Focal Therapy in Grade Group 3 Prostate Cancer.

PURPOSE OF THIS REVIEW: Treatment of intermediate risk prostate cancer remains controversial. Clearly some patients with low volume favorable intermediate risk can be followed with active surveillance. Those with high volume bilateral disease need more radical whole gland therapy. The question remains on how to best treat low volume localized unfavorable intermediate risk prostate cancer (GG3) while maintaining quality of life. Focal therapy has been becoming a popular option for many patients with localized prostate cancer. Most studies looking at focal therapy for prostate cancer have been limited to GG1 and GG2, many of whom may not need treatment. We set out to review the literature evaluating the safety and efficacy of focal therapy for GG3 prostate cancer. RECENT FINDINGS: We reviewed multiple peer review articles obtained from a PubMed search. While in field biopsy recurrence rates approach 20%, failure free survival and overall survival exceeds 90%. While focal therapy for unfavorable GG3 intermediate risk prostate cancer may have higher rates of local recurrence with appropriate post procedure follow up, patients who need salvage therapy are easily identified and survival rates are very high. Focal therapy is a good option for patients with localized low volume GG3 prostate cancer without compromising cancer survival and preserving quality of life.

Prognostic Impact and Clinical Implications of Adverse Tumor Grade in Very Favorable Low- and Intermediate-Risk Prostate Cancer Patients Treated with Robot-Assisted Radical Prostatectomy: Experience of a Single Tertiary Referral Center.

OBJECTIVES: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). METHODS: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model. RESULTS: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840-10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057-5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. CONCLUSIONS: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed.

The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

Clinical Validation of the Intermediate-risk Non-muscle-invasive Bladder Cancer Scoring System and Substratification Model Proposed by the International Bladder Cancer Group: A Multicenter Young Academic Urologists Urothelial Working Group Collaboration.

BACKGROUND AND OBJECTIVE: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) encompasses a broad spectrum of disease, with heterogeneous outcomes in terms of disease recurrence and progression. The International Bladder Cancer Group (IBCG) recently proposed an updated scoring model for IR substratification that is based on five key risk factors. Our aim was to provide a clinical validation of the IBCG scoring system and substratification model for IR NMIBC. METHODS: This was an international multicenter retrospective study. Patients diagnosed with IR NMIBC between 2012 and 2022 and treated with transurethral resection of the bladder and adjuvant intravesical chemotherapy were included. According to the presence or absence of risk factors, patients with IR NMIBC were further categorized in IR-low (no risk factors), IR-intermediate (1-2 risk factors), and IR-high (≥3 risk factors) groups. The 1-yr and 3-yr rates for recurrence-free survival (RFS) and progression-free survival (PFS) were evaluated for each subgroup. Cox regression analyses were used to compare oncological outcomes between the groups. KEY FINDINGS AND LIMITATIONS: Of the 677 patients with IR NMIBC included in the study, 231 (34%), 364 (54%), and 82 (12%) were categorized in the IR-low, IR-intermediate, and IR-high groups, respectively. There were significant differences in RFS and PFS rates between these groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: We provide the first clinical validation of the IBCG scoring system and model for substratification of IR NMIBC. PATIENT SUMMARY: Our study demonstrates that patients with intermediate-risk non-muscle-invasive bladder cancer can be correctly classified into three distinct subgroups according to their risk of both disease recurrence and progression. Our results support use of this scoring system in clinical practice.

Long-term follow-up of patients with intermediate-risk neuroblastoma treated with response- and biology-based therapy: A report from the Children's Oncology Group study ANBL0531.

