Acceptable False Negative Rate Research Articles

The surgical technique and protocol for dynamic sentinel node biopsy for penile cancer at a Southeast Asian regional hospital.

Lymph node status is a key prognostic factor in penile cancer. The European Association of Urology (EAU) recommends intermediate-risk (pT1a, Grade 2) or high-risk (pT1b or greater) penile cancer patients with clinically non-palpable inguinal lymph node (cN0) to undergo either an invasive bilateral modified inguinal lymph node dissection (ILND) or dynamic sentinel node biopsy (DSNB). DSNB has been reported to have acceptable false negative rates, and lower rates of long-term morbidity compared to ILND. We developed a protocol for DSNB at a regional hospital in Singapore that was adopted from St James's University Hospital, Leeds Teaching Hospitals Trust. Four patients with cN0 penile cancer underwent DSNB between November 2021 and October 2022 according to this protocol. Our surgical technique and protocol are described. The patients' oncological characteristics and their outcomes were evaluated. In this small case series, there was no complication attributable to the performance of DSNB, and there was no groin that was documented to be false negative over a median follow up of 15.5 months (range, 12 to 22 months). Using our protocol, 5 of 8 groins (62.5%) were able to avoid ILND in the cN0 setting. We recommend the adoption of DSNB for the surgical staging of inguinal lymph nodes for patients with intermediate to high-risk penile cancer and non-palpable inguinal nodes due to its significantly lower risks of long-term morbidity compared to ILND. Appropriate specialist training and a multi-disciplinary team is vital to ensure the success of the procedure.

Accuracy of the Enhanced Liver Fibrosis Test in Patients With Type 2 Diabetes Mellitus and Its Clinical Implications

Background and AimsThe diagnostic performance of the Fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is poor in patients with type 2 diabetes mellitus (T2DM). We determined the usefulness of the enhanced liver fibrosis (ELF) test in patients with T2DM. MethodsA total of 1,228 patients with biopsy-proven NAFLD were enrolled. The diagnostic performance of the ELF test for predicting advanced fibrosis in participants with or without T2DM was evaluated in comparison with the FIB-4 index and NFS. ResultsOverall, the area under the curve of the ELF test for predicting advanced fibrosis was greater (0.828) than that of the FIB-4 index (0.727) and NFS (0.733). The diagnostic performance of the ELF test (area under the curve 0.820) was also superior to that of the FIB-4 index (0.698) and NFS (0.700) in patients with T2DM. With the low cutoff values for each non-invasive test, the ELF test provided an acceptable false-negative rate (cutoff value 9.8, 6.7%) in this population, unlike the FIB-4 index (1.30, 14.5%) and NFS (−1.455, 12.4%). After propensity score matching to avoid selection bias including age, sex, body mass index, and the prevalence of advanced fibrosis, the ELF test with a low cutoff value showed a high sensitivity (≥91.4%) and a high negative predictive value (≥96.8%), irrespective of the presence or absence of T2DM. ConclusionThe high diagnostic performance of the ELF test for predicting advanced fibrosis in individuals with or without T2DM could address an unmet medical need for accurate assessment of liver fibrosis in patients with diabetes and NAFLD.

Low axillary sampling to stage post neoadjuvant axilla in breast cancer patients - A practical approach in developing world

