Prostate-specific antigen nadir and testosterone level at prostate-specific antigen failure following radiation and androgen suppression therapy for unfavorable-risk prostate cancer and the risk of all-cause and prostate cancer-specific mortality.

BACKGROUND: Although both PSA nadir (PSAn) and testosterone levels at PSA failure are known prognostic factors in men undergoing radiation therapy (RT) and androgen deprivation therapy (ADT) for unfavorable-risk prostate cancer (PC), it is unclear whether their prognostic significance is independent or overlapping. METHODS: Seventy-five men treated with RT with or without 6 months of ADT for unfavorable-risk nonmetastatic PC enrolled in 2 prospective clinical trials between 1986 and 2001 formed the study cohort. Competing risks and Cox multivariable regression were used to assess whether low versus normal serum testosterone at the time of PSA failure and higher PSAn after initial therapy were independently associated with the risk of PC-specific (PCSM) and all-cause mortality (ACM) adjusting for PC prognostic factors. RESULTS: After a median follow-up of 15.34 years (interquartile range, 6.66-16.88 years), there were 53 deaths (73.3%): 30 (56.6%) were from PC. Low testosterone at PSA failure was significantly associated with an increased risk of PCSM (adjusted HR [AHR], 7.77; 95% CI, 1.14-52.99; P = .04) and ACM (AHR, 3.01; 95% CI, 1.01-8.96; P = .05), as was higher PSAn (PCSM AHR, 1.03; 95% CI, 1.01-1.05; P < .01; ACM AHR, 1.04; 95% CI, 1.02-1.07; P < .01), although the prognostic significance of PSAn was only noted in men with a normal testosterone at PSA failure. CONCLUSIONS: Low testosterone level at PSA failure in high-risk patients with PC treated with RT is associated with increased PCSM and ACM risk. In men with normal testosterone levels at the time of PSA failure, an elevated PSAn was associated with worse PCSM and ACM risk. LAY SUMMARY: This study investigates whether the prostate-specific antigen (PSA) nadir and normal versus low testosterone at the time of PSA failure provide mutually exclusive or overlapping prognostic information following treatment with radiation and androgen deprivation therapy for unfavorable-risk patients with prostate cancer using data from 2 prospective clinical trials. It was found that both provided prognostic information; however, higher PSA nadir was only found to be of prognostic significance in men with normal testosterone levels at PSA failure.

Impact of time to testosterone rebound and comorbidity on the risk of cause-specific mortality in men with unfavorable-risk prostate cancer.

BACKGROUND: Herein, the authors evaluated how the time to testosterone rebound (TTR) after radiotherapy (RT) and 6 months of androgen deprivation therapy (ADT) impacted the risk of prostate cancer-specific mortality (PCSM) and cardiovascular-specific mortality (CVM) among men with varying comorbidity extent. METHODS: Between 1995 and 2001, a total of 206 men who were randomized to receive RT either alone or with 6 months of ADT for unfavorable-risk PC and who had a comorbidity score assigned using the Adult Comorbidity Evaluation 27 metric comprised the study cohort. Multivariable competing risk regression was used to evaluate the impact of and possible interaction between comorbidity and TTR on PCSM and CVM. RESULTS: After a median follow-up of 18.19 years, 30 men (18.6%), 39 men (24.2%), and 92 men (57.1%), respectively, had died of PC, CV disease, or other causes. As TTR increased, PCSM significantly decreased in men with no or minimal (adjusted hazard ratio [AHR], 0.53, 95% confidence interval [95% CI], 0.34-0.84 [P =.007]) and moderate to severe (AHR, 0.37; 95% CI, 0.14-0.99 [P = .048]) comorbidity. However, increasing TTR significantly increased the risk of CVM among men with moderate to severe comorbidity (AHR, 1.87; 95% CI, 1.40-2.49 [P <.001]), but not those with no or minimal comorbidity (AHR, 0.86; 95% CI, 0.57-1.29 [P =.46]), leading to a significant interaction between TTR and comorbidity (P = .001). CONCLUSIONS: The results of the current study indicate that considering an intermittent course of ADT such that the TTR approaches 18 months, instead of continuous long-term administration of ADT, in men with moderate to severe comorbidity and high-risk PC may reduce the increased risk of CVM without increasing the risk of PCSM. Cancer 2018;124:1391-9. © 2018 American Cancer Society.

Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

BACKGROUND: Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. METHODS: Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. RESULTS: After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. CONCLUSIONS: Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society.

Early Versus Delayed Initiation of Salvage Androgen Deprivation Therapy and Risk of Prostate Cancer-Specific Mortality.

