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Simple Summary: The use of radioactive iodine (RAI) for the treatment of patients with thyroid cancer at intermediate risk of recurrence is controversial. Evidence to date has not conclusively proven that there are benefits of this strategy to survival or recurrence after surgery for thyroid cancer. We describe key elements that can help clinicians decide when to prescribe RAI to this group of patients. These include a thorough discussion of the purpose of RAI therapy, better prediction of recurrence risk, the use of tumor markers after surgery, the use of the genetic profile of the tumor when available, and a detailed evaluation of the adverse effects of RAI, patient medical problems, and patient preferences. Integration of these variables will ensure a more comprehensive assessment of the risks and benefits of RAI treatment with the ultimate goal of avoiding overtreatment and reducing harm. The use of radioactive iodine (RAI) after total thyroidectomy for patients at the American Thyroid Association (ATA) who are at intermediate risk of recurrence is controversial. This is due to the lack of prospective randomized trials proving a benefit to recurrence or survival of RAI therapy in this group. In the absence of such evidence, clinicians struggle to recommend for or against this therapeutic approach which frequently results in overtreatment. This review describes key elements in the decision-making process that help clinicians more comprehensively evaluate the need for RAI therapy in patients with thyroid cancer at intermediate risk of recurrence. A clear definition of the purpose of RAI therapy should be conveyed to patients. In this sense, adjuvant RAI therapy intends to decrease recurrence, and ablation therapy is used to facilitate surveillance. Better stratification of the intermediate risk category into a low–intermediate subgroup and an intermediate–high-risk subgroup results in less heterogeneity and a more precise prediction of recurrence risk. The evaluation of post-operative thyroglobulin levels may prevent the overtreatment of low–intermediate-risk patients when their thyroglobulin level is <2.5 ng/mL. the integration of tumor genomics (when available) alongside pathologic features can enhance the ability of the clinician to predict iodine concentration in thyroid cancer cells. Finally, a detailed consideration of the adverse effects of RAI, patients' comorbidities, and patient preferences will result in a patient-centered personalized approach. Systematic examination of these variables will ultimately provide a framework for making more educated decisions on the use of RAI in patients at intermediate risk of recurrence that will prevent overtreatment and minimize harm. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Breast cancer screening guidelines vary for women at intermediate risk (15%-20% lifetime risk) for developing breast cancer across jurisdictions. Currently available risk assessment models have differing strengths and weaknesses, creating difficulty and ambiguity in selecting the most appropriate model to utilize. Clarifying which model to utilize in individual circumstances may help determine the best screening guidelines to use for each individual. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Vaginal brachytherapy remains the main treatment for intermediate operated endometrial cancer, with very low rates of local relapse and an acceptable toxicity profile. 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. 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. 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. [ABSTRACT FROM AUTHOR]

L'objectif était de rapporter une mise au point sur les modalités de la surveillance active (SA) dans le cancer de la prostate (CaP) à risque intermédiaire. Une recherche sur la base de données PubMed et un examen narratif des articles en français ou en anglais ont été effectués en février 2024 afin de proposer une revue compréhensive de la littérature sur le sujet. Dans l'essai ProtecT qui incluait 34 % de patients à risque intermédiaire ou élevé, en utilisant un protocole de SA allégé, la surveillance a démontré sa capacité à maintenir une survie similaire en comparaison aux traitements radicaux. Dans une récente méta-analyse incluant 29 673 patients à risque intermédiaire non sélectionnés (incluant les ISUP 3), le risque de traitement définitif et de métastase était augmenté en comparaison aux patients à faible risque, mais était similaire en analyse en sous-groupe lorsque les patients ISUP 3 étaient exclus. Les patients avec une maladie ISUP 2 sont candidats à la SA si la maladie présente par ailleurs des critères favorables (PSA < 10 ng/mL, stade ≤ T2a), une faible charge tumorale à la biopsie (< 3 biopsies positives et < 50 % d'envahissement par biopsie) et une faible proportion de grade 4 (< 10 %). Les modalités de surveillance les plus communément admis ont été énumérées dans les recommandations du CCAFU et dans le consensus DETECTIVE et incluent un toucher rectal annuel, un contrôle régulier du PSA (tous les 6 mois), et la réalisation d'IRM et de biopsies de suivi. La SA est une option pour certains patients sélectionnés à risque intermédiaire. Les patients doivent néanmoins être informés du faible niveau de preuve disponible et s'astreindre à une surveillance rigoureuse. To report an update on the modalities of active surveillance (AS) in intermediate-risk prostate cancer (PCa). A search of the PubMed database and a narrative review of articles in French or English were carried out in February 2024 to provide a comprehensive review of the literature. In the ProtecT trial, which included 34% of intermediate- or high-risk patients, using a mild AS protocol, monitoring demonstrated its ability to maintain a survival rate similar to that of radical treatments. In a recent meta-analysis including 29,673 unselected intermediate-risk patients (including ISUP 3), the risk of definitive treatment and metastasis was increased compared with low-risk patients but was similar in subgroup analysis when ISUP 3 patients were excluded. Patients with ISUP 2 disease are candidates for AS if the disease otherwise has favorable criteria (PSA < 10 ng/mL, stage ≤ T2a), a low biopsy tumor burden (< 3 positive biopsies and < 50% biopsy core involvement) and a low proportion of grade 4 (< 10%). The most commonly accepted surveillance modalities were listed in the CCAFU guidelines and the DETECTIVE study and include an annual digital rectal examination, regular PSA monitoring (every 6 months), and MRI + biopsies during follow-up. AS is an option for selected intermediate-risk patients. However, patients should be informed of the low level of evidence available and undertake rigorous monitoring. [ABSTRACT FROM AUTHOR]

Purpose: The 2015 American Thyroid Association risk stratification system (2015-RSS) is used to assess the tumor recurrence rate and guide the initial treatment. At the current moment, patients with one or multiple intermediate risk factors (IRF) have the same treatment. This study was conducted to evaluate the impact of the number of IRF characteristics on tumor persistence or recurrence rates. Methods: Patients with intermediate risk papillary thyroid cancer (PTC) were selected and analyzed, furthermore, they were divided into two subgroups, one with 1–2 IRF and another with ≥3 IRF. Those data were analyzed in relation to response to therapy at the end of the first year and in last appointment, time to reach non evidence of disease (NED) state and time in NED state. Results: A total of 257 patients were evaluated. Extrathyroidal invasion, vascular invasion, the total number of IRF and the subgroup of ≥3 IRF were associated with non-excellent response in last consultation; IRF lymph node metastasis was associated with non-excellent response in the first year and in last appointment and prolonged time in NED state; vascular invasion was associated with a shorter time in NED state; total number of IRF and aggressive histology were related to delay in the achievement of NED state. Conclusions: Higher number of IRF was a predictive factor of non-excellent response in the last visit and was associated with longer time to reach the NED state. Those data suggest a benefit from closer follow-up and more intensive treatment in these patients. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated the thrombolytic treatment in patients with intermediate-high risk pulmonary embolism, making this study more valuable. Material and methods: It was a prospective, non-randomized, open-label, single-center study. Eligible patients at the age of 18 or older with an acute pulmonary embolism (PE) confirmed by CT pulmonary angiography with onset until 14 day and signs of right ventricular (RV) overload on echocardiography took part in the study. Pulmonary Arterial CT Obstruction Index Rate (PACTOIR) was used to define the localization and the expansion zone of thromboembolism. This study included 18 patients with intermediate risk and acute submassive pulmonary thromboembolism. In thrombolysis (TT) group (n=9) were used 50 mg of tissue-plasminogen activator (t-PA) administered in infusion as 0.4 mg/h for 2 hours. In the standard anticoagulation group, unfractioned heparin (UFH) was administered as a bolus of 70 units/kg or a maximum of 5000 units, followed by continuous infusion at an initial rate of 16 units/kg or a maximum of 1000 units/h. Results: The mean age for TT group was 69 vs 63 for the UFH group. PACTOIR was 100% in 3 patients in the half-dose rt-PA group and in 2 patients in the UFH group. RV/LV diameter ratio decreased from baseline to 48 h post-procedure (1.55 vs. 1.13; mean difference, -0.42; p < 0.0001). Mean pulmonary artery systolic pressure was 55 mm Hg in both groups (p < 0.05), with 53 [43–60] in TT group vs. 41.5 [37–45] mmHg in UFH group, P< 0.05). The rate of secondary endpoints was significantly higher in the UFH group with a high rate of pulmonary hypertension (0 vs. 19%, p=0.003). Conclusions: Half-dose thrombolytic therapy in patients diagnosed with submassive pulmonary embolism significantly reduced death and hemodynamic decompensation in the first 7 days compared to anticoagulant therapy only. With all that being said, it can be concluded that patients with high-intermediate risk PE could benefit from reduced-dose TT.

Objective To analyze the recurrence factors of the patients with intermediate risk papillary thyroid carcinoma (PTC) after radioactive iodine treatment (RAIT). Methods A total of 254 intermediate risk PTC patients after RAIT from January 2018 to May 2020 in our hospital were enrolled into this study. Chi square test and multivariate analysis were applied to analyze the main recurrence factors after RAIT. Results Thirty four (13.4%) patients with intermediate risk PTC relapsed after RAIT. The primary tumor size, lymph node metastasis staging, and pre-ablation stimulated thyroglobulin (psTg) were associated with tumor recurrence. According to the receiver operating characteristic （ROC） curve, psTg 25.6 μg/L was the best cutoff value for predicting recurrence. Further multivariate analysis revealed that lymph node metastasis staging and psTg levels were independent factors of predicting PTC recurrence. When the patients with N1b and psTg≥25.6 μg/L, the incidence of tumor recurrence after RAIT was 58.3%. While the patients with N1a and psTg

Objectives: This study aimed to report the treatment outcomes of radiation therapy for early‐stage endometrial cancer patients. In addition, this study intended to identify high‐risk factors that require pelvic radiotherapy (PRT) in addition to vaginal brachytherapy (VBT) for intermediate‐risk endometrial cancer patients. Methods: Patients with early‐stage endometrial cancer receiving postoperative VBT alone or with PRT were included. Propensity score matching was used to balance the two study groups. The primary endpoint was locoregional recurrence (LRR). Age‐adjusted Charlson comorbidity index and substantial lymphovascular space invasion were selected for subgroup analyses to identify the benefits of PRT over VBT alone. Results: From 2005 to 2017, a total of 288 patients underwent analysis following propensity score matching. Of these, 144 received VBT and 144 received PRT. There was no significant difference in 5‐year LRR between VBT and PRT for both intermediate (0% vs. 0%) and high‐intermediate risk patients (3.5% VBT vs. 5.4% PRT; HR 0.54: 0.05–6.00; p = 0.616). The subgroup analyses revealed no significant factors favoring PRT over VBT. Patients with high comorbidities may have higher risks of non‐cancer death after receiving PRT. Conclusions: Postoperative VBT alone is sufficient for early‐stage intermediate‐risk endometrial cancer patients. [ABSTRACT FROM AUTHOR]

Optimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML. We retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. The neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years. MST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years. [ABSTRACT FROM AUTHOR]

Abstract Active surveillance has been proposed as a therapeutic option in selected intermediate risk patients with biopsy grade group 2 prostate cancer. However, its oncologic safety in this setting is debated. Therefore, we conducted a non-systematic literature research of contemporary surveillance protocols including patients with grade group 2 disease to collect the most recent evidence in this setting. Although no randomized controlled trial compared curative-intent treatments, namely radical prostatectomy and radiotherapy vs. active surveillance in patients with grade group 2 disease, surgery is associated with a benefit in terms of disease control and survival when compared to expectant management in the intermediate risk setting. Patients with grade group 2 on active surveillance were at higher risk of disease progression and treatment compared to their grade group 1 counterparts. Up to 50% of those patients were eventually treated at 5 years, and the metastases-free survival rate was as low as 85% at 15-years. When considering low- and intermediate risk patients treated with radical prostatectomy, grade group 2 was one of the strongest predictors of grade upgrading and adverse features. Available data is insufficient to support the oncologic safety of active surveillance in all men with grade group 2 prostate cancer. Therefore, those patients should be counselled regarding the oncologic efficacy of upfront active treatment modalities and the lack of robust long-term data supporting the safety of active surveillance in this setting.

The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with operated papillary thyroid cancer (PTC) in low and intermediate-risk. One hundred sixty-one patients with PTC in the low and intermediate-risk were evaluated. Most patients (89.4%) were in the low-risk, and 10.6% were in the intermediate-risk. When the patients were divided into two groups according to the date of receiving RAI treatment after surgery, those who received early treatment (≤3 months) constituted the majority of the patients (72.7%). Seventeen patients received 1.85 Gigabecquerel (GBq), 119 3.7 GBq, 25 5.55 GBq RAI. Most patients (82%) achieved ablation success after the first RAI treatment. The time interval between surgery and RAI treatment did not affect ablation success. Stimulated Tg level measured on the RAI treatment day was an independent predictive factor for successful ablation (p<0.001). The cut-off value of Tg found to predict ablation failure was 5.86 ng/ml. It was concluded that 5.55 GBq RAI treatment could predict ablation success compared to 1.85 GBq dose (p=0.017). It was concluded that having a T1 tumor may predict treatment success compared to a T2 or T3 tumor (p=0.001, p<0.001, retrospectively). The time interval does not affect ablation success in low and intermediate-risk PTC. The ablation success rate may decrease in patients who receive low-dose RAI and have high Tg levels before treatment. The most crucial factor in achieving ablation success is giving enough doses of RAI to ablate the residual tissue. [ABSTRACT FROM AUTHOR]

Active surveillance has been proposed as a therapeutic option in selected intermediate risk patients with biopsy grade group 2 prostate cancer. However, its oncologic safety in this setting is debated. Therefore, we conducted a non-systematic literature research of contemporary surveillance protocols including patients with grade group 2 disease to collect the most recent evidence in this setting. Although no randomized controlled trial compared curative-intent treatments, namely radical prostatectomy and radiotherapy vs. active surveillance in patients with grade group 2 disease, surgery is associated with a benefit in terms of disease control and survival when compared to expectant management in the intermediate risk setting. Patients with grade group 2 on active surveillance were at higher risk of disease progression and treatment compared to their grade group 1 counterparts. Up to 50% of those patients were eventually treated at 5 years, and the metastases-free survival rate was as low as 85% at 15-years. When considering low- and intermediate risk patients treated with radical prostatectomy, grade group 2 was one of the strongest predictors of grade upgrading and adverse features. Available data is insufficient to support the oncologic safety of active surveillance in all men with grade group 2 prostate cancer. Therefore, those patients should be counselled regarding the oncologic efficacy of upfront active treatment modalities and the lack of robust long-term data supporting the safety of active surveillance in this setting. [ABSTRACT FROM AUTHOR]

High-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking. Patients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported. A total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar. These data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer, with the success of preserving fertility rate exceeding 90%. However, certain high-risk histologic features such as positive lymph nodes, positive surgical margins, parametrial invasion or intermediate-risk factors may require additional treatments that can negatively affect fertility. This review provides an overview of the occurrence of these high- or intermediate-risk histologic features, the available treatment options and the variations in approaches among different treatment centers worldwide. Parametrial invasion in tumors less than 2 cm was found to be rare, supporting the rationale for omitting parametrectomy in small tumors. In cases of positive lymph nodes at frozen section analysis, a hysterectomy is not recommended prior to adjuvant (chemo)radiation, as leaving the uterus in place reduces the risk of complications during surgery and radiation therapy. Adjuvant chemotherapy after FSS could be an alternative treatment option considering its effectiveness, safety and potential for fertility preservation. Background: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer (ECC); however, certain risk factors may necessitate additional treatments and impact fertility. This review examines the prevalence of these risk factors and available treatment options. Methods: A systematic search was conducted of studies including patients with ECC (IA1 with LVSI, IA2, IB1 (FIGO 2009)) who underwent FSS. Results: Sixty-four articles, comprising a total of 4118 women planned for FSS, were included. High- or intermediate-risk histologic features were found in 638 (15.5%) women: 5.1% had positive lymph node(s), 4.1% had positive resection margins, 0.3% had parametrial involvement, 1.0% had unspecified high-risk features, and 5.1% had intermediate-risk histology (primarily based on the Sedlis criteria). Adjuvant treatment impaired fertility in all women with adjuvant hysterectomy and/or (chemo)radiation (58.7%). Adjuvant chemotherapy was given to 1351 (32.8%) patients, which may reduce fertility. Conclusions: Fertility preservation could be achieved in most women; but high- or intermediate-risk factors necessitate more extensive surgery or radiotherapy leading to infertility. Adjuvant chemotherapy could be an alternative treatment option considering its effectiveness, safety and higher change in fertility preservation. The low incidence of parametrial involvement justifies waiving parametrectomy in tumors < 2 cm. [ABSTRACT FROM AUTHOR]

Objectives: To validate the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non‐muscle invasive bladder cancer and provide a more accurate stratification model for a heterogeneous intermediate‐risk group. Methods: A total of 1610 patients, who underwent transurethral resection, diagnosed with non‐muscle invasive bladder cancer in nine collaborating hospitals were retrospectively reviewed. They were classified into low‐risk, intermediate‐risk, high‐risk, and highest‐risk groups, and recurrence‐free survival, progression‐free survival, cancer‐specific survival, and overall survival were compared among the groups. The intermediate‐risk group was subdivided into two groups based on the multivariable Cox regression model of recurrence and progression risk factors, and a revised risk model was created. Results: The progression‐free survival, cancer‐specific survival, and overall survival were well stratified, while the recurrence‐free survival of the intermediate‐risk group was the shortest among the four groups (p < 0.001). The independent risk factors for recurrence and progression‐free survival in the intermediate‐risk group were as follows: age ≥ 70 years, sex, multiple tumors, tumor size ≥3 cm, and recurrent cases. The intermediate‐risk group was subdivided into two groups: favorable intermediate‐risk group and unfavorable intermediate‐risk group. The revised risk model showed significant differences. Conclusion: We validated the Japanese Urological Association guidelines 2019 stratification model. The revised risk model provided a more accurate treatment selection for this disease subset. [ABSTRACT FROM AUTHOR]

Purpose: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. Methods: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1–2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). Results: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1–4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. Conclusions: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted. [ABSTRACT FROM AUTHOR]

Objective: The study aims to explore the possibility of prelaryngeal and/or pretracheal lymph node metastasis in identifying papillary thyroid carcinoma with more than 5 metastatic central lymph nodes from unilateral lobe cT1-2N0 papillary thyroid carcinoma. Methods: A retrospective analysis was conducted on patients who underwent the initial thyroid surgery for unilateral lobe cT1-2N0 PTC in a single tertiary center between July 2018 to December 2022. Multivariable binary logistic regression analysis was used to identify risk factors for unilateral lobe cT1-2N0 papillary thyroid carcinoma with more than 5 metastatic central lymph nodes. Results: A total of 737 patients were included in the study and 399 patients were confirmed to suffer from occult central lymph node metastasis. The larger size of the largest diameter of tumor (> 1cm; OR = 3.3, 95%CI 1.6 - 6.83; p = 0.001), pretracheal lymph node metastasis (OR = 5.91, 95%CI 2.73 - 12.77; p < 0.001), prelaryngeal lymph node metastasis (OR = 3.74, 95%CI 1.73 - 8.1; p = 0.001), ipsilateral paratracheal lymph node metastasis (OR = 12.22, 95%CI 3.43 - 43.48; p < 0.001), and contralateral paratracheal lymph node metastasis (OR = 7.68, 95% CI 3.86 - 15.3; p < 0.001) were confirmed to be risk factors for unilateral lobe cT1-2N0 PTC with more than 5 metastatic central lymph nodes. When more than two metastatic prelaryngeal and/or pretracheal lymph nodes occurred, the incidence of more than 5 metastatic central lymph nodes was 71.2%. Conclusion: Prelaryngeal and/or pretracheal lymph node metastasis could help to identify papillary thyroid carcinomawithmore than 5 metastatic central lymph nodes from unilateral lobe cT1-2N0 papillary thyroid carcinoma. When more than two metastatic pretracheal and/or prelaryngeal lymph nodes occurred, total thyroidectomy and ipsilateral central lymph node dissection should be performed and contralateral paratracheal lymph node dissection might be also necessary. [ABSTRACT FROM AUTHOR]

Introduction: Stratification of risk for major complications (including mortality) is the current fundamental clinical strategy for making therapeutic decisions in patients with pulmonary arterial hypertension. However, it is noticeable that most of patients are grouped in the intermediate category both at the time of diagnosis and during follow-up. Highlighting the relevance and necessity to improve discrimination and therapeutic options for patients at intermediate risk. Objective: To define a series of recommendations on the proper subclassification, follow-up, and treatment of adult patients with pulmonary arterial hypertension at intermediate risk, adapted to the Colombian context. Method: 15 experts in pulmonary hypertension were invited. They voted according to the modified Delphi methodology around 14 questions, on which a systematic review of the literature was carried out in several bibliographic bases: VHL, Cochrane Library, PubMed, Medline and Web of Science. The MeSh and DeCs criteria for each question were used without language or time limits. Results and discussion: The present study provides a series of 18 consensus recommendations on stratification, treatment and other sections. Additionally, the initiative makes it possible to identify the insufficiency of scientific studies in our country that determine the behavior of the disease, access barriers and availability of medicines in our country. [ABSTRACT FROM AUTHOR]

The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer. We analyzed data from patients with IR cervical cancer (tumor size 2–4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study. Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT−) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; P DFS = 0.365) and overall survival (88.7% and 89.0%; P OS = 0.281) were not significantly different between the AT− and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: P DFS = 0.365; P OS = 0.282). Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy. • We investigated the survival benefit of adjuvant therapy (AT) after radical surgery in intermediate-risk (IR) cervical cancer. • Of 692 IR cervical cancer patients in the SCANN study, 60.4% received AT (AT+) and 39.6% did not (AT−). • 5-year DFS (83.2% vs. 80.3%) and OS (88.7% vs. 89.0%) rates were similar in the AT− and AT+ groups. • AT did not confer a significant survival benefit even after applying propensity score matching for confounding factors. [ABSTRACT FROM AUTHOR]

Background and Aims: The objective of this study was to compare the safety and efficacy of endoscopic resection with surgical resection in the treatment of intermediate-risk gastric gastrointestinal stromal tumors (GISTs) and to further evaluate whether imatinib adjuvant treatment is necessary for resected intermediate-risk gastric GIST by ER. Methods: We retrospectively studied 128 cases for intermediate-risk gastric GISTs that were distributed in endoscopic (n = 33) and surgical groups (n = 95) at our center between December 2009 to July 2020. We statistically compared the clinical features, pathological reports, perioperative data, and long-term follow-up outcomes. Results: Compared with the surgery group, the endoscopy group was associated with smaller tumor size (2.4 ± 1.0 vs. 6.0 ± 1.7 cm, p < 0.001), shorter operating time (67.3 ± 36.5 vs. 145.9 ± 74.8 min, p < 0.001), fewer incidence of short-term postoperative complications (3% vs. 32.6%, p = 0.002). Shorter postoperative hospital days (4.5 ± 1.4 vs. 8.5 ± 2.4 days, p < 0.001), shorter gastric functional recovery time (p < 0.001), and a lower overall medical cost of hospitalization (p < 0.001) was detected in the endoscopy group. During the median 44.5 months follow-up period, there were no cases of recurrence, metastasis, and death in the endoscopy group. Among 128 patients, 68 accepted adjuvant therapy with imatinib after resection. It was observed that the OS of the adjuvant treatment group with imatinib was lower than that of the group without imatinib (p = 0.033). Conclusion: Endoscopic resection for intermediate-risk gastric GIST is a feasible and safe method, and there is no significant benefit for patients with intermediate-risk gastric GIST to accept imatinib adjuvant treatment after ER. [ABSTRACT FROM AUTHOR]

There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan–Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71–2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45–2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders. • The trial effect is not apparent in prostate cancer patients treated with radiotherapy. • Trial participants receive lower radiation doses than non-participants. • High-risk trial participants receive longer ADT than non-participants. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma is the most common form of thyroid cancer and is usually associated with a good outcome. However, there are some aggressive variants wherein the prognosis may not be as good as for a conventional papillary thyroid carcinoma. Three cases of aggressive variants of papillary thyroid carcinoma are reported in the present series, namely, tall cell, hobnail, and columnar cell variants. This series is being reported to highlight the characteristic histopathological features which help in diagnosing these variants, especially diagnostic challenge in recognizing columnar cell variant due to lack of the classical nuclear features of papillary thyroid carcinoma in this variant. This case series also highlights the clinical importance of recognizing these variants because, according to American Thyroid Association, these variants come under intermediate risk with a poor clinical outcome, requiring aggressive management with neck dissection, radioiodine ablation, and closer disease surveillance. [ABSTRACT FROM AUTHOR]

Abstract Background We compared the oncological outcomes of patients who received seed brachytherapy (SEED-BT) with those who received radical prostatectomy (RP) for intermediate-risk prostate cancer. Methods Candidates were patients treated with either SEED-BT (n = 933) or RP (n = 334). One-to-one propensity score matching was performed to adjust the patients’ backgrounds. We compared the biochemical recurrence (BCR)-free rate using the Phoenix definition (prostate-specific antigen [PSA] nadir plus 2 ng/mL) for SEED-BT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free rates using the same PSA cut-off value of 0.2 ng/mL for both SEED-BT and RP. Results In the propensity score-matched analysis with 214 pairs, the median follow-up treatment was 96 months (range 1–158 months). Fifty-three patients (24.7%) were treated with combined SEED-BT and external-beam radiotherapy. Forty-three patients (20.0%) received salvage radiotherapy after RP. Comparing the BCR-free rate using the above definitions for SEED-BT and RP showed that SEED-BT yielded a significantly better 8-year BCR-free rate than did RP (87.4% vs. 74.3%, hazard ratio [HR] 0.420, 95% confidence interval [CI] 0.273–0.647). Comparing the 8-year BCR-free rate using the surgical definition for both treatments showed no significant difference between the two treatments (76.7% vs. 74.3%, HR 0.913, 95% CI 0.621–1.341). SEED-BT had a significantly better 8-year salvage hormonal therapy-free rate than did RP (92.0% vs. 85.6%, HR 0.528, 95% CI 0.296–0.942, P = 0.030). The 8-year metastasis-free survival rates (98.5% vs. 99.0%, HR 1.382, 95% CI 0.313–6.083, P = 0.668) and overall survival rates (91.9% vs. 94.6%, HR 1.353, 95% CI 0.690–2.650) did not significantly differ between the treatments. Conclusions The BCR-free rates did not significantly differ between patients treated with SEED-BT and those treated with RP for intermediate-risk prostate cancer even when they were directly compared using the surgical definition for BCR. SEED-BT and RP can be adequately compared for oncological outcomes.

Background The present study evaluated the clinical implications of adjuvant chemotherapy according to the mismatch repair (MMR) status and clinicopathologic features of patients with intermediate- and high-risk stage II colon cancer (CC). Methods This study retrospectively reviewed 5,774 patients who were diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The patients were enrolled according to the following criteria: (1) pathologically diagnosed with primary CC; (2) stage II CC classified based on the 7th edition of the American Joint Committee on Cancer staging system; (3) intermediate- and high-risk features; and (4) available test results for MMR status. A total of 286 patients met these criteria and were included in the study. Results Among the 286 patients, 54 (18.9%) were identified as microsatellite instability-high (MSI-H) or deficient MMR (dMMR). Although all the patients identified as MSI-H/dMMR showed better survival outcomes, T4 tumors and adjuvant chemotherapy were identified as independent prognostic factors for survival. For the intermediate-risk patients identified as MSI-low (MSI-L)/microsatellite stable (MSS) or proficient MMR (pMMR), adjuvant chemotherapy exhibited a significantly better disease-free survival (DFS) but had no impact on overall survival (OS). Oxaliplatin-containing regimens showed no association with DFS or OS. Adjuvant chemotherapy was not associated with DFS in intermediate-risk patients identified as MSI-H/dMMR. Conclusion The current study found that the use of adjuvant chemotherapy was correlated with better DFS in MSI-L/MSS or pMMR intermediate-risk stage II CC patients.

Abstract Background Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid malignancy that tends to metastasize to cervical lymph nodes. In the present study, we aimed to investigate which clinicopathologic and ultrasound features of PTC are associated with clinical lymph node metastasis (LNM) and numbers of pathological LNM. Methods From January 2016 to December 2018, we identified a cohort of patients with PTC who underwent cervical ultrasonography and were diagnosed through operation and pathology. Clinical N1(cN1) and > 5 pathologic N1(pN1) were considered in the postoperative stratification to have an intermediate risk according to the 2015 ATA guidelines. Clinicopathological and ultrasound features in PTC patients were performed in accordance with the independent risk factors of cN1 and > 5pN1 respectively by using the univariate and multivariate analyses. Results We collected 748 PTC patients in the final inclusion criteria. There were 688 cN0 cases and 60 cN1 cases. From the analyses, primary tumor size > 2 cm, capsule contact, extrathyroidal extensions (ETE) and central LNM remained independent risk factors for cN1 in PTC patients. In the 748 PTC patients, 707 cases had ≤ 5 pN1, and 41 cases had > 5 pN1. Multifocality, primary tumor size > 2 cm, capsule contact and ETE are significant independent risk factors for > 5 pN1. Conclusions We concluded that multifocality, primary tumor size > 2 cm, capsule contact, ETE and central LNM were independent risk factors for the intermediate risk stratification in patients with PTC. Ultrasonography is a good technique for the preoperative lymph node staging of PTC and is helpful for detecting LNM.

• Outcome from HDR-BT alone in intermediate and high-risk prostate cancer at 10 years. • 19 Gy 10 year bRFI was 64 % compared to 72–76 % after 2 and 3 fraction schedules. • Grade 3 urinary toxicity after 19 Gy was 8 % and IPSS ≥ 20 was 31 % at 10 years. Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. 293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT. [ABSTRACT FROM AUTHOR]

Background: Fertility-sparing surgery (FSS) is a viable option for young women with early-stage cervical cancer (ECC); however, certain risk factors may necessitate additional treatments and impact fertility. This review examines the prevalence of these risk factors and available treatment options. Methods: A systematic search was conducted of studies including patients with ECC (IA1 with LVSI, IA2, IB1 (FIGO 2009)) who underwent FSS. Results: Sixty-four articles, comprising a total of 4118 women planned for FSS, were included. High- or intermediate-risk histologic features were found in 638 (15.5%) women: 5.1% had positive lymph node(s), 4.1% had positive resection margins, 0.3% had parametrial involvement, 1.0% had unspecified high-risk features, and 5.1% had intermediate-risk histology (primarily based on the Sedlis criteria). Adjuvant treatment impaired fertility in all women with adjuvant hysterectomy and/or (chemo)radiation (58.7%). Adjuvant chemotherapy was given to 1351 (32.8%) patients, which may reduce fertility. Conclusions: Fertility preservation could be achieved in most women; but high- or intermediate-risk factors necessitate more extensive surgery or radiotherapy leading to infertility. Adjuvant chemotherapy could be an alternative treatment option considering its effectiveness, safety and higher change in fertility preservation. The low incidence of parametrial involvement justifies waiving parametrectomy in tumors < 2 cm.

Papillary thyroid carcinoma is the most common form of thyroid cancer and is usually associated with a good outcome. However, there are some aggressive variants wherein the prognosis may not be as good as for a conventional papillary thyroid carcinoma. Three cases of aggressive variants of papillary thyroid carcinoma are reported in the present series, namely, tall cell, hobnail, and columnar cell variants. This series is being reported to highlight the characteristic histopathological features which help in diagnosing these variants, especially diagnostic challenge in recognizing columnar cell variant due to lack of the classical nuclear features of papillary thyroid carcinoma in this variant. This case series also highlights the clinical importance of recognizing these variants because, according to American Thyroid Association, these variants come under intermediate risk with a poor clinical outcome, requiring aggressive management with neck dissection, radioiodine ablation, and closer disease surveillance.

En Europe, le cancer de l'endomètre représente le quatrième cancer en termes d'incidence chez les femmes, avec une majorité de diagnostics réalisés à un stade localisé. Le traitement standard repose alors sur une hystérectomie avec salpingo ovariectomie plus ou moins une stadification ganglionnaire. Les facteurs histopronostiques guident, à travers l'évaluation du niveau de risque – faible, intermédiaire, intermédiaire-élevé, haut – les stratégies thérapeutiques adjuvantes. Si le pronostic des cancers de l'endomètre de faible risque ou de haut risque est bien connu, celui des risques intermédiaires ou intermédiaires-élevés est plus hétérogène, et l'index thérapeutique de leurs traitements adjuvants plus discutable. Plusieurs essais (Postoperative Radiation Therapy in Endometrial Carcinoma [PORTEC] I, Gynecologic Oncology Group [GOG] 99, A Study in the Treatment of Endometrial Cancer [ASTEC] EN.5, PORTEC II, essai suédois de Sorbe et al.) ont évalué la surveillance, la curiethérapie du fond vaginal et/ou la radiothérapie externe pelvienne dans cette population. La curiethérapie du fond vaginal permet de réduire le taux de récidive locale, et la radiothérapie externe pelvienne celui des récidives pelviennes, mais sans bénéfice en termes de survie globale ni de survenue de métastases à distance. Comparativement à la surveillance, la curiethérapie, et plus encore la radiothérapie externe, sont associées à une majoration de la morbidité, et à une diminution de la qualité de vie des patientes. Afin d'améliorer l'index thérapeutique, et d'optimiser les décisions médico-économiques, des stratégies de désescalade thérapeutique, basées essentiellement sur les apports de la classification moléculaire, émergent dans des essais thérapeutiques, et dans les recommandations de prise en charge des cancers de l'endomètre de risque intermédiaire ou intermédiaire-élevé. L'évaluation des quatre principaux profils moléculaires mis en évidence par les analyses génomiques issues de The Cancer Genome Atlas (TCGA) – mutation polymerase epsilon (POLE), profil moléculaire non spécifique, déficience M is M atch repair (MMR), et mutation p53 – mais aussi la quantification des emboles lymphovasculaires (absents, focaux ou substantiels), et l'évaluation de la surexpression de L1 cell adhesion molecule (L1CAM) occupent une place grandissante. Ils ouvrent des perspectives de personnalisation des traitements adjuvants, avec une désescalade thérapeutique attendue pour environ la moitié des patientes ayant un cancer de l'endomètre de risque intermédiaire-élevé. Cependant, en l'absence de données prospectives disponibles, l'inclusion dans des essais thérapeutiques évaluant l'impact d'un traitement adjuvant guidé par la classification moléculaire demeure la meilleure opportunité thérapeutique. In Europe, endometrial cancer is the fourth most common cancer among women. The majority of patients are diagnosed at a localized stage. For these patients, the standard of care is based on an hysterectomy with salpingo oophorectomy ± lymph node staging. Through the assessment of histopathologic features, risk groups are determined: low, intermediate, high-intermediate, and high risk. Adjuvant strategies are guided by these risk groups. While the prognosis of low-risk and high-risk is well known, that of intermediate and high-intermediate risk is more heterogeneous, and the therapeutic index of adjuvant treatments is more questionable. Several trials (PORTEC [Post Operative Radiation Therapy in Endometrial Carcinoma] I, GOG [Gynecologic Oncology Group] 99, ASTEC [A Study in the Treatment of Endometrial Cancer] EN.5, PORTEC II, Sorbe et al trial) have assessed observation, vaginal cuff brachytherapy and/or pelvic external beam radiotherapy in this population. Vaginal cuff brachytherapy reduces the local recurrence rate, and pelvic external beam radiotherapy the pelvic recurrence rate. However, no benefit in terms of overall survival or occurrence of distant metastases is highlighted. Compared to observation, brachytherapy and above all external beam radiotherapy are associated with an increased morbidity, and with a decreased quality of life. In order to improve the therapeutic ratio and to optimize medico-economic decisions, therapeutic de-escalation strategies, based on the molecular profiles, are emerging in clinical trials, and in the recommendations for the management of intermediate and high-intermediate risk endometrial cancers. The four main molecular profiles highlighted by the genomic analyzes of The Cancer Genome Atlas (TCGA) – POLE (polymerase epsilon) mutation, non-specific molecular profile, MMR (MisMatch repair) deficiency, and p53 mutation – but also the quantification of lymphovascular space invasion (absent, focal or substantial), and the assessment of L1CAM (L1 cell adhesion molecule) overexpression represent growing concerns. Thus, the use of molecular-integrated risk profile to determine the best adjuvant treatment represent a major way to personalize adjuvant treatment of endometrial cancers, with therapeutic de-escalation opportunity for around half of the high-intermediate risks. However, in the absence of prospective data, inclusion in clinical trials assessing molecular profile-based treatment remains the best therapeutic opportunity. [ABSTRACT FROM AUTHOR]

