Briganti’s 2012 nomogram is an independent predictor of prostate cancer progression in EAU intermediate-risk class:results from 527 patients treated with robotic surgery

The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060;95% CI: 1.021–1.100;P = 0.002);moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052;95% CI: 1.298–3.243;P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.

Navigating the evolving diagnostic and therapeutic landscape of low-and intermediate-risk prostate cancer

In this nonsystematic review of the literature,we explored the changing landscape of detection and treatment of low-and intermediate-risk prostate cancer(PCa).Through emphasizing improved cancer assessment with histology classification and genomics,we investigated key developments in PCa detection and risk stratification.The pivotal role of prostate magnetic resonance imaging(MRI)in the novel diagnostic pathway is examined,alongside the benefits and drawbacks of MRI-targeted biopsies for detection and tumor characterization.We also delved into treatment options,particularly active surveillance for intermediate-risk PCa.Outcomes are compared between intermediate-and low-risk patients,offering insights into tailored management.Surgical techniques,including Retzius-sparing surgery,precision prostatectomy,and partial prostatectomy for anterior cancer,are appraised.Each technique has the potential to enhance outcomes and minimize complications.Advancements in technology and radiobiology,including computed tomography(CT)/MRI imaging and positron emission tomography(PET)fusion,allow for precise dose adjustment and daily target monitoring with imaging-guided radiotherapy,opening new ways of tailoring patients’treatments.Finally,experimental therapeutic approaches such as focal therapy open new treatment frontiers,although they create new needs in tumor identification and tracking during and after the procedure.

The role of endogenous testosterone in relationship with low-and intermediate-risk prostate cancer:a systematic review

An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer);that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes;(2) association between endogenous testosterone density and the tumor load;and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature’s results.

Treatment of intermediate-risk prostate cancer with active surveillance in the routine care—Long-term outcomes of a prospective noninterventional study(HAROW)

Background:We report here the long-term outcomes of patients with intermediate-risk prostate cancer(PCa)treated with active surveillance(AS)in a daily routine setting.Material andmethods:HAROW(2008–2013)was a noninterventional,health service research study investigating themanagement of localized PCa in a community setting.A substantial proportion of the study centers were office-based urologists.A follow-up examination of all intermediate-risk patients with AS was conducted.Overall,cancer-specific,metastasis-free,and treatment-free survival rates,as well as reasons for discontinuation,were determined and discussed.Results:Of the 2957 patients enrolled,52 with intermediate-risk PCa were managed with AS and were available for evaluation.The median follow-up was 6.8 years(interquartile range,3.4–8.6 years).Seven patients(13.5%)died of causes unrelated to PCa,of whom 4 were under AS or under watchful waiting.Two patients(3.8%)developed metastasis.The estimated 8-year overall,cancer-specific,metastasis-free,and treatment-free survival rates were 85%(95%confidence interval[CI],72%–96%),100%,93%(95%CI,82%–100%),and 31%(95%CI,17%–45%),respectively.Onmultivariable analysis,prostate-specific antigen density of≥0.2 ng/mL2 was significantly predictive of receiving invasive treatment(hazard ratio,3.29;p=0.006).Reasons for discontinuation were more often due to patient's or physician's concerns(36%)than due to observed clinical progression.Conclusions:Although survival outcome data for intermediate-risk patients managed with AS in real-life health care conditions were promising,rates of discontinuation were high,and discontinuation was often a patient's decision,even when the signs of disease progression were absent.This might be an indication of higher levels of mental burden and anxiety in this specific subgroup of patients,which should be considered when making treatment decisions.From a psychological perspective,not all intermediate-risk patients are optimal candidates for AS.

Genomics-based Approach and Prognostic Stratification Significance of Gene Mutations in Intermediate-risk Acute Myeloid Leukemia

Objective： Intermediate-risk acute myeloid leukemia （IR-AML）, which accounts for a substantial number of AML cases, is highly heterogeneous. We systematically summarize the latest research progress on the significance ofgene mutations for prognostic stratification of IR-AML. Data Sources： We conducted a systemic search from the PubMed database up to October, 2014 using various search terms and their combinations including IR-AML, gene mutations, mutational analysis, prognosis, risk stratification, next generation sequencing （NGS）. Study Selection： Clinical or basic research articles on NGS and the prognosis of gene mutations in 1R-AML were included. Results： The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis, and some of them have been used for prognostic risk stratification. Several studies have consistently identified that some gene mutations have prognostic relevance, however, there are still many controversies for some genes because of lacking sufficient evidence. In addition, tumor cells harbor hundreds of mutated genes and multiple mutations often coexist, therefore, single mutational analysis is not sufficient to make accurate prognostic predictions. The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years. Conclusions： NGS represents a pioneering and helpful approach to prognostic risk stratification of 1R-AML patients. Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.

Outcomes of intermediate-risk to high-risk stage I endometrial cancer: 10-year clinical experiences of using in-house multi-channel applicators in a single center

Background: There are only very few reports on clinical outcomes using multi-channel applicators (MCA) for patients with endometrial cancer (EC) in China. We aimed to evaluate the clinical experience of treating intermediate-risk (IR) to high-risk (HR) stage I EC using in-house made multi-channel applicators (IH-MCA) in a single institution. Methods: Three hundred and ninety patients with stage I IR to HR EC were treated with hysterectomy and adjuvant radiotherapy from 2003 to 2015. All patients received post-operative vaginal cuff brachytherapy (VBT) alone or as a boost after external beam radiotherapy (EBRT). The prescriptions were 500 cGy per fraction for a total of 5 to 6 fractions with brachytherapy alone or 400 to 600 cGy per fraction for 2 to 3 fractions if it was combined with EBRT. Two types of applicators including a traditional rigid IH-MCA and a recent model custom-made with 3 dimension printing technology were used for treatment. The Kaplan-Meier method was used to calculate survival rate. Results: Follow-up rate was 92.8% and the median follow-up time was 48 months (range 4–172 months). The 5-year overall survival (OS), progression-free survival, local recurrence, and distant metastasis rates for all patients were 96.3%, 92.1%, 2.9%, and 4.8% respectively. Two patients had isolated relapse in vagina outside the irradiated volume. The univariate and multivariate analysis showed that age and grade were the prognostic factors correlated with OS (hazard ratio: 0.368, 95% confidence interval [CI]: 0.131–1.035, P = 0.048;hazard ratio: 0.576, 95% CI: 0.347–0.958, P = 0.026,). Conclusions: For patients with IR to HR stage I EC, adjuvant VBT alone or in combination with EBRT using IH-MCA led to excellent survival and recurrence rates. Age and grade were the prognostic factors correlated with OS.

Association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism

Objective To investigate the association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism. Methods We retrospectively recruited 110 intermediate-risk acute pulmonary embolism patients ( right ventricular dysfunction was confirmed by echocardiography and CT scan with or without the elevated levels of cardiac injuiy biomarkers) in the first and the second affiliated hospital of Harbin medical university from January 1 , 2011 to December 31 , 2014. The patients aged 58. 4 ± 14. 9 years old.

Adjuvant chemotherapy for early-stage cervical cancer

The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery （RS） has not yet been established, and radiation therapy （RT） or concurrent chemoradiotherapy （CCRT） is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life （QOL） or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival （OS） with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin （TP） regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group （GOG）, had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial （RCT） of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable condition, it is necessary that the therapeutic strategies should be improved with considering adverse events and QOL for long-term survivors.

Image-Guided Radiotherapy Dose Escalation in Intermediate and High Risk Cancer Prostate Patients and Its Effect on Treatment Toxicity

Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.