Predictors Of Treatment Failure Research Articles

Incidence and Predictors of Treatment Failure among Adult on First-Line Antiretroviral Therapy in Gullele Sub City, Addis Ababa, Ethiopia 2023: A Retrospective Study in Selected Public Health Facilities

Incidence and Predictors of Treatment Failure among Adult on First-Line Antiretroviral Therapy in Gullele Sub City, Addis Ababa, Ethiopia 2023: A Retrospective Study in Selected Public Health Facilities

Plasma miRNAs and Treatment Failure in Participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

To identify plasma miRNAs related to treatment failure in youth with type 2 diabetes (T2D). We examined whether a panel of miRNAs could predict treatment failure in training/test data sets among participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study (N = 209). We also examined whether individual miRNAs were associated with treatment failure. Participants were age 14.5 years, and 62% were female. A panel of miRNAs did not predict treatment failure. However, for each doubling, miR-4306 was associated with a 12% decrease (P = 0.040) and miR-483-3p was marginally associated with a 12% increase (P = 0.080) in failure independently of sex, race/ethnicity, BMI, Tanner stage, HbA1c, maternal diabetes, oral disposition index, and treatment arm. The addition of both miRNAs improved model fit (log likelihood without vs. with miRNAs -360.3 vs. -363.5; P = 0.040). miR-483-3p and miR-4306 may be associated with treatment failure in youth with T2D.

Red cell distribution width to albumin ratio predicts treatment failure in peritoneal dialysis-associated peritonitis.

This study aims to investigate the potential correlation between baseline red cell distribution width (RDW) to albumin ratio (RAR) levels and treatment failure in peritoneal dialysis-associated peritonitis (PDAP) patients. A retrospective single-center study was conducted on 286 PDAP patients. Logistic regression and generalized estimation equation (GEE) analyses were employed to assess the relationship between RAR and treatment failure. RAR emerged as a robust predictor of treatment failure in PDAP patients. Elevated RAR levels were associated with an increased risk of treatment failure, exhibiting a linear relationship. Even after adjusting for demographic and clinical variables, this association remained statistically significant. ROC analysis revealed that RAR outperformed RDW and albumin individually in predicting PDAP prognosis. This study highlights RAR as a superior prognostic marker for treatment failure in PDAP patients, offering new insights into risk assessment and management strategies for this challenging condition.

Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn’s Disease: A Multicenter Study

Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P= .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Outcome and Predictors of Treatment Failure in Chronic Osteomyelitis Using Bioactive Glass Granules and Putty Formulations.

The aim of this study is to evaluate the outcome of patients with cavitary chronic osteomyelitis undergoing adjuvant treatment with bioactive glass (BAG) S53P4 and identify the independent risk factors (RFs) for recurrence in 6- and 12-month patient follow-up. A retrospective, multicentre observational study conducted in tertiary specialised hospitals among patients undergoing the surgical treatment of chronic cavitary osteomyelitis using BAG-S53P4 in a granule and/or putty formulation to assess the clinical outcome and RFs for failure in 6- and 12-month patient follow-up. Of the 92 and 78 patients with 6-month and 12-month follow-ups, infection was eradicated in 85.9% and 87.2%, respectively. In the 6-month follow-up, BAG-S53P4 in the granule formulation presented a greater risk of recurrence compared to the bioactive glass putty formulation or combined granules and putty (prevalence ratio (PR) = 3.04; confidence interval 95% [CI95%]: 1.13-10.52) and neoplasia (PR = 5.26; CI95%: 1.17-15.52). In the 12-month follow-up cohort of 78 patients, smoking (PR = 4.0; 95% CI: 1.03-15.52) and nonfermenting GNB infection (PR = 3.87; CI95%: 1.09-13.73) presented a greater risk of recurrence. BAG-S53P4 is a viable option for bone-void filling and the treatment of chronic cavitary osteomyelitis. Formulations of BAG with putty or in combination with granules showed better results.

