Effect Of Treatment Delay Research Articles

Delayed definitive management of localized prostate cancer: what do we know?

Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.

The effect of treatment delay on quality of life and overall survival in head and neck cancer patients.

ObjectiveHead and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health‐related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival.MethodsPatients with mucosal HNSCC were prospectively included. HRQOL and 2‐year overall survival were analysed using linear mixed‐model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation.ResultsMedian CPI was 39 days for the 173 patients included. A trend towards higher HRQOL‐scores (indicating better HRQOL) during 2‐year follow‐up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score—β: 2.62, 95% CI: 0.57–4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65–15.76, p = 0.005) and stage‐IV tumours (HR: 12.37, 95% CI: 2.81–54.39, p = 0.001). Delay was not associated with worse overall survival.ConclusionTimely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL‐scores or decreased overall survival during 2‐year follow‐up.

Patients’ views of delayed fertility care during the COVID-19 pandemic as a conception catastrophe: the experience of U.S. FertilityIQ users

Background Assessment of psychological reactions to delays in fertility treatment have often utilized single clinic samples during the time that fertility treatments were paused. We, therefore, assessed emotional reactions to treatment cancelations due to COVID-19 in infertility patients across the United States after treatments had begun to resume. Study design Cross-sectional survey emailed on 27 May 2020 and closed on 30 June 2020, to 53,600 FertilityIQ.com website users inquiring about their experience since the COVID-19 pandemic. A subset of FertilityIQ users (n = 13,490) opened the survey invitation and 1806 respondents participated in the survey (13.4% response rate). Results The majority of respondents (female, 67.4%; male, 61.7%) were 31-40 years old; most were planning to start treatment immediately (women, 42.6%; men, 44.7%) or were undergoing treatment (women, 34.9%; men, 29.8%) at the time of treatment cancelation. Patients (women, 21.1%; men 19.1%) or clinics (women, 57.7%; men, 40.4%) canceled treatment. Most clinics had resumed treatment at the time of the study (women, 90.0%; men, 73.7%). Cancelation resulted in sadness (women, 83.9%; men 86.7%) and anger (women, 45.4%; men, 36.7%); greater than half of the participants whose treatment was canceled (women: 66.8%, n = 630; men: 73.7%, n = 14) agreed with cancelations. Greater than 70% of respondents were at least somewhat concerned about reproductive chances (women, 84.7%; men, 72.4%) and exclusion of partners (women, 73.3%; men, 72.4%). Distress/concern was associated with clinic cancelation, disagreement with delays, age, diagnosis, and concern about delays and pregnancy chances (p <.05). Conclusions Respondents were distressed/concerned about the effect of the pandemic on their fertility. Distress was highest in women with a poorer fertility prognosis, no control over treatment cancelation, and high concern about the effect of treatment delay on pregnancy chances. Emotional support, education regarding treatment delay and fertility, and efforts where possible, to include patients in decisions to delay treatment are warranted in future treatment delays.

Management of Oblique Root Fracture Using Mineral Trioxide Aggregate: A Case Report

Management of Oblique Root Fracture Using Mineral Trioxide Aggregate: A Case Report

Association between Delay to Radical Prostatectomy and Clinically Meaningful Outcomes among Patients with Intermediate and High-Risk Localized Prostate Cancer.

There are limited data regarding the effect of treatment delays on important long-term outcomes among men with intermediate/high-risk prostate cancer (PC). We identified 3,962 men with intermediate/high-risk disease from the SEARCH cohort treated with radical prostatectomy (RP) from 1988 to 2018. Cox proportional hazard models assessed the association between time from biopsy to RP (up to 1 year) and time to castration-resistant PC (CRPC), metastasis and all-cause mortality. Interaction terms were used to test for effect modification by risk group. Of the 3,962 men, 167 developed CRPC, 248 developed metastases and 884 died after a median followup of 85 months. Longer delays between biopsy and RP were associated with a decreased risk of CRPC (adjusted HR=0.88, 95% CI: 0.80-0.98, p=0.02), independent of D'Amico risk group (interaction p >0.05). In men with intermediate and high-risk disease, we found no statistically significant association between length of time to RP and risk of developing metastases (p=0.5 and 0.9, respectively) or all-cause mortality (p=0.1 and 0.1, respectively). Among men with intermediate and high-risk PC, we found no statistically significant increased risk of adverse long-term outcomes, including CRPC, metastasis and death, for men who had treatment delays up to 1 year following PC diagnosis.