Background: This study sought to ascertain whether there is an association between prostate cancer (PC)-specific mortality (PCSM) and timing of salvage androgen deprivation therapy (ADT) among men with short versus long prostate-specific antigen doubling times (PSA-DTs). Methods: The study cohort was selected from 206 men with localized unfavorable-risk PC randomized to radiation therapy (RT) or RT plus 6 months of ADT between 1995 and 2001. A total of 54 men who received salvage ADT for PSA failure after a median follow-up of 18.72 years following randomization defined the study cohort. The Fine-Gray competing risks regression model was used to analyze whether the timing of salvage ADT was associated with an increased risk of PCSM after adjusting for age, comorbidity, known PC prognostic factors, and previously identified interactions. Results: After a median follow-up of 5.68 years (interquartile range, 3.05-9.56) following salvage ADT, 49 of the 54 men (91%) died, of which 27 from PC (54% of deaths). Increasing PSA-DT as a continuous covariate (per month increase) was associated with a decreasing risk of PCSM (adjusted hazard ratio [HR], 0.33; 95% CI, 0.13-0.82; P=.02). Among men with a long PSA-DT (≥6 months), initiating salvage ADT later (PSA level >12 ng/mL, upper quartile) versus earlier was associated with an increased risk of PCSM (adjusted HR, 8.84; 95% CI, 1.99-39.27; P=.004), whereas for those with a short PSA-DT (<6 months; adjusted HR, 1.16; 95% CI, 0.38-3.54; P=.79) this was not true. Conclusions: Early initiation of salvage ADT for post-RT PSA failure in men with a PSA-DT of ≥6 months may reduce the risk of PCSM.

The likelihood of death from prostate cancer in men with favorable or unfavorable intermediate-risk disease.

BACKGROUND: Recently, men with intermediate-risk prostate cancer (PC) were classified into favorable and unfavorable categories; however, whether the risk of PC-specific mortality (PCSM) among men with high-risk PC versus unfavorable intermediate-risk PC is increased is unknown. METHODS: In a prospective, randomized trial conducted between 1995 and 2001, 206 men with intermediate-risk or high-risk PC were randomized to receive 70 Gy with or without 6 months of androgen-suppression therapy (AST). The subgroup of 197 patients with information available on the percentage of positive biopsies formed the cohort. Fine and Gray regression analysis was used to assess whether men with high-risk PC versus unfavorable intermediate-risk PC had an increased risk of PCSM. RESULTS: After a median follow-up of 14.3 years, there were 127 deaths (64.5%), including 22 deaths (17.3%) from PC. There were no PC deaths in the favorable intermediate-risk group. There was an increase in the risk of PCSM among men with high-risk PC versus unfavorable intermediate-risk PC, but the difference was not significant (adjusted hazard ratio, 1.59; 95% confidence interval, 0.66-3.83; P = .30) after adjusting for age, randomized treatment arm, and comorbidity. CONCLUSIONS: The lack of PC deaths among men with favorable intermediate-risk PC suggests that adding AST may not reduce their risk of PCSM; whereas many men with unfavorable intermediate-risk PC are at risk for harboring occult PC with Gleason scores from 8 to 10 and, if proven, would benefit from long-term AST. Multiparametric magnetic resonance imaging and targeted biopsy of suspicious lesions should be considered to identify PC with Gleason scores from 8 to 10 in these men.

Risk of malignancy in renal biopsy: A review.

The risks of malignancy for cytologic categories in renal biopsy specimens differ from the risks in most other sites. There are obvious areas in which cytopathologists can do better at classifying these cases, and the routine use of immunohistochemistry and core-needle biopsy may improve the accuracy of the classification of these specimens.

Modified Bethesda criteria for thyroid aspirates significantly decrease nondiagnostic rates without decreasing sensitivity.