Outcomes and predictors of treatment failure after anti-reflux mucosectomy for management of gastroesophageal reflux disease

BackgroundAnti-reflux mucosectomy is a novel endoscopic treatment for gastroesophageal reflux disease that serves as an intermediate therapy between medical and surgical intervention. We aimed to evaluate outcomes and identify predictors of treatment failure in patients requiring anti-reflux mucosectomy. MethodsA prospective quality database was retrospectively reviewed. Upper endoscopy, pH testing, and functional luminal impedance planimetry were obtained at preop and 1 year post-operation. Quality of life outcomes were assessed by Gastroesophageal Reflux Disease–Health Related Quality of Life, Reflux Symptom Index, and dysphagia scores preoperatively and up to 5 years postoperatively. ResultsFifty-eight patients requiring anti-reflux mucosectomy were analyzed between 2016 and 2023. Preop Gastroesophageal Reflux Disease–Health Related Quality of Life mean scores improved at all time points 3 weeks to 2 years postoperatively (all P < .05). Preop mean Reflux Symptom Index scores also significantly improved at 6-month, 1-year, and 2-year timepoints (all P < .05). Dysphagia at 3 weeks was higher than preop scores (1.2 vs 2.1, P < .01) but returned to baseline. Upon follow-up, 43 patients (74.1%) had symptom improvement off proton pump inhibitors, 29 of whom reported complete symptom resolution. Out of 58 patients, 31 (53.4%) failed treatment due to DeMeester score (n = 22), erosive esophagitis (n = 2), Gastroesophageal Reflux Disease–Health Related Quality of Life ≥13 (n = 4), or <70% symptom resolution in the absence of pH or survey data (n = 3). Current smoking status was predictive of treatment failure (odds ratio 3.52, P < .031). Body mass index, DeMeester score, acid exposure time, and hiatal hernia ≤2 cm were not associated with treatment failure. ConclusionAnti-reflux mucosectomy is associated with significant improvement in quality of life; however, symptom resolution may not correlate with objective reflux control. Smoking is a predictor of treatment failure and should be considered in patient selection.

ABC transporters are predictors of treatment failure in acute myeloid leukaemia

IntroductionTo date, no chemoresistance predictors are included in acute myeloid leukaemia (AML) prognostic scoring systems to distinguish responding and refractory AML patients prior to chemotherapy. ABC transporters have been described as altering AML chemosensitivity; however, a relevant study investigating their role at various molecular levels was lacking. MethodsGene expression, genetic variants, methylation and activity of ABCA2, ABCA5, ABCB1, ABCB6, ABCC1, ABCC3 and ABCG2 were analysed in AML blasts and healthy myeloblasts. Differences between responding and refractory AML in a cohort of 113 patients treated with 3 + 7 induction therapy were explored. ResultsABCC3 variant rs2301837 (p = 0.049), ABCG2 variant rs11736552 (p = 0.044), higher ABCA2 (p = 0.021), ABCC1 (p = 0.017), and ABCG2 expression (p = 0.023) and a higher number of concurrently overexpressed transporters (p = 0.002) were predictive of treatment failure by multivariate analysis. Expression of ABCA5 (p = 0.003), ABCB6 (p = 0.001) and ABCC3 (p < 0.0001) increased significantly after chemotherapy. Higher ABCG2 promoter methylation correlated with lower ABCG2 expression (p = 0.0001). ABCC1 was identified as the most active transporter in AML blasts by functional analysis. ConclusionsABC transporters, especially ABCC1 seem to contribute substantially to AML chemoresistance. A detailed understanding of chemoresistance mechanisms and the clinical implications of chemosensitivity predictors may lead to alternative therapeutic approaches for AML patients with unveiled chemoresistance signatures.

Day 4 and day 0 neutrophil-to-lymphocyte ratios as predictors of treatment failure with single-dose methotrexate for ectopic pregnancies.