Lung cancer mortality due to delayed treatment: Literature review

Lung cancer is still leading in the structure of cancer incidence and mortality worldwide. Delay in appropriate treatment increases the probability of death from this disease.&#x0D; Purpose: to study foreign scientific publications of recent years on the mortality from lung cancer due to delayed treatment.&#x0D; Results: The analysis of global literature for 2010-2020 shows that any delay in lung cancer treatment after establishing the diagnosis reduces the survival rates. Recent studies provide a qualitative assessment of the effect of delay in treatment on cancer mortality for prioritization and modeling. The indications for surgery, systemic treatment, and radiation therapy in seven types of cancer, including lung cancer, evidence a significant association between delay in treatment and increased mortality.&#x0D; The researchers believe that early diagnostics increase the treatment efficacy.&#x0D; Conclusion: Analyzing the barriers to timely treatment for lung cancer can help clarify and assess the impact of delayed treatment on survival. Policies designed to minimize delays in treatment can improve survival outcomes.

Factors associated with length of stay and treatment outcome of Ebola patients treated at an Ebola treatment center in Sierra Leone during the peak period of the West African Ebola outbreak 2013\u20132016

BackgroundThe World Health Organization (WHO) declared the West Africa Ebola epidemic as a Public Health Emergency of International Concern in August 2014. During the outbreak period, there were calls for the affected countries to construct Ebola treatment centres and reliable diagnostic laboratories closer to areas of transmission in order to improve the quality care of Ebola Virus Disease (EVD) patients. Delay in seeking treatment has been reported to have led to poor treatment outcome of EVD patients. Sierra Leone recorded more than 8000 probable and confirmed cases and more than 4000 EVD -related deaths nation-wide.MethodsIn this retrospective study, we investigated the effects of treatment delay, length of symptomatic period, EVD patients’ sex, age, occupation, region of residence, and clinical characteristics on the treatment outcome of 205 laboratory-confirmed EVD patients who were admitted at the Kenema Government Hospital Ebola Treatment Center (KGHETC) from 13/09/2014–26/11/2014; i.e. during the peak of 2013–2016 EVD outbreak in Sierra Leone. Specifically also, we determined the factors that were associated with the length of stay for EVD treatment for patients who were discharged alive.ResultsMajority (66.3%, n = 205/309) of the 309 suspected EVD patients with medical records at the KGHETC triage during the period under review were tested positive for EVD using reverse-transcriptase-polymerase chain reaction (RT-PCR) and had a definitive treatment outcome. Few (33.7%, n = 104/309) suspected EVD patients were not included in our analysis and were classified thus: 29.1% (n = 90/309) suspect EVD cases with negative RT-PCR results, 4.5% (n = 14/309) suspect cases with non-available RT-PCR result.Of the 205 patients, 99 (48.3%) had a fatal outcome. For EVD patients that survived, we recorded a significant association (− 0.06, 95% Confidence Interval (CI) = − 0.14 – - 0.02, p = 0.004) between the Length of Stay (LOS) and for each kilometer travelled to seek treatment at the KGHETC. However, the association between EVD patients that were low skilled workers (− 5.91, 95% CI = − 24.60 – 12.79, p = 0.73), EVD patients who were children and pupils in junior school (− 0.86, 95% CI = − 12.86 – 11.14, p = 0.73), health seeking delay for EVD patients who resided in Kenema District where the KGHETC was located (− 0.49, 95% CI = − 0.12 – 1.09, p = 0.24), sex (− 1.77, 95% CI = − 8.75 – 5.21, p = 0.50), age (0.21, 95% CI = − 0.36 – 0.77, p = 0.57), referral status (1.21, 95% CI = − 17.67 – 20.09, p = 0.89) and the LOS in surviving patients were not statistically significant.ConclusionThe high LOS for either treatment outcome for EVD patients that resided in the district in which the EVD treatment facility was located compared to those patients from other districts implies that health authorities should consider intensive health education with high priority given to seeking early EVD treatment, and the construction of strategic ETCs as important components in their response strategy.