BackgroundPost-neoadjuvant sentinel lymph node biopsy or targeted axillary dissection in carcinoma breast patients need costly infrastructure, making it out of reach for resource constrained developing countries. This study assesses the diagnostic accuracy of low axillary node sampling to predict the nodal status of the post-chemotherapy node-negative axilla. Materials and methodsThis is a prospective study which included cytology proven node positive carcinoma breast patients who had node negative axilla after chemotherapy and underwent low axillary sampling with complete axillary lymph node dissection. Nodes below second intercostobrachial nerve were sent as low axillary sample. Results211 patients with carcinoma breast underwent FNAC of the axillary node prior to neoadjuvant systemic therapy (NAST). Low axillary sampling was performed on 77 patients who had clinically and radiologically node negative axilla after NAST. Out of 77, 24 (31%) had early breast cancer and 32 (41.5%) had T4 disease prior to NAST. In this cohort, 36 patients (47%) had a good biology tumour, 57 (74%) had Grade 3 tumour and 20 (26%) had lymphovascular invasion (LVI). Pathological complete response of breast and axilla was seen in 24 patients (31%). Low axillary sampling had a range of 1–12 nodes with median lymph nodal yield of 6. The false negative rate (FNR) of low axillary sampling was 8.3%. Good tumour biology, post NAST residual breast tumour and lymphovascular invasion were the independent predictors of positive low axillary nodes. ConclusionsLow axillary sampling is an economical and feasible option to de-escalate axillary surgery with acceptable false negative rate in carcinoma breast patients who had node negative axilla post neoadjuvant systemic therapy.

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Axillary Conversion after Neoadjuvant Chemotherapy-A Single-Tertiary Centre Experience and Review of the Literature.

(1) Introduction: Sentinel lymph node biopsy (SLNB) is widely used in breast cancer patients who undergo neoadjuvant chemotherapy (NAC), replacing axillary lymph node dissection. While commonly accepted for cN0 patients, its role in cN1/2 patients remains controversial. Our study aims to investigate the role of SLNB in BC patients who underwent prior NAC and compare our results to those of other studies presented in the literature. (2) Materials and methods: Our retrospective study included 102 breast cancer patients who received NAC before 99mTc-albumin Nanocolloid SLN mapping and SLNB was performed, completed or not with axillary dissection. A review based on the PRISMA statement was also carried out, encompassing 20 studies. (3) Results: The lymphoscintigraphy performed after the administration of NAC presented an identification rate (IR) of 93.13%. IR for SLNB was 94.11%, with a false-negative rate (FNR) of 7.4%. After a median follow-up of 31.3 months, we obtained a distant disease-free survival rate of 98%. The results obtained by other groups were similar to those of our study, presenting IR in the range 80.8-96.8%, with FNR varying from 0 to 22%. (4) Conclusions: on conclusion, SLNB can accurately determine the lymph node status, with an acceptable FNR and maintain its expected prognostic role with low recurrence rates, and our results are comparable to those obtained by other studies.

Omitting Sentinel Lymph Node Biopsy after Neoadjuvant Systemic Therapy for Clinically Node Negative HER2 Positive and Triple Negative Breast Cancer: A Pooled Analysis.

Recent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST. Hence, for selected patients, particularly those who are clinically node-negative (cN0) at diagnosis, the probability of disease in the sentinel node after NAST could be low enough to justify omitting axillary surgery. The aim of this pooled analysis was to determine the rate of sentinel node positivity (ypN+) in patients with TNBC or HER2-positive breast cancer who were initially cN0, achieving rCR and/or pCR in the breast after NAST. MedLine was searched using appropriate search terms. Five studies (N = 3834) were included in the pooled analysis, yielding a pooled ypN+ rate of 2.16% (95% CI: 1.70-2.63). This is significantly lower than the acceptable false negative rate of sentinel lymph node biopsy (SLNB) and supports consideration of omission of SLNB in this subset of patients.

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients.

To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers. In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test. A total of 964 women comprised the development (603 women, 54 ± 11years) and validation (361 women, 53 ± 10years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts. Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

A Low-Cost Sequencing Platform for Rapid Genotyping in ADPKD and its Impact on Clinical Care