BACKGROUND: We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results. METHODS: All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible. Treatment was based on prognostic biomarkers and overall response. Event-free survival (EFS) and OS were estimated by the Kaplan-Meier method. RESULTS: The 10-year EFS and OS for the entire study cohort (n = 404) were 82.0% (95% confidence interval (CI), 77.2%-86.9%) and 94.7% (95% CI, 91.8%-97.5%), respectively. International Neuroblastoma Staging System stage 4 patients (n = 133) had inferior OS compared with non-stage 4 patients (n = 271; 10-year OS: 90.8% [95% CI, 84.5%-97.0%] vs 96.6% [95% CI, 93.9%-99.4%], p = .02). Infants with stage 4 tumors with ≥1 unfavorable biological feature (n = 47) had inferior EFS compared with those with favorable biology (n = 61; 10-year EFS: 66.8% [95% CI, 50.4%-83.3%] vs 86.9% [95% CI, 76.0%-97.8%], p = .02); OS did not differ (10-year OS: 84.4% [95% CI, 71.8%-97.0%] vs 95.0% [95% CI, 87.7%-100.0%], p = .08). Inferior EFS but not OS was observed among patients with tumors with (n = 26) versus without (n = 314) 11q loss of heterozygosity (10-year EFS: 68.4% [95% CI, 44.5%-92.2%] vs 83.9% [95% CI, 78.7%-89.2%], p = .03; 10-year OS: 88.0% [95% CI, 72.0%-100.0%] vs 95.7% [95% CI, 92.8%-98.6%], p = .09). CONCLUSIONS: The ANBL0531 trial treatment algorithm resulted in excellent long-term survival. More effective treatments are needed for subsets of patients with unfavorable biology tumors.

The association of carotid plaque burden and composition and the coronary artery calcium score in intermediate cardiovascular risk patients.

Both the carotid ultrasound and coronary artery calcium (CAC) score quantify subclinical atherosclerosis and are associated with cardiovascular disease and events. This study investigated the association between CAC score and carotid plaque quantity and composition. Adult participants (n = 43) without history of cardiovascular disease were recruited to undergo a carotid ultrasound. Maximum plaque height (MPH), total plaque area (TPA), carotid intima-media thickness (CIMT), and plaque score were measured. Grayscale pixel distribution analysis of ultrasound images determined plaque tissue composition. Participants then underwent CT to determine CAC score, which were also categorized as absent (0), mild (1-99), moderate (100-399), and severe (400+). Spearman correlation coefficients between carotid variables and CAC scores were computed. The mean age of participants was 63 ± 11 years. CIMT, TPA, MPH, and plaque score were significantly associated with CAC score (ρ = 0.60, p < 0.0001; ρ = 0.54, p = 0.0002; ρ = 0.38, p = 0.01; and ρ = 0.49, p = 0.001). Echogenic composition features %Calcium and %Fibrous tissue were not correlated to a clinically relevant extent. There was a significant difference in the TPA, MPH, and plaque scores of those with a severe CAC score category compared to lesser categories. While carotid plaque burden was associated with CAC score, plaque composition was not. Though CAC score reliably measures calcification, carotid ultrasound gives information on both plaque burden and composition. Carotid ultrasound with assessment of plaque features used in conjunction with traditional risk factors may be an alternative or additive to CAC scoring and could improve the prediction of cardiovascular events in the intermediate risk population.

Development of a predictive nomogram for intermediate-risk differentiated thyroid cancer patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation.

Objectives: The objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA). Methods: Data from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram. Results: The study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto's thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770-0.895). The nomogram's predicted probabilities aligned closely with actual clinical outcomes. Conclusions: This study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed.

Preliminary results of adjuvant image-guided vaginal brachytherapy alone for early stage endometrial carcinoma.

Objective: This retrospective study evaluated the preliminary outcomes of image-guided vaginal brachytherapy (IG-VBT) in the adjuvant treatment of high intermediate risk endometrial cancer. Materials and Methods: Data were collected from 48 patients who underwent adjuvant IG-VBT between 2019 and 2022 at the Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University. The vaginal cuff clinical target volume (CTV-VC) is composed of a 4-mm-thick band around vaginal cylinder at the upper 3 cm of the vaginal cuff. A total dose of 21 Gy in three fractions was delivered to the CTV-VC, and the dose to the bladder and rectum were evaluated. Treatment details, patient characteristics, and outcomes were analyzed. Descriptive statistics were used for analysis, and Kaplan-Meier method was employed for survival analysis. Results: The mean age was 62 years, with mainly endometrioid carcinoma pathology (96 %). All patients were at stage I, with 87.5 % receiving complete surgical staging. Mean total treatment time was 10 days with mean D90 of CTV-VC was 29.7 Gy, and D2cc of bladder, rectum, and sigmoid were 24.6 Gy, 21.0 Gy, and 7.7 Gy, respectively. At a median follow-up of 37 months, 3-year local control, disease-free survival, and overall survival rates were 100 %, 100 %, and 97.9 %. respectively. Two patients (4.2 %) experienced grade 1-2 gastrointestinal toxicity, while no genitourinary toxicity or serious adverse events were observed. Conclusions: The preliminary results of IG-VBT in endometrial cancer demonstrated favorable outcomes in terms of vaginal control and toxicity. Further studies with larger cohorts and longer follow-up durations are warranted.