The effect of 5-azacytidine treatment delays and dose reductions on the prognosis of patients with myelodysplastic syndrome: how to optimize treatment results and outcomes.

The regimen of 5-azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5-azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5-azacytidine initiation, OST ) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P=0·033] or pre-existing neutropenia (HR, 1·42; P=0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P=0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response.

Mycobacterium Tuberculosis Blood Stream Infection Prevalence, Diagnosis, and Mortality Hazard in HIV-Positive Adults: A Systematic Review and Meta-Analysis of Individual Patient Data

Background: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis blood stream infection (MTB-BSI) is incompletely understood. We hypothesised that MTB-BSI prevalence has been underestimated, that MTB-BSI independently predicts death, and sputum Xpert has suboptimal diagnostic yield for MTB-BSI. Methods: We conducted a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood-culture (TBBC), including HIV-positive adults aged ≥13-years with suspected tuberculosis. Predicted probabilities of MTB-BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum (Xpert or culture if Xpert unavailable) and urinelipoarabinomannan for MTB-BSI were obtained by two-level random-effect meta-analysis, mortality hazard of MTB-BSI by mixed-effect Cox proportional-hazard modelling, and effect of treatment delay with propensity-score analysis. Findings 5751 patients met inclusion criteria. Predicted probability of MTB-BSI was 45% (95%CI 38-52%) for danger-sign positive tuberculosis inpatients with cohort median CD4 count of 76 cells/μL. Diagnostic yield of sputum was 77% (95%CI 63–87%), rising to 89% (95%CI 80-94%) when combined with urinelipoarabinomannan testing. MTB-BSI increased hazard of death before 30-days (aHR2·5, 95%CI 2·1–3·1). In a propensity-score matched cohort (n=630), mortality increased with treatment delay >4 days in MTB-BSI (OR 3·2, 95%CI 1·1–10·3). Interpretation: In critically-ill adults with HIV-tuberculosis, MTB-BSI is a very frequent manifestation of tuberculosis and strongly predicts mortality. Better diagnostic yield in patients with MTB-BSI can be achieved by parallel use of sputum-Xpert and urine-LAM. Treatment delay may increase mortality hazard. Funding Statement: This study was supported by Wellcome fellowships 109105z/15/a, 105165/Z14/A. Charlotte Schutz was funded by the South African Medical Research Council under the National Health Scholars Programme. Moshi, Tanzania research was supported by an International Studies on AIDS Associated Co-infections (ISAAC) award, a program funded by the US National Institutes of Health (NIH) (U01 AI062563). John A. Crump receives support from US NIH R01AI121378. Elizabeth L. Corbett is supported by a Wellcome trust senior fellowship in clinical science (WT200901). Gary Maartens was supported in part by National Research Fund incentive funding (UID: 85810). Susan E. Dorman was supported by contract #HHSN2722000900050C and grant K24AI104830 (to SED), both from the US National Institutes of Health. Douglas Wilson was supported by BMS Secure the Future. Graeme Meintjes was supported by the Wellcome Trust (098316 and 203135/Z/16/Z), the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787), NRF incentive funding (UID: 85858) and the South African Medical Research Council through its TB and HIV Collaborating Centres Programme with funds received from the National Department of Health (RFA# SAMRC-RFA-CC: TB/HIV/AIDS-01-2014). Declaration of Interests: David Alland is on the Scientific Advisory Board of Specific Technologies and receives a portion of the licensing income paid by Cepheid to Rutgers University for sales of the Xpert Ultra assay. Neil Martinson has received institutional grants for collection of specimens for Roche and Becton Dickinson, and from Pfizer for assessing incident pneumonia. All other authors declare no competing interests. Ethics Approval Statement: PROSPERO registration: CRD42016050022.