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Because of the heterogeneity in disease progression in ADPKD, parameters predicting future outcome are important. The disease-causing genetic variant is one of these parameters. A multiplex polymerase chain reaction (PCR)-based panel (MPP) was established for analysis of 6 polycystic kidney disease (PKD) genes (PKD1, PKD2, HNF1B, GANAB, DZIP1L, and PKHD1) in 441 patients with ADPKD. Selected patients were additionally sequenced using Sanger sequencing or a custom enrichment-based gene panel. Results were combined with clinical characteristics to assess the impact of genetic data on clinical decision-making. Variants of unclear significance (VUS) were considered diagnostic based on a classic ADPKD clinical phenotype. Using the MPP, disease-causing variants were detected in 65.3% of patients. Sanger sequencing and the custom gene panel in 32 patients who were MPP-negative revealed 20 variants missed by MPP, (estimated overall false negative rate 24.6%, false-positive rate 9.4%). Combining clinical and genetic data revealed that knowledge of the genotype could have impacted the treatment decision in 8.2% of patients with a molecular genetic diagnosis. Sequencing only the PKD1 pseudogene homologous region in MPP-negative patients resulted in an acceptable false-negative rate of 3.28%. The MPP yields rapid genotype information at lower costs and allows for simple extension of the panel for new disease genes. Additional sequencing of the PKD1 pseudogene homologous region is required in negative cases. Access to genotype information even in settings with limited resources is important to allow for optimal patient counseling in ADPKD.

Learning Curve for CT-Guided Percutaneous Transthoracic Needle Biopsy: Retrospective Evaluation Among 17 Thoracic Imaging Fellows at a Tertiary Referral Hospital.

BACKGROUND. CT-guided percutaneous transthoracic needle biopsy (PTNB) is widely used for evaluation of indeterminate pulmonary lesions, although guidelines are lacking regarding the experience needed to gain sufficient skill. OBJECTIVE. The purpose of our study was to investigate the learning curve among a large number of operators in a tertiary referral hospital and to determine the number of procedures required to obtain acceptable performance. METHODS. This retrospective study included CT-guided PTNBs with coaxial technique performed by 17 thoracic imaging fellows from March 2, 2011, to August 8, 2017, who were novices in the procedure. A maximum number of 200 consecutive procedures per operator were included. The cumulative summation method was used to assess learning curves for diagnostic accuracy, false-negative rate, pneumothorax rate, and hemoptysis rate. Operators were assessed individually and in a pooled analysis. Pneumothorax risk was also assessed in a model adjusting for risk factors. Acceptable failure rates were defined as 0.1 for diagnostic accuracy and false-negative rate, 0.45 for pneumothorax rate, and 0.05 for hemoptysis rate. RESULTS. The study included 3261 procedures in 3134 patients (1876 men, 1258 women; mean age, 67.7 ± 12.1 [SD] years). Overall diagnostic accuracy was 94.2% (2960/3141). All 17 operators achieved acceptable diagnostic accuracy (37 procedures required in the pooled analysis; median, 33 procedures required [range, 19-67 procedures required]). Overall false-negative rate was 7.6% (179/2370). All 17 operators achieved acceptable false-negative rate (52 procedures required in the pooled analysis; median, 33 procedures required [range, 19-95 procedures required]). Pneumothorax occurred in 32.6% of the procedures (1063/3261 procedures), and hemoptysis occurred in 2.7% of the procedures (89/3261 procedures). All 17 operators achieved acceptable pneumothorax rate (20 procedures required in the pooled analysis; median, 19 procedures required [range, 7-63 procedures required]). In the risk-adjusted model, 15 operators achieved acceptable pneumothorax rate (54 procedures required in the pooled analysis; median, 36 procedures required [range, 10-192 procedures required]). Sixteen operators achieved acceptable hemoptysis rate (67 procedures required in the pooled analysis; median, 55 procedures required [range, 41-152 procedures required]). CONCLUSION. For CT-guided PTNB, at least 37 and 52 procedures are required to achieve acceptable diagnostic accuracy and false-negative rate, respectively. Not all operators achieved acceptable complication rates. CLINICAL IMPACT. The findings may help set standards for training, supervision, and ongoing assessment of operator proficiency for this procedure.

Targeted Axillary Dissection for Patients Who Convert to Clinically Node Negative After Neoadjuvant Chemotherapy for Node-Positive Breast Cancer

The use of neoadjuvant chemotherapy (NAC) for breast cancer (BC) can eradicate axillary disease in > 40% of patients. The standard of care for node-positive BC has been axillary lymph node dissection. In this review, we examine the data for de-escalating axillary surgery after NAC. Studies have shown that sentinel lymph node biopsy (SLNB) is accurate after NAC. False negative rates (FNR) of SLNB after NAC in node-positive patients have been reduced with a combination of dual tracers and localization of the clipped positive node. Clipped nodes may be localized with a variety of methods. Targeted axillary dissection (removal of clipped node in conjunction with SLNB) results in an acceptable FNR and can be considered in certain patients with axillary clinical response to neoadjuvant chemotherapy. Patient selection is important, as those with persistently positive nodes on clinical exam should proceed directly to axillary dissection.

Crowdsourced reliable labeling of safety-rule violations on images of complex construction scenes for advanced vision-based workplace safety

Construction workplace hazard detection requires engineers to analyze scenes manually against many safety rules, which is time-consuming, labor-intensive, and error-prone. Computer vision algorithms are yet to achieve reliable discrimination of anomalous and benign object relations underpinning safety violation detections. Recently developed deep learning-based computer vision algorithms need tens of thousands of images, including labels of the safety rules violated, in order to train deep-learning networks for acquiring spatiotemporal reasoning capacity in complex workplaces. Such training processes need human experts to label images and indicate whether the relationship between the worker, resource, and equipment in the scenes violate spatiotemporal arrangement rules for safe and productive operations. False alarms in those manual labels (labeling no-violation images as having violations) can significantly mislead the machine learning process and result in computer vision models that produce inaccurate hazard detections. Compared with false alarms, another type of mislabels, false negatives (labeling images having violations as “no violations”), seem to have fewer impacts on the reliability of the trained computer vision models.This paper examines a new crowdsourcing approach that achieves above 95% accuracy in labeling images of complex construction scenes having safety-rule violations, with a focus on minimizing false alarms while keeping acceptable rates of false negatives. The development and testing of this new crowdsourcing approach examine two fundamental questions: (1) How to characterize the impacts of a short safety-rule training process on the labeling accuracy of non-professional image annotators? And (2) How to properly aggregate the image labels contributed by ordinary people to filter out false alarms while keeping an acceptable false negative rate? In designing short training sessions for online image annotators, the research team split a large number of safety rules into smaller sets of six. An online image annotator learns six safety rules randomly assigned to him or her, and then labels workplace images as “no violation” or ‘violation” of certain rules among the six learned by him or her. About one hundred and twenty anonymous image annotators participated in the data collection. Finally, a Bayesian-network-based crowd consensus model aggregated these labels from annotators to obtain safety-rule violation labeling results. Experiment results show that the proposed model can achieve close to 0% false alarm rates while keeping the false negative rate below 10%. Such image labeling performance outdoes existing crowdsourcing approaches that use majority votes for aggregating crowdsourced labels. Given these findings, the presented crowdsourcing approach sheds lights on effective construction safety surveillance by integrating human risk recognition capabilities into advanced computer vision.

Sentinel lymph nodes (SLN) in endometrial cancer: The relationship between primary tumor histology, SLN metastasis size, and non-sentinel node metastasis

ObjectivesTo examine sentinel lymph node pathology and describe relationships to uterine pathology, non-sentinel pelvic lymph nodes, and para-aortic lymph nodes. MethodsPatients with apparent uterine-confined endometrial cancer underwent robotic hysterectomy, SLN mapping, completion pelvic lymphadenectomy (LND), and para-aortic (PaLND) directed by frozen section. Patients were risk stratified by histology: low-risk (LR) endometrioid <50% depth-of-invasion (DOI), intermediate-risk (IR) endometrioid ≥50% DOI, and high-risk (HR) type II histology for comparison to other pelvic/aortic metastases. Results414 patients were stratified: 275 LR, 80 IR, and 59 HR cases. PaLND was performed in 84.2% of IR/HR patients and 25.1% LR patients. Pelvic node metastasis was detected in 11.6% LR, 50.0% IR, and 39.0% HR patients. PaLN metastasis was detected in 2.9% LR, 11.3% IR, and 16.9% HR patients. Proportionally, isolated tumor cells (ITC) SLNs were more common in LR or IR vs. HR group (51.6% and 44.7% vs. 15.0%, p < 0.05). The SLN false negative rates (FNR) were 0% LR, 2.5% IR, and 5.1% HR. Non-sentinel pelvic node metastases were present in 28(31.5%) of all SLN+ cases, but only 3(8.3%) of SLN with ITC. PaLN metastasis was found in 18.8% LR, 11.8% IR, and 33.3% HR cases with ITC SLNs. After controlling for DOI, LVSI, and grade, ITC-positive SLNs had a significant association with non-sentinel pelvic and aortic metastasis (p = 0.03 and p = 0.008, respectively). ConclusionsPatients with HR histology have more micro/macro-metastases in both SLNs and non-SLN metastases compared to LR/IR patients. SLN ITCs were associated with a clinically significant incidence of PaLN metastasis across all histology risk groups. There were no cases of isolated aortic node metastasis in this study. SLN mapping had an increased, although clinically acceptable FNR in the HR cohort compared to LR patients.

Non-Invasive Prediction of High-Risk Varices in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis.

Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of saved endoscopies for each prediction rule. Prevalence of VNT was 13%. Baveno-VI criteria had a 0% FNR in PBC and PSC, saving 39 and 30% of EGDs, respectively. In PBC the other LSM-TE-based criteria resulted in FNRs >5%. In PSC the expanded Baveno criteria had an adequate performance. In both conditions LSM-TE-independent criteria resulted in an acceptable FNR but saved less EGDs. Baveno-VI criteria can be applied in patients with cACLD due to ChLDs, which would result in saving 30-40% of EGDs. Expanded criteria in PBC would lead to FNRs >5%.

A Pragmatic Study to Evaluate the Use of a Rapid Diagnostic Test to Detect Group A Streptococcal Pharyngitis in Children With the Aim of Reducing Antibiotic Use in a UK Emergency Department.

Sore throat is a common presentation to the children's emergency department (ED), and many patients are likely prescribed antibiotics unnecessarily. We aimed to reduce antibiotic prescribing for sore throat in our UK ED through use of an established scoring system combined with a rapid diagnostic test (RDT) to detect group A streptococcal (GAS) pharyngitis. AB single-subject and diagnostic accuracy studies were used to measure both antibiotic prescribing rates over time and the performance of the McIsaac clinical score combined with RDT to screen for and treat GAS pharyngitis. All children between the age of 6 months and 16 years with symptoms of sore throat were eligible for inclusion. The study adhered to SQUIRE guidelines. During 2014 and 2016, antibiotic prescribing rates for 210 children at baseline (median age, 3 years) and 395 children during the intervention (median age, 2 years) were assessed. The baseline prescribing rate was 79%, whereas rates after intervention were 24% and 27%, respectively. The RDT had an acceptable false-negative rate of 7.9%, poor sensitivity of 64.3%, and a negative predictive value of 92.1% when compared with conventional throat culture. A McIsaac score of 3 or more had good sensitivity (92.11%) but very low specificity (12.62%) for predicting GAS infection. Despite poor RDT sensitivity and the McIsaac score's poor specificity in children, their use in combination decreased antibiotic prescribing rates in a children's ED setting.

What is an acceptable false negative rate in the detection of prostate cancer?

What is an acceptable false negative rate in the detection of prostate cancer?

Abstract P3-01-16: How hot is enough for accurate sentinel lymph node axillary staging in breast cancer?

Abstract Purpose: Sentinel lymph node (SLN) biopsy is a well-established procedure for staging of the axilla in early-stage breast cancer and has replaced axillary lymph node dissection as the standard of care in patients with clinically lymph node–negative axilla. No consensus exists about the number of sentinel lymph nodes (SLNs) that should be removed based on radioactivity counts in breast cancer, although the “10% rule” is often used. In order to determine the frequency with which the hottest SLN 'fails' to be pathologically positive, and to determine which criteria best define the radioactive lymph node to be removed, we reviewed and analyzed our cases in which more than one SLN was detected and where there was also at least one pathologically positive node. Methods: We retrospectively studied 1062 breast cancer patients who underwent lymphoscintigraphy by injection of radioactive colloid and SLN biopsy between 2006 and 2015, with intraoperative determination of radioactive counts of nodes by a gamma probe. Results: A total of 247 patients (23.3%) had more than 1 SLN removed (mean 2.29); 53 patients (21.5%) had nodal metastases. Of the node-positive patients, the hottest SLN was positive in 90.6% (48 of 53). The lowest radioactive count of a positive SLN was 32% of that of the hottest node. Conclusions: In our study, most positive SLNs had the highest radioactivity and the hottest lymph node was not the pathologically positive node only in 9.4 %. Our institutional experience indicates that to obtain an acceptable false-negative rate, nodes should be removed until the 10% rule is met. Citation Format: Lee MH, Kang SH, Cho J. How hot is enough for accurate sentinel lymph node axillary staging in breast cancer? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-16.

What is an acceptable false negative rate in the detection of prostate cancer?

BackgroundIn prostate cancer (PCa) screening men and their physicians aim to rule out the presence of potentially life threatening PCa. To date, prostate specific antigen (PSA) testing and systematic prostate biopsy (Bx)—in case of an elevated PSA—are still the main modes of PCa detection. Often uncertainty remains when a PSA-test is <3.0 ng/mL or a Bx shows a benign result, leading to the continuous repeating of procedures. Here we assess the potential consequences of false negatives by studying follow-up data of a purely PSA-based approach with applying sextant Bx, an approach considered to have a high risk of missing PCa diagnosis.MethodsOur study population consisted of 19,970 men from the ERSPC project section Rotterdam, initially screened in 1993–1999. We assessed clinically significant Gleason ≥3+4 PCa (csPCa) diagnosis within the 4-year screening interval and subsequent screening round 4 years later in men having a PSA <3.0 ng/mL at initial screening (no Bx) and men with Bx (PSA >3.0 ng/mL), but no PCa detected at that time. In addition, we addressed PCa mortality and PCa diagnosis for men with a negative PSA test and negative Bx, who were retested every 4 years covering a 15-year follow-up.ResultsA total of 14,935 men had PSA <3.0 ng/mL in the initial screening round, of whom 75 (0.5%) were diagnosed with csPCa at a subsequent screening examination and 2 (<0.1%) in the 4-year screening interval. For 2,260 men with a previously negative Bx at first screening, the figures were 17 (0.8%) and 2 (0.1%) respectively. Indolent PCa (Gleason ≤3+3) was diagnosed in 312 (2%) men with PSA <3.0 ng/mL initially and 115 (5%) men with initial negative Bx. After a 15-year follow-up, 45 (0.3%) PCa deaths occurred in men with initially low PSA, and 29 men (0.2%) had metastasis. For men with negative Bx, 11 (0.5%) PCa deaths occurred and 4 (0.2%) experienced metastasis.ConclusionsThe false negative rates for men with PSA <3.0 ng/mL and negative sextant Bx are extremely low but not negligible. Proper risk stratification before deciding to biopsy is expected to hardly miss any clinical significant PCa diagnosis. This is especially relevant with the increased use of the relatively expensive multi-parametric magnetic resonance imaging (mpMRI) guided targeted Bx procedures.

What false-negative rates of non-invasive testing are active surveillance patients and uro-oncologists willing to accept in order to avoid prostate biopsy?

Repeat prostate biopsies in active surveillance patients are associated with significant complications. Novel imaging and blood/urine-based non-invasive tests are being developed to better predict disease grade and volume progression. We conducted a theoretical study to determine what test performance characteristics and costs would a non-invasive test(s) require in order for patients and their physicians to comfortably avoid biopsy. Surveys were administered to two populations to determine an acceptable false-negative rate and cost for such test(s). Active surveillance patients were recruited at time of followup in clinic at Princess Margaret Cancer Centre. Physician members of the Society of Urological Oncology were targeted via an online survey. Participants were questioned about their demographics and other characteristics that might influence chosen error rates and cost. 136 patients and 670 physicians were surveyed, with 130 (95.6%) and 104 (15.5%) responses obtained, respectively. A vast majority of patients (90.6%) were comfortable with a non-invasive test(s) in place of biopsy, with 64.8% accepting a false-negative rate of 5-20%. Most physicians (93.3%) were comfortable with a non-invasive test, with 77.9% accepting a rate of 5-20%. Most patients and physicians felt that a cost of less than $1000 per administration would be reasonable. Most patients/physicians are comfortable with a non-invasive test(s). Although a 5% error rate seems acceptable to many, a substantial subset feels that 99% or higher negative predictive value is required. Thus, a personalized approach with shared decision-making between patients and physicians is essential to optimize patient care in such situations.

MP77-18 WHAT FALSE NEGATIVE RATE OF NON-INVASIVE TESTING ARE ACTIVE SURVEILLANCE PATIENTS AND URO-ONCOLOGISTS WILLING TO ACCEPT IN ORDER TO AVOID PROSTATE BIOPSY?

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII1 Apr 2017MP77-18 WHAT FALSE NEGATIVE RATE OF NON-INVASIVE TESTING ARE ACTIVE SURVEILLANCE PATIENTS AND URO-ONCOLOGISTS WILLING TO ACCEPT IN ORDER TO AVOID PROSTATE BIOPSY? Rashid Sayyid, Dharmendra Dingar, Katherine Fleshner, Taylor Thorburn, Joshua Diamond, Erik Yao, Karen Hersey, Karen Chadwick, Nathan Perlis, Laurence Klotz, Antonio Finelli, Alexandre Zlotta, Robert Hamilton, Girish Kulkarni, and Neil Fleshner Rashid SayyidRashid Sayyid More articles by this author , Dharmendra DingarDharmendra Dingar More articles by this author , Katherine FleshnerKatherine Fleshner More articles by this author , Taylor ThorburnTaylor Thorburn More articles by this author , Joshua DiamondJoshua Diamond More articles by this author , Erik YaoErik Yao More articles by this author , Karen HerseyKaren Hersey More articles by this author , Karen ChadwickKaren Chadwick More articles by this author , Nathan PerlisNathan Perlis More articles by this author , Laurence KlotzLaurence Klotz More articles by this author , Antonio FinelliAntonio Finelli More articles by this author , Alexandre ZlottaAlexandre Zlotta More articles by this author , Robert HamiltonRobert Hamilton More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , and Neil FleshnerNeil Fleshner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2126AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Repeat prostate biopsies in active surveillance patients are associated with significant complications. Novel imaging and blood/urine based non-invasive tests are being developed to better predict disease grade and volume progression. We conducted a theoretical study to determine what test performance characteristics and costs would a non-invasive test(s) require in order for patients and their physicians to comfortably avoid biopsy. METHODS Surveys were administered to two populations to determine an acceptable false-negative rate and cost for such test(s). AS patients were recruited at time of visit to the prostate cancer clinic at Princess Margaret Cancer Centre, beginning August 2015 for a period of four months. Responses from urologic oncologists worldwide were obtained in March 2016 by circulating an online survey via the Society of Urologic Oncology. Participants were questioned about their demographics and other characteristics that might influence chosen error rates and cost. Differences between patient and physician choices were tested using the Chi-square test. RESULTS 136 patients and 670 physicians were surveyed, with 130 (96%) and 104 (16%) responses obtained, respectively. 90.6% of patients were comfortable with a non-invasive test(s) in place of biopsy, with 64.8% accepting a false-negative rate of 5% or worse. 25.8% of patients requested a FN rate of 1% or lower. 93.3% of physicians were comfortable with a non-invasive test, with 77.9% accepting a rate of 5% or worse. 15.4% of physicians requested a FN rate of 1% or lower. 75% of patients and 77% of physicians felt that a cost of less than $1,000, per administration, would be reasonable. No significant differences existed between patient and physicians choices for FN rate or costs (p>0.05). CONCLUSIONS Most patients/physicians are comfortable with a non-invasive test(s). Although a 5% error rate seems acceptable to many, a substantial subset feels that 99% or higher negative predictive value is required. Thus, a personalized approach with shared-decision making between patients and physicians is essential to optimize patient care in such situations. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1028-e1029 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Rashid Sayyid More articles by this author Dharmendra Dingar More articles by this author Katherine Fleshner More articles by this author Taylor Thorburn More articles by this author Joshua Diamond More articles by this author Erik Yao More articles by this author Karen Hersey More articles by this author Karen Chadwick More articles by this author Nathan Perlis More articles by this author Laurence Klotz More articles by this author Antonio Finelli More articles by this author Alexandre Zlotta More articles by this author Robert Hamilton More articles by this author Girish Kulkarni More articles by this author Neil Fleshner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract P2-01-29: In the era of conservative surgery, can patients presenting with node positive breast cancer be spared axillary node dissection post neoadjuvant chemotherapy? A meta-analysis and review of literature