A phase II trial of apalutamide for intermediate-risk prostate cancer and molecular correlates.

OBJECTIVES: To determine whether 6 months of preoperative apalutamide for intermediate-risk prostate cancer (IRPCa) reduces the aggregate postoperative radiotherapy risk and to evaluate associations of molecular perturbations with clinical outcomes in this study cohort. PATIENTS AND METHODS: Between May 2018 and February 2020, eligible patients with IRPCa (Gleason 3 + 4 or 4 + 3 and clinical T2b-c or prostate-specific antigen level of 10-20 ng/mL) were treated with apalutamide 240 mg/day for 6 months followed by radical prostatectomy (RP) in this single-arm, phase II trial. The primary endpoint was presence of any adverse pathological feature at risk of pelvic radiation (pathological T stage after neoadjuvant therapy [yp]T3 or ypN1 or positive surgical margins). Translational studies, including germline and somatic DNA alterations and RNA and protein expression, were performed on post-apalutamide RP specimens, and assessed for associations with clinical outcomes. RESULTS: A total of 40 patients underwent a RP, and only one patient discontinued apalutamide prior to 6 months. In all, 40% had adverse pathological features at time of RP, and the 3-year biochemical recurrence (BCR) rate was 15%, with 27.5% being not evaluable. Genomic alterations frequently seen in metastatic PCas, such as androgen receptor (AR), tumour protein p53 (TP53), phosphatase and tensin homologue (PTEN), or BReast CAncer associated gene (BRCA1/2) were underrepresented in this localised cohort. Adverse pathological features and BCR at 3-years were associated with increased expression of select cell cycle (e.g., E2F targets: adjusted P value [Padj] < 0.001, normalised enrichment score [NES] 2.47) and oxidative phosphorylation (Padj < 0.001, NES 1.62) pathways. CONCLUSIONS: Preoperative apalutamide did not reduce the aggregate postoperative radiation risk to the pre-specified threshold in unselected men with IRPCa. However, transcriptomic analysis identified key dysregulated pathways in tumours associated with adverse pathological outcomes and BCR, which warrant future study. Further investigation of preoperative therapy is underway for men with high-risk PCa.

Canadian Cost-Effectiveness of Coronary Artery Calcium Screening Based on the Multi-Ethnic Study of Atherosclerosis.

Background: Cost-effectiveness of testing for coronary artery calcium (CAC) relative to other treatment strategies is not established in Canada. Objectives: The purpose of this study was to evaluate the cost-effectiveness of using CAC score-guided statin treatment compared with universal statin therapy among intermediate-risk, primary prevention patients eligible for statins. Methods: A state transition, microsimulation model used data from Canadian sources and the Multi-Ethnic Study of Atherosclerosis to simulate clinical and economic consequences of cardiovascular disease from a Canadian publicly funded health care system perspective. In the CAC score-guided treatment arm, statins were started when CAC ≥1. Outcome of interest was the incremental cost-effectiveness ratio at 5 and 10 years; an incremental cost-effectiveness ratio <$50,000 per quality-adjusted life year (QALY) gained was considered cost-effective. Sensitivity analyses examined uncertainty in model parameters. Results: Compared with universal statin treatment at 5 and 10 years, CAC score-guided statin treatment was projected to increase mean costs by $326 (95% CI: $325-$326) and $172 (95% CI: $169-$175), increase mean QALYs by 0.01 (95% CI: 0.01-0.01) and 0.02 (95% CI: 0.02-0.02), and cost $54,492 (95% CI: $52,342-$56,816) and $8,118 (95% CI: $7,968-$8,279) per QALY gained, respectively. The model was most sensitive to statin cost, CAC testing cost, adherence to statin monitoring, and disutility associated with daily statin use. At 5 years, CAC score-guided statin treatment was cost-effective when CAC test costs ranged from $80 to $160 in different scenarios. Conclusions: CAC score-guided statin initiation in comparison to universal statin treatment was borderline cost-neutral at 5 years and cost-effective at 10 years in statin-eligible Canadian patients at intermediate cardiovascular disease risk.