Effect of Surgery Type on Time to Adjuvant Chemotherapy and Impact of Delay on Breast Cancer Survival: A National Cancer Database Analysis

Timeliness of care is emerging as a quality indicator for breast cancer care. We sought to evaluate the impact of surgical treatment type on time to adjuvant chemotherapy and impact of treatment delay on survival. Patients with stage I-III breast cancer treated with both surgery and adjuvant chemotherapy from 2010 to 2014 were identified from the National Cancer Database (NCDB). Delay in treatment was defined as > 120days from diagnosis to chemotherapy. Multivariable analysis was performed to assess factors associated with delay in treatment and the effect of treatment delay on overall survival. Of 172,043 patients identified, 89.5% initiated chemotherapy within 120days of diagnosis. Median time from diagnosis to surgery was shorter in patients undergoing breast conservation (25days) than mastectomy (29days, p < 0.001) and within mastectomy patients was shorter for mastectomy without reconstruction (26 versus 35days, p < 0.001). Time from diagnosis to surgery showed larger differences between surgical groups than time from surgery to chemotherapy. On multivariable analysis of mastectomy patients, reconstruction remained significantly associated with delay to chemotherapy [odds ratio (OR) 1.7, p < 0.001]. For all patients regardless of type of surgery, after adjusting for patient, clinical, and treatment factors, delay of > 120days from diagnosis to chemotherapy was associated with worse overall survival [hazard ratio (HR) 1.29, p < 0.001]. Initiation of chemotherapy greater than 120days after diagnosis was associated with poorer overall survival. Time interval from diagnosis to surgery had the greatest impact on time from diagnosis to chemotherapy, with reconstruction resulting in the greatest delay.

The Effect of Treatment Delay on Infection in Open Tibia Fractures: A Retrospective Study in Ethiopia

AIM: Assess the effect of delay in treatment greater than 24 hours on the development of infection for open tibia fractures. MATERIALS & METHODS: A retrospective review of all patients was conducted to identify skeletally mature patients with an open tibia fracture treated with the Surgical Implant Generation Network (SIGN) intramedullary nail from February 2006 and June 2015. Descriptive data, time to treatment, fracture characteristics, and presence of infection were collected and analyzed. RESULTS: Infection occurred in 19 (11%) patients (Gustilo I 1/44, 2%; Gustilo II 6/39, 15%, Gustilo IIIa 9/44, 21%; Gustillo IIIb 3/44, 7%). One hundred forty-four patients were treated within 24 hours from injury (mean, 8.2 hours) and 28 were treated after 24 hours (mean, 41.1 hours). There was no significant difference in the rates of infection for fractures before or after six hours from the time of injury (15% vs. 11%, P = 0.6207). Infection rate was similar in patients treated within 24 hours and beyond 24 hours (10% vs. 14%, P = 0.518). The average time to treatment of patients with and without infectious outcome were not significantly different (15.6 vs 13.4 hours, P = 0.700). There was an association between more severe Gustilo types and infection, yet this did not reach significance (P = 0.402) CONCLUSION: Our results show that initial treatment beyond 24 hours did not lead to a significant increase in the rate of infection. While not significant, a greater proportion of infections occurred in higher Gustilo types. Our results suggest that fracture type rather than time to treatment may be a more important predictor of infection.

The Effect of Treatment Delay on Infection in Open Tibia Fractures: A Retrospective Study in Ethiopia