INTRODUCTION: Previous studies suggest that the adequacy rate of thyroid aspirates can be improved by altering the adequacy criteria of the Bethesda System. We sought to measure the performance of these altered criteria in a prospective fashion. MATERIALS AND METHODS: Over a 6-year period, cases with 1 to 59 follicular cells were prospectively classified as "nondiagnostic, favor benign" or "scant but adequate". "Scant but adequate" cases were classified as either benign (Bethesda category 2) or atypia of undetermined significance (AUS) (Bethesda category 3). Bethesda category 3 cases were referred for Afirma testing (Veracyte, San Francisco, CA). RESULTS: Of 5147 cases, 131 (3%) were classified as "nondiagnostic, favor benign"; 45 (65%) of these had follow-up with a risk of malignancy of 2.6%. Additionally, 436 (8%) of all 5147 cases were classified as "scant but adequate" and "benign"; 49 (11%) of these had follow-up with a risk of malignancy of 0%. Lastly, 197 (4%) of all 5147 cases were classified as "scant but adequate" with AUS; 177 (90%) of these 197 cases had an adequate Afirma result. The "suspicious" rate was not significantly different than that of cases classified as "adequate" and AUS (Bethesda category 3 and 4) (35 of 197 [18%] versus 140 of 848 [17%] P = 0.67), and there was no significant difference in the risk of malignancy for these 2 categories ("scant but adequate" 9 of 18, "adequate" 50% versus 27 of 85, 32%, P = 0.10). Overall, the modified Bethesda criteria reduced the nondiagnostic rate from 22% to 10% (P <0.001) without lowering the sensitivity of the test. CONCLUSIONS: Modified Bethesda adequacy criteria can significantly lower nondiagnostic rates without lowering sensitivity.

Diagnostic terminology for benign/low-risk tumors on renal cytology.

Biopsy of benign and low-risk tumors of the kidney can be grouped into three distinct categories with different levels of risk, and the suggested diagnoses of these tumors should be tailored to their respective category.

Posttreatment prostate specific antigen nadir predicts prostate cancer specific and all cause mortality.

PURPOSE: We investigated whether the prostate specific antigen nadir predicts prostate cancer specific and all cause mortality in men treated in a randomized trial of radiation with or without 6 months of androgen deprivation therapy. MATERIALS AND METHODS: The study included 204 men with cT1b-T2bN0M0 prostate adenocarcinoma and at least 1 unfavorable factor, including prostate specific antigen less than 10 to 40 ng/ml, Gleason 7 or greater, or T3 on magnetic resonance imaging. We performed Fine and Gray regression, and Cox multivariable analysis to determine whether an increasing prostate specific antigen nadir was associated with prostate cancer specific and all cause mortality, adjusting for treatment, age, Adult Comorbidity Evaluation 27 score and cancer prognostic factors. RESULTS: At a 6.9-year median followup median prostate specific antigen nadir was 0.7 ng/ml for radiation alone and 0.1 ng/ml for radiation plus androgen deprivation therapy. The prostate specific antigen nadir (adjusted HR 1.18/ng/ml increase, 95% CI 1.07-1.31, p=0.001) and Gleason 8 or greater (adjusted HR 8.05, 95% CI 1.01-64.05, p=0.049) significantly predicted increased prostate cancer specific mortality. Moderate/severe comorbidity carried a decreased risk (adjusted HR 0.13, 95% CI 0.02-0.96, p=0.045). Higher prostate specific antigen nadir (adjusted HR 1.10/ng/ml increase, 95% CI 1.04-1.17), older age (adjusted HR 1.10/year, 95% CI 1.04-1.15) and interaction between comorbidity score and randomization arm (each p<0.001) increased the all cause mortality risk. Men who achieved a prostate specific antigen nadir of the median value or less had lower estimated prostate cancer specific and all cause mortality at 7 years (3.7% vs 18.3%, p=0.0005 and 31.5% vs 55.0%, p=0.002). CONCLUSIONS: Posttreatment prostate specific antigen nadir is significantly associated with the risk of prostate cancer specific and all cause mortality after radiation with or without androgen deprivation therapy. A suboptimal prostate specific antigen nadir may identify candidates for earlier intervention to prolong survival.

Gene expression correlates of clinical prostate cancer behavior.

Prostate tumors are among the most heterogeneous of cancers, both histologically and clinically. Microarray expression analysis was used to determine whether global biological differences underlie common pathological features of prostate cancer and to identify genes that might anticipate the clinical behavior of this disease. While no expression correlates of age, serum prostate specific antigen (PSA), and measures of local invasion were found, a set of genes was identified that strongly correlated with the state of tumor differentiation as measured by Gleason score. Moreover, a model using gene expression data alone accurately predicted patient outcome following prostatectomy. These results support the notion that the clinical behavior of prostate cancer is linked to underlying gene expression differences that are detectable at the time of diagnosis.

Cytology should create structured data sets without using synoptic reporting.

Structured data sets can be created from cytology reports without the addition of synoptic reports using either natural language processing or minor changes to laboratory information systems structure.

Sclerosis of the clavicle--A challenging diagnosis.