Comparison of postoperative adjuvant platinum-based chemotherapy and no further therapy after radical surgery in intermediate-risk early-stage cervical cancer.

OBJECTIVE: To identify a relatively high-risk population in postoperative intermediate-risk cervical cancer and evaluate the effect of platinum-based adjuvant chemotherapy (CT). METHODS: We retrospectively reviewed the medical records of patients with stage IA2-IIA cervical cancer who had been treated with radical hysterectomy and pelvic lymphadenectomy and classified as the intermediate-risk group for recurrence by postoperative pathological examination from January 2007 to December 2018 at 3 medical centers in Japan. First, patients with intermediate-risk were stratified by histological type and the number of intermediate-risk factors (IRF; large tumor diameter, lymph vascular space invasion, and deep cervical stromal invasion) and then divided into 2 groups: high and low-risk population (estimated 5-year recurrence-free survival [RFS] rate with no further therapy [NFT] <90% and ≥90%, respectively). Second, the efficacy of CT for the high-risk population was evaluated by comparing RFS and overall survival (OS) between the patients receiving CT and those with NFT. RESULTS: In total, 133 patients were included in the analysis. Among patients with squamous cell carcinoma (SCC) with all IRF or those with non-SCC with 2 to 3 IRF, the 5-year estimated RFS was <90% when treated with NFT. In this population, adjuvant CT was significantly superior to NFT regarding RFS (log-rank, p=0.014), although there was no statistical difference in OS. CONCLUSION: Patients with SCC with all 3 IRFs and those with non-SCC with 2 to 3 IRFs were at high risk for recurrence. Adjuvant CT is a valid treatment option for these populations.

Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

2012 Briganti nomogram predict prostate cancer progression in EAU intermediate risk with unfavorable tumor grade: A single center experience.

BACKGROUND: To investigate the potential prognostic impact of Briganti's 2012 nomogram in EAU intermediate-risk patients presenting with an unfavorable tumor grade and treated with robot-assisted radical prostatectomy, eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, the study included 179 EAU intermediate-risk patients presenting with an unfavorable tumor grade (ISUP 3), eventually associated with a PSA of 10-20 ng/ml and/or cT-2b. Briganti's 2012 nomogram was assessed as both a continuous and dichotomous variable, categorized according to the median (risk score ⩾7% vs <7%). Disease progression, defined as biochemical recurrence and/or metastatic progression, was evaluated using Cox proportional hazards in both univariate and multivariate analyses. RESULTS: Disease progression occurred in 43 (24%) patients after a median (95% CI) follow-up of 78 (65.7-88.4) months. The nomogram risk score predicted disease progression, evaluated both as a continuous variable (hazard ratio, HR = 1.064; 95% CI: 1.035-1.093; p < 0.0001) and as a categorical variable (HR = 3.399; 95% CI: 1.740-6.638; p < 0.0001). This association was confirmed in multivariate analysis, where hazard ratios remained consistent even after adjusting for clinical and pathological factors. CONCLUSIONS: In EAU intermediate-risk PCa cases presenting with an unfavorable tumor grade and treated surgically, Briganti's 2012 nomogram was associated with disease progression after surgery. Consequently, as the nomogram risk score increased, patients were more likely to experience PCa progression, facilitating the stratification of the patient population into distinct prognostic subgroups.

Clinical outcomes of endoscopic resection for the treatment of intermediate- or high-risk gastric small gastrointestinal stromal tumors: a multicenter retrospective study.

BACKGROUND AND AIMS: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). CONCLUSION: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.

The Role of IVC Filters in the Management of Acute Pulmonary Embolism.

Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a prevalent cardiovascular condition, ranking third globally after myocardial infarction and stroke. The risk of VTE rises with age, posing a growing concern in aging populations. Acute PE, with its high morbidity and mortality, emphasizes the need for early diagnosis and intervention. This review explores prognostic factors for acute PE, categorizing it into low-risk, intermediate-risk, and high-risk based on hemodynamic stability and right ventricular strain. Timely classification is crucial for triage and treatment decisions. In the contemporary landscape, low-risk PE patients are often treated with Direct Oral Anticoagulants (DOACS) and rapidly discharged for outpatient follow-up. Intermediate- and high-risk patients may require advanced therapies, such as systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy, and IVC filter placement. The latter, particularly IVC filters, has witnessed increased usage, with evolving types like retrievable and convertible filters. However, concerns arise regarding complications and the need for timely retrieval. This review delves into the role of IVC filters in acute PE management, addressing their indications, types, complications, and retrieval considerations. The ongoing debate surrounding IVC filter use, especially in patients with less conventional indications, reflects the need for further research and data. Despite complications, recent studies suggest that clinically significant issues are rare, sparking discussions on the appropriate and safe utilization of IVC filters in select PE cases. The review concludes by highlighting current trends, gaps in knowledge, and potential avenues for advancing the role of IVC filters in future acute PE management.

Differences in real-world outcomes by risk classification for localized prostate cancer patients after radiation therapy.

BACKGROUND: Limited real-world evidence exists on the long-term clinical outcomes of patients with localized prostate cancer (LPC) who received external beam radiation therapy (EBRT) as the initial treatment. This study evaluated clinical outcomes of US patients with high-risk LPC (HR-LPC) and low/intermediate-risk LPC (LIR-LPC) who received EBRT. METHODS: This retrospective study using Surveillance, Epidemiology, and End Results-Medicare linked data from 2012 to 2019 included patients ≥ 65 years old who received EBRT as initial therapy. Baseline patient characteristics were summarized, metastasis-free survival (MFS), overall survival, and time to initiation of advanced prostate cancer treatment were compared using Kaplan-Meier (KM) and adjusted Cox proportional hazard (PH) models. 5-year survival probabilities stratified by race/ethnicity (non-Hispanic [NH] White, NH Black, NH Asian, and Hispanic) were assessed. RESULTS: Of 11,313 eligible patients, 41% (n = 4600) had HR-LPC and 59% (n = 6713) had LIR-LPC. Patient characteristics for both groups were comparable, with mean age at EBRT initiation > 70 years, 86% white, and mean follow-up time >40 months. More patients in the HR-LPC than LIR-LPC groups (78% vs 34%) had concurrent androgen deprivation therapy use and for a longer duration (median 10.4 months vs. 7.4 months). A higher proportion of HR-LPC patients developed metastasis, died, or received advanced prostate cancer treatment. Adjusted Cox PH survival analyses showed significantly (p < 0.0001) higher risk of mortality (hazard ratios [HR], 1.57 [1.38, 2.34]), metastasis or death (HR, 1.97 [1.78, 2.17]), and advanced prostate cancer therapy use (HR, 2.57 [2.11, 3.14]) for HR-LPC than LIR-LPC patients. Within 5 years after the initial EBRT treatment, 18%-26% of patients with HR-LPC are expected to have died or developed metastasis. The 5-year MFS rate in the HR-LPC group was lower than the LIR-LPC group across all racial/ethnic subgroups. NH Black patients with HR-LPC had the highest all-cause mortality rate and lowest rate of receiving advanced prostate cancer treatment, compared to other racial/ethnic subgroups. CONCLUSIONS: This real-world study of clinical outcomes in patients with LPC treated with EBRT suggests substantial disease burden in patients with HR-LPC and highlights the need for additional treatment strategies to improve clinical outcomes in patients with HR-LPC.

Oncological Outcomes in Men With Favorable Intermediate Risk Prostate Cancer Enrolled in Active Surveillance.

BACKGROUND/AIM: To evaluate the long-term oncological outcomes in men with intermediate risk prostate cancer (PCa) enrolled in active surveillance (AS). PATIENTS AND METHODS: From April 2015 to December 2022, 30 men with Gleason score 3+4/ISUP Grade Group2 (GG2), greatest percentage of cancer (GPC) ≤50%, Gleason pattern 4 ≤10%, ≤3 positive biopsy cores were enrolled in AS. All patients underwent confirmatory transperineal saturation biopsy (SPBx: 20 cores) 12 months from diagnosis plus multiparametric magnetic resonance (mpMRI) evaluation. At the last follow-up, 68Ga prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) was added: lesions with PIRADS score ≥3 and/or standardized uptake value (SUVmax) >5 were submitted to four targeted cores. RESULTS: Three out of 30 (10%) men with GG2 PCa were reclassified at confirmatory biopsy. At the last follow-up (median 5.2 years), only 2 of 27 (7.4%) men were reclassified and 23/30 (76.6%) continued AS. CONCLUSION: Men with favorable GG2 PCa enrolled in AS have good long-term oncological results. The use of selective criteria (i.e., SPBx, mpMRI, PSMA PET/CT) reduces the risk of reclassification.