Background: Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as large tumor diameter, stromal invasion to the outer half, and lymphovascular space invasion (LVSI). However, the indications and types of adjuvant therapy for the IR group remain controversial. This study aimed to analyze the differences in patient outcomes in the IR group to provide novel insights for tailoring adjuvant therapy. Methods: Data from 6192 patients with cervical cancer who underwent radical hysterectomy at 116 institutions belonging to the Japanese Gynecologic Oncology Group were reviewed. Results: In total, 1688 patients were classified into the IR group, of whom 37.3% did not receive adjuvant therapy. Conversely, approximately equal proportions of the remaining patients received adjuvant radiotherapy, concurrent chemoradiotherapy, and chemotherapy. Patients with all three risk factors showed worse overall survival than those with one or two risk factors. In addition to LVSI, non-squamous cell carcinoma histology, and vaginal invasion were identified as independent risk factors for both recurrence and mortality in multivariate analyses. Tumor diameter greater than 40 mm and surgical center volume were identified as independent risk factors for recurrence. Stromal invasion to the outer half and ovarian metastasis were identified as independent risk factors for mortality. Conclusions: This study revealed the significant differences in prognosis in the IR group. The indications for adjuvant therapy should be further studied, focusing on conventional risk factors and other pathological findings. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) can have a wide range of hemodynamic effects, from asymptomatic to a life-threatening medical emergency. Pulmonary embolism (PE) is associated with high mortality and requires careful risk stratification for individualized management. PE is divided into three risk categories: low risk, intermediate-risk, and high risk. In terms of initial therapeutic choice and long-term management, intermediate-risk (or submassive) PE remains the most challenging subtype. The definitions, classifications, risk stratification, and management options of intermediate-risk PE are discussed in this review. [ABSTRACT FROM AUTHOR]

Despite the innovations introduced in the 2022 European Society of Cardiology/European Respiratory Society Guidelines on Pulmonary Hypertension, risk discrimination and management of pulmonary arterial hypertension (PAH) patients at intermediate risk still represents a grey zone. Additionally, clinical evidence derived from currently available studies is limited. This expert panel survey intends to aid physicians in choosing the best therapeutic strategy for patients at intermediate risk despite ongoing oral therapy. An expert panel of 24 physicians, specialized in cardiology and/or pulmonology with expertise in handling all drugs available for the treatment of PAH participated in the survey. All potential therapeutic options for patients at intermediate risk were explored and analyzed to produce graded consensus statements regarding: the switch from endothelin receptor antagonist (ERA) or phosphodiesterase 5 inhibitor (PDE5i) to another oral drug of the same class; the addition of a drug targeting the prostacyclin pathway administered by different routes; the switch from PDE5i to riociguat., Competing Interests: Declaration of competing interest S. Ghio reports personal fees from MSD and Ferrer, outside the submitted work. R. Badagliacca reports personal fees from UT, Dompè, Ferrer, Bayer, MSD and AOP Orphan Pharmaceuticals, outside the submitted work. R. Benza reports receiving grants from Actelion, Bayer AG, Bellerophon Therapeutics and Eiger Biopharmaceuticals, outside the submitted work. C. D. Vizza reports personal fees from GSK, UT, Dompè, Bayer and MSD, outside the submitted work. Other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous transcatheter valve therapy registry analyses of transcatheter mitral valve in valve (MViV) replacement of degenerated bioprosthesis reported early experience in the United States. Given recent increases in transseptal MViV volumes and introduction of the SAPIEN 3 Ultra valve, it is important to determine contemporary outcomes for patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV replacement., Methods: The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry was used to extract data for all patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV from 2015 to September 2022. Primary efficacy outcome was 1-year all-cause mortality. Secondary end points included 30-day mortality, functional class, quality of life, and mitral valve performance. Primary safety outcomes were device success and in-hospital complications., Results: A total of 4243 patients with a mean STS score of 9.2±7.7 underwent transseptal MViV at 455 sites. The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in-hospital, 30-day, and 1-year mortality rates were 3.2%, 4.3%, and 13.4%, respectively. Significant improvements in New York Heart Association class (New York Heart Association I/II, 18% to 87%) and quality of life (Kansas City Cardiomyopathy Questionnaire score, 38 to 78) were noted at 1 year ( P <0.0001 for both) after MViV. Upon stratifying by STS scores, it was observed that the low-risk group (STS<4) had a significantly lower in-hospital mortality rate of 0.4%, whereas the intermediate-risk group (STS, 4-8) had an in-hospital mortality rate of 1.9%. From 2015 to 2022, the number of transseptal MViV cases/year increased significantly, whereas procedure times, length of stay, and intensive care unit hours shortened significantly. At the same time, there was a significant trend toward reduced in-hospital ( P =0.0005), 30-day ( P =0.004), and 1-year mortality rates ( P =0.01)., Conclusions: This multicenter, prospective study reports excellent procedural outcomes, 1-year mortality rates, and a significant improvement in quality of life for patients undergoing transseptal MViV in the contemporary era. Patients in the low-risk and intermediate-risk STS score categories had significantly better outcomes compared with those in the high-risk category. MViV is a reasonable therapy for the majority of patients with degenerated bioprosthetic mitral valves, who are anatomical candidates.

Background Neurons can be effectively regulated by serotonin and dopamine. Their role in anti-inflammatory pathways opens new doors for therapeutic research, particularly in chemotherapeutics. The present study investigated serotonin's role in suppressing inflammation and its potential anticancer effects in KERATIN-forming tumor cell line HeLa cells (KB cells).  Methods - in vitro and in silico analysis The study delved further into the molecular mechanisms by assessing the expression levels of key markers involved in inflammation and cancer progression, such as B-cell leukemia/lymphoma 2 protein (BCl-2), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) using Real-time reverse-transcriptase-polymerase chain reaction at concentrations below the IC 50 (50 and 100 µg/ml). The binding capability of serotonin (CID 5202) with glycoform of human interleukin 6 (PDB: 7NXZ) was analyzed with the help of Schrodinger molecular suites. Results The findings showcased serotonin's potent growth inhibition in KB cells, with an IC 50 value of 225±3.1µg/ml. Additionally, it demonstrated a multifaceted impact by downregulating the expression of BCl-2, TNF-α, and IL-6, pivotal factors in cancer cell survival and inflammation regulation. The docking score was - 5.65 (kcal/mol) between serotonin and glycoform of Human Interleukin 6. It is bound with ASN 143 by two hydrogen bonds. Thus, molecular docking analysis showed an efficient bounding pattern. The research findings indicate that serotonin successfully blocks NF-κB pathways in KB cells, underscoring its therapeutic promise against colon cancer and offering vital information for additional clinical investigation.  Conclusion According to the study's conclusion, serotonin has a remarkable anticancer potential by effectively blocking NF-κB B pathways in KB cells, revealing its promising potential as a therapeutic agent against colon cancer. These comprehensive findings offer significant insights into serotonin's intricate molecular interactions and its profound impact on cancer-related signaling pathways, paving the way for further exploration and potential clinical applications in cancer treatment strategies., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Maheshwarla Saravanan et al.)

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., (© 2024 Wiley Periodicals LLC.)

Currently, thrombolytic therapy (TLT) for pulmonary embolism (PE) is recommended only for patients with high-risk PE. At the same time, in real practice, TLT is often performed in hemodynamically stable patients. The main contradiction arises due to the different risk-benefit ratio of TLT in comparison with anticoagulant monotherapy.Aim. To assess the benefits of TLT, compared with unfractionated heparin (UFH) monotherapy, in hemodynamically stable patients with PE in reducing mortality, recurrence of PE and risk of bleeding.Material and methods. Randomized controlled trials were searched in PubMed, Embase, and Cochrane Library databases. Of the 3050 publications found, 100 papers were selected for a detailed study. As a result of detailed analysis, 7 randomized clinical trials (n=1611) remained according to established criteria.Results. TLT in hemodynamically stable patients with PE, in comparison with UFH, showed a tendency to decrease in the inhospital death rate: 2,39% vs 3,68 (odds ratio (OR): 0,73; 95% confidence interval (СI): 0,34-1,57), and a decrease in the composite endpoint (death and/or recurrent PE): 3,14% vs 5,15% (OR: 0,61; CI: 0,37-1,01). There was a significant increase in the number of major bleeding: 8,81% vs 2,70% (OR: 3,35; 95% CI: 2,06-5,45). TLT in hemodynamically stable patients with PE to a greater extent can reduce the pulmonary blood pressure, perfusion defects according to lung scintigraphy, as well as the need for therapy intensification. However, the heterogeneity of studies and the small number of participants require caution when interpreting their results.Conclusion. TLT in patients with PE and stable hemodynamics tends to reduce mortality and/or recurrence of PE, but increases the incidence of major bleeding. Further studies need to determine the phenotypes of hemodynamically stable patients with PE who would benefit from TLT.

Background: Intermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia. Objective: This study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer. Method: This trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8-12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes. Results: Sixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (<80% reduction of the initial values) 6 months after the end of enzalutamide treatment. The most frequent adverse events were hypertension, asthenia, and gynecomastia. There were no significant changes in bone density, body mass index (BMI), or patient-reported outcomes (PROs). Conclusion: Enzalutamide monotherapy is very effective along with hEBRT in reducing PSA levels for patients with intermediate-risk prostate cancer. Longer follow-up is needed to confirm the potential use of this combination in future randomized trials. [ABSTRACT FROM AUTHOR]

The intermediate-risk category of papillary thyroid cancer (PTC) comprises heterogeneous patients within a wide range of stages and varied care management. Understanding the risk features of recurrence observed after the initial therapy should be emphasized. We aimed to evaluate the prognostic significance of radioactive iodine-avid lymph nodes observed during the initial treatment of patients with PTC that were considered to be at intermediate risk. Data on patients with intermediate-risk PTC treated from 2012 to 2018 were retrospectively reviewed. Post-therapeutic SPECT/CT (Rx SPECT/CT) was evaluated in the enrolled patients. The clinical, pathologic, and incidence of radioiodine-avid (RAI-avid) lymph node metastasis (mLN) on Rx SPECT/CT were reviewed, and risk factors related to recurrent disease were analyzed. After a median follow-up of 37.26 (30.90, 46.33) months, structural persistent/recurrent disease was detected in 9.81% (36/367) of patients with intermediate-risk tumors. The incidence of recurrence was higher in patients who demonstrated RAI-avid mLN after the initial therapy than in those who did not (p < 0.001). In a multivariate Cox proportional hazard regression analysis, RAI-avid mLN appeared to be a robust risk factor for recurrent disease after the initial therapy (HR: 8.967, 95% CI: 3.433–23.421, p = 0.000). RAI-avid mLN is a significant risk factor for recurrent intermediate-risk PTC after the initial treatment. [ABSTRACT FROM AUTHOR]

Accurate estimation of risk with both imaging and biochemical parameters in intermediate risk pulmonary embolism (PE) remains challenging. The aim of the study was to evaluate echocardiographic parameters that reflect right and left heart hemodynamic as predictors of adverse events in intermediate risk PE. This was a retrospective observational study on patients with computed tomography pulmonary angiography diagnosis of PE admitted at Cardiology department of the Clinical Emergency Hospital of Oradea, Romania between January 2018—December 2021. Echocardiographic parameters obtained at admission were studied as predictors of in hospital adverse events. The following adverse outcomes were registered: death, resuscitated cardiac arrest, hemodynamic deterioration and need of rescue thrombolysis. An adverse outcome was present in 50 patients (12.62%). PE related death was registered in 17 patients (4.3%), resuscitated cardiac arrest occurred in 6 patients (1.51%). Another 20 patients (5.05%) required escalation of therapy with thrombolysis and 7 (1.76%) patients developed haemodynamic instability. Echocardiographic independent predictors for in hospital adverse outcome were RV/LV ≥ 1 (HR = 3.599, 95% CI 1.378–9.400, p = 0.009) and VTI ≤ 15 mm (HR = 11.711, 95% CI 4.336–31.633, p < 0.001). The receiver operator curve renders an area under curve for LVOT VTI ≤ 15 mm of 0.792 (95% CI 0.719–0.864, p < 0.001) and for a RV/LV ≥ 1 of 0.746 (95% CI 0.671–0.821, p < 0.001). A combined criterion (LVOT VTI ≤ 15 and RV/LV ≥ 1) showed a positive predictive value of 75% and a negative predictive value of 95% regarding in hospital adverse outcomes. Low LVOT VTI and increased RV/LV are useful for identifying normotensive patients with PE at risk for short term adverse outcomes. Combining an LVOT VTI ≤ 15 cm with a RV/LV ≥ 1 can identify with increased accuracy PE patients with impending risk of clinical deterioration. [ABSTRACT FROM AUTHOR]

BackgroundIntermediate-risk prostate cancer (PCa) is usually treated by a combination of external beam radiation therapy (EBRT) and a short course of androgen deprivation therapy (ADT). ADT is associated with multiple side effects, including weight gain, loss of libido, and hot flashes. In contrast, anti-androgen monotherapy is generally better tolerated in spite of higher rates of gynecomastia.ObjectiveThis study assessed the effectiveness of enzalutamide monotherapy combined with hypofractionated EBRT (Hypo-EBRT) for treating intermediate risk prostate cancer.MethodThis trial was a multicenter, open-label phase II study of 6 months of enzalutamide monotherapy combined with Hypo-EBRT for intermediate-risk prostate cancer. Hypo-EBRT was initiated 8–12 weeks after initiating enzalutamide. The primary endpoint was PSA decline >80% measured at the 25th week of enzalutamide administration. Secondary end-points included assessment of toxicity, changes in anthropomorphic body measurements, sexual hormones, and metabolic changes.ResultsSixty-two patients were included in the study from January 2018 to February 2020. A PSA decline of >80% was observed in all evaluable patients at the end of enzalutamide treatment and 92% achieved PSA values under 0.1 ngr/ml. All patients remain in PSA response (

Aim: To assess sorafenib survival outcomes in renal cell carcinoma patients using standard International Metastatic Renal Cell Carcinoma Data Consortium (IMDC) risk criteria. Patients & methods: The authors restratified a real-world cohort of 3255 advanced renal cell carcinoma patients, obtained from Japanese sorafenib postmarketing surveillance, to assess survival outcomes using IMDC criteria; intermediate risk was subdivided into intermediate 1 (Int-1) and imterdemiate 2 (Int-2; one and two risk factors, respectively). Results: Overall, 2225 (68%) IMDC-evaluable patients were reclassified as favorable (17%), intermediate (62%) and poor (21%) risk, with median progression-free survival of 10.4, 8.1 and 3.4 months, respectively. Int-1 (36%) and Int-2 (26%) subgroups had median progression-free survival of 10.1 and 6.0 months, respectively. Sorafenib had acceptable safety/tolerability. Conclusion: Sorafenib effectiveness was promising for IMDC intermediate risk, particularly Int-1, warranting further investigation. [ABSTRACT FROM AUTHOR]

Background: We compared the oncological outcomes of patients who received seed brachytherapy (SEED-BT) with those who received radical prostatectomy (RP) for intermediate-risk prostate cancer.Methods: Candidates were patients treated with either SEED-BT (n = 933) or RP (n = 334). One-to-one propensity score matching was performed to adjust the patients' backgrounds. We compared the biochemical recurrence (BCR)-free rate using the Phoenix definition (prostate-specific antigen [PSA] nadir plus 2 ng/mL) for SEED-BT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free rates using the same PSA cut-off value of 0.2 ng/mL for both SEED-BT and RP.Results: In the propensity score-matched analysis with 214 pairs, the median follow-up treatment was 96 months (range 1-158 months). Fifty-three patients (24.7%) were treated with combined SEED-BT and external-beam radiotherapy. Forty-three patients (20.0%) received salvage radiotherapy after RP. Comparing the BCR-free rate using the above definitions for SEED-BT and RP showed that SEED-BT yielded a significantly better 8-year BCR-free rate than did RP (87.4% vs. 74.3%, hazard ratio [HR] 0.420, 95% confidence interval [CI] 0.273-0.647). Comparing the 8-year BCR-free rate using the surgical definition for both treatments showed no significant difference between the two treatments (76.7% vs. 74.3%, HR 0.913, 95% CI 0.621-1.341). SEED-BT had a significantly better 8-year salvage hormonal therapy-free rate than did RP (92.0% vs. 85.6%, HR 0.528, 95% CI 0.296-0.942, P = 0.030). The 8-year metastasis-free survival rates (98.5% vs. 99.0%, HR 1.382, 95% CI 0.313-6.083, P = 0.668) and overall survival rates (91.9% vs. 94.6%, HR 1.353, 95% CI 0.690-2.650) did not significantly differ between the treatments.Conclusions: The BCR-free rates did not significantly differ between patients treated with SEED-BT and those treated with RP for intermediate-risk prostate cancer even when they were directly compared using the surgical definition for BCR. SEED-BT and RP can be adequately compared for oncological outcomes. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid malignancy that tends to metastasize to cervical lymph nodes. In the present study, we aimed to investigate which clinicopathologic and ultrasound features of PTC are associated with clinical lymph node metastasis (LNM) and numbers of pathological LNM.Methods: From January 2016 to December 2018, we identified a cohort of patients with PTC who underwent cervical ultrasonography and were diagnosed through operation and pathology. Clinical N1(cN1) and > 5 pathologic N1(pN1) were considered in the postoperative stratification to have an intermediate risk according to the 2015 ATA guidelines. Clinicopathological and ultrasound features in PTC patients were performed in accordance with the independent risk factors of cN1 and > 5pN1 respectively by using the univariate and multivariate analyses.Results: We collected 748 PTC patients in the final inclusion criteria. There were 688 cN0 cases and 60 cN1 cases. From the analyses, primary tumor size > 2 cm, capsule contact, extrathyroidal extensions (ETE) and central LNM remained independent risk factors for cN1 in PTC patients. In the 748 PTC patients, 707 cases had ≤ 5 pN1, and 41 cases had > 5 pN1. Multifocality, primary tumor size > 2 cm, capsule contact and ETE are significant independent risk factors for > 5 pN1.Conclusions: We concluded that multifocality, primary tumor size > 2 cm, capsule contact, ETE and central LNM were independent risk factors for the intermediate risk stratification in patients with PTC. Ultrasonography is a good technique for the preoperative lymph node staging of PTC and is helpful for detecting LNM. [ABSTRACT FROM AUTHOR]

Abstract Background Benefit of thrombolytic therapy in patients with massive pulmonary embolism (PE) is evident. However, evidence supporting benefit in clinical outcomes of this approach in intermediate risk PE is lacking. Objective To determine the impact of thrombolysis on overall survival in intermediate risk PE patients. Methods We searched in MEDLINE (OVID), EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from present day. We also searched in other databases and unpublished literature. We included clinical trials without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. The primary outcome was overall survival. Secondary outcomes were adverse events, including major bleeding, and all‐cause mortality. The measure of the effect was the risk ratio with a 95% confidence interval (CI). Results We included 11 studies in the qualitative and quantitative analysis, with a total of 1855 patients. Risk of bias was variable among the study items. There were no results reported about overall survival in any of the studies. The risk ratio (RR) for all‐cause mortality was 0.68 95% CI (0.40 to 1.16). The RR of overall bleeding, major bleeding and stroke were 2.72 95% CI (1.58 to 4.69), 2.17 95% CI (1.03 to 4.55), and 2.22 95% CI (0.17 to 28.73), respectively. Additionally, the RR for recurrent PE was 0.56 95% CI (0.23 to 1.37). Conclusions In patients with intermediate risk PE, the risk of bleeding is higher when thrombolysis is used. There was no significant difference between thrombolysis and anticoagulation in recurrence of PE, stroke, and all‐cause mortality.