Condensing osteitis of the clavicle is a rare benign disease described as an increase in bone density at the medial end of the clavicle. Its clinical and radiographic presentation can frequently be equivocal and tissue sampling is necessary for diagnostic confirmation. Here we present the case of a 29-year-old female with condensing osteitis of the right medical clavicle, who remained undiagnosed for many years despite obtaining imaging studies and undergoing an initial biopsy. This disease presents oftentimes a challenging diagnosis due to its imaging features overlapping with many benign and malignant bone lesions. A qualified multidisciplinary team with expertise in rare bone conditions becomes oftentimes essential to arrive at an accurate diagnosis.

Non-diagnostic rates for thyroid fine needle aspiration are negatively correlated with positive for malignancy rates.

INTRODUCTION: Non-diagnostic rates for thyroid fine needle aspiration vary considerably, but reasons for this variation are poorly understood. METHODS: Our group reviewed the results of all thyroid aspirations with surgical resection for the last 13 years at our institutions, combined these with those in the literature, and correlated non-diagnostic rates with positivity rates. RESULTS: Non-diagnostic rates were negatively correlated with positivity rates (R2=0.55). Studies that had significantly lower non-diagnostic rates than the rest of the literature (2 vs. 15%, p=0.002) had different or undefined adequacy criteria or used core biopsies in addition to fine needle aspiration. CONCLUSIONS: Non-diagnostic rates for thyroid fine needle aspirations are negatively correlated with positivity rates. These data provide more realistic estimates of achievable adequacy rates.

Rapid pre-screening is more sensitive in liquid-based cytology than in conventional smears.

Rapid pre-screening (RPS) is a useful tool to measure and improve performance in the cytology laboratory. Whether RPS is more or less effective in liquid-based cytology than in conventional smears is unknown. We compared the estimated sensitivity in a laboratory of 11 cytotechnologists which converted from conventional smears to SurePath™ (Becton Dickinson, Franklin Lakes, N.J., USA) liquid based cytology. In the 9 months prior to conversion, 23,286 smears were screened compared with 30,610 smears in the 12 months immediately after conversion. The estimated sensitivity of rapid pre-screening for 90 s improved significantly with liquid based cytology for all abnormalities (58.7 vs. 68.7%, p<0.001), atypical squamous cells of undetermined significance+low-grade squamous intra-epithelial lesion (52.6 vs. 63.1%, p<0.001), and high-grade squamous intra-epithelial alone (76.2 vs. 85%, p<0.001). Histologic follow up for 156 cases identified by rapid pre-screening of SurePath slides showed 32 (21%) cases of CIN1 or greater and 18 cases (12%) with CIN3 or worse. We conclude that rapid pre-screening is significantly more sensitive in liquid-based cytology compared with conventional smears, and detects significant lesions that are missed by routine screening.

Improving Reporting of Tumor Size in Synoptic Reports.

CONTEXT.­: Tumor size is an important prognostic feature in many synoptic reports. The best format to report this feature is not clearly defined. OBJECTIVE.­: To define formatting features that impact the significance of tumor size. DESIGN.­: We reviewed multiple formatting features of tumor size in synoptic reports and correlated them with size distribution, reproducibility, and other pathologic features. RESULTS.­: Reporting tumors in millimeters rather than centimeters was more precise because of reduced rounding error and was significantly more reproducible (P = .01). Tumor sizes where the pathologist was concerned that the size may be underestimated are associated with significantly higher tumor N stage than tumors of similar size that are not so identified. Reported tumor sizes in multifocal tumors are also associated with significantly higher N stage than unifocal tumors of the same size. CONCLUSIONS.­: Tumor sizes should be reported in millimeters, and when tumors are reported as either "at least" a specific size or as "multifocal" this information should also be recorded because these sizes likely underestimate the true biologic potential of the tumor.

High-grade urothelial carcinoma with hypochromatic chromatin in urine cytology.

INTRODUCTION: Some high-grade urothelial carcinomas (UCs) in urine cytology have hypochromatic chromatin, but the incidence and criteria for diagnosis are not well described. MATERIALS AND METHODS: Urine cytology cases with biopsy follow up were reviewed. RESULTS: Cytospin preparations from 331 cases with biopsy follow up (230 benign/low-grade UC, 101 malignant) were reviewed. There were no false-positive cases. Cases with malignant cells with hypochromatic chromatin were identified in a total of 17 cases (16.8% of all malignancies). These comprised 2 carcinoma in situ, 11 high-grade papillary UC, 3 invasive UC, and 1 adenocarcinoma. Sixteen of 93 high-grade UCs (17.2%) had cells with hypochromatic chromatin. These cells were the only type of malignant cell in 4 of 101 cases (4.0%). All cases had cells with high nuclear-to-cytoplasmic ratios and markedly indented and irregular nuclear membranes that could be identified on both cytology and subsequent histology. CONCLUSIONS: Malignant urothelial cells in urine cytology with hypochromatic chromatin can be present in 17% of cases and can be diagnosed as "positive for malignancy" based on their high nuclear-to-cytoplasmic ratio, and markedly indented and irregular nuclear membranes.

Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.

PURPOSE: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist. METHODS: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors. RESULTS: After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL. CONCLUSION: Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.

Thyroid FNA: Is cytopathologist review of ultrasound features useful?

Cytopathologist review of thyroid ultrasound (US) has been proposed to be useful in diagnosis and patient triage. This review explores the implications for practicing cytopathologists of integrating US review into the thyroid fine-needle aspiration diagnosis. At present, there is no agreed-upon system for combining cytologic and US features and communicating those results as a single report. If cytologists are performing tasks that require expertise in US interpretation, then they should know and be fully conversant with US interpretation. Whether cytologists performing aspirations require expertise in US interpretation is not clear. Regardless, cytologists should avoid using US results to alter their cytologic interpretations unless they clearly communicate that this is what they are doing. An evidence-based integrated reporting system that would allow cytologists to clearly explain to other physicians exactly how they reached their interpretation might provide value beyond current standard practice.

Malignancy risk for solitary and multiple nodules in Hürthle cell-predominant thyroid fine-needle aspirations: A multi-institutional study.

BACKGROUND: Hürthle cell metaplasia is common in hyperplastic nodules, particularly within the setting of lymphocytic thyroiditis (LT). The Bethesda System for Reporting Thyroid Cytopathology indicates that it is acceptable to classify Hürthle cell-predominant fine-needle aspiration (HC FNA) specimens as atypia of undetermined significance (AUS) rather than suspicious for a Hürthle cell neoplasm (HUR) within the setting of multiple nodules or known LT. The goal of the current study was to address whether this approach is justified. METHODS: HC FNA specimens were identified and correlated with ultrasound and surgical pathology reports if available. Multinodularity was determined based on findings on macroscopic examination if imaging results were unavailable. RESULTS: A total of 698 HC FNA specimens were identified, including 576 resected nodules, 455 of which (79%) were benign. The overall risk of malignancy for HUR was 27%, whereas the risk of malignancy for AUS was 10%. The mean size of the benign nodules was 2.1 cm on surgical resection specimens, with multiple nodules noted in 293 cases (64%) and histologic LT noted in 116 cases (25%). The mean size of the malignant nodules was 2.8 cm, with multiple nodules and histologic LT noted in 74 cases (61%) and 22 cases (18%), respectively. The malignancy rate did not differ between solitary or multiple nodules (P = .52) or in the presence or absence of LT (P = .12). However, size did significantly differ between malignant and benign nodules (P < 0.01). CONCLUSIONS: The malignancy rate did not differ significantly in the presence of multiple nodules or LT, although the latter demonstrated a statistical trend. A diagnosis of AUS over HUR based solely on the presence of multinodularity is not warranted.

Surrogate indicators of sensitivity in gynecologic cytology: can they be used to improve the measurement of sensitivity in the laboratory?

BACKGROUND: Measuring the sensitivity of screening in gynecologic cytology in real life is problematic. However, other quality measures may correlate with sensitivity, including the atypical squamous cells (ASC)/squamous intraepithelial lesion (SIL) ratio. Whether these other measures can function as "surrogate indicators" for sensitivity and improve the assessment of sensitivity in the laboratory is not known. MATERIALS AND METHODS: We compared multiple quality measures with true screening sensitivity in a variety of situations. RESULTS: The abnormal rate, ASC rate, and ASC/SIL ratio were all highly correlated (r =.83 or greater) with sensitivity when the overall laboratory sensitivity was low (85%) but became less correlated (.64 or less) or uncorrelated when the screening sensitivity was higher (88% or 95%, respectively). Sensitivity was more highly correlated with the abnormal rate than the ASC/SIL ratio at low screening sensitivity. While thresholds could be set that were highly sensitive and specific for suboptimal screening, these thresholds were often less than one standard deviation away from the mean. CONCLUSION: The correlation of the abnormal rate and the ASC/SIL ratio with sensitivity depends on overall sensitivity. Standards to define minimum screening sensitivity can be defined, but these standards are relatively narrow. These features may limit the utility of these quality measures as surrogates for sensitivity.