Prevención cardiovascular en la diabetes mellitus. ¿Es adecuado hablar de riesgo moderado o intermedio? / Cardiovascular prevention in diabetes mellitus. Is it appropriate to speak of moderate or intermediate risk?

La diabetes, especialmente la tipo 2, está considerada como una situación de riesgo de enfermedad cardiovascular aterosclerosa (ECVA). Los sujetos con diabetes tipo 2 tienen una mortalidad por ECVA 3 veces superior a la de la población general, atribuida a la hiperglucemia y a la frecuente asociación de otros factores de riesgo cardiovascular, como la dislipidemia aterogénica. Numerosas sociedades científicas han establecido una clasificación de riesgo de ECVA en la diabetes basada en 3 grados (moderado, alto y muy alto). Los objetivos del control de la dislipidemia están claramente definidos y aceptados, y varían dependiendo del riesgo cardiovascular previamente establecido. En el riesgo moderado o intermedio, las guías proponen una intervención menos intensiva, manteniendo cifras de c-LDL<100mg/dL y de c-no-HDL<130mg/dL, y esperar 10 años hasta alcanzar la categoría de alto riesgo para iniciar un tratamiento más intensivo. Sin embargo, durante la década de seguimiento preconizada en las guías, el depósito de colesterol en la pared arterial va aumentando, facilitando el desarrollo de una placa de ateroma inestable e inflamatoria, y el desarrollo de ECVA. Alternativamente, se podría considerar desde el inicio que la diabetes conlleva una situación de alto riesgo y el objetivo debería ser c-LDL<70mg/dL. Además, mantener cifras de c-LDL<70mg/dL contribuye a reducir y estabilizar la placa de ateroma, evitando o disminuyendo episodios de mortalidad por ECVA durante esos años de evolución de la diabetes. ¿Deberíamos mantener los objetivos propuestos en los sujetos con diabetes y riesgo moderado durante una década hasta alcanzar la fase de alto riesgo cardiovascular o, por el contrario, adoptar desde el inicio una postura más intensiva buscando reducir el riesgo cardiovascular en la mayoría de los pacientes con diabetes? ¿Es mejor esperar o prevenir con medidas terapéuticas efectivas desde el primer momento? (AU)

Diabetes, especially type 2, is considered a risk situation for atherosclerotic cardiovascular disease (ASCVD). Subjects with diabetes type 2 have a mortality rate due to ASCVD 3 times higher than that found in the general population, attributed to hyperglycemia and the frequent association of other cardiovascular risk factors, such as atherogenic dyslipidemia. Numerous scientific societies have established a risk classification for ASCVD in diabetes based on 3 degrees (moderate, high and very high). The objectives of dyslipidemia control are clearly defined and accepted, and vary depending on the previously established cardiovascular risk. In moderate or intermediate risk, the guidelines propose a less intensive intervention, maintaining LDL-C levels<100mg/dL and NO-HDL-C levels<130mg/dL, and waiting 10 years until reaching the high-risk category to initiate more intensive treatment. However, during the decade of follow-up recommended in the guidelines, cholesterol deposition in the arterial wall increases, facilitating the development of an unstable and inflammatory atheromatous plaque, and the development of ASCVD. Alternatively, diabetes could be considered from the outset to be a high-risk situation and the goal should be LDL-C<70mg/dL. Furthermore, maintaining LDL-C levels<70mg/dL contributes to reducing and stabilizing atheromatous plaque, avoiding or reducing mortality episodes due to ASCVD during those years of diabetes evolution. Should we maintain the proposed objectives in subjects with diabetes and moderate risk for a decade until reaching the high cardiovascular risk phase or, on the contrary, should we adopt a more intensive stance from the beginning seeking to reduce cardiovascular risk in the majority of patients with diabetes? Is it better to wait or prevent with effective therapeutic measures from the first moment? (AU)

Tumor upgrading among very favorable intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy: how can it impact the clinical course?

PURPOSE: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression. METHODS: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses. RESULTS: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2. CONCLUSIONS: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment.