearance margin in surgery for rectal cancer from the histologically observed extent of distal spread, neglecting the tissue variability that occurs after resection and fixation of the rectal specimen. PURPOSE: To measure the length of the distal resection margin in the fresh and fixed specimen following partial mesorectal excision for rectal cancer using magnetic resonance imaging (MRI) to document tissue shrinkage after surgical removal and fixation. MATERIAL AND METHODS: The length of the distal resection margin was measured by MRI of the fresh and fixed specimen and at histopathological examination of the fixed specimen in 10 patients who underwent surgery for upper rectal cancer. In addition, tissue shrinkage was estimated by measuring the total length of the fresh and fixed specimen and distance from the peritoneal reflection anteriorly to the distal cut edge of the specimen. RESULTS: Measured by MRI, the distal resection margin was in the range of 0.6-10.2 cm (mean, 4.6 cm) in the fresh specimen, and 0.5-6.2 cm (mean, 3.2 cm) in the fixed specimen. The tissue shrinkage ratio was a mean of 69% (interquartile range, 61-77%). Taking all ratios from MRI and histopathological examination of tissue shrinkage into account, the collective tissue shrinkage ratio was 70% (95% confidence interval, 67-73%) CONCLUSION: The length of the distal resection margin was reduced by 30% after surgical removal and fixation of the specimen.

Reduced T2*-weighted placental MRI predicts foetal growth restriction in women with chronic rheumatic disease-a Danish explorative study.

OBJECTIVES: Women with chronic rheumatic disease (CRD) are at greater risk of foetal growth restriction than their healthy peers. T2*-weighted magnetic resonance imaging of placenta (T2*P-MRI) is superior to conventional ultrasonography in predicting birth weight and works as a proxy metabolic mirror of the placental function. We aimed to compare T2*P-MRI in pregnant women with CRD and healthy controls. In addition, we aimed to investigate the correlation between T2*P-MRI and birth weight. METHODS: Using a General Electric (GE) 1.5 Tesla, we consecutively performed T2*-weighted placental MRI in 10 women with CRD and 18 healthy controls at gestational week (GW)24 and GW32. We prospectively collected clinical parameters during pregnancy including birth outcome and placental weight. RESULTS: Women with CRD had significantly lower T2*P-MRI values at GW24 than healthy controls (median T2*(IQR) 92.1 ms (81.6; 122.4) versus 118.6 ms (105.1; 129.1), p = 0.03). T2*P-MRI values at GW24 showed a significant correlation with birth weight, as the T2*P-MRI value was reduced in all four pregnancies complicated by SGA at birth. Three out of four pregnancies complicated by SGA at birth remained undetected by routine antenatal ultrasound. CONCLUSION: This study demonstrates reduced T2*P-MRI values and a high proportion of SGA at birth in CRD pregnancies compared to controls, suggesting an increased risk of placental dysfunction in CRD pregnancies. T2*P-MRI may have the potential to focus clinical vigilance by identifying pregnancies at risk of SGA as early as GW24. Key Points • Placenta-related causes of foetal growth restriction in women with rheumatic disease remain to be investigated. • T2*P-MRI values at gestational week 24 predicted foetuses small for gestational age at birth. • T2*P-MRI may indicate pregnant women with chronic rheumatic disease (CRD) in need of treatment optimization.

Pelvic Insufficiency Fractures and Bone Pain after Radiation Therapy for Anal Cancer: Relation to Pelvic Bone Dose-Volume Parameters.