AIM: Assess the effect of delay in treatment greater than 24 hours on the development of infection for open tibia fractures. MATERIALS &amp; METHODS: A retrospective review of all patients was conducted to identify skeletally mature patients with an open tibia fracture treated with the Surgical Implant Generation Network (SIGN) intramedullary nail from February 2006 and June 2015. Descriptive data, time to treatment, fracture characteristics, and presence of infection were collected and analyzed. RESULTS: Infection occurred in 19 (11%) patients (Gustilo I 1/44, 2%; Gustilo II 6/39, 15%, Gustilo IIIa 9/44, 21%; Gustillo IIIb 3/44, 7%). One hundred forty-four patients were treated within 24 hours from injury (mean, 8.2 hours) and 28 were treated after 24 hours (mean, 41.1 hours). There was no significant difference in the rates of infection for fractures before or after six hours from the time of injury (15% vs. 11%, P = 0.6207). Infection rate was similar in patients treated within 24 hours and beyond 24 hours (10% vs. 14%, P = 0.518). The average time to treatment of patients with and without infectious outcome were not significantly different (15.6 vs 13.4 hours, P = 0.700). There was an association between more severe Gustilo types and infection, yet this did not reach significance (P = 0.402) CONCLUSION: Our results show that initial treatment beyond 24 hours did not lead to a significant increase in the rate of infection. While not significant, a greater proportion of infections occurred in higher Gustilo types. Our results suggest that fracture type rather than time to treatment may be a more important predictor of infection.

Effects of Treatment Delay on Efficacy of Tecovirimat Following Lethal Aerosol Monkeypox Virus Challenge in Cynomolgus Macaques.

BackgroundTecovirimat (ST-246) is being developed as an antiviral therapeutic for smallpox for use in the event of an accidental or intentional release. The last reported case of smallpox was 1978 but the potential for use of variola virus for biowarfare has renewed interest in smallpox antiviral therapeutics.MethodsCynomolgus macaques were challenged with a lethal dose of monkeypox virus (MPXV) by aerosol as a model for human smallpox and treated orally with 10 mg/kg tecovirimat once daily starting up to 8 days following challenge. Monkeys were monitored for survival, lesions, and clinical signs of disease. Samples were collected for measurement of viremia by quantitative real-time polymerase chain reaction, and for white blood cell counts.ResultsSurvival in animals initiating treatment up to 5 days postchallenge was 100%. In animals treated starting 6, 7, or 8 days following challenge, survival was 67%, 100%, and 50%, respectively. Treatment initiation up to 4 days following challenge reduced severity of clinical manifestations of infection.ConclusionsTecovirimat treatment initiated up to 8 days following a lethal aerosol MPXV challenge improves survival and, when initiated earlier than 5 days after challenge, provides protection from clinical effects of disease, supporting the conclusion that it is a promising smallpox antiviral therapeutic candidate.

The effect of treatment delay on survival in patients with hepatocellular cancer.

e15645 Background: Hepatocellular cancer (HCC) is the fastest increasing cause of cancer related death in the U.S. Only one-third of patients are candidates for curative treatment, and treatment delays occur in 30% of patients. Data on the effect of treatment delays on HCC survival outcomes are limited to small single center studies. The aim of this study was to identify predictors of treatment delays and the impact of treatment delay on survival. Methods: We conducted a retrospective study using a national cohort of patients from the Department of Veterans Affairs who were diagnosed with HCC from October 1, 2004 to September 30, 2011. Demographics, clinical factors, treatment and death were ascertained from the medical records. Treatment delay was defined as greater than 60 days between HCC diagnosis and first treatment. Treatment was categorized as curative (surgery or ablation), liver-directed therapy, or chemotherapy. Cox Proportional Hazard models were used to examine the effect of treatment delay on survival stratified by stage (BCLC 0 and A, B, or C). Results: Among 742 patients with HCC, 223 (30%) had a treatment delay. The majority of patients were Barcelona Stage C (43%), and 131 patients (17.7%) had metastatic disease. On univariate analysis, patients with treatment delay were more likely to have tumor board discussion, single tumors, and PTSD (p &lt; 0.05). Treatment delay was not associated with increased risk of death for patients with BCLC stage 0 and A (HR 0.74 [0.48-1.14]) or BCLC stage B (HR 0.83 [0.61-1.14]). For BCLC stage C, treatment delay was associated with a 50% decrease in risk of death (HR 0.50 [0.37-0.67]), adjusting for demographics, clinical factors, stage, and treatment. Patients with BCLC stage C HCC and treatment delay were more likely to have curative intent therapy (32.9% vs 16.3%) or liver directed therapy (43.4% vs 36.3%, p = 0.0006) than those with no delay. Conclusions: Treatment delays occurred in 30% of patients. Treatment delay was not associated with increased risk of death for earlier stage HCC, but treatment delay was associated with decreased risk of death for patients with BCLC stage C. This finding may be due to delays from coordination of curative and liver directed therapy that may result in improved survival.