To evaluate changes in the neutrophil-to-lymphocyte ratio (NLR) between day 4 and day 0 in ectopic pregnancy (EP) patients treated with single-dose methotrexate (MTX) and investigate its predictive value for treatment outcome. A total of 406 EP patients receiving single-dose MTX therapy at Shanghai First Maternity and Infant Hospital from January 10, 2013 to September 30, 2019 were studied. A multivariate model was constructed to predict treatment outcome. Among the 406 patients, 281 were treated successfully. Treatment success declined significantly when NLR decreased by less than 23% (74.8% vs 58.5%, P = 0.004). Multivariate regression analysis identified NLR reduction of less than 23% on day 4 (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.27-3.44), a human chorionic gonadotropin (hCG) decrease of 15% or less (OR 3.17, 95% CI 1.62-6.34), and an hCG increase of more than 15% on day 4 (OR 5.47, 95% CI 3.05-10.22) as independent risk factors for single-dose MTX treatment failure. The final predictive model had a sensitivity of 0.768 and a specificity of 0.569, using a cut-off value of 3. The area under the receiver operating characteristic curve was 0.712. Patients with a predictive score of ≥3 were more likely to fail single-dose MTX therapy. The present study concluded that an NLR decrease of less than 23% on day 4, a plateau or increase in serum hCG on day 4, and an hCG value greater than 1000 mIU/mL on day 0 were predictors of single-dose MTX treatment failure in EP patients.

A retrospective cohort analysis of treatment outcomes of patients with tuberculosis who used substances in Tel Aviv, Israel.

To outline the demographic, clinical, laboratory characteristics, and treatment outcomes of tuberculosis (TB) patients who used substances. This retrospective cohort study compared 50 TB patients who used substances with a matched random sample of 100 TB patients who did not use substances between 2007 and 2017. Treatment failure was defined as a sputum smear or culture that tested positive after 5months of treatment, loss to follow-up, unevaluated patients, or death. TB patients who used substances were typically younger, experienced homelessness, smokers, and had fewer chronic diseases than those who did not use substances. They also were hospitalized for longer periods, their treatment durations were longer, had higher rates of multidrug resistant strains, increased rates of treatment failure, and higher mortality. Individuals whose treatment failed predominantly originated from the former Soviet Union, experienced homelessness, and had chronic diseases compared with those whose treatment was successful. In the multivariate analysis, homelessness [odds ratios (OR) = 6.7], chronic diseases (OR = 12.4), and substance use (OR = 4.0) were predictors of treatment failures. TB patients who used substances were more likely to have treatment failure. Targeted interventions, including early diagnosis and enhanced support during treatment, are essential to achieve treatment success in this vulnerable population, in addition to TB-alcohol/drug collaborative activities.

Levonorgestrel-releasing intrauterine system versus oral progestogens for non-atypical endometrial hyperplasia: predictors for treatment failure

Levonorgestrel-releasing intrauterine system versus oral progestogens for non-atypical endometrial hyperplasia: predictors for treatment failure

Kawasaki Disease: Recent Diagnostics, Treatment, and Predictors for Treatment Failure and Coronary Artery Involvement

Kawasaki Disease: Recent Diagnostics, Treatment, and Predictors for Treatment Failure and Coronary Artery Involvement

Incidence and predictors of treatment failure among children with HIV on first-line antiretroviral therapy in Wolaita zone, Southern Ethiopia: A multicenter retrospective cohort study

BackgroundAntiretroviral therapy has improved the life expectancy of HIV-positive children. Treatment failure and drug resistance among children with HIV remain major public health concerns despite the rise in ART use. A dearth of evidence exists regarding treatment failure among Ethiopian children from multicenter settings. Therefore, this study sought to assess the incidence and predictors of treatment failure among children with HIV on first-line antiretroviral therapy at health facilities in Wolaita zone, Southern Ethiopia. MethodsA facility-based retrospective cohort study was conducted from January 1, 2017, to December 30, 2021, at health facilities providing ART in Wolaita zone, Southern Ethiopia. A total of 425 children with HIV on first-line ART were selected using a simple random sampling technique. Data were extracted by reviewing the patient's medical record. The data were entered using epi-data version 4.6 and exported to STATA version 15 for analysis. Both bi-variable and multivariable Cox regression analysis were employed. A p-value of less than 0.05 and a hazard ratio with 95 % CI was used to estimate the association between the predictor factors and treatment failure. ResultsThe overall incidence density rate of treatment failure was 3.2 per 1000 person-months of observation (95 % CI: 2.4–4.6). The factors significantly associated with antiretroviral treatment failure were caregiver marital status, single (AHR = 4.86, 95 % CI: 1.52, 15.60), and widowed (AHR = 3.75, 95 % CI: 1.16, 12.11), duration of follow-up (AHR = 4.95, 95 % CI: 1.81, 13.54), and baseline CD4 count (AHR = 4.70, 95 % CI: 1.68, 13.14). ConclusionThe incidence rate of ART failure among children with HIV was found to be significant. Low baseline CD4 count, short follow-up duration on ART, and having a single or widowed caregiver were significantly associated with antiretroviral treatment failure. Early identification of children with low CD4 count and subsequent initiation of ART should be emphasized by stakeholders working in HIV care programs. Healthcare professionals should pay special attention to and regularly monitor the treatment progress of children who have single or widowed caregivers, and those with shorter duration of follow-ups.

Postchemoradiation magnetic resonance imaging circumferential resection margin predicts treatment failure after multidisciplinary directed sphincter preservation in low rectal cancer.

This study aimed to review the magnetic resonance imaging (MRI) features of patients with low rectal cancer (LRC) undergoing preoperative chemoradiotherapy (CRT) and investigate the risk factors for treatment failure after sphincter preserving surgery following preoperative CRT based on multidisciplinary approach. Patients who underwent standard CRT and sphincter preserving radical surgery for LRC between January 2000 and December 2011 were retrospectively reviewed. Sphincter preservation failure (SPF) was defined as any one of the following: positive pathologic circumferential resection margin, local recurrence, failure to repair ileostomy, or permanent stoma formation due to anastomotic complications. Among the 191 patients, there were no overall significant differences between sphincter preservation success (n = 161) and SPF (n = 30) groups. SPF group showed a higher MRI circumferential resection margins (mrCRM) positive rate before and after CRT (before CRT: 33.3% vs. 16.1%, p = 0.027; after CRT: 23.3% vs. 6.2%, p = 0.002). Multivariate analysis showed that only mrCRM after CRT was associated with SPF (hazard ratio = 4.596, p = 0.005). SPF group showed worse 5-year cancer-specific survival (51% vs. 92.7%, p < 0.001). MRI-based assessment of the tumor after CRT plays a crucial role in predicting the success and feasibility of sphincter preservation as well as oncological outcomes in patients with LRC.

Relevance of circulating Semaphorin 4A for rheumatoid arthritis response to treatment

The lack of validated tools to predict rheumatoid arthritis (RA) disease course warrants the development of new reliable biomarkers. Our aim was to evaluate the merit of circulating SEMA4A for the prediction of outcomes in patients with RA. In a first cohort of 101 consecutive RA patients followed up for 41 ± 15 months, increased baseline SEMA4A levels were identified as an independent predictor of treatment failure (hazard ratio, HR 2.71, 95% CI 1.14–6.43), defined by the occurrence of patient-reported flares and initiation or change of targeted therapy. The highest predictive value of treatment failure was obtained with the combination of increased circulating SEMA4A and/or Disease Activity Score (DAS) 28-CRP > 3.2 and/or active synovitis on doppler ultrasound (HR 10.42, 95% CI 1.41–76.94). In a second independent cohort of 40 consecutive RA patients who initiated new therapy because of insufficient disease control, baseline SEMA4A levels were significantly higher in patients who further experienced none or moderate response, and SEMA4A concentrations were markedly decreased in the group of patients with good clinical response as compared to non-responders. Circulating SEMA4A appears as an appealing biomarker in RA with ability to predict treatment failure, and with association with response to therapy.

Sex differences in variables affecting short-term success in substance use disorder treatment

Because of the stigma surrounding patients with substance use disorder (SUD) and difficulties with follow-up, data on outcomes is limited. We explore real-world data from a prospectively collected database to determine characteristics that contribute to the completion of acute treatment. Our cohort consisted of data from 1039 patients treated at a single facility. Success was defined as successful discharge from the program. Failure was defined as relapse or signing out against medical advice during treatment. We examined 43 distinct features collected at time of treatment using multivariate analysis. In the total cohort and both sexes, longer length of stay (p ≤ 0.01) was linked to treatment failure. When we examined the cohort by sex, variables associated with success and failure differed between groups. Among females, goal-directed thinking (p ≤ 0.05) correlated with treatment success. Taking unnecessary risks (p < 0.05), having a detailed suicide plan (p ≤ 0.001), and constricted thinking (p ≤ 0.01) predicted treatment failure. In males, prior arrest for driving under the influence (p ≤ 0.05), and presence of phobias, paranoias, and delusions (p ≤ 0.05) were associated with treatment failure. Identifying patients prone to acute therapy failure may guide more personalized treatment, thereby increasing success rates. When considering SUD treatments for patients, we must stratify based on patient characteristics.

Outcome prediction by interim positron emission tomography and IgM monoclonal gammopathy in diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), a positive interim positron emission tomography (PET) scan predicts treatment failure, but the proportion of high-risk patients thus identified is small. To improve prediction, we combined the interim PET result with the presence or absence of an associated IgM gammopathy. Of 108 DLBCL patients participating in a prospective trial, nine (8%) were interim PET positive and 19 (18%) had an IgM gammopathy. The monoclonal protein was not associated with distinguishing genetic features, and its light chain restriction was not always concordant with the light chain restriction of the lymphoma. The information provided by interim PET and IgM gammopathy was combined to dichotomize the population into sizeable high-risk (1-2 adverse factors) and low-risk groups (no adverse factor) with widely different outcomes (population size, 25% vs. 75%; 3-year risk of progression, 51% vs. 10%; 3-year overall survival, 64% vs. 95%). Multivariable analyses including established risk factors revealed the interim PET result and the IgM gammopathy status to be the only factors significantly associated with outcome. Information about interim PET response and IgM gammopathy may be useful in studies testing risk-adapted treatment strategies.

Development of a clinical risk score system for peritoneal dialysis-associated peritonitis treatment failure

ObjectiveThis study aimed to construct a clinical risk score system for peritoneal dialysis-associated peritonitis (PDAP) treatment failure to provide a theoretical basis for clinical workers.MethodsA total of 161 PDAP individuals admitted to our hospital were included, among whom 70 cases were in the treatment-improved group and 87 cases were in the treatment failure group. We compared the general condition, clinical manifestations, and laboratory examination indicators of the two groups of individuals, used multivariate logistic regression analysis to identify the factors influencing PDAP treatment failure, and developed a clinical risk score system. The diagnostic performance of the risk score system was evaluated utilizing the receiver operating characteristic (ROC) curve.ResultsSignificant differences (P < 0.05) were observed between the two groups in terms of contamination, peritoneal fluid culture results, blood urea nitrogen (BUN) level, C-reactive protein (CRP) level, B-type natriuretic peptide (BNP) level, average residual urine (RU) volume, and urea clearance rate (UCR). Multivariate logistic regression analysis showed that BUN level, CRP level, BNP level, average RU volume, and UCR were independent risk factors affecting PDAP patient treatment outcomes (P < 0.05). The ROC curve analysis of the risk score system for predicting treatment failure in PDAP individuals showed an area under the curve of 0.895 [95% confidence interval (0.847–0.943)]. The optimal cut-off point was 2.5 points, with corresponding sensitivity and specificity of 88.5% and 74.3%, separately.ConclusionBUN level, CRP level, BNP level, average RU volume, and UCR are independent risk factors for PDAP treatment failure. The clinical risk score system based on these five independent risk factors can accurately predict the risk of treatment failure in PDAP individuals.

High-flow nasal cannula oxygen therapy for the treatment of acute respiratory failure secondary to SARS-CoV-2 pneumonia out of ICU.

High-flow nasal cannula oxygen therapy (HFNC) has been successfully used for the treatment of acute hypoxaemic respiratory failure (AHRF) secondary to SARS-CoV-2 pneumonia and being effective in reducing progression to invasive mechanical ventilation. The objective of this study was to assess the usefulness of HFNC on a hospital ward for the treatment of AHRF secondary to SARS-CoV-2 pneumonia and its impact on the need for intensive care unit (ICU) admission and endotracheal intubation. Other objectives include identifying potential physiological parameters and/or biomarkers for predicting treatment failure and assessing the clinical course and survival. Observational study based on data collected prospectively between March 2020 and February 2021 in a single hospital on patients diagnosed with AHRF secondary to SARS-CoV-2 pneumonia who received HFNC outside an ICU. One hundred and seventy-one patients out of 1090 patients hospitalised for SARS-CoV-2 infection. HFNC was set as the ceiling of treatment in 44 cases; 12 survived (27.3%). Among the other 127 patients, intubation was performed in 25.9% of cases with a mortality of 11.8%. Higher creatinine levels (OR 1.942, 95% CI 1.04; 3.732; p= 0.036) and Comorbidity-Age-Lymphocyte-LDH (CALL) score (OR 1.273, 95% CI 1.033; 1.617; p= 0.033) were associated with a higher risk of intubation. High platelet count at HFNC initiation was predictive of good treatment response (OR 0.935, 95% CI 0.884; 0.983; p= 0.012). HFNC outside an ICU is a treatment with high success rate in patients with AHRF secondary to SARS-CoV-2 pneumonia, including in patients in whom this therapy was deemed to be the ceiling of treatment.

Derivation and validation of a clinical prediction model for risk-stratification of children hospitalized with severe pneumonia in Bangladesh.

Children with severe pneumonia in low- and middle-income countries (LMICs) suffer from high rates of treatment failure despite appropriate World Health Organization (WHO)-directed antibiotic treatment. Developing a clinical prediction rule for treatment failure may allow early identification of high-risk patients and timely intervention to decrease mortality. We used data from two separate studies conducted at the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) to derive and externally validate a clinical prediction rule for treatment failure of children hospitalized with severe pneumonia. The derivation dataset was from a randomized clinical trial conducted from 2018 to 2019, studying children aged 2 to 59 months hospitalized with severe pneumonia as defined by WHO. Treatment failure was defined by the persistence of danger signs at the end of 48 hours of antibiotic treatment or the appearance of any new danger signs within 24 hours of enrollment. We built a random forest model to identify the top predictors. The top six predictors were the presence of grunting, room air saturation, temperature, the presence of lower chest wall indrawing, the presence of respiratory distress, and central cyanosis. Using these six predictors, we created a parsimonious model with a discriminatory performance of 0.691, as measured by area under the receiving operating curve (AUC). We performed external validation using a temporally distinct dataset from a cohort study of 191 similarly aged children with severe acute malnutrition and pneumonia. In external validation, discriminatory performance was maintained with an improved AUC of 0.718. In conclusion, we developed and externally validated a parsimonious six-predictor model using random forest methods to predict treatment failure in young children with severe pneumonia in Bangladesh. These findings can be used to further develop and validate parsimonious and pragmatic prognostic clinical prediction rules for pediatric pneumonia, particularly in LMICs.

Protocol for a prospective study evaluating circulating tumour cells status to predict radical prostatectomy treatment failure in localised prostate cancer patients (C-ProMeta-1)

BackgroundTreatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence.MethodsWe plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood samples (20 ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time.DiscussionCTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment.Trial registrationISRCTN17332543.