Purpose: Chemoradiation therapy is the primary treatment for anal cancer. Radiation therapy (RT) can weaken the pelvic bone structure, but the risk of pelvic insufficiency fractures (PIFs) and derived pain in anal cancer is not yet established. We determined the frequency of symptomatic PIFs after RT for anal cancer and related this to radiation dose to specific pelvic bone substructures. Methods and Materials: In a prospective setting, patients treated with RT for anal cancer had magnetic resonance imaging 1 year after RT. PIFs were mapped to 17 different bone sites, and we constructed a guideline for detailed delineation of pelvic bone substructures. Patients were interviewed regarding pain and scored according to Common Terminology Criteria for Adverse Effects. Dose-volume relationships for specific pelvic bone substructures and PIFs were determined for V20 to V40 Gy mean and maximum doses. Results: Twenty-seven patients were included, and 51.9% had PIFs primarily located in the alae of the sacral bone. Patients with PIFs had significantly more pelvic pain (86% vs 23%, P = .001) and 43% had grade 2 bone pain. Dose-volume parameters for sacral bone and sacral alae were significantly higher in patients with PIFs (P < .05). V30 Gy (%) for sacral bone and alae implied an area under the curve of 0.764 and 0.758, respectively, in receiver operating characteristic analyses. Conclusions: We observed a high risk of PIFs in patients treated with RT for anal cancer 1 year after treatment. A significant proportion had pain in the sites where PIFs were most frequently found. Radiation dose to pelvic bone substructures revealed relation to risk of PIFs and can be used for plan optimization in future clinical trials.

Danish Prostate Cancer Consortium Study 1 (DPCC-1) protocol: Multicentre prospective validation of the urine-based three-microRNA biomarker model uCaP.

INTRODUCTION: The primary objective of the Danish Prostate Cancer Consortium Study 1 (DPCC-1) is to provide validation for a novel urine-based microRNA biomarker, called uCaP, for a diagnosis of prostate cancer. METHODS AND ANALYSIS: Eligible participants are biopsy naïve men aged ≥18 years with prostate-specific antigen (PSA) levels ≥3 ng/mL, who are referred to prostate MRI due to suspicion of PC at one of the following three major urology/uroradiology centers: Aarhus University Hospital, Herlev & Gentofte University Hospital, or Odense University Hospital, where MRI and targeted biopsy are implemented in clinical use. Exclusion criteria include previous diagnosis of urogenital cancer, contraindication to MRI, gender reassignment treatment or PSA level >20 ng/mL. The participants will be asked to donate a urine sample in connection with their MRI. The study is observational, uses a diagnostic accuracy testing setup and will integrate into the current diagnostic pathway.We will measure the levels of the three microRNAs in the uCaP model (miR-222-3 p, miR-24-3 p and miR-30c-5p) in extracellular vesicle-enriched cell-free urine samples, to assess if uCaP can improve specificity and retain sensitivity for International Society of Urological Pathology Grade Group ≥2 PC, when used as a reflex test to PSA ≥3 ng/mL. We hypothesise that uCaP can improve selection for prostate MRI and reduce the number of unnecessary scans and biopsies. ETHICS AND DISSEMINATION: This study is approved by the Central Denmark Region Committee on Health Research Ethics (reference number: 1-10-72-85-22). All participants will provide written informed consent. Study results will be published in peer-reviewed journals and presented in scientific meetings. TRIAL REGISTRATION NUMBER: NCT05767307 at clinicaltrials.gov.

Results from the PRIMA Trial: Comparison of the STHLM3 Test and Prostate-specific Antigen in General Practice for Detection of Prostate Cancer in a Biopsy-naïve Population.

BACKGROUND: Current management of prostate cancer (PC) lacks biomarker tests and diagnostic procedures that can accurately distinguish clinically significant and clinically insignificant PCs at an early stage of the disease. OBJECTIVE: To compare the Stockholm 3 (STHLM3) test and prostate-specific antigen (PSA) as entry tests for magnetic resonance imaging (MRI) in a prospective study of PC diagnosis in general practice. DESIGN, SETTING, AND PARTICIPANTS: Participants were biopsy-naïve men aged 50-69 yr who had a PSA test in general practice. Participants with PSA 1-10 ng/ml also had an STHLM3 test and were referred for MRI if the STHLM311 test was positive (risk ≥11%) and/or PSA ≥3 ng/ml, and to targeted MRI-guided biopsy (MRGB) if their Prostate Imaging-Reporting and Data System (PI-RADS) score was ≥3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number of International Society of Urological Pathology grade group ≥2 (GG ≥2) cases detected with a positive STHLM311 test versus PSA ≥3 ng/ml. Post hoc analysis was performed using a higher STHLM3 test cutoff (risk ≥15%; positive STHLM315 test). RESULTS AND LIMITATIONS: Between January 2018 and December 2021, we recruited 1905 men. The STHLM3 test was performed in 1134 participants. Of these, 437 underwent MRI and 117 underwent MRGB, which detected 38 (32.5%) GG ≥2 and 52 (44.4%) with GG 1 cases. In comparison to PSA ≥3 ng/ml, a positive STHLM311 test increased detection of GG ≥2 from 30 to 37 cases (23.3%, 95% confidence interval [CI] 5.6-52.2%) and detection of GG 1 from 37 to 50 cases (35.1%, 95%CI 11.6-66.7%). STHLM315 positivity did not differ from PSA ≥3 ng/ml regarding detection of GG ≥2 PC (30 vs 32; 6.6%, 95% CI -8.1% to 25.9%), GG 1 PC (37 vs 37; 0.0%, 95% CI -19.6% to 25.0%), or MRGB use (88 vs 83; -5.7%, 95% CI -17.9% to 7.4%), but reduced MRI scans from 320 to 236 (-26.2%, 95% CI -33.1% to -18.9%). CONCLUSIONS: The STHLM311 test improved sensitivity but not specificity for detection of GG ≥2 PC in the clinical setting of nonsystematic PC testing in general practice. Further studies are needed to validate a possible benefit of using a higher cutoff for STHLM3 positivity as an entry test for MRI. PATIENT SUMMARY: We used a test called STHLM3 for detection of prostate cancer in general practice and compared its performance to the conventional PSA (prostate-specific antigen) test. We found that STHLM3 test results of 11% or above were not better at selecting men for MRI (magnetic resonance imaging) scans than the PSA test with a cutoff of 3 ng/ml or above. Analysis suggested that a higher cutoff for a positive STHLM3 test may improve selection of men for MRI scans, but further validation is needed.

Cost-Effectiveness Analysis of Stockholm 3 Testing Compared to PSA as the Primary Blood Test in the Prostate Cancer Diagnostic Pathway: A Decision Tree Approach.

OBJECTIVE: This study evaluated the cost effectiveness of using Stockholm 3 (STHLM3) testing compared to the prostate-specific antigen (PSA) test in the diagnostic pathway for prostate cancer. METHODS: We created a decision tree model for PSA (current standard) and STHLM3 (new alternative). Cost effectiveness was evaluated in a hypothetical cohort of male individuals aged 50-69 years. The study applied a Danish hospital perspective with a time frame restricted to the prostate cancer diagnostic pathway, beginning with the initial PSA/STHLM3 test, and ending with biopsy and histopathological diagnosis. Estimated values from the decision-analytical model were used to calculate the incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the base-case analysis. RESULTS: The model-based analysis revealed that STHLM3 testing was more effective than the PSA, but also more costly, with an incremental cost-effectiveness ratio of €511.7 (95% credible interval, 359.9-674.3) for each additional correctly classified individual. In the deterministic sensitivity analysis, variations in the cost of STHLM3 had the greatest influence on the incremental cost-effectiveness ratio. In the probabilistic sensitivity analysis, all iterations were positioned in the north-east quadrant of the incremental cost-effectiveness scatterplot. At a willingness to pay of €700 for an additional correctly classified individual, STHLM3 had a 100% probability of being cost effective. CONCLUSIONS: Compared to the PSA test as the initial testing modality in the prostate cancer diagnostic workup, STHLM3 testing showed improved incremental effectiveness, however, at additional costs. The results were sensitive to the cost of the STHLM3 test; therefore, a lower cost of the STHLM3 test would improve its cost effectiveness compared with PSA tests.