Prostate cancer outcomes and delays in care.

To examine the survival effect of treatment delays from the time of confirmed diagnosis of prostate cancer to first treatment in an Australian population. Three thousand one hundred and forty patients were identified from the South Australian Prostate Cancer Clinical Outcomes Collaborative database for analysis. Selected patients had dates recorded for both diagnosis and treatment. We examined the effect of treatment delay (the time from diagnosis to date of first treatment) on survival using Cox and competing risks regression and compared quartiles of delay across the cohort. Adjustment was made for age, PSA levels, treatment modality and Gleason score. Outcomes included overall survival (OS) and prostate cancer-specific mortality (PCSM). Quartiles of delay were as follows (days)-Q1: 35, Q2: 86, Q3: 138.0, Q4: 264. Shorter delays were associated with hormonal treatment, high Gleason score and high PSA values. Measuring PCSM with Q2 as reference, age-adjusted associations were-Q1: sHR 4.37 (2.75-6.94), Q3: sHR 1.29 (0.73-2.28), Q4: sHR 1.55 (0.91-2.63). After additional adjustment for treatment type, Gleason score and PSA, Q1 remained at increased risk [sHR 2.46 (1.10-5.54)]. A similar trend was observed for OS. In analysis stratified by Gleason score, delays were not significantly associated with OS. Factors associated with shorter delay in treatment include high Gleason score, high PSA and hormonal treatment. After adjustment for these variables, increased delays were not associated with OS or PCSM in this cohort. The nonlinear association of delay with risk may explain conflicting reports in the literature.

Evaluating the effect of time from prostate cancer diagnosis to radical prostatectomy on cancer control: Can surgery be postponed safely?

ObjectiveTo test the prognostic role of treatment delay in patients affected by prostate cancer (PCa). Materials and methodsThe study included 2,653 patients treated with radical prostatectomy (RP) at a single institution between 2006 and 2011. The evaluated outcomes were biochemical recurrence (BCR) and clinical recurrence (CR). Multivariable Cox regression analysis was used to test the association between time from diagnosis to RP and oncological outcomes. Nonparametric curve fitting methods were used to graphically explore the relationship between time from diagnosis to RP and oncological outcomes. Sensitivity analyses were repeated in the subgroups of low-, intermediate-, and high-risk patients. ResultsAt median follow-up of 56 months (interquartile range: 26, 92), 283 patients experienced BCR, and 84 patients developed CR. Median time from PCa diagnosis to surgery was 2.8 months (interquartile range: 1.6, 4.7). At multivariable Cox regression analysis, time from biopsy to RP was significantly associated with an increased risk of BCR (hazard ratio = 1.02, P = 0.0005) and CR (hazard ratio = 1.03, P = 0.0002). Using Nonparametric curve fitting methods, a significant increased risk of BCR and CR after approximately 18 months was observed. However, when sensitivity analyses were repeated according to risk groups, this effect was maintained in high-risk patients only, and such time interval was reduced to 12 months. ConclusionsDespite the overall trend on higher rate of cancer relapse after RP, the effect of treatment delay from biopsy to RP was significantly evident in high-risk patients only. Even in high-risk patients surgical treatment can be postponed safely, but not beyond the 12-month landmark.

PD30-06 ASSESSING THE ROLE OF TIME FROM PROSTATE CANCER DIAGNOSIS TO RADICAL PROSTATECTOMY: CAN SURGERY BE POSTPONED SAFELY?