Abstract Background:The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial. Methods: A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR). Results: Nineteen articles were used in the analysis yielding 3398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. Conclusions: SLNB after NAC in biopsy-proven node positive patients results in reasonably acceptable FNR and IR making it a valid alternative management strategy to axillary dissection. Although the results are not matched with those in clinically node negative patients, a FNR of 13% is very unlikely to adversely affect overall survival. Its impact on locoregional recurrence should be evaluated in adequately powered future studies. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population. Citation Format: Headon H, Chehade HEH, El Tokhy O, Wazir U, Heeney J, Kasem A, Mokbel K. In the era of conservative surgery, can patients presenting with node positive breast cancer be spared axillary node dissection post neoadjuvant chemotherapy? A meta-analysis and review of literature [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-29.

How Often Is Treatment EffectIdentified in Axillary Nodes with a Pathologic Complete Response After Neoadjuvant Chemotherapy?

False-negative rates (FNR) of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in node-positive (N+) breast cancer patients are <10% when ≥3 negative SNs are obtained. Marking positive nodes has been suggested to reduce FNR. Identification of treatment effect in the nodes post-NAC is an alternative to decrease FNR. We evaluated the frequency of treatment effect in N+ patients after a pathologic complete response (pCR) with NAC. Biopsy-proven N+ patients receiving NAC were identified. Patients with nodal pCR after axillary lymph node dissection (ALND) or SNB with dual mapping and ≥3 SNs removed were evaluated for treatment effect; ALND and SNB patients were compared. From January 2009 to December 2015, 528 N+ patients received NAC. Of these, 204 had a nodal pCR, 135 had an ALND, and 69 had SNB. Median age was 49years, 15% were hormone receptor positive (HR+)/HER2-, 27% triple negative, and 58% HER2+. The median number of nodes removed in ALND patients was 17 versus 4 in SNB patients. Treatment effect in nodes was identified in 192 patients (94%) and was more common in ALND versus SNB patients (97 vs 88%; p=.02). HR+ patients and patients without a breast pCR were less likely to have treatment effect in the nodes (p=.05). Other characteristics did not differ. Following NAC, SNs with treatment effect were retrieved in 88% of patients without marking nodes, suggesting that nodal clipping may not be necessary to achieve an acceptable FNR. Longer follow-up is needed to determine regional recurrence rates in the SN-only cohort.