Training of radiology specialists in local staging of primary rectal cancer on MRI: a prospective intervention study exploring the impact of various educational elements on the interpretive performance.

BACKGROUND: MRI interpretation and accurate radiological staging are crucial to the important treatment decisions and a consequent successful patient outcome in rectal cancer. AIMS: To investigate the effect of intensive training on rectal cancer MRI staging performance of radiologists and the impact of different course elements on learning outcomes. METHODS: In this prospective intervention study, 17 radiology specialists and 1 radiology registrar participated in a training programme including a 6-hour imaging workshop, a 3-hour session of individual feedback and independent MRI readings of primary rectal cancer cases. Their rectal MRI interpretive performance was evaluated through repeated readings of 30 training cases before and after each course element and a time interval with no educational intervention. A proforma template for MRI staging of primary rectal cancer was used and the results were compared with a reference standard of an expert panel. Participants repeatedly reported on confidence scores and self-assessed learning outcome. Outcomes were analysed using mixed-effects models. RESULTS: At baseline the quality of rectal MRI assessment varied significantly, with a higher interpretive performance among participants with shorter radiological experience (10.2 years vs 19.9 years, p=0.02). The ability to perform correct treatment allocation improved from 72% to 82% (adjusted OR=2.36, 95% CI 1.64 to 3.39). The improvement was largely driven by the participants with lower performance at baseline and by prevention of overstaging. Individual feedback had a significant impact on the improved interpretive performance (adjusted OR=1.82, 95% CI 1.27 to 2.63), whereas no significant change was seen after workshop or case readings only. Confidence scores increased significantly during training. CONCLUSIONS: Targeted and individualised training improves the rectal cancer MRI interpretive performance essential to successful patient treatment, especially among radiology specialists with lower performance at baseline.

Prostate Cancer Detection Rate of Manually Operated and Robot-assisted In-bore Magnetic Resonance Imaging Targeted Biopsy.

Background: The diagnostic efficacy regarding prostate cancer (PC) detection by manually operated in-bore magnetic resonance imaging (MRI) targeted prostate biopsy (MO-MRGB) versus robot-assisted in-bore MRI targeted prostate biopsy (RA-MRGB) is lacking evidence. Objective: We hypothesized that the detection rates (DRs) for PC of MO-MRGB and RA-MRGB were similar and aimed to compare these. Design setting and participants: We prospectively included all patients who received in-bore MRI targeted prostate biopsy (MRGB) of the prostate in the Central Denmark Region from August 2014 to February 2020. From August 2014, MO-MRGB was used, and from March 2018, RA-MRGB was preferred. Referral to in-bore MRGB was based on multiparametric MRI (mpMRI). Outcome measurements and statistical analysis: We compared PC DRs of MO-MRGB and RA-MRGB with Pearson's chi-square test. We made three binary regression models and calculated the risk difference (RD) of PC between the in-bore MRGB systems. Results and limitations: A total of 3107 patients were referred to mpMRI, and 884 (28%) patients went on to receive in-bore MRGB. The MO-MRGB and RA-MRGB systems were used in 505 (57%) and 379 (43%) patients, respectively. Taking clinically relevant covariates into account, we found no statistically significant difference in PC DRs between MO-MRGB and RA-MRGB (72% vs 73%, RD 1%, 95% confidence interval -4% to 7%, p = 0.6). The main limitation was a shift in population characteristics. Conclusions: We did not see evidence of an effect on the DR or the RD for PC when we compared MO-MRGB with RA-MRGB. Cost effectiveness should be considered carefully when choosing the MRGB system. Patient summary: We compared two magnetic resonance imaging guided prostate tissue sampling systems regarding prostate cancer (PC) detection. One system was manually operated, and the other system was robot assisted. Comparing the systems, we found no evidence of a difference in their ability to detect PC.