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II1 Apr 2016PD30-06 ASSESSING THE ROLE OF TIME FROM PROSTATE CANCER DIAGNOSIS TO RADICAL PROSTATECTOMY: CAN SURGERY BE POSTPONED SAFELY? Vito Cucchiara, Nicola Fossati, Nazareno Suardi, Andrea Gallina, Armando Stabile, Marta Picozzi, Emanuele Zaffuto, Giorgio Gandaglia, Paolo Dell’Oglio, Alessandro Larcher, Andrea Salonia, Francesco Montorsi, and Alberto Briganti Vito CucchiaraVito Cucchiara More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Nazareno SuardiNazareno Suardi More articles by this author , Andrea GallinaAndrea Gallina More articles by this author , Armando StabileArmando Stabile More articles by this author , Marta PicozziMarta Picozzi More articles by this author , Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Paolo Dell’OglioPaolo Dell’Oglio More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.537AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The impact of time elapsed from prostate cancer (PCa) diagnosis to radical prostatectomy (RP) on cancer control remains controversial. We hypothesized that time from biopsy to surgery is significantly associated with an increased risk of biochemical recurrence (BCR) and clinical recurrence (CR) after RP METHODS The study included 2,767 patients treated with RP between 2000 and 2015. The evaluated outcomes were BCR and CR. Biochemical recurrence was defined as two consecutive PSA values ≥0.2ng/ml. Clinical recurrence was defined as positive imaging during follow-up after the onset of BCR. Multivariable Cox regression analysis was used to test the association between time from biopsy to RP and oncologic outcomes (namely, BCR and CR). Covariates consisted of PSA level at diagnosis, clinical stage (T1 vs. T2 vs. T3), biopsy Gleason score (≤6 vs. 7 vs. ≥8), and percentage of positive cores. Multivariable locally weighted scatter plot smoothing (st-lowess) methods were used to graphically explore the relationship between time from biopsy to RP and oncologic outcomes. Sensitivity analyses were repeated in the sub-group of low-, intermediate-, and high-risk patients, according to D'Amico classification RESULTS At median follow-up of 56 months (inter-quartile range [IQR]: 26, 92), 283 (10%) patients experienced BCR, and 84 (3.0%) patients developed clinical recurrence. Median time from PCa diagnosis to surgery was 2.8 months (1.6, 4.7). At multivariable Cox regression analysis, time from biopsy to RP was significantly associated with an increased risk of BCR (HR: 1.02; 95% CI: 1.01, 1.03; p=0.0005) and CR (HR: 1.03; 95% CI: 1.01, 1.04; p=0.0002), after adjusting for all covariates. Using st-lowess methods, a significant increased risk of BCR and CR after approximately 18 months from biopsy to RP was observed. However, when sensitivity analyses were repeated according to risk-groups, this effect was maintained in high-risk patients only, where such time interval was reduced to 12 months (Figure 1). CONCLUSIONS Despite the overall trend on higher rate of cancer relapse after RP, the effect of treatment delay from biopsy to RP was significantly evident in high-risk patients only. Even in high-risk patients surgical treatment can be postponed safely, but not beyond the 12-month landmark © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e713-e714 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Vito Cucchiara More articles by this author Nicola Fossati More articles by this author Nazareno Suardi More articles by this author Andrea Gallina More articles by this author Armando Stabile More articles by this author Marta Picozzi More articles by this author Emanuele Zaffuto More articles by this author Giorgio Gandaglia More articles by this author Paolo Dell’Oglio More articles by this author Alessandro Larcher More articles by this author Andrea Salonia More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4–6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34–0.78) and reduced death (OR 0.32, 95% CI 0.14–0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

Effect of Treatment Delay, Age, and Stroke Severity on the Effects of Intravenous Thrombolysis with Alteplase for Acute Ischaemic Stroke: A Meta-analysis of Individual Patient Data from Randomized Trials: Emberson J, Lees KR, Lyden P, et al. Lancet 2014;384:1929–35.

Effect of Treatment Delay, Age, and Stroke Severity on the Effects of Intravenous Thrombolysis with Alteplase for Acute Ischaemic Stroke: A Meta-analysis of Individual Patient Data from Randomized Trials: Emberson J, Lees KR, Lyden P, et al. Lancet 2014;384:1929–35.

Pooled RCTs: alteplase within 4.5 hours of ischemic stroke improves the likelihood of good outcome.

Source Citation Emberson J, Lees KR, Lyden P, et al; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Aug 5. Epub ahead of